Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. Psychopharmacological treatment of panic disorder and related states: A Placebo controlled study of alprazolam Treatment of Panic Disorder with Agoraphobia: Randomized Placebo‐Controlled Trial of Four Psychosocial Treatments Combined with Imipramine or Placebo Do antidepressants selectively suppress spontaneous (unexpected) panic attacks? A replication. Clomipramine and fluoxetine effects in the treatment of panic disorder. Interactive Model of Therapeutic Response in Panic Disorder: Moclobemide, a Case in Point Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trial. The effect of citalopram in panic disorder. Forms of atypical depression and their response to antidepressant drugs Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatients Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia? Global measures of outcome in a controlled comparison of pharmacological and psychological treatment of panic disorder and agoraphobia in primary care. The effect of mirtazapine in panic disorder: an open label pilot study with a single-blind placebo run-in period Specific Side Effects of Long-Term Imipramine Management of Panic Disorder A prospective naturalistic study of 326 panic-agoraphobic patients treated with antidepressants. Superiority of clomipramine over imipramine in the treatment of panic disorder: a placebo-controlled trial. A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder. Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder. Sertraline in the treatment of panic disorder: a flexible-dose multicenter trial. The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study. Mirtazapine versus fluoxetine in the treatment of panic disorder. Rate of improvement during and across three treatments for panic disorder with or without agoraphobia: cognitive behavioral therapy, selective serotonin reuptake inhibitor or both combined. The use of the Panic and Agoraphobia Scale (P & A) in a controlled clinical trial. Adverse effects associated with the short-term treatment of panic disorder with imipramine, alprazolam or placebo Imiprmaine vs. Sertraline in Panic Disorder: 24-Week Treatment Completers Alprazolam in the treatment of generalized anxiety and panic disorders: A double-blind placebo-controlled study Controlled trials of inositol in psychiatry Open‐Label Support for Duloxetine for the Treatment of Panic Disorder Olanzapine Augmentation in Treatment-Resistant Panic Disorder: A 12-Week, Fixed-Dose, Open-Label Trial A 15-year follow-up study of patients with panic disorder. Time to response in panic disorder in a naturalistic setting: combination therapy with alprazolam orally disintegrating tablets and serotonin reuptake inhibitors compared to serotonin reuptake inhibitors alone. Alprazolam, Propranolol, and Placebo in the Treatment of Panic Disorder and Agoraphobia with Panic Attacks Carbon dioxide/oxygen challenge test in panic disorder Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial. Antipanic Drug Modulation Of 35% CO2 Hyperreactivity and Short-Term Treatment Outcome Drug treatment of panic disorder: early response to treatment as a predictor of final outcome Treatment of panic disorder with agoraphobia: comparison of fluvoxamine, placebo, and psychological panic management combined with exposure and of exposure in vivo alone. Effect of Antipanic Treatment on Response to Carbon Dioxide Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam. Changes in Appetite and Weight during the Pharmacological Treatment of Patients with Panic Disorder * Clonazepam in the treatment of panic disorder: a double-blind, placebo-controlled trial investigating the correlation between clonazepam concentrations in plasma and clinical response. Double-blind clonazepam vs placebo in panic disorder treatment. Efficacy, safety, and gradual discontinuation of clonazepam in panic disorder: a placebo-controlled, multicenter study using optimized dosages. Antidepressant discontinuation in the context of cognitive behavioral treatment for panic disorder. Radio electric treatment vs. Es-Citalopram in the treatment of panic disorders associated with major depression: an open-label, naturalistic study. Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison. A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder SECOND-STAGE TREATMENTS FOR RELATIVE NONRESPONDERS TO COGNITIVE BEHAVIORAL THERAPY (CBT) FOR PANIC DISORDER WITH OR WITHOUT AGORAPHOBIA-CONTINUED CBT VERSUS SSRI: A RANDOMIZED CONTROLLED TRIAL. Influence of panic-agoraphobic spectrum symptoms on treatment response in patients with recurrent major depression. Clomipramine in the treatment of agoraphobic inpatients resistant to behavioral therapy. D-cycloserine does not improve but might slightly speed up the outcome of in-vivo exposure therapy in patients with severe agoraphobia and panic disorder in a randomized double blind clinical trial. Sertraline and alprazolam in the treatment of panic desorder. Reboxetine and citalopram in panic disorder: a single-blind, cross-over, flexible-dose pilot study A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study. 12-month prevalence of panic disorder with or without agoraphobia in the Swedish general population Suicidal ideation and suicide attempts in panic disorder and attacks. A randomized clinical trial of cognitive behavioral therapy and interpersonal psychotherapy for panic disorder with agoraphobia. Aripiprazole as an augmentor of selective serotonin reuptake inhibitors in depression and anxiety disorder patients Evidence that decreased function of lymphocyte beta adrenoreceptors reflects regulatory and adaptive processes in panic disorder with agoraphobia. Efficacy and tolerability of controlled-release paroxetine in the treatment of panic disorder. Effects of the 5-HT1A receptor agonist flesinoxan in panic disorder Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group. Improvement of quality of life in panic disorder with escitalopram, citalopram, or placebo. Longitudinal outcome with pharmacotherapy in a naturalistic study of panic disorder. Do selective serotonin re-uptake inhibitors enhance the efficacy of very brief cognitive behavioral therapy for panic disorder? A pilot study 5-HT1A responsivity in patients with panic disorder before and after treatment with aerobic exercise, clomipramine or placebo Randomised placebo-controlled trial of moclobemide, cognitive-behavioural therapy and their combination in panic disorder with agoraphobia. Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. I. Efficacy in short-term treatment. Placebo-controlled study of gabapentin treatment of panic disorder. Chronology of panic and avoidance, age of onset in panic disorder, and prediction of treatment response Avoidance behaviour: A predictor of the efficacy of pharmacotherapy in panic disorder? Effect of a selective serotonin uptake inhibitor in agoraphobia with panic attacks A double‐blind comparison of zimeldine, imipramine and placebo The use of low-dose intranasal midazolam to treat panic disorder: a pilot study. Two-year course trajectories of anxiety disorders: do DSM classifications matter? Therapeutic response to benzodiazepine in panic disorder subtypes.
BACKGROUND Tricyclic antidepressants and selective serotonin reuptake inhibitors ( SSRIs ) as well as benzodiazepines have been shown to be effective for the treatment of panic disorder . The introduction of SSRIs has enabled a greater underst and ing of the role of serotonin in the etiology of panic disorder ; however , the role of norepinephrine has been more challenging to ascertain . The aim of this study was to determine the efficacy and tolerability of reboxetine , a novel selective norepinephrine reuptake inhibitor , in patients with panic disorder with and without agoraphobia . METHOD Eighty-two patients ( aged 18 - 65 years ) with DSM-III-R panic disorder , with or without agoraphobia , were r and omly assigned to receive 6 to 8 mg/day of reboxetine ( 42 patients ) or placebo ( 40 patients ) for 8 weeks in this placebo-controlled , parallel-group , double-blind clinical trial . RESULTS Of the 82 patients enrolled in the trial , 75 were considered in the analysis ( 37 patients in the reboxetine group and 38 patients in the placebo group ) . At last assessment , there was a significant reduction in the mean number of panic attacks ( range , 9.3 - 1.2 ) and phobic symptoms ( range , 8.1 - 3.2 ) in the reboxetine group compared with the placebo group ( ranges , 8.5 - 5.8 and 7.7 - 5.2 , respectively ; p < .05 ) . Improvement in Hamilton Rating Scale for Depression , Hopkins Symptom Checklist-90 , and Sheehan Disability Scale scores were also greater in the reboxetine group compared with the placebo group . Adverse events reported more frequently with reboxetine than placebo included dry mouth ( 36 % vs. 16 % ) , constipation ( 27 % vs. 22 % ) , and insomnia ( 26 % vs. 22 % ) . CONCLUSION Reboxetine was effective and well tolerated in the treatment of panic disorder BACKGROUND Escitalopram , the therapeutically active isomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram , has shown significant anxiolytic effects in placebo-controlled clinical trials of social anxiety disorder , generalized anxiety disorder , and anxiety symptoms associated with major depression . This study evaluated the safety and efficacy of escitalopram in out patients diagnosed with panic disorder . METHOD Male and female out patients between 18 and 80 years of age meeting DSM-IV criteria for panic disorder , with or without agoraphobia , were r and omly assigned to 10 weeks of double-blind treatment with escitalopram , citalopram , or placebo in a study conducted from September 1999 to July 2001 . The primary measure of efficacy was panic attack frequency at week 10 relative to baseline , as assessed by the Modified Sheehan Panic and Anticipatory Anxiety Scale . RESULTS A total of 366 subjects ( 128 escitalopram patients , 119 citalopram patients , and 119 placebo patients ) received at least 1 dose of double-blind treatment . The frequency of panic attacks was statistically significantly improved ( p = .04 ) , and the increase in percentage of patients with zero panic attacks reached borderline significance ( p = .051 ) , in the escitalopram-treated group relative to the placebo-treated group . Both escitalopram and citalopram statistically significantly reduced panic disorder symptoms and severity versus placebo at endpoint ( p < /=.05 ) , as measured by the Panic and Agoraphobia Scale total score , the Clinical Global Impressions scale , the Patient Global Evaluation , and the Quality of Life Enjoyment and Satisfaction Question naire . Treatment with escitalopram was safe and well tolerated , with a similar incidence of the most common adverse events for the escitalopram and placebo groups . The rate of discontinuation for adverse events was 6.3 % for escitalopram , 8.4 % for citalopram , and 7.6 % for placebo . CONCLUSION Escitalopram is efficacious , safe , and well tolerated in the treatment of panic disorder The paper consists of two parts . A review of the relationship of panic disorder to the phobic states and the treatment of these disorders by means of tricyclic antidepressants , MAOIs , beta blocking drugs and benzodiazepines . A double blind study of alprazolam and placebo in 118 patients with agoraphobia and panic is presented . In an eight week study alprazolam was found to be significantly superior to placebo in the treatment of panic attacks , phobic avoidance , anticipatory anxiety and general anxiety Few r and omized controlled trials have included panic disorder patients with moderate to severe agoraphobia . Therefore , this population was studied using pharmacotherapy as well as psychotherapy . At the time of the study , imipramine was widely used as a pharmacological treatment . Also , current practice guidelines for patients with panic disorder find selective serotonin reuptake inhibitors and tricyclic antidepressants roughly comparable in terms of efficacy . Therefore , the main objective of this study is to compare four psychosocial treatments — cognitive and grade d in vivo exposure treatments , grade d in vivo exposure , cognitive treatment , and supportive therapy — to evaluate the benefits of combining cognitive therapy with exposure in vivo . These treatments were combined with imipramine or placebo for a total of eight experimental conditions . Participants presented moderate to severe agoraphobia . The method involved a r and omized , double‐blind , placebo‐controlled trial with 137 participants who completed a 14‐session protocol involving the treatments just mentioned . Measures were taken at baseline and posttreatment and at 3‐ , 6‐ , and 12‐month follow‐up . All treatment conditions were statistically and clinical ly effective in reducing self‐reported panic – agoraphobia symptoms over the 1‐year follow‐up . No statistical differences were observed between imipramine and placebo conditions . This study found that all treatment modalities helped reduce panic and agoraphobic symptomatology over a 1‐year follow‐up period . These surprising results support the need to document the relations among the various components of an intervention . This would make it possible to assess the relative efficacy of the treatment components rather than of the intervention as a whole The purpose of this study was to test the following interrelated hypotheses in a larger sample by attempting to replicate supportive results from a small therapeutic study : ( 1 ) the pathogenesis of panic disorder includes at least two identifiable components : a biological component represented by spontaneous ( unexpected ) panic attacks , and a cognitive component represented by situational attacks and especially by phobias ; ( 2 ) these components respond differently to treatment ; ( 3 ) many biological processes respond to an effective intervention in proportion to their deviance from " normal " prior to treatment ( " Law of Initial Value " ) ; and ( 4 ) the response of spontaneous panic attacks to an effective treatment conforms to that model . Previously , the authors reanalyzed an 8-week therapeutic study of panic disorder that included groups treated with  placebo  and with  imipramine ( 225 mg daily ) . The criteria of response were spontaneous panic attacks ( biological component ) , situational panic attacks ( both components ) , and agoraphobia ratings ( cognitive component ) . The analyses compared the regression lines for posttreatment status on pretreatment status in the imipramine and placebo groups . The effect of imipramine on spontaneous panic attacks fitted the hypothesized model : the pre-post slope in the placebo group was approximately 1 ( 45 degrees ) , whereas the slope in the imipramine group was approximately 0 . There was no significant difference in pre-post slopes between the imipramine and placebo groups for situational panic attacks or agoraphobia ratings . For this report , the authors applied the same approach to another larger data set from a study using a similar design , but a different antidepressant . In this multicenter , double-blind study , patients with panic disorder were r and omly assigned to receive 10 weeks of treatment with  placebo ( N = 78 ) or fluoxetine 10 mg ( N = 84 ) or 20 mg ( N = 81 ) daily . Spontaneous and situational panic attacks were registered in a daily diary , and agoraphobia was rated at each visit . Using baseline and endpoint data , fluoxetine had a statistically significant , dose-dependent , suppressive effect on spontaneous panic attacks , as measured by the pre-post slopes in the three treatment groups . The placebo group showed some response ( slope = 0.69 ) . There were no significant drug effects on situational panic attacks . On ratings of agoraphobia , the slopes in the placebo and the fluoxetine 20 mg groups did not differ , but the slope in the fluoxetine 10 mg group was significantly less than that in the placebo group , suggesting a therapeutic drug effect on agoraphobia only at the lower dose . These results are consistent with the stated hypotheses . They suggest that the therapeutic effects of antidepressants on panic disorder may be due primarily to the specific suppression of spontaneous panic attacks among patients with high baseline pathologic findings . Implication s of these results for concepts of pathogenesis , clinical practice , and therapeutic research regarding panic disorder are discussed Panic disorder ( PD ) is an acute psychobiologic reaction manifested by intense anxiety and panic attacks , that occur unpredictably with subjective sense of intense apprehension or terror , accompanied by temporary loss of the ability to plan , think , or reason and the intense desire to escape or flee the situation . Panic attacks may last from a few seconds to an hour or longer . Symptoms typically include , among others , palpitations , tachycardia , hypertension , chest pain , dyspnoea , and fear of loosing control or going crazy and vague feeling of imminent doom or death . Since pharmacotherapy of PD includes the administration of selective serotonin reuptake inhibitors and tricyclic antidepressants , the objective of this study was to perform a pilot double blind clinical trial design ed to compare the effects of two studied drugs in the treatment of PD . A total number of 40 patients with a history of panic disorder were r and omly assigned into two groups of 20 patients each . Hamilton anxiety rating scale and St and ard Psychiatric Interview were methods for PD assessment . One group was treated with clomipramine hydrochloride ( ANAFRANIL ) 75 mg/day and the other with fluoxetine ( OXETIN ) 60 mg/day . Both drugs were administrated by mouth ( PO ) two times-a-day in equally divided doses for 6 weeks . Both studied agents produced similar antipanic effectiveness . Favourable response was achieved in 95 % of patients treated with fluoxetine and 90 % of patients treated with clomipramine . The onset of antipanic effects was quicker in all clomipramine treated patients , while fluoxetine produced more-favourable response in male patients . The duration of treatment with both antidepressants studied should be at least 10 weeks , instead of 6 weeks It was proposed that pre-post regression slopes be used to index treatment response when the effect of baseline scores differed among treatments ( interaction between treatment and baseline score ) . Reanalyses of two studies using imipramine and fluoxetine in panic disorder showed doserelated decreases in pre-post slopes for the frequency of unexpected panic attacks , but not for the frequency of situational panic attacks or measures of agoraphobia . This report presents similar analyses of data from a study using moclobemide .  Patients ( N = 452 ) with panic disorder were r and omized to placebo  or a fixed dose of moclobemide ( 75 , 150 , 300 , 600 , or 900 mg/day ) . They were treated double-blindly and evaluated at baseline and 1 , 2 , 3 , 4 , 6 , and 8 weeks later . The authors analyzed the frequency of unexpected and situational panic attacks compiled from a daily diary , and fear and avoidance ratings based on the patient ’s main phobia using baseline ( pre ) and end-point ( post ) values for all r and omized patients . Adjoining dose groups were combined . Both unexpected and situational panic attacks showed systematic doserelated suppression of pre-post treatment slopes . Neither pre-post slopes nor adjusted posttreatment means for fear and avoidance differed reliably between treatment arms . This study replicates the authors ’ earlier findings , except for situational panic attacks , which probably were not reliably identified . Antidepressants selectively suppress panic attacks , especially unexpected attacks , but not agoraphobia . The findings are consistent with the hypothesis that panic disorder with agoraphobia has clinical ly separable biologic and cognitive components that respond differentially to treatment . Antidepressants benefit primarily patients with many unexpected panic attacks . Investigators should evaluate pre-post treatment slopes before comparing adjusted posttreatment means ( analysis of covariance ) BACKGROUND Although serotonin reuptake inhibitors are effective in panic disorder , questions concerning whether doses associated with antidepressant efficacy are also effective for panic disorder remain . AIMS To assess the efficacy of the usual antidepressant dose of fluoxetine in treating full panic attacks . METHOD Patients with panic disorder were r and omised to placebo or to fluoxetine initiated at 10 mg daily for 1 week and then increased to 20 mg daily . The trial lasted 12 weeks , but after 6 weeks patients who had failed to achieve a satisfactory response were eligible for dose escalation to a maximum of 60 mg of fluoxetine daily . RESULTS Fluoxetine was associated with a statistically significantly greater proportion of panic-free patients compared with placebo after 6 weeks and at end-point . CONCLUSIONS Fluoxetine at a dose of 20 mg daily is safe and efficacious in reducing symptoms of panic disorder . Patients who fail to obtain a satisfactory response at 20 mg daily may benefit from further dose increases BACKGROUND Citalopram is a serotonin reuptake inhibitor which has been demonstrated to be highly selective and with a superior tolerability profile to the classical tricyclic antidepressants . This study was design ed to test whether there was any difference in efficacy in the management of panic disorder ( PD ) between citalopram and placebo . METHOD This was a double-blind , placebo and clomipramine controlled , parallel group eight-week study . A total of 475 patients with PD , with or without agoraphobia , were r and omised to treatment with either placebo , clomipramine 60 or 90 mg/day , or citalopram 10 or 15 mg/day , or 20 or 30 mg/day , or 40 or 60 mg/day . Doses were increased over the first three weeks , stabilised during the fourth week and fixed between weeks five and eight . RESULTS Treatment with citalopram at 20 or 30 mg , 40 or 60 mg and clomipramine were significantly superior to placebo , judged by the number of patients free of panic attacks in the week prior to the final assessment . All rating scales examined suggested that citalopram 20 or 30 mg was more effective than citalopram 40 or 60 mg . CONCLUSION The most advantageous benefit/risk ratio for the treatment of PD was associated with citalopram 20 or 30 mg/day Three definitions of atypical depression are evaluated with respect to the effects of monoamine oxidase inhibitors ( MAOIs ) and tricyclic antidepressants ( TCAs ) on the basis of pooled data from several double-blind studies . Those three definitions of atypical depression are depression with associated panic , depression secondary to a diagnosis of anxiety , and depression with reversed vegetative change . In none of these forms was a drug difference observed . However , when gender was taken into account , MAOIs were superior to TCAs in depressed women with panic attacks , whereas TCAs were superior to MAOIs in depressed men with panic attacks Serotonergic mechanisms have been implicated in panic disorder , and several preliminary studies suggest that fluvoxamine , a selective serotonin reuptake inhibitor ( SSRI ) , is helpful in its treatment . This 8-week double-blind parallel-group study compared fluvoxamine with a placebo in 188 patients with DSM-III-R defined panic disorder with or without agoraphobia . Efficacy assessment s included a Daily Panic Attack Inventory , the Sheehan Disability Scale , the Clinical Anxiety Scale and the Clinical Global Impression Scale . When compared with the placebo , fluvoxamine produced highly significant improvements in most measures of the frequency and severity of panic disorder and in the more global aspects of disability and distress . Significant improvement was evident as early as week 1 for some panic variables . Fluvoxamine is a potent anti-panic agent with a relatively rapid onset of action OBJECTIVE Recently , pharmacological treatment guidelines for panic disorder have changed as newer treatment options have become available . The authors examined how the use of psychotropic drugs has shifted over the course of 10 years to determine if prescribing patterns have changed to reflect these revised treatment guidelines . METHOD A total of 443 patients with panic disorder were enrolled in the Harvard/Brown Anxiety Research Project , a prospect i ve longitudinal study of anxiety disorders . These patients were interviewed over the course of 10 years to examine their use of psychotropic medications . RESULTS Despite efforts aim ed at increasing the use of selective serotonin reuptake inhibitors ( SSRIs ) in patients with panic disorder ( e.g. , APA 's practice guideline for panic disorder , Food and Drug Administration approval of particular SSRIs for the treatment of panic disorder ) , only a modest increase in their use was found . Treatment patterns for psychotropic drugs  appear to have remained stable over the past decade , with benzodiazepines being the most commonly used medication for panic disorder . In comparison , SSRI use throughout the follow-up period has remained low . Patients using an SSRI did not have a more favorable clinical course than those using a benzodiazepine , nor were there significantly better rates of remission in patients using SSRIs and benzodiazepines concomitantly . CONCLUSIONS These results highlight a gap between pharmacological treatment guidelines and actual delivery of care in that recommendations to use SSRIs to treat panic disorder are not being followed . Factors potentially associated with promoting and ignoring treatment recommendations are discussed BACKGROUND Panic disorder , with and without agoraphobia , is a prevalent condition which presents primarily in general practice . Previous clinical outcome studies have been conducted mainly in specialist university departments or hospital setting s , and have tended to employ complex rating scales that are not well suited for use as outcome measures in primary care . AIM To evaluate the outcome , in a primary care setting , of fluvoxamine versus cognitive behaviour therapy , each used alone and in combination in a double-blind placebo-controlled framework , balanced for therapist contact . METHOD A total of 149 patients satisfying DSMIII-R criteria for panic disorder were r and omly allocated to receive one of the following : fluvoxamine , placebo , fluvoxamine plus cognitive behaviour therapy , placebo plus cognitive behaviour therapy , and cognitive behaviour therapy alone . These five treatment groups represent the minimum number acceptable for such a comparison to be made . All patients received an identical schedule of contact over 13 weeks . Measures of symptom severity , general health and social disruption were taken at entry point and end point ; measures of change in symptoms were taken at end point only . Outcome was reported in terms of brief global ratings of severity of illness and change in symptoms , and of ratings of general health and social disruption that are suitable for use in general practice . RESULTS All active treatment groups showed statistically significant advantages over placebo over a range of outcome ratings . The groups employing cognitive behaviour therapy showed the most robust and consistent response . CONCLUSION The brief global measures reported here proved adequate to the task of assessing treatment outcome . Results indicate that treatments including cognitive behaviour therapy can be effective in the treatment of panic disorder and agoraphobia in primary care In this open label pilot study , we studied the efficacy of mirtazapine ( Remeron ) in panic disorder . Twenty-eight patients with a DSM-IV diagnosis of panic disorder , with or without agoraphobia ( 10 males/18 females ) , were included and 19 patients completed the study . The 15-week trial started with a 3-week single-blind placebo run-in period . After this run-in period , the 12-week active treatment phase started . As primary efficacy measures , we studied the decrease in the number of full symptom panic attacks and the number of patients completely free of panic during the last 3 weeks of the study . Seventy-four percent of the patients were considered responders , according to a decrease of at least 50 % in panic attack frequency . All primary and secondary efficacy measures showed a significant improvement from the second week of active treatment onwards to endpoint . The main side-effects were different from the usual side-effects in selective serotonin reuptake inhibitors ( SSRIs ) ( initial drowsiness , weight gain and pain in the legs ) . The results of this open label study in panic disorder suggest that mirtazapine seems to be a fast and effective treatment alternative for SSRIs in panic disorder In a recent study , the authors suggested that tachycardia , dry mouth , and sweating continued to burden patients with panic disorder with agoraphobia who have shown marked and stable response to 6 months of imipramine treatment at the fixed , weight-adjusted dose of 2.25 mg/kg/day . Although sexual dysfunction and weight gain were not a significant burden in that study , they are important problems in long-term treatment with antidepressant drugs . In the present study , in the context of a r and omized , double-blind , placebo-controlled , 1-year discontinuation and maintenance study of 53 patients with panic disorder with agoraphobia who respond to imipramine  , the authors examine the extent and the specificity of these five side effects of imipramine maintenance using data at pretreatment , at the end of 24 weeks of open imipramine treatment ( or month 0 of r and omization ) , and at months 2 , 4 , 6 , 8 , 10 , and 12 of r and omized treatment . Hierarchical linear modeling and repeated measures of analyses of variance in sub sample s of completers confirmed that dry mouth , sweating , and increased heart rate constitute a significant and specific enduring burden of imipramine maintenance treatment . The data also revealed that weight gain is a significant and specific side effect of 1-year imipramine maintenance treatment ; however , the likelihood of reporting sexual dysfunction decreased over time , with no difference between the placebo and imipramine maintenance conditions . The results are discussed in the context of previous studies of imipramine  side effects in the management of depression and the available literature of sexual and weight side effects of antidepressant medications in the treatment of anxiety disorders OBJECTIVE How far the results of r and omized controlled studies apply to everyday care can not be judged without regular measurements of outcomes in daily practice . We report on systematic data from a 3-year naturalistic prospect i ve study on panic disorder-agoraphobic ( PDA ) patients treated with antidepressants in a setting of routine clinical practice . Our aim is to describe the evolution of PDA in relation to the treatments employed , and to explore demographic and clinical characteristics that might be predictive of outcome . METHODS 326 DSM-III-R PDA patients treated with antidepressants in a setting of routine clinical practice were included in a 3-year naturalistic prospect i ve study . We utilized structured and semi-structures instruments , including the Structured Clinical Interview for Diagnosis and the Longitudinal Interview Follow-up Examination . The main antidepressants used were imipramine ( 39 % ) , clomipramine ( 28.5 % ) and paroxetine ( 23.3 % ) ; only 9 % of patients received other antidepressants . RESULTS 147 patients ( 45.1 % ) stayed on medication throughout the entire period of the follow-up . Of those who interrupted the treatment , 38 % stayed in remission . The probability of achieving at least one remission during the 3-year follow-up period was 96.5 % for PD and 95.9 % for Agoraphobia . Relapses after a period of at least 2 months of complete remission were also common , and the probability of presenting at least one relapse during the 3-years follow-up period was 67.1 % for PD and 39 % for Agoraphobia . The longest period of remission of PD is associated with low severity , medium-lasting course in patients with an onset of the illness in young adulthood . Less severe agoraphobia associated with moderately severe panic attacks appears to confer a better control of phobic behavior . All three major drugs were reasonably well tolerated ( only 9 % dropped out because of side effects ) , with sexual dysfunction and increased appetite being the most common side effects at the last evaluation ; in the first phase of the treatment anticholinergic effects and jitteriness were more common with TCAs . CONCLUSION Both classical antidepressants and paroxetine emerge as a useful treatment in the long-term management of PDA ; paroxetine appears particularly useful in PDA patients because it was significantly less likely to induce jitteriness , thereby reducing barriers to compliance A double-blind , placebo-controlled trial was undertaken to compare the effects of imipramine and clomipramine in the treatment of panic disorder with or without agoraphobia . The number of dropouts in the placebo-treated group was 7 ; in the imipramine-treated group , 4 ; and in the clomipramine treated group , 0 . Ten subjects fulfilled the 12 weeks of treatment in the placebo group , 25 in the imipramine group , and 22 in the clomipramine group . To minimize dropouts because of side effects , a flexible dose regimen with a careful escalation of doses was applied . The maximal dose allowed was 250 mg/day . The mean ( + /- SEM ) daily doses reached were 124 + /- 9 mg ( range , 50 - 250 mg ) of imipramine and 109 + /- 8 mg ( range , 25 - 200 mg ) of clomipramine . At the end of the trial , the number of panic attacks as well as the anxiety between attacks ( measured using the Hamilton Rating Scale for Anxiety ) were markedly reduced in patients treated with either of the two antidepressant drugs , but only slightly decreased in patients on placebo . With respect to all major outcome parameters , i.e. , full panic attacks , total number of anxiety attacks ( full plus mild ) , and anxiety between attacks , the effect of clomipramine was clearly and significantly superior to that of imipramine ( p less than 0.001 , p less than 0.002 , and p less than 0.002 , respectively ) . Moderate intake of diazepam was allowed ; in the clomipramine group ( p less than 0.006 ) , but neither in the imipramine group nor in the placebo group , a significant decrement in diazepam intake was observed during the course of the trial . The finding that clomipramine may have a higher potency and /or efficacy than imipramine in the treatment of panic disorder supports the concept that the antipanic effect of antidepressant drugs is due to the influence of these compounds on serotonergic rather than noradrenergic neurotransmission To date , no large-scale , controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported . This double-blind study compares the efficacy of venlafaxine extended-release ( ER ) and paroxetine with placebo . A total of 664 nondepressed adult out patients who met DSM-IV criteria for panic disorder ( with or without agoraphobia ) were r and omly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER ( 75 mg/day or 150 mg/day ) , or paroxetine 40 mg/day . The primary measure was the percentage of patients free from full-symptom panic attacks , assessed with the Panic and Anticipatory Anxiety Scale ( PAAS ) . Secondary measures included the Panic Disorder Severity Scale , Clinical Global Impressions -- Severity ( CGI-S ) and --Improvement ( CGI-I ) scales ; response ( CGI-I rating of very much improved or much improved ) , remission ( CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks ) ; and measures of depression , anxiety , phobic fear and avoidance , anticipatory anxiety , functioning , and quality of life . Intent-to-treat , last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo . No significant differences were observed between active treatment groups . Panic-free rates at end point with active treatment ranged from 54 % to 61 % , compared with 35 % for placebo . Approximately 75 % of patients given active treatment were responders , and nearly 45 % achieved remission . The placebo response rate was slightly above 55 % , with remission near 25 % . Adverse events were mild or moderate and similar between active treatment groups . Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder OBJECTIVE This study was design ed to determine the minimum paroxetine dose effective for treating panic disorder . METHOD Of 425 patients with DSM-III-R panic disorder with or without agoraphobia who underwent a 2-week drug-free screening period , 278 patients were r and omly assigned to double-blind treatment with a 10-week course of placebo or paroxetine at a dose of 10 , 20 , or 40 mg/day . RESULTS At 40 mg/day , paroxetine was superior to placebo across the majority of outcome measures . Despite a mean of 9.5 to 11.6 full panic attacks during the screening period , 86.0 % of the patients taking 40 mg of paroxetine , 65.2 % of those taking 20 mg , 67.4 % of those taking 10 mg , and 50.0 % of the placebo-treated patients were free of full panic attacks during the 2 weeks ending at week 10 . The 40-mg paroxetine group experienced significantly greater global improvement than the placebo group and significantly greater improvement in frequency of full and limited-symptom panic attacks , intensity of full panic attacks , phobic fear , anxiety , and depressive symptoms , usually evident by week 4 . All doses of paroxetine were well tolerated , and adverse effects were consistent with those associated with selective serotonin reuptake inhibitors . CONCLUSIONS Paroxetine is an effective and well-tolerated short-term treatment of panic disorder . The minimum dose demonstrated to be significantly superior to placebo was 40 mg/day , although some patients did respond at lower doses BACKGROUND The serotonin selective reuptake inhibitors are increasingly being used for the treatment of panic disorder . We examined the efficacy and safety of the serotonin selective reuptake inhibitor sertraline hydrochloride in patients with panic disorder . METHODS One hundred seventy-six nondepressed out patients with panic disorder , with or without agoraphobia , from 10 sites followed identical protocol s that used a flexible-dose design . After 2 weeks of single-blind placebo , patients were r and omly assigned to 10 weeks of double-blind , flexible-dose treatment with either sertraline hydrochloride ( 50 - 200 mg/d ) or placebo . RESULTS Sertraline-treated patients exhibited significantly greater improvement ( P=.01 ) at end point than did patients treated with placebo for the primary outcome variable , panic attack frequency . Significant differences between groups were also evident for clinician and patient assessment s of improvement as measured by the Clinical Global Impression Improvement ( P=.01 ) and Severity ( P=.009 ) Scales , Panic Disorder Severity Scale ratings ( P=.03 ) , high end-state function assessment ( P=.03 ) , Patient Global Evaluation rating ( P=.01 ) , and quality of life scores ( P=.003 ) . Adverse events , generally characterized as either mild or moderate , were not significantly different in overall incidence between the sertraline and placebo groups . CONCLUSION Results support the safety and efficacy of sertraline for the short-term treatment of patients with panic disorder BACKGROUND AND OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are currently the first-line treatment for panic disorder , although up to 30 % of patients either do not respond to SSRIs or withdraw due to adverse events . Reboxetine , a selective norepinephrine reuptake inhibitor ( selective NRI ) , is effective in treating depression and may alleviate depression-related anxiety . This study aim ed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs . METHOD In this 6-week , open-label study , 29 adult out patients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2 mg/day , titrated to a maximum of 8 mg/day over the first 10 days .  Efficacy was assessed using the Panic Self- Question naire ( PSQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the 17-item Hamilton Rating Scale for Depression ( HRSD ) and the Global Assessment of Functioning ( GAF ) Scale . RESULTS The 24 patients who completed the study responded well to reboxetine treatment . Significant improvement ( p < 0.001 ) was observed in the number of daily panic attacks , and on the scales measuring anxiety , depression and functioning . Reboxetine was generally well tolerated . Five patients withdrew due to  adverse events . CONCLUSIONS Reboxetine appears to be effective in the treatment of SSRI-refractory panic disorder patients and warrants further clinical investigation Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents ( selective serotonin reuptake inhibitors ) used in the treatment of panic disorder . The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind , r and omized , flexible-dose trial conducted with out patients . After a 1-week single-blind placebo run-in , 27 patients entered an 8-week double-blind phase in which they were r and omly assigned to treatment with either mirtazapine or fluoxetine . Both groups improved significantly in all but one efficacy measure ( P < or = 0.01 ) . ANOVA showed no significant differences between the two treatment groups in number of panic attacks , Hamilton Anxiety Scale or Sheehan Phobic Scale , whereas measures of patient global evaluation of phobic anxiety were significantly different between groups ( F1,20 = 6.91 , P = 0.016 ) favoring mirtazapine . For the 22 patients who completed the study , the mean daily dose of mirtazapine was 18.3 + /- 1.3 vs 14.0 + /- 1.0 mg for fluoxetine at the endpoint . Weight gain occurred more frequently in the mirtazapine group ( 50 vs 7.7 % , P = 0.04 ) and nausea and paresthesia occurred more often in the fluoxetine group ( P = 0.01 ) . Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder BACKGROUND Existing literature on panic disorder ( PD ) yields no data regarding the differential rates of improvement during Cognitive Behavioral Therapy ( CBT ) , Selective Serotonin Reuptake Inhibitor ( SSRI ) or both combined ( CBT+SSRI ) . METHOD Patients were r and omized to CBT , SSRI or CBT+SSRI which each lasted one year including three months of medication taper . Participating patients kept record of the frequency of panic attacks throughout the full year of treatment . Rate of improvement on panic frequency and the relationship between rate of improvement and baseline agoraphobia ( AG ) were examined . RESULTS A significant decline in frequency of panic attacks was observed for each treatment modality . SSRI and CBT+SSRI were associated with a significant faster rate of improvement as compared to CBT . Gains were maintained after tapering medication . For patients with moderate or severe AG , CBT+SSRI was associated with a more rapid improvement on panic frequency as compared to patients receiving either mono-treatment . LIMITATIONS Frequency of panic attacks was not assessed beyond the full year of treatment . Second , only one process variable was used . CONCLUSIONS Patients with PD respond well to each treatment as indicated by a significant decline in panic attacks .  CBT is associated with a slower rate of improvement as compared to SSRI and CBT+SSRI . Discontinuation of SSRI treatment does not result in a revival of frequency of panic attacks . Our data suggest that for patients without or with only mild AG , SSRI-only will suffice . For patients with moderate or severe AG , the combined CBT+SSRI treatment is recommended BACKGROUND A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia , the Panic and Agoraphobia Scale ( P & A ) . The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients ( panic attacks , avoidance , anticipatory anxiety , disability and worries about health ) . The application of this scale in a double-blind placebo-controlled panic disorder trial is described . At the same time , the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy . METHODS Patients with Panic disorder ( DSM-IV ) were r and omly assigned to three treatment modalities : running ( n=45 ) , clomipramine ( n=15 ) or placebo ( n=15 ) . Treatment efficacy was measured with the Panic and Agoraphobia Scale ( P & A ) and other rating scales . RESULTS According to the P & A and other scales , both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment . Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise . The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability . CONCLUSIONS The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments . Analysis of the scales five subscores may help to underst and mechanisms of action of panic disorder treatments Side effects play a significant role in the selection of drugs to be used in panic disorder/agoraphobia whose polyphobic symptomatology often includes a suspiciousness about taking drugs and a fear of undesired side effects which may lead to the refusal of treatment . The safety , side effects and patients ' acceptance of alprazolam and imipramine versus placebo were evaluated in 1168 subjects with panic disorder/agoraphobia who had been enrolled in the second phase of the Upjohn World Wide Panic Study . Side effects that worsened over baseline to a greater extent with alprazolam than with imipramine and placebo were sedation , fatigue/weakness , memory problems , ataxia and slurred speech . In the imipramine group blurred vision , tachycardia/palpitations , insomnia , sleep disturbance , excitement/nervousness , malaise , dizziness/faintness , headache , nausea/vomiting and decrease in appetite were worse than in the other groups . In the placebo group the anxious symptoms were most prominent . The highest level of compliance was shown in the alprazolam-treated group and the lowest in the placebo-treated group . Strong predictors of side effects were not observed . If a side effect profile is known , it will be easier for a clinician to choose the right drug and the appropriate management by taking into account compliance , safety and efficacy in each patient under treatment . Further information about side effects in long-term maintenance treatment would be of great clinical pertinence in ensuring safety and enhancing patients ' quality of life Despite the acknowledged favorable side effects profile of selective serotonin reuptake inhibitors ( SSRIs ) , comparative studies have not found significant differences in efficacy between tricyclics ( TCAs ) such as imipramine and clomipramine , and SSRIs in the treatment of panic disorder . The present study focuses on treatment completers to inform patients who adhere to a recommended course of treatment on the possible differential patterns of improvement and of change in side effects between sertraline and imipramine . From an intent to treat consecutive sample of patients participating in the 24-week open phase protocol ized treatment of a long-term controlled maintenance/discontinuation study , 20 imipramine completers and 16 sertraline completers with moderate to severe baseline symptomatology were compared using primarily repeated measures analysis of variance on measures of symptom severity , on 15 side effects systematic ally elicited using an inventory and on heart rate and weight . The results revealed greater early improvement with imipramine compared to sertraline but no enduring differences beyond week 8 of treatments . Side effects , in particular dry mouth , constipation , tremors , sweating , and cardiovascular complaints increased more in severity and were more frequent and persistent during imipramine than sertraline but , except for the 10 beats/min increase in heart rate , side effects were clinical ly insignificant at the end of both treatments . Change in sexual complaints and weight did not differ between the treatments . The more favorable side effect profile of SSRIs versus TCAs was demonstrated even in the best case scenario of treatment completers . The more rapid improvement with imipramine needs replication but , tentatively , it may be attributed to the greater motivational effects toward action observed with noradrenergic or dual action antidepressants compared to SSRIs In a double-blind controlled study lasting 8 weeks , 50 anxious psychoneurotic out patients with a primary diagnosis of generalized anxiety or panic disorder were r and omly assigned to alprazolam ( n=30 ) , a new benzodiazepine , or placebo ( n=20 ) , after a washout period of 1 week . Alprazolam at dosages between 0.25 and 3 mg/day was found to be significantly better than placebo in the treatment of either disorder . The finding that alprazolam was effective in the treatment of panic disorder is of interest as this diagnostic category is usually treated with tricyclic antidepressants or MAO inhibitors Inositol is a simple polyol precursor in a second messenger system important in the brain . Cerebrospinal fluid inositol has been reported as decreased in depression . A double-blind controlled trial of 12 g daily of inositol in 28 depressed patients for four weeks was performed . Significant overall benefit for inositol compared to placebo was found at week 4 on the Hamilton Depression Scale . No changes were noted in hematology , kidney or liver function . Since many antidepressants are effective in panic disorder , twenty-one patients with panic disorder with or without agoraphobia completed a double-blind , placebo-controlled , four week , r and om-assignment crossover treatment trial of inositol 12 g per day . Frequency and severity of panic attacks and severity of agoraphobia declined significantly with inositol compared to placebo .  Side-effects were minimal . Since serotonin re-uptake inhibitors benefit obsessive compulsive disorder ( OCD ) and inositol is reported to reverse desensitization of serotonin receptors , thirteen patients with OCD completed a double-blind controlled crossover trial of 18 g inositol or placebo for six weeks each . Inositol significantly reduced scores of OCD symptoms compared with placebo . A controlled double-blind crossover trial of 12 g daily of inositol for a month in twelve anergic schizophrenic patients , did not show any beneficial effects . A double-blind controlled crossover trial of 6 g of inositol daily vs. glucose for one month each was carried out in eleven Alzheimer patients , with on clearly significant therapeutic effects . Antidepressant drugs have been reported to improve attention deficit disorder ( ADDH ) with hyperactivity symptomatology . We studied oral inositol in children with ADDH in a double-blind , crossover , placebo-controlled manner . Eleven children , mean age 8.9 + /- 3.6 years were enrolled in an eight week trial of inositol or placebo at a dose of 200 mg/kg body weight . Results show a trend for aggravation of the syndrome with myo-inositol as compared to placebo . Recent studies suggest that serotonin re-uptake inhibitors are helpful in at least some symptoms of autism . However a controlled double-blind crossover trial of inositol 200 mg/kg per day showed no benefit in nine children with autism . Cholinergic agonists have been reported to ameliorate electroconvulsive therapy (ECT)-induced memory impairment . Inositol metabolism is involved in the second messenger system for several muscarinic cholinergic receptors . Inositol 6 g daily was given in a crossover-double-blind manner for five days before the fifth or sixth ECT to a series of twelve patients , without effect . These results suggest that inositol has therapeutic effects in the spectrum of illness responsive to serotonin selective re-uptake inhibitors , including depression , panic and OCD , and is not beneficial in schizophrenia , Alzheimer 's ADDH , autism or ECT-induced cognitive impairment Panic disorder with or without agoraphobia is a common , often chronic and refractory anxiety disorder . Although a number of pharmacotherapies are now indicated for panic disorder , many patients do not respond to available interventions . We hypothesized that duloxetine , a serotonin‐norepinephrine reuptake inhibitor ( SNRI ) that has greater initial noradrenergic effects than venlafaxine , would have broad efficacy for individuals with panic disorder . Fifteen individuals with panic disorder with or without agoraphobia received 8 weeks of open label duloxetine flexibly dosed from 60 to 120 mg per day . Duloxetine treatment result ed in significant anxiolysis as measured by the primary outcome measure , the Panic Disorder Severity Scale ( PDSS ) ( paired t(df ) = 4.02(14 ) , P= 0.0013 ) , as well as measures of generalized anxiety , depression and quality of life ( all P < 0.05 ) . Although definitive conclusions are limited due to its small open‐label nature , this first prospect i ve study provides preliminary support for the efficacy of duloxetine for panic disorder and suggests larger r and omized controlled study is warranted The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder ( PD ) with or without agoraphobia . In this 12-week , open-label study , 31 adult out patients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine ( 5 mg/d ) in addition to SSRI .  Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale ( PAAAS ) , the Agoraphobic Cognitions Question naire ( ACQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Hamilton Rating Scale for Depression ( HAM-D ) , the Global Assessment of Functioning Scale ( GAF ) , and the Clinical Global Impression of Improvement ( CGI-I ) . Twenty-six patients completed the trial period with a dropout rate of 16.1 % . At week 12 , 21 patients were responders ( 81.8 % ) , and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia . Fifteen patients ( 57.7 % ) achieved remission . Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness . No extrapyramidal symptoms were reported . Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD , but study limitations must be considered and placebo-controlled studies are needed BACKGROUND Panic disorder ( PD ) is generally regarded as a chronic condition with considerable variation in severity of symptoms . AIMS To describe the long-term outcome of naturalistically treated PD . METHODS Fifty-five out patients with PD , who participated in a placebo-controlled drug trial of the efficacy of alprazolam and imipramine 15 years ago were reassessed with the same instruments used in the original study . RESULTS Complete recovery ( no panic attacks and no longer on medication during the last 10 years ) was seen in 18 % of patients , and an additional 13 % recovered but were still on medication . Fifty-one percent experienced recurrent anxiety attacks whereas 18 % still met diagnostic criteria for PD . The incidence of agoraphobia decreased from 69 % to 20 % . Patients with agoraphobia at admission tended to have a poorer long-term outcome according to daily functioning compared with patients without agoraphobia at admission , although both groups reported improved daily functioning at follow-up . Maintenance medication was common . No benzodiazepine abuse was reported . CONCLUSION PD has a favourable outcome in a substantial proportion of patients . However , the illness is chronic and needs treatment . The short-term treatment given in the drug trial had no influence on the long-term outcome OBJECTIVE This study evaluated time to response in the treatment of panic disorder with a selective serotonin reuptake inhibitor ( SSRI ) or serotonin norepinephrine reuptake inhibitor ( SNRI ) combined with alprazolam orally disintegrating tablets ( ODT ) , or SSRI/SNRI alone . DESIGN Subjects were r and omized to eight weeks open-label treatment with alprazolam ODT ( 4 weeks treatment followed by 3 - 4 week taper ) combined with an SSRI or SNRI , or treatment with SSRI/SNRI alone . SETTING The study was conducted under naturalistic conditions at 62 primary care and 34 psychiatric practice s. PARTICIPANTS Male or female subjects ≥18 years of age diagnosed with panic disorder , with or without agoraphobia . MEASUREMENTS The primary efficacy measure was time to response , defined as ≥50-percent decrease from baseline Hamilton Rating Scale for Anxiety ( HAM-A ) total score . Secondary measures included change from baseline in HAM-A scores and the Clinical Global Impression of Improvement ( CGI-I ) and Patient Global Impression ( PGI ) scales . RESULTS The intent-to-treat ( ITT ) population comprised 245 subjects . There was no statistical difference between treatment groups in time to response in the ITT population ; however , a prospect ively defined per protocol analysis revealed a statistically significant earlier onset of effect in subjects receiving SSRI/SNRI plus alprazolam ODT ( P<0.05 ) . Mean change from baseline in HAM-A total score and clinician and patient measures of global improvement also showed statistically significant early advantages for combination therapy compared with SSRI/SNRI monotherapy . CONCLUSION Combined treatment of panic disorder with alprazolam ODT and an SSRI/SNRI may be associated with more rapid improvement in anxiety symptoms compared with an SSRI/SNRI alone Fifty-five patients completed a 5-week double-blind study comparing alprazolam , propranolol , and placebo in the treatment of panic disorder and agoraphobia with panic attacks . There was no concomitant behavioral treatment . Patient and therapist rating scales included Sheehan 's Panic and Anxiety Attack Scales , the Marks-Sheehan Phobia Scale , the Hamilton Anxiety Scale , the Hamilton Depression Scale , and the Side Effects Checklist . The results generally support the efficacy of alprazolam , but not propranolol , in the treatment of panic disorder and agoraphobia with panic attacks . The significance of the results are discussed , as well as a number of the unique aspects of our procedures and patient population The effects of a single inhalation of a 35 % CO2/65 % O2 gas mixture were examined in 71 patients with panic disorder with or without agoraphobia and 44 normal control subjects . Compared with the placebo condition , inhalation of air , the CO2/O2 mixture elicited a clear anxiety reaction only in panic disorder patients , who experienced a sudden rise of subjective anxiety as well as of several panic symptoms . Respiratory symptoms and the fear of dying best distinguished the patients from the control subjects . Baseline anxiety was not the key factor in explaining this differential reaction . The clinical features of panic disorder ( namely , frequency of panic attacks , agoraphobia , anticipatory anxiety , and duration of illness ) were not significantly related to the response to the challenge test , suggesting that CO2 reactivity might be a trait marker of panic disorder The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder ( PD ) . Twenty-five out patients having PD with or without agoraphobia were included . These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day . Treatment-resistant PD was defined as a less than 20 % reduction in score on the Panic Self- Question naire ( number of attacks per week ) ( PSQ ) and the Clinical Anxiety Scale With Panic Attacks ( CAS+PA ) . These patients continued to receive fluoxetine 20 mg/day and were r and omly assigned to additionally receive either pindolol ( 2.5 mg three times daily ) or placebo for the following 4 weeks . Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety , the Hamilton Rating Scale for Depression ( HAM-D ) , the CAS+PA , the NIMH Anxiety Scale , the PSQ , and the Clinical Global Impression Scale . The data were analyzed using a repeated- measures analysis of variance ( ANOVA ) and a t-test for independent sample s. Patients treated with the combination of pindolol and fluoxetine ( N = 13 ) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales , with the exception of HAM-D. The statistical differences were shown using the repeated- measures ANOVA ( baseline , week 2 , week 4 ) and also with t-tests from the second week of the trial . These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD Carbon dioxide ( CO2 ) inhalation induces acute anxiety and panic attacks in patients with Panic Disorder ( PD ) . Anti-panic drugs decrease CO2 reactivity after the first days of treatment ; however , the clinical meaning of this finding has not yet been established . This study investigated the effects of treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors ( SSRIs ) on CO2 reactivity and compared the relationships between 35 % CO2 hyperreactivity modulation and short-term clinical outcome .  One hundred twenty-three patients with PD with or without agoraphobia who were hyperreactive to CO2 were r and omly assigned to treatment groups with imipramine , clomipramine , paroxetine , sertraline , or fluvoxamine . A double-blind , r and omized design was applied . Each patient received the 35 % CO2 challenge on days 0 , 7 , and 30 . The severity of clinical symptomatology was measured on days 0 and 30 . Decreased hyperreactivity to 35 % CO2 in all five treatment groups was already evident after the first week . The decrease in CO2 reactivity at the end of treatment was proportional to the degree of clinical improvement . Multiple regression analyses showed that the decrease in CO2 reactivity after the first week was a significant predictor for good clinical outcome after one month . The results of this study confirm evidence that psychoactive drugs effective in the treatment of PD decrease CO2 hyperreactivity . They also suggest that precocious modulation of CO2 reactivity might fairly reliably predict short-term clinical outcome in patients with “ respiratory ” PD One of the core problems in clinical research is the detection of early changes in target symptoms that predict future therapeutic outcome . To analyze potential predictors of outcome , data of a multicenter study on patients with panic disorder were used . A total of 1010 patients were r and omly allocated either to alprazolam , imipramine or placebo treatment . Early improvement in the number of spontaneous panic attacks within the first week of treatment predicted outcome exclusively in the alprazolam group . In contrast , placebo responders and nonresponders were differentiated by early changes in anticipatory anxiety intensity . For tricyclic antidepressants such as imipramine an evaluation period of more than one week is required to allow conclusions about outcome OBJECTIVE The purpose of this comparative outcome study was to investigate whether the effects of exposure in vivo treatment for panic disorder with agoraphobia could be enhanced by adding interventions specifically for panic attacks before the start of exposure treatment . The additional effect of two types of treatment for panic attacks -- pharmacological ( fluvoxamine ) and psychological ( repeated hyperventilation provocations and respiratory training)--was examined . Thus , the combined treatment of panic interventions with exposure in vivo could be compared to exposure in vivo alone . METHOD Ninety-six patients were r and omly assigned to four treatment conditions : double-blind , placebo-controlled fluvoxamine followed by exposure in vivo , psychological panic management followed by exposure , and exposure in vivo alone . Outcome was assessed by self-report measures , a st and ardized multitask behavioral avoidance test , and continuous monitoring of panic attacks .  Seventy-six patients completed the study . RESULTS All four treatments were effective and result ed in a significant decrease of agoraphobic avoidance . Moreover , the combination of fluvoxamine and exposure in vivo demonstrated efficacy superior to that of the other treatments and had twice as large an effect size ( difference between pre- and posttreatment scores ) on self-reported agoraphobic avoidance . The other treatments did not differ among each other in effectiveness . CONCLUSIONS Results of the study indicate that the short-term outcome of exposure in vivo treatment can be enhanced by adding fluvoxamine treatment . Psychological panic management combined with exposure was not superior to exposure alone of equal duration BACKGROUND Disordered breathing among patients with panic disorder , including hyperventilation during attacks and increased anxiogenic response to carbon dioxide ( CO2 ) inhalation , is well established . We wished to assess whether there is a change in the physiological response to CO2 after patients have undergone antipanic therapy with either tricyclic antidepressants or cognitive behavioral therapy ( CBT ) . METHODS Twenty-nine patients with panic disorder underwent baseline CO2 sensitivity testing using the traditional Read rebreathing method and then received either antidepressant treatment ( n = 21 ) or CBT ( n = 8) . After completing treatment , CO2 testing was repeated . A comparison sample of 14 normal volunteers also had two CO2 sensitivity tests , separated by an average of 21.6 ( SD = 8.8 ) weeks . RESULTS Using a liberal st and ard , in which all CO2 sensitivity tests whose correlations between minute ventilation and end-tidal CO2 were at least .75 were used , patients , but not controls , demonstrated a significant reduction in CO2 sensitivity between the first and second test . Using a more conservative .90 correlation st and ard reduced the sample size available and result ed in trend reduction in patients but no significant change in controls . There was a suggestion that the change was most pronounced in treatment responders , although the number of patient nonresponders is extremely small in this sample . CONCLUSIONS These data indicate that treatment reduces CO2 sensitivity in patients with panic disorder . We speculate that manipulation of the serotonergic and noradrenergic neurotransmission systems , both known to play a role in the control of respiration , may have a specific effect in reducing respiratory hyperactivity in panic disorder OBJECTIVE The current study examines whether antidepressants , contrary to current thinking , are safe and effective treatments for generalized anxiety disorder ( GAD ) not complicated by depression or panic disorder . DESIGN R and omized , double-blind , placebo-controlled , flexible-dose , 8-week treatment study comparing imipramine hydrochloride ( mean maximum daily dose , 143 mg ) , trazodone hydrochloride ( 255 mg ) , and diazepam ( 26 mg ) . PATIENTS Two hundred thirty patients with a DSM-III diagnosis of GAD in whom major depression and panic disorder has been excluded , and who had a Hamilton Anxiety Scale total score of at least 18 . SETTING Seventy-five percent of patients were treated in family practice setting s in the community , with the remainder treated in psychiatric practice s , either academic or private . RESULTS Patients treated with diazepam showed the most improvement in anxiety ratings during the first 2 weeks of treatment , with somatic symptoms being most responsive . From week 3 through week 8 trazodone achieved comparable , and imipramine somewhat better , anxiolytic efficacy when compared with diazepam , with psychic symptoms of tension , apprehension , and worry being more responsive to the antidepressants . Among completers , moderate to marked improvement was reported by 73 % of patients treated with imipramine , 69 % of patients treated with trazodone , 66 % of patients treated with diazepam , but only 47 % of patients treated with placebo . Overall , patients treated with antidepressants reported a higher rate of adverse effects than diazepam-treated patients , but attention rates were the same across all treatments . CONCLUSIONS The results of the study need replication , but suggest a potentially important role for antidepressants , particularly imipramine , in patients suffering from GAD Antidepressants reportedly increase appetite , carbohydrate craving and weight in some patients with depression and panic disorder . This paper presents the results of changes in appetite and weight in patients with panic disorder treated with imipramine , diazepam or placebo in a double-blind prospect i ve study . Forty-four patients with panic disorder were r and omly assigned imipramine , diazepam and placebo . The investigators monitored weight and the patients rated their appetite and cravings during the eight week study . No significant increases in weight or appetite were found in the patients with panic disorder patients Thirty-two out patients with a DSM-III diagnosis of panic disorder or agoraphobia with panic attacks were r and omly assigned to 4 weeks of treatment with clonazepam or placebo , after a 1-week placebo washout period . Twenty-nine patients entered the double-blind phase of the study and were eligible for intent-to-treat analysis . Clonazepam-treated patients experienced significantly fewer panic attacks , and these were of lesser intensity and short duration than those in placebo-treated patients ( p < 0.001 ) . Clonazepam was also superior to placebo with respect to symptoms of anxiety and depression ( p < 0.001 ) . The mean dose of clonazepam at week 4 was 2.2 mg ( st and ard deviation , 0.7 mg ) . There was significant ( p < 0.05 ) correlation between drug concentration in plasma and decrease in the global measure of the severity of panic disorder ( r = 0.68 ) ; similar trends were seen for the decreases in frequency ( r = 0.60 ) and severity ( r = 0.55 ) of panic attacks , but not between concentration in plasma and decline in generalized anxiety . The most common adverse event was drowsiness , which occurred in 9 of 13 clonazepam-treated patients OBJECTIVE To assess the effectiveness of clonazepam , in a fixed dose ( 2 mg/day ) , compared with placebo in the treatment of panic disorder patients . METHOD 24 panic disorder patients with agoraphobia were r and omly selected . The diagnosis was obtained using the structured clinical interview for DSM-IV . All twenty-four subjects were r and omly assigned to either treatment with clonazepam ( 2 mg/day ) or placebo , during 6 weeks . Efficacy assessment s included : change from baseline in the number of panic attacks ; CGI scores for panic disorder ; Hamilton rating scale for anxiety ; and panic associated symptoms scale . RESULTS At the therapeutic endpoint , only one of 9 placebo patients ( 11.1 % ) were free of panic attacks , compared with 8 of 13 ( 61.5 % ) clonazepam patients ( Fisher exact test ; p=0,031 ) . CONCLUSION the results provide evidence for the efficacy of clonazepam in panic disorder patients BACKGROUND The purpose of this multicenter , double-blind , placebo-controlled study was to evaluate the efficacy and safety of optimized dosages of clonazepam for the treatment of panic disorder and assess the tolerability of a schedule for gradual discontinuation . METHOD Adult patients with panic disorder with or without agoraphobia ( DSM-III-R criteria ) were r and omly assigned to receive either placebo or clonazepam in individually adjusted doses over 3 weeks to approximate an optimal dosage , which was then maintained for an additional 3 weeks , amounting to a 6-week therapeutic phase . The daily dose range was 0.25 to 4.0 mg administered in 2 divided doses . In the following 7-week discontinuance phase , the doses were tapered gradually to cessation . RESULTS At the therapeutic endpoint , clonazepam ( N = 222 ) proved clinical ly and statistically superior to placebo ( N = 216 ) in change in the number of panic attacks and in Clinical Global Impressions-Severity of Illness ( CGI-S ) and CGI-Change scores , Patient 's Global Impression of Change scores , amount of fear and avoidance associated with phobic symptoms , and duration of anticipatory anxiety . The gradual tapering of clonazepam was not associated with symptoms suggestive of withdrawal syndrome . Although patients taking clonazepam experienced some clinical worsening compared with the status achieved at endpoint , particularly in terms of number of panic attacks , no deterioration was observed using their condition at baseline as point of reference . No overall evidence of rebound was found . All regimens were generally well tolerated . Somnolence was the main adverse event associated with clonazepam therapy . The percentage of patients who reported adverse events was higher in the clonazepam group than in the placebo group , as was the mean number of adverse events per patient . CONCLUSION In this placebo-controlled trial , clonazepam was an efficacious and safe shortterm treatment of the symptoms of panic disorder . Discontinuance during and after slow tapering was well tolerated Cognitive behavioral treatment ( CBT ) has been shown to reduce risk for adverse reactions ( e.g. , rebound panic ) following benzodiazepine taper for patients with panic disorder ( PD ) . This study evaluated the effects of antidepressant discontinuation for patients with PD in the context of CBT .  Patients with PD ( n=21 ) on a stable dose of antidepressants completed a 12-week group CBT treatment and were r and omly assigned to discontinue antidepressants during week 8 of the treatment . There were no statistically significant differences between groups at posttreatment or 6-month follow-up . Data indicate no apparent immediate or long-term adverse effects for antidepressant discontinuation for patients with PD receiving CBT Simultaneous coexistence of anxiety with depressive disorders is probably one of the major current problems in Medicine . The pharmacological approach for Panic Disorder and Major Depression includes " high-powered " benzodiazepines for the rapid , but transitory relief of same symptoms and especially antidepressant compounds . Recently physical-instrumental approaches have been tested for the treatment of these complex diseases , like Cranial Electrotherapy Stimulation ( CES ) , Trans-cranial Magnetic Stimulation ( TMS ) , and Radio Electric Asymmetric Treatment ( REAC ) . The REAC apparatus was design ed to deliver an alternate current of several hundred picoamperes for a time span of 0.5 seconds by means of a small metallic probe directly connected to the properly fabricated electronic circuit in an AC/RF generator with frequency of 2.4 , 5.8 or 10.5 GHz and power of 20 mW. Compared the efficacy of  REAC  and Es-Citalopram in the treatment of simultaneous coexistence of Panic Disorder with Major Depression in 9-weeks open label naturalistic study . After the 1st week , patients treated with  REAC therapy  showed a significant relief of depressive symptoms compared with Es-Citalopram .  For Panic Disorder ,  REAC treatment had more effective results than the drug especially after the 3rd week of observation . The REAC treatment obtained better results during the entire study , and its high safety and tolerability profile has been confirmed OBJECTIVE Several classes of medications have demonstrated efficacy in panic disorder , but direct comparison of 2 proven treatments is still uncommon . The purpose of this study was to compare sertraline and paroxetine in the acute treatment of panic disorder . METHOD Adult out patients with panic disorder with or without agoraphobia ( DSM-IV and ICD-10 criteria ) were r and omly assigned in double-blind fashion to 12 weeks of treatment with flexible doses of sertraline ( titrated up to 50 - 150 mg/day ; N = 112 ) or paroxetine ( titrated up to 40 - 60 mg/day ; N = 113 ) . Patients were then tapered off medication over 3 weeks . The primary analysis was a noninferiority analysis of Panic and Agoraphobia Scale ( PAS ) scores . Secondary measures included panic attack frequency and the Clinical Global Impressions-Improvement scale ( CGI-I ) ( with responders defined as those with a CGI-I score < or = 2 ) . Data were collected from January 2000 to June 2001 . RESULTS Sertraline and paroxetine were associated with equivalent levels of improvement on the PAS total score , as well as on all secondary outcome measures . Eighty-two percent of patients taking sertraline versus 78 % of those taking paroxetine were CGI-I responders at endpoint . Numerically more patients on paroxetine treatment compared with sertraline treatment discontinued due to adverse events ( 18 % vs. 12 % ; NS ) , and a significantly higher proportion of paroxetine patients showed > or = 7 % weight gain ( 7 % vs. < 1 % ; p < .05 ) . During the taper period , the proportion of panic-free patients increased by 4 % with sertraline but decreased by 11 % with paroxetine ( p < .05 ) . CONCLUSION Sertraline and paroxetine had equivalent efficacy in panic disorder , but sertraline was significantly better tolerated and was associated with significantly less clinical worsening during taper than paroxetine RATIONALE Few r and omized , placebo-controlled trials have evaluated the comparative efficacy and tolerability of more than one pharmacological agent for panic disorder . OBJECTIVES The primary objective of this study was to compare the efficacy and tolerability of venlafaxine extended release ( ER ) with placebo in treating panic disorder . Secondary objectives included comparing paroxetine with venlafaxine ER and placebo . METHODS Out patients aged > or = 18 years ( placebo , n = 157 ; venlafaxine ER 75 mg , n = 156 ; venlafaxine ER 225 mg , n = 160 ; paroxetine , n = 151 ) , with a primary diagnosis of panic disorder ( + /-agoraphobia ) based on the Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition ) criteria for > or =3 months were r and omly assigned to receive venlafaxine ER ( titrated to 75 mg/day or 225 mg/day ) , paroxetine ( titrated to 40 mg/day ) , or placebo for 12 weeks . The primary efficacy measure was the percentage of patients free of full-symptom panic attacks ( > or = four symptoms ) at endpoint . Key secondary outcomes included the Panic Disorder Severity Scale ( PDSS ) mean score change and response . RESULTS At endpoint , all active treatment groups showed a significantly ( P < 0.01 ) greater proportion of patients free of full-symptom panic attacks , compared with placebo , and were superior ( P < 0.05 ) on most secondary measures . The venlafaxine ER 225 mg group had significantly ( P < 0.05 ) greater mean PDSS score improvement than the paroxetine group ( -12.58 vs -11.87 ) and a significantly higher proportion of patients free of full symptom panic attacks ( 70.0 vs 58.3 % ) . Both drugs were generally well tolerated . CONCLUSION Venlafaxine ER 75 mg/days and 225 mg/days and paroxetine 40 mg/day were both well tolerated and effective for short-term treatment of panic disorder BACKGROUND Cognitive behavioral therapy ( CBT ) and pharmacotherapy are efficacious for the short-term treatment of panic disorder . Less is known about the efficacy of these therapies for individuals who do not respond fully to short-term CBT .  METHOD The current trial is a second-step stratified r and omized design comparing two treatment conditions-selective serotonin reuptake inhibitor ( SSRI ; paroxetine or citalopram ; n = 34 ) and continued CBT  ( n = 24)-in a sample of individuals classified as treatment nonresponders to an initial course of CBT for panic disorder . Participants were r and omized to 3 months of treatment and then followed for an additional 9 months . Only treatment responders after 3 months were maintained on the treatment until 12-month follow-up . Data analysis focused on panic disorder symptoms and achievement of response status across the first 3 months of treatment . Final follow-up data are presented descriptively . RESULTS Participants in the SSRI condition showed significantly lower panic disorder symptoms as compared to continued CBT at 3 months . Results were similar when excluding individuals with comorbid major depression or analyzing the entire intent-to-treat sample . Group differences disappeared during 9-month naturalistic follow-up , although there was significant attrition and use of non study therapies in both arms . CONCLUSIONS These data suggest greater improvement in panic disorder symptoms when switching to SSRI after failure to fully respond to an initial course of CBT . Future studies should further investigate relapse following treatment discontinuation for nonresponders who became responders . Clinical trials.gov Identifier : NCT00000368 ; https:// clinical trials.gov/show/NCT00000368 OBJECTIVE The authors tested the hypothesis that a lifetime history of panic-agoraphobic spectrum symptoms predicts a poorer response to  depression treatment . METHOD A threshold for clinical ly meaningful panic-agoraphobic spectrum symptoms was defined by means of receiver operating characteristic curve analysis of total scores on the Structured Clinical Interview for Panic-Agoraphobic Spectrum in a group of 88 out patients with and without panic disorder . This threshold was then applied to a group of 61 women with recurrent major depression , who completed a self-report version of the same instrument , in order to compare treatment outcomes for patients above and below this clinical threshold . RESULTS Women with high scores ( > or = 35 ) on the Panic-Agoraphobic Spectrum Self-Report were less likely than women with low scores ( < 35 ) to respond to interpersonal psychotherapy alone ( 43.5 % versus 68.4 % , respectively ) . Women with high scores also took longer ( 18.1 versus 10.3 weeks ) to respond to a sequential treatment paradigm ( adding a  selective serotonin reuptake inhibitor  when depression did not remit with interpersonal psychotherapy alone ) . This effect was only partially accounted for by the higher likelihood that patients with high scores required the addition of antidepressants . Although four domains from the Panic-Agoraphobic Spectrum Self-Report were individually associated with a longer time to remission , only stress sensitivity emerged as significant in multivariate regression analyses . CONCLUSIONS A lifetime burden of panic-agoraphobic spectrum symptoms predicted a poorer response to  interpersonal psychotherapy  and an 8-week delay in sequential treatment response among women with recurrent depression . These results lend clinical validity to the spectrum construct and highlight the need for alternate psychotherapeutic and pharmacologic strategies to treat depressed patients with panic spectrum features BACKGROUND Both behavior-modification methods and antidepressants have proved to be effective in the treatment of agoraphobia . The authors examined the effects of clomipramine on agoraphobia in patients who failed to respond to exposure-based behavioral treatment . METHOD Eighteen patients with panic disorder with agoraphobia who had not responded to previous inpatient behavioral treatment  were recruited to a 12-week , placebo-controlled , double-blind crossover study of clomipramine , at top doses of 150 mg/day for 3 weeks . The patients were assessed on measures of phobic avoidance , agoraphobic cognitions , panic , state and trait anxiety , subjective anxiety , and depression . RESULTS One patient dropped out of the study after 6 weeks . On most outcome measures , the 17 study completers had significantly ( p < .05 ) lower symptom scores at posttest in the active drug period than at posttest in the placebo period ; however , the clinical gains were modest . CONCLUSION The short-term efficacy of clomipramine for agoraphobic patients who failed to respond lastingly to behavioral treatment was demonstrated . It remains to be shown that clomipramine can lead to clinical ly significant and lasting benefits in these patients D-cycloserine (DCS)-augmented exposure therapy has proven efficacy in the treatment of acrophobia , social phobia , panic disorder and OCD . Here we studied whether DCS can also improve the effect of cognitive behavioral therapy ( CBT ) in patients with agoraphobia and panic disorder . To this end , 39 patients with the diagnoses of agoraphobia and panic disorder were treated with 11 sessions of CBT including three individual in-vivo exposure sessions ( flooding ) , augmented with either 50 mg of DCS ( N=20 ) or placebo ( N=19 ) in a r and omized double blind design . Primary outcome was the total score of the panic and agoraphobia scale . Both groups profited considerably from therapy and DCS did not significantly improve this outcome ( p=0.475 ; η(2)p = 0.01 ) . However , there was a statistical trend ( p=0.075 ; η(2)p = 0.17 ) in the more severely ill patients  that DCS accelerated symptom reduction in the primary outcome at post-therapy . No serious adverse effects occurred during the trial . We conclude that in patients with agoraphobia and panic disorder  , DCS seems to lack an additional benefit to efficient cbt , probably due to a floor effect . Nonetheless , the acceleration of symptom reduction in severely ill patients might represent a valuable treatment option deserving further investigation A compared , 12 week , placebo controlled study , with fixed dose , outpatient study of patients diagnosed with panic disorder with and without agoraphobia according to ICD-10 , was conducted to evaluate the efficacy and safety of sertraline and alprazolam . The study included 40 patients , divided in two groups . We evaluated number of ICD-10-defined panic attacks , agoraphobia and anticipatory anxiety .  All patients were aged 18 year and older and were r and omized to either sertraline or alprazolam . Sertraline applied in fixed doses of 20 mg/day and alprazolam in doses 1 - 1,5 mg/day significantly reduced the frequency of panic attacks in panic disorder patients , reduced symptoms of agoraphobia and anticipatory anxiety Both noradrenergic and serotonergic systems have been implicated in the pathophysiology of panic disorder . The advent of selective serotonin ( 5-HT ) reuptake inhibitors ( SSRIs ) ( e.g. citalopram ) and , more recently , selective noradrenergic ( NA ) reuptake inhibitors ( NRIs ) ( e.g. reboxetine ) has provided potentially important avenues of treatment for the disorder . To date , the comparative efficacy of selective NA and 5-HT reuptake inhibitors for panic disorder remains unresolved . Nineteen patients with panic disorder were r and omized in a single-blind , cross-over design to either citalopram or reboxetine for 8 weeks and after a 2-week washout were switched to the other study drug . At week 18 , seven of 13 patients ( 54 % ) in the intent-to-treat sample responded to reboxetine and nine of 11 patients responded to citalopram ( 82 % ) . Both citalopram and reboxetine led to significant improvements in panic attack severity with no apparent between-drug differences in efficacy . However , citalopram demonstrated superior efficacy in treating depressive symptoms . One non-responder to citalopram responded to reboxetine and three non-responders to reboxetine responded to citalopram . Although SSRIs are viewed as a first-line treatment for panic disorder , these results suggest that a NA agent such as reboxetine may also have a role . These data also suggest an advantage for citalopram in treating comorbid depressive symptoms , although some patients may respond preferentially to an SSRI and other patients to an NRI BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs Objective The present study examined the prevalence of  panic disorder  with or without agoraphobia according to DSM-IV criteria in the Swedish general population . Method Data were obtained by means of a postal survey administrated to 1000 r and omly selected adults . The panic disorder module of the World Health Organization 's Composite International Diagnostic Interview ( CIDI ) was included in the survey . Results 12-month prevalence was estimated at 2.2 % ( CI 95 % 1.02 % – 3.38 % ) . There was a significant sex difference , with a greater prevalence for women ( 5.6 % ) compared to men ( 1 % ) . Conclusion The Swedish panic disorder prevalence is relatively consistent with findings in most other parts of the western world Panic disorder , which is found in about 1.5 percent of the population at some time in their lives , includes recurrent episodes of sudden , unpredictable , intense fear accompanied by symptoms such as palpitations , chest pain , and faintness . Panic attacks , which do not meet these diagnostic criteria fully , are two to three times more prevalent . Since panic symptoms can mimic those of other medical disorders , patients with these symptoms use medical services frequently . To determine the risk of suicidal ideation and suicide attempts in panic disorder and attacks , we studied a r and om sample of 18,011 adults drawn from five U.S. communities . Subjects who had panic disorder , as compared with other psychiatric disorders , had more suicidal ideation and suicide attempts , with an adjusted odds ratio for suicide attempts of 2.62 ( 95 percent confidence interval , 1.83 to 3.74 ) . The odds ratio was 17.99 ( 95 percent confidence interval , 12.18 to 26.58 ) when the group with panic disorder was compared with subjects who had no psychiatric disorder . Twenty percent of the subjects with panic disorder and 12 percent of those with panic attacks had made suicide attempts . These results could not be explained by the coexistence of major depression or of alcohol or drug abuse . We conclude that panic disorder and attacks are associated with an increased risk of suicidal ideation and suicide attempts . Physicians working in general medical setting s and emergency departments should be alert to this problem BACKGROUND Interpersonal psychotherapy ( IPT ) seems to be as effective as cognitive behavioral therapy ( CBT ) in the treatment of major depression . Because the onset of panic attacks is often related to increased interpersonal life stress , IPT has the potential to also treat panic disorder . To date , a preliminary open trial yielded promising results but there have been no r and omized controlled trials directly comparing CBT and IPT for panic disorder . METHOD This study aim ed to directly compare the effects of CBT versus IPT for the treatment of panic disorder with agoraphobia . Ninety-one adult patients with a primary diagnosis of DSM-III or DSM-IV panic disorder with agoraphobia were r and omized . Primary outcomes were panic attack frequency and an idiosyncratic behavioral test . Secondary outcomes were panic and agoraphobia severity , panic-related cognitions , interpersonal functioning and general psychopathology . Measures were taken at 0 , 3 and 4 months ( baseline , end of treatment and follow-up ) . RESULTS Intention-to-treat ( ITT ) analyses on the primary outcomes indicated superior effects for CBT in treating panic disorder with agoraphobia . Per- protocol analyses emphasized the differences between treatments and yielded larger effect sizes . Reductions in the secondary outcomes were equal for both treatments , except for agoraphobic complaints and behavior and the credibility ratings of negative interpretations of bodily sensations , all of which decreased more in CBT . CONCLUSIONS CBT is the preferred treatment for panic disorder with agoraphobia compared to IPT . Mechanisms of change should be investigated further , along with long-term outcomes More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve . We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic , aripiprazole . We report on patients with depression and anxiety disorders , including panic disorder , generalized anxiety disorder , social anxiety and post-traumatic stress disorder , who had an incomplete response to a variety of selective serotonin reuptake inhibitors ( SSRIs ) and who received augmentation with aripiprazole .  The primary outcome measure was the Clinical Global Impression of Improvement ( CGI-I ) . In the intent-to-treat analysis , the mean±SD CGI-S was 3.8±1.3 at endpoint . Fifty-nine percent of subjects received CGI-I ratings of 1 or 2 , ‘ much improved ’ or ‘ very much improved , ’ in terms of their depression and anxiety symptoms at the end of 12 weeks . Several patients showed an early ( weeks 1–5 ) , as well as sustained , response to augmentation with doses of aripiprazole between 15 and 30 mg/day . The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment . Because this is a retrospective case review , further prospect i ve studies are required to confirm these findings OBJECTIVE This study was design ed to clarify the nature of the reduced function of the peripheral beta adrenoceptor system observed in panic disorder with agoraphobia . The authors hypothesized that this phenomenon reflected a regulatory and adaptive process . METHODS Lymphocyte beta adrenoreceptor density and affinity , basal lymphocyte cAMP level , and isoproterenol-stimulated cAMP generation were measured in 27 untreated out patients with panic disorder with agoraphobia and 24 healthy comparison subjects .  Lymphocyte beta receptor attributes were again assessed in patients after 4 weeks of double-blind treatment with adinazolam ( slow-release form ) or placebo .  Panic frequency , agoraphobic symptoms , overall anxiety , and improvement with treatment were assessed with st and ard rating instruments . RESULTS Multivariate statistics revealed significantly lower beta receptor density and isoproterenol-stimulated cAMP generation in patients than in comparison subjects . beta receptor density tended to normalize after adinazolam but not after placebo . Pretreatment beta receptor density was lower in treatment responders than nonresponders . Patients with mild agoraphobia had lower cAMP responsivity than patients with moderate or severe agoraphobia . CONCLUSIONS Decreased function of lymphocyte beta receptors in panic disorder with agoraphobia is expressed as both decreased density and decreased cAMP responsivity . This pattern of changes , and the tendency for receptor density to normalize with treatment , is consistent with an active , regulatory process rather than a structural deficit in the beta receptor system . Preliminary clinical findings suggest that these changes may reflect adaptive processes associated with a favorable clinical course in panic disorder with agoraphobia OBJECTIVE To assess the efficacy and tolerability of controlled-release paroxetine ( paroxetine CR ) in the treatment of adults with panic disorder . METHOD  Paroxetine CR ( 25 - 75 mg/day ; N = 444 ) was compared with  placebo ( N = 445 ) in patients with DSM-IV panic disorder with or without agoraphobia in 3 identical , double-blind , placebo-controlled , 10-week clinical trials that were pooled for analysis . RESULTS Paroxetine CR was statistically superior to placebo in the primary outcome measure , percentage of patients who were free of panic attacks in the 2 weeks prior to endpoint . Of the total population that completed or prematurely terminated treatment , 63 % and 53 % of paroxetine CR- and placebo-treated patients , respectively , were panic-free during the final 2 weeks ( p < .005 ; odds ratio [ OR ] = 1.63 ; 95 % CI = 1.21 to 2.19 ) . For week 10 completers ( 72 % of total ) , 73 % and 60 % of paroxetine CR- and placebo-treated patients , respectively , were panic-free at week 10 ( p < .005 ; OR = 2.11 ; 95 % CI = 1.45 to 3.07 ) . Paroxetine CR was also statistically superior to placebo on the global improvement and severity items of the Clinical Global Impressions scale and in reducing anxiety symptoms as measured by the Hamilton Rating Scale for Anxiety total score and total fear and avoidance on the Marks-Sheehan Phobia Scale . Adverse events leading to study withdrawal were minimal and occurred in 11 % of the paroxetine CR group and 6 % of the placebo group . Most of the treatment-emergent adverse events were rated as mild to moderate in severity and occurred early in the study . There were no unexpected adverse events , and serious adverse events were uncommon ( 10 [ 2.3 % ] of the 444 patients treated with paroxetine CR vs. 8 [ 1.8 % ] of the 445 patients treated with placebo ) . CONCLUSION Paroxetine CR is an effective and well-tolerated treatment for panic disorder . Paroxetine CR is associated with low rates of treatment-emergent anxiety as well as low dropout rates from adverse events The effects of flesinoxan , a potent and selective 5-HT1A agonist , were studied in two pilot studies in panic disorder patients to explore the role of 5-HT1A receptors in the mechanism of action of antipanic agents . This paper reports on the results of these two studies with flesinoxan . In study I , using a single-blind crossover design , five patients were treated for 1 week with placebo , 4 weeks with flesinoxan ( up to 2.4 mg per day ) , and 2 weeks with placebo .  In study II , 15 patients were enrolled in a double-blind , three-armed study with placebo and two dosages of flesinoxan .  After a single-blind placebo run-in phase of 1 week , patients were treated for 8 weeks with placebo , 0.6 or 1.2 mg/day flesinoxan . In pilot study I patients ’ condition worsened during the 4-week flesinoxan treatment period . Anxiety was frequently reported as an adverse event . Symptoms returned to the pre-treatment level during the 2-week placebo washout period . In pilot study II , no treatment effects in either group were observed . Anxiety as an adverse event was less prominent than in the first pilot study . A lowering of mood was seen in some patients . The sample sizes of these two pilot studies are too small to draw firm conclusions on the efficacy of flesinoxan in panic disorder , but the present data are not encouraging in this respect . The worsening of symptoms seen with the highest dose of flesinoxan is intriguing and might give a clue to the underst and ing of the mechanism underlying similar effects seen with antidepressants in panic disorder patients OBJECTIVE Although panic attacks account for only a portion of the morbidity of panic disorder and panic attack frequency assessment s are unreliable , studies of drug efficacy in panic disorder have generally used reduction in panic attack frequency as the primary measure of improvement . The authors studied the efficacy of fluoxetine treatment in panic disorder and measured the relative contributions of changes in symptoms to overall improvement . METHOD Patients with a diagnosis of panic disorder ( N = 243 ) were r and omly assigned to treatment with 10 or 20 mg/day of fluoxetine or placebo . Primary outcome measures were change in panic attack frequency and clinician-rated Clinical Global Impression improvement scores . Other assessment s included a panic attack inventory , clinician-rated and patient-rated versions of the Panic and Phobic Disorder Change Scale , a phobia rating scale , the Hamilton Anxiety Rating Scale , the 21-item Hamilton Depression Rating Scale , and the Sheehan Disability Scale . Correlations were determined between outcomes in individual symptom domains and overall clinical outcome . RESULTS Fluoxetine , particularly the 20-mg/day dose , was associated with more improvement than was placebo in patients with panic disorder across multiple symptom measures , including global improvement , total panic attack frequency , phobic symptoms , and functional impairment . Global improvement was most highly correlated with reductions in overall anxiety and phobic symptoms and least correlated with reduction in panic attacks .  Fluoxetine treatment for panic disorder was well tolerated , with a safety profile consistent with that observed for fluoxetine in other disorders . CONCLUSIONS These data provide support for the efficacy and safety of fluoxetine treatment in reducing panic attacks , phobic symptoms , anxiety , and depressive symptoms in patients with panic disorder . Reductions in panic attack frequency in subjects given either fluoxetine or placebo were less closely related to overall clinical improvement than reductions in phobic avoidance , anxiety , depressive symptoms , and functional impairment , suggesting that outcome measures in this disorder should be more broadly based BACKGROUND It has been argued that measurement of outcome in panic disorder should not be limited to monitoring the number of panic attacks , but should include all domains that affect patient quality of life . METHODS Data from a r and omized prospect i ve comparison of escitalopram , citalopram , and placebo in patients with DSM-IV panic disorder were analyzed with regard to measurements of impairment of quality of life . The subscales of the Panic and Agoraphobia Scale ( P&A ) ( Panic Attacks , Agoraphobic Avoidance , Anticipatory Anxiety , Functional and Social Disability , and Worries about Health ) and the Quality of Life Enjoyment and Satisfaction Question naire ( Q-LES-Q ) were analyzed . RESULTS Treatment with escitalopram was associated with significant improvement on all 5 subscales of the P&A.  Citalopram was significantly different from placebo in 3 subscales . Escitalopram and citalopram were significantly better than placebo in improving quality of life ( measured by the total score of the Q-LES-Q Scale ) . Escitalopram was superior to placebo on 12 of 16 items of the Q-LES-Q , while citalopram was superior on 7 items . CONCLUSION The P&A scale was more robust than measurement of panic frequency in differentiating medication from placebo . Escitalopram treatment was associated with improvement on all assessed domains that impair quality of life in panic disorder . Measurement of clinical improvement should not be solely based on panic attack frequency , but should also include assessment of a broad range of domains that affect patient quality of life BACKGROUND Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [ Am . J. Psychiatry 155 ( 1998 ) 1 ] , despite a paucity of data systematic ally examining outcome for periods greater than 3 - 6 months . It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder . METHODS Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder , a prospect i ve , naturalistic study . Participants were categorized by their maintenance treatment condition at remission : benzodiazepine alone ( N = 45 , 58 % ) , antidepressant alone ( N = 12 , 16 % ) , and combined treatment with a benzodiazepine and an antidepressant ( N = 21 , 27 % ) . RESULTS Approximately half ( N = 36 , 46 % ) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period , despite continued and adequate pharmacotherapy . There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy . LIMITATIONS Interpretation of the data is limited by the naturalistic nature of the study , and by the relatively low sample size . CONCLUSIONS This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy , despite continued treatment . In addition , the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy Selective serotonin re-uptake inhibitors ( SSRIs ) and cognitive behavioral therapies ( CBTs ) are both considered as first-line treatments for panic disorder , but the advantages of a combined therapy have yet to be definitively demonstrated . We evaluated in this pilot study the effects of combining SSRIs ( vs. a placebo ) with a very brief form of cognitive-behavioral therapy provided to all participants . Thirty-three subjects with DSM-IV panic disorder , with or without agoraphobia , were r and omized to receive either paroxetine or a placebo with flexible dosing ( 10 - 50 mg/day ) . Medication visits were brief ( 15 min ) , infrequent ( 6 in total ) and non-directive . An expert cognitive-behavior therapist administered one initial 45-min session and one subsequent 30-min session of very brief CBT ( vbCBT ) at weeks 5 and 7 , respectively . Sessions were supplemented with educational and directive reading material s. Patients in both groups ( i.e. vbCBT+paroxetine ; vbCBT+placebo ) improved similarly and substantially on most measures during the 10 weeks of acute treatment . At week 10 , the proportion of panic-free patients was significantly higher in the paroxetine-treated group than in the placebo group ( 80 vs. 25 % ; P<0.007 ) , as was the proportion of subjects who rated themselves as ' very much improved ' at week 10 ( 60 vs. 13 % ; P<0.017 ) . These findings point to the need for additional studies to confirm the effectiveness of very brief forms of CBT , and to document the circumstances in which combined treatment with an SSRI would be warranted Blunted neuroendocrine and physiological responses to the selective 5-HT(1A ) receptor agonist , ipsapirone , have been observed in patients with panic disorder and /or agoraphobia ( PDA ) . In order to examine whether this hyporesponsiveness to ipsapirone is modified by pharmacological or non-pharmacological therapeutic interventions , challenges with an oral dose of ipsapirone ( 0.3 mg/kg ) and placebo were performed in patients with PDA before and after 10 weeks of treatment with clomipramine , aerobic exercise and placebo . Before treatment , administration of ipsapirone was followed by significant increases of cortisol , anxiety and other psychopathological symptoms in comparison to the placebo challenge . In addition , a significant decrease of body temperature was observed . After the 10-week treatment period , the psychological responses to ipsapirone were significantly reduced in the clomipramine and the exercise group . In contrast , there was a non-significant trend towards higher cortisol responses after clomipramine and exercise treatment . The hypothermic response to ipsapirone was significantly reduced by clomipramine treatment . In conclusion , our results demonstrate that effective treatment of panic disorder has divergent effects on the psychological , neuroendocrine and temperature responses to ipsapirone BACKGROUND In the treatment of panic disorder with agoraphobia  , the efficacy of pharmacological , psychological and combined treatments has been established . Unanswered questions concern the relative efficacy of such treatments . AIMS To demonstrate that moclobemide and cognitive-behavioural therapy ( CBT ) are effective singly and more effective in combination . METHOD Fifty-five patients were r and omly assigned to an eight-week treatment of : moclobemide plus CBT ; moclobemide plus clinical management ( ' psychological placebo ' ) ; placebo plus CBT ; or placebo plus clinical management . RESULTS Comparisons between treatments revealed strong effects for CBT . Moclobemide with clinical management was not superior to placebo . The combination of moclobemide with CBT did not yield significantly better short-term results than CBI with placebo . The CBT results remained stable during a six-month follow-up , although a substantial proportion of patients treated with placebo plus CBT needed additional treatment . CONCLUSIONS CBT was highly effective in the treatment of panic disorder with agoraphobia and reduced agoraphobia to levels that were comparable to those of non- clinical controls Following promising preliminary evidence , the benzodiazepine-derivative alprazolam was studied in a large , placebo-controlled , eight-week , flexible-dose trial in patients with agoraphobia with panic attacks and panic disorder . Of 526 patients , 481 completed three weeks of treatment ; however , significantly more placebo ( 102/234 ) than alprazolam ( 21/247 ) recipients subsequently dropped out of the trial , primarily citing ineffectiveness ( of placebo ) as the reason . Alprazolam was found to be effective and well tolerated . There were significant alprazolam-placebo differences in improvement for ( 1 ) spontaneous and situational panic attacks , ( 2 ) phobic fears , ( 3 ) avoidance behavior , ( 4 ) anxiety , and ( 5 ) secondary disability , all significant by the end of week 1 . At the primary comparison point ( week 4 ) , 82 % of the patients receiving alprazolam were rated moderately improved or better vs 43 % of the placebo group . At that point , 50 % of the alprazolam recipients vs 28 % of placebo recipients were free of panic attacks A r and omized , double-blind , placebo-controlled , parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of  panic disorder . One hundred three patients were r and omly assigned to receive double-blind treatment with either gabapentin ( dosed flexibly between 600 and 3,600 mg/day ) or placebo for 8 weeks . No overall drug/placebo difference was observed in scores on the Panic and Agoraphobia Scale ( PAS ) ( p = 0.606 ) . A post hoc analysis was used to evaluate the more severely ill patients as defined by the primary outcome measure ( PAS score > or = 20 ) . In this population , the gabapentin-treated patients showed significant improvement in the PAS change score ( p = 0.04 ) . In patients with a PAS score of 20 or greater , women showed a greater response than men regardless of treatment . Adverse events were consistent with the known side effect profile of gabapentin and included somnolence , headache , and dizziness . One patient experienced a serious adverse event during the study . No deaths were reported . The results of this study suggest that gabapentin may have anxiolytic effects in more severely ill patients with panic disorder Summary The relevance of the chronology between panic disorder and avoidance behavior and of an early , medium or late onset of panic disorder was tested . Groups from the sample of the cross-national collaborative panic study ( CNCPS ) were compared for differences in basic characteristics and for the ability to predict treatment response . Patients who developed avoidance behavior before the full syndrome of panic disorder had less often a full agoraphobia but were not different in their response to treatment . Patients with an early onset of panic disorder suffered more often from agoraphobia . The treatment response was similar in the groups with early , medium or late onset of panic disorder . Neither the chronology between panic disorder and avoidance behavior nor the age of onset of panic disorder predicted outcome in short-term treatment with alprazolam or impiramine Summary The impact of the avoidance behaviour on the psychopharmacological treatment of panic disorder was explored in the Cross National Collaborative Panic Study ( n=1134 patients ) ; in this double blind r and omized trial alprazolam , imipramine and placebo were compared during an 8-week treatment period . Patients with extensive avoidance behaviour ( agoraphobia ) had the most profit from the active drugs . Counter expectancy these specific drug effects were most pronounced in avoidance behaviour . Active drugs ( in particular imipramine ) were especially more effective than placebo if the patients presented with associated avoidance behaviour . The results suggest that agoraphobia defines more a particular type of anxiety disorder overlapping with panic disorder than merely a severe state of panic disorder ABSTRACT A double‐blind clinical trial of zimeldine , a potent inhibitor of central serotonin reuptake , versus imipramine and placebo was carried out on 44 patients suffering from agoraphobia with panic attacks .  Zimeldine was a superior treatment on all rating scales other than a global rating scale which did not reach statistically significant superiority . Imipramine was not shown to be superior to placebo . The implication s of these results for further research on the underlying pathophysiology of agoraphobia with panic attacks are discussed BACKGROUND Drug therapy of panic disorder , despite the intermittent nature of the panic attack , requires daily administration of antidepressants , which are often not tolerated , or benzodiazepines , which can result in physical dependence and withdrawal . The use of rapidly acting , low-dose intranasal midazolam to prevent incipient panic suggested itself to us as a novel alternative treatment strategy . METHOD We conducted a 6-week double-blind , placebo-controlled , crossover- design pilot study of the safety and efficacy of p.r.n . low-dose intranasal midazolam in five patients diagnosed with DSM-III-R panic disorder . RESULTS One to two drops of midazolam ( approximately 0.25 to 0.5 mg ) was well tolerated and highly effective in preventing incipient panic attacks and in reducing the overall weekly frequency of attacks . CONCLUSION Intermittent intranasal midazolam shows promise as a novel alternative treatment for panic , but a controlled study of its efficacy and safety ( including abuse potential ) must be conducted OBJECTIVE Anxiety disorders have been shown to differ in their course , but it is unknown whether DSM-categories represent clinical ly relevant course trajectories . We aim to identify anxiety course trajectories using a data -driven method and to examine whether these course trajectories correspond to DSM-categories or whether other clinical indicators better differentiate them . METHOD 907 patients with panic disorder with agoraphobia , panic disorder without agoraphobia , agoraphobia , social phobia , or generalized anxiety disorder according to DSM-IV criteria were derived from a prospect i ve cohort study ( Netherl and s Study of Depression and Anxiety ) . Baseline data were collected between September 2004 and February 2007 ; follow-up data , between October 2006 and March 2009 . Latent class growth analysis was conducted , based on symptoms of anxiety and avoidance assessed with the Life Chart Interview covering a 2-year time period . Identified course trajectories were compared with DSM-IV diagnoses and a wider set of predictors . RESULTS We identified a class with minimal symptoms over time ( 41.7 % ) , a moderately severe chronic class ( 42.8 % ) , and a severe chronic class ( 15.4 % ) . Panic disorder with agoraphobia ( OR = 2.14 ; 95 % CI , 1.48 - 3.09 ) and social phobia ( OR = 1.97 ; 95 % CI , 1.46 - 2.68 ) predicted moderately severe chronicity ; panic disorder with agoraphobia ( OR = 2.70 ; 95 % CI , 1.66 - 4.40 ) , social phobia ( OR = 2.46 ; 95 % CI , 1.62 - 3.74 ) , and generalized anxiety disorder ( OR = 1.86 ; 95 % CI , 1.23 - 2.82 ) predicted a severe chronic course . However , baseline severity , duration of anxiety , and disability better predicted severe chronic course trajectories than DSM-categories . Additionally , partner status , age at onset , childhood trauma , and comorbid depressive disorder predicted chronic courses . CONCLUSIONS Course of anxiety was pleomorphic with over 40 % having a favorable course , thereby question ing the common notion of chronicity of anxiety disorders . Severity , duration of anxiety , and disability were able to better identify severe chronic course trajectories as compared with DSM-IV categories . These findings facilitate the identification of chronic course trajectories of anxiety disorders in clinical care and support current debates on staging and profiling of mental disorders CONTEXT This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam , a benzodiazepine . OBJECTIVES To evaluate the clinical efficacy of clonazepam in a fixed dosage ( 2 mg/day ) , compared to placebo , in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes . TYPE OF STUDY R and omized study with clonazepam and placebo . SETTING Outpatient Anxiety and Depression Unit of the Institute of Psychiatry , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil . PARTICIPANTS 34 patients with a diagnosis of panic disorder with agoraphobia , between 18 and 55 years old . PROCEDURES Administration of clonazepam or placebo for 6 weeks , in panic disorder patients , after they were classified within two subtypes of panic disorder : respiratory and non-respiratory . MAIN MEASUREMENTS Changes in the number of panic attacks in comparison with the period before the beginning of the study ; Hamilton Anxiety Scale ; Global Clinical Impression Scale ; and Patient 's Global Impression scale . RESULTS In the group that received clonazepam , by the end of the 6th week there was a statistically significant clinical improvement , shown by the remission of panic attacks ( p < 0.001 ) and decrease in anxiety ( p = 0.024 ) . In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder , regarding the therapeutic response to clonazepam . CONCLUSION Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder , suggesting there is no difference in the therapeutic response between the two subtypes
We observed the same finding when classes of antidepressants were compared with placebo .
When looking at dropouts due to adverse effects , which can be considered as a measure of tolerability , we found moderate- quality evidence showing that antidepressants as a whole are less well tolerated than placebo .
The identified studies comprehensively address the objectives of the present review .Based on these results , antidepressants may be more effective than placebo in treating panic disorder .
Antidepressants may also have benefit in comparison with placebo in terms of number of dropouts , but a less favourable profile in terms of dropout due to adverse effects .
However , the tolerability profile varied between different classes of antidepressants .
BACKGROUND Panic disorder is characterised by repeated , unexpected panic attacks , which represent a discrete period of fear or anxiety that has a rapid onset , reaches a peak within 10 minutes , and in which at least four of 13 characteristic symptoms are experienced , including racing heart , chest pain , sweating , shaking , dizziness , flushing , stomach churning , faintness and breathlessness .
It is common in the general population with a lifetime prevalence of 1 % to 4 % .
The treatment of panic disorder includes psychological and pharmacological interventions .
Amongst pharmacological agents , the National Institute for Health and Care Excellence ( NICE ) and the British Association for Psychopharmacology consider antidepressants , mainly selective serotonin reuptake inhibitors ( SSRIs ) , as the first-line treatment for panic disorder , due to their more favourable adverse effect profile over monoamine oxidase inhibitors ( MAOIs ) and tricyclic antidepressants ( TCAs ) .
Several classes of antidepressants have been studied and compared , but it is still unclear which antidepressants have a more or less favourable profile in terms of effectiveness and acceptability in the treatment of this condition .
OBJECTIVES To assess the effects of antidepressants for panic disorder in adults , specifically:1 .
to determine the efficacy of antidepressants in alleviating symptoms of panic disorder , with or without agoraphobia , in comparison to placebo;2 .
to review the acceptability of antidepressants  in panic disorder , with or without agoraphobia , in comparison with placebo ; and 3 .
to investigate the adverse effects of antidepressants  in panic disorder , with or without agoraphobia , including the general prevalence of adverse effects , compared to placebo .