Treatment of Panic Disorder with Agoraphobia: Randomized Placebo‐Controlled Trial of Four Psychosocial Treatments Combined with Imipramine or Placebo Does brief dynamic psychotherapy reduce the relapse rate of panic disorder? Randomised placebo-controlled trial of moclobemide, cognitive-behavioural therapy and their combination in panic disorder with agoraphobia. A randomized clinical trial of cognitive behavioral therapy and interpersonal psychotherapy for panic disorder with agoraphobia. Does concurrent drug intake affect the long-term outcome of group cognitive behaviour therapy in 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. A randomized controlled trial of fluoxetine and cognitive behavioral therapy for bulimia nervosa: short-term outcome. Cognitive-behavioral therapy helps prevent relapse and recurrence of panic disorder following alprazolam discontinuation: a long-term follow-up of the Peoria and Dartmouth studies. Emotion-focused psychotherapy for patients with panic disorder. Longitudinal outcome with pharmacotherapy in a naturalistic study of panic disorder. The efficacy of drugs and psychotherapy in the treatment of acute depressive episodes. Study and course of the psychological profile in 77 patients expressing panic disorder with agoraphobia after cognitive behaviour therapy with or without buspirone. A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder. A crossover study of focused cognitive therapy for panic disorder. Delivering cognitive-behavior therapy for panic disorder with agoraphobia in videoconference. Treatment of panic disorder with agoraphobia: comparison of fluvoxamine, placebo, and psychological panic management combined with exposure and of exposure in vivo alone. Panic and avoidance in agoraphobia. Application of path analysis to treatment studies. Self-exposure therapy for panic disorder with agoraphobia: randomised controlled study of external v. interoceptive self-exposure. Comparing Physical Exercise in Groups to Group Cognitive Behaviour Therapy for the Treatment of Panic Disorder in a Randomized Controlled Trial Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy alone or in combination with antidepressant medication. A comparative trial of psychotherapy and pharmacotherapy for "pure" dysthymic patients. MAOA and mechanisms of panic disorder revisited: from bench to molecular psychotherapy Long‐term outcome of pharmacological and psychological treatment for panic disorder with agoraphobia: a 2‐year naturalistic follow‐up 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. Stress hormones during flooding therapy and their relationship to therapy outcome in patients with panic disorder and agoraphobia. Academic achievement and emotional status of children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. Efficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders. Combining psychotherapy and antidepressants in the treatment of depression. Treating Treatment-Resistant Patients with Panic Disorder and Agoraphobia Using Psychotherapy: A Randomized Controlled Switching Trial A randomized trial of cognitive-behavioral therapy or selective serotonin reuptake inhibitor or both combined for panic disorder with or without agoraphobia: treatment results through 1-year follow-up. 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. Three year naturalistic outcome study of panic disorder patients treated with paroxetine The benefit of an insight-oriented and experiential approach on panic and agoraphobia symptoms. Results of a controlled comparison of client-centered therapy alone and in combination with behavioral exposure. Adaptation of Interpersonal Psychotherapy to Borderline Personality Disorder: A Comparison of Combined Therapy and Single Pharmacotherapy The expert consensus guideline series. Pharmacotherapy of depressive disorders in older patients. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. Paroxetine, clomipramine, and cognitive therapy in the treatment of panic disorder. Transdiagnostic group CBT vs. standard group CBT for depression, social anxiety disorder and agoraphobia/panic disorder: Study protocol for a pragmatic, multicenter non-inferiority randomized controlled trial Does the addition of cognitive behavioral therapy improve panic disorder treatment outcome relative to medication alone in the primary-care setting? Maintenance drug therapy of panic disorder. A comparison study of antidepressants and structured intensive group psychotherapy in the treatment of bulimia nervosa.
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 BACKGROUND Although panic disorder can be effectively alleviated by drug treatment , the relapse rate is high . By adding brief dynamic psychotherapy focused on the psychosocial vulnerability of patients with panic disorder to an established drug treatment regimen , we hypothesized that this would result in a lower relapse rate after pharmacotherapy . METHODS Patients with panic disorder ( defined by DSM-III-R ) were r and omized to treatment with either clomipramine for 9 months ( n = 20 ) , or clomipramine for 9 months combined with 15 weekly sessions of brief dynamic psychotherapy ( n = 20 ) . Measures of anxiety and depression were collected at intake and at regular intervals . The patients had blind follow-up interviews at 6 , 12 , and 18 months after beginning treatment . RESULTS All patients in both groups became free of panic attacks within 26 weeks of the start of treatment . On termination of pharmacotherapy , the relapse rate was significantly higher in the clomipramine-only group during the follow-up period . There were significantly lower scores for most anxiety measures in the clomipramine plus psychotherapy group at the 9-month follow-up . CONCLUSION The addition of brief dynamic psychotherapy to treatment with clomipramine significantly reduces the relapse rate of panic disorder compared with clomipramine treatment alone 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 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 The present study investigated the impact of pre-existing pharmacotherapy regimes on the long-term outcome of brief intensive group cognitive-behavioural therapy ( BIGCBT ) in the treatment of panic disorder with or without agoraphobia in 106 patients ( 74 females ) . Forty patients were allocated to BIGCBT without medication , 40 to BIGCBT plus anti-anxiety medication , 10 to BIGCBT plus anti-depressant medication and 16 to BIGCBT plus combined anti-anxiety and anti-depressant medications . The mean follow-up period was 3.2 yr and ranged from 1.1 to 6.2 yr . The results demonstrated that patients who received BIGCBT concurrent with pre-existing medication regimes did not differ significantly ( P > 0.001 ) from each other or from patients who underwent BIGCBT without medication on any of the dependent measures either at pre-treatment assessment or long-term follow-up . However , BIGCBT ( with or without pharmacotherapy ) was associated with significant ( P < 0.001 ) long-term improvements in frequency of panic attacks , avoidance behaviour and question naire measures of anxiety , depression and agoraphobia . Furthermore , the large majority ( 80 % ) of patients in the BIGCBT without medication group remained medication-free at long-term follow-up . Of those patients who underwent BIGCBT concurrent with pre-existing pharmacotherapy , a large percentage ( 44 % ) reported no longer taking medication for their condition at long-term follow-up . Overall , it is concluded that pre-existing medication regimes ( anti-anxiety , anti-depressant or combinations of these ) do not significantly enhance or detract from the long-term outcome of a BIGCBT program used in the treatment of panic disorder and agoraphobia 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 This study compared and combined fluoxetine and individual cognitive behavioral therapy in the treatment of bulimia nervosa . Participants were 76 women who sought treatment at the Eating Disorders Program of the Toronto Hospital and who met DSM-III-R criteria for bulimia nervosa . Subjects were r and omly assigned to receive fluoxetine alone , cognitive behavior therapy alone , or the two in combination and were treated over 16 weeks . Short-term outcome revealed that all three treatment conditions were associated with clinical improvement across a wide range of parameters . The combination of pharmacotherapy and psychotherapy was superior to pharmacotherapy alone on specific parameters and there was no statistically significant advantage to the combination over psychotherapy alone . Limitations to the study include the absence of a placebo pill group and a waiting list control group as well as a substantial dropout rate across all three treatment conditions The present research evaluated patients from 2 previous studies ( 1 conducted in Peoria , the other at Dartmouth ) during a 2- to 5-year posttreatment period . Results showed that 75 % of the Peoria sample and 76 % of the Dartmouth sample were able to discontinue alprazolam therapy , remain abstinent of any type of treatment for panic disorder , and maintain their acute-treatment clinical gains over this follow-up period . The degree to which patients ' anxiety sensitivity declined during treatment predicted relapse versus survival during the 1st 6 months of follow-up , when most relapses occurred . Implication s of these findings for benzodiazepine discontinuation , combined pharmacotherapy and psychotherapy , and relapse prevention in panic disorder are discussed OBJECTIVE Recent studies have suggested that most patients treated for panic disorder receive forms of psychotherapy other than cognitive behavior therapy , even though there is little information about the efficacy of such treatments or how they compare to proven active treatments . The authors compared one of these other forms , emotion-focused psychotherapy ( given to 30 patients with panic disorder ) , to results obtained with recommended st and ard treatment ( either cognitive behavior therapy [ N=36 ] or imipramine [ N=22 ] ) . The authors also compared emotion-focused psychotherapy to results obtained in subjects given pill placebo ( N=24 ) . METHOD Subjects met DSM-IV criteria for panic disorder with no more than mild agoraphobia . Treatment consisted of approximately 3 months of weekly visits followed by 6 monthly maintenance visits . Assessment s were conducted after each treatment phase and at a follow-up visit after 6 months of no treatment . RESULTS Emotion-focused psychotherapy  was less effective for symptoms of panic disorder than treatment with either cognitive behavior therapy or imipramine ; results obtained with emotion-focused psychotherapy after the acute and maintenance phases were similar to those seen with placebo .  Treatment expectations were not different among the different groups . Patients receiving emotion-focused psychotherapy had the highest completion rate . CONCLUSIONS The results suggest that emotion-focused psychotherapy ( a supportive form of psychotherapy ) has low efficacy for the treatment of panic disorder . However , emotion-focused psychotherapy may be superior to medical management in helping patients stay in treatment 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 The efficacy of tricyclic antidepressants and various psychotherapies , in comparison with one another or in combination , has not been fully established in r and omized clinical trials . The authors present a r and omized controlled trial comparing the combination of amitriptyline and short-term interpersonal psychotherapy , either treatment alone , and nonscheduled supportive psychotherapy in ambulatory patients with acute depression . They found that pharmacotherapy and psychotherapy alone were equally efficacious and better than nonscheduled treatment . The combination treatment of  psychotherapy and pharmacotherapy was more effective than either treatment alone and delayed the onset of symptomatic failure BACKGROUND The change of psychopathological dimensions during treatment of panic disorder is attracting increasing interest . METHODS A population of subjects experiencing panic disorder with agoraphobia is evaluated with the French version of the factor structure of the Symptom Checklist 90 R ( SCL 90 R ) . Two groups of patients are compared : a group receiving cognitive behaviour therapy ( CBT ) combined with buspirone and a group receiving cognitive behaviour therapy combined with placebo .  RESULTS Comparative analysis of pre- and post-test changes between both groups completing treatment showed that the combination cognitive behaviour therapy plus buspirone provided better results than those in patients who had received cognitive behaviour therapy plus placebo . This difference between treatments did not persist at the 1-year follow-up , since , while results had been effectively maintained in the CBT plus buspirone group , the CBT plus placebo group continued to improve significantly for the target dimensions of treatment . CONCLUSIONS Psychopathological dimensions on the SCL 90 R show that combination of buspirone and cognitive behaviour therapy accelerates the behaviour modification process only in the short term BACKGROUND Panic disorder is a prevalent , often disabling condition among patients in the primary care setting . Although numerous studies have assessed the effectiveness of treatments for depression in primary care , few such studies have been conducted for panic disorder . OBJECTIVE To implement and test the effectiveness of a combined pharmacotherapy and cognitive-behavioral intervention for panic disorder tailored to the primary care setting . DESIGN R and omized , controlled study comparing intervention to treatment as usual . SETTING Six primary care clinics associated with 3 university medical schools , serving an ethnically and socioeconomically diverse patient population . PARTICIPANTS Two hundred thirty-two primary care patients meeting DSM-IV criteria for panic disorder . Comorbid mental and physical disorders were permitted , provided these did not contraindicate the treatment to be provided and were not acutely life threatening . INTERVENTION Patients were r and omized to receive either treatment as usual or an intervention consisting of a combination of up to 6 sessions ( across 12 weeks ) of cognitive-behavioral therapy ( CBT ) modified for the primary care setting , with up to 6 follow-up telephone contacts during the next 9 months , and algorithm-based pharmacotherapy provided by the primary care physician with guidance from a psychiatrist . Behavioral health specialists , the majority inexperienced in CBT for panic disorder , were trained to deliver the CBT and coordinated overall care , including pharmacotherapy . MAIN OUTCOMES MEASURES Proportion of subjects remitted ( no panic attacks in the past month , minimal anticipatory anxiety , and agoraphobia subscale score < 10 on Fear Question naire ) and responding ( Anxiety Sensitivity Index score < 20 ) and change over time in World Health Organization Disability Scale and short form 12 scores . RESULTS The combined cognitive-behavioral and pharmacotherapeutic intervention result ed in sustained and gradually increasing improvement relative to treatment as usual , with significantly higher rates at all points of both the proportion of subjects remitted ( 3 months , 20 % vs 12 % ; 12 months , 29 % vs 16 % ) and responding ( 3 months , 46 % vs 27 % ; 12 months , 63 % vs 38 % ) and significantly greater improvements in World Health Organization Disability Scale ( all points ) and short form 12 mental health functioning ( 3 and 6 months ) scores . These effects were obtained in spite of similar rates of delivery of guideline -concordant pharmacotherapy to the 2 groups . CONCLUSION Delivery of evidence -based CBT and medication using the collaborative care model and a CBT-naive , midlevel behavioral health specialist is feasible and significantly more effective than usual care for primary care panic disorder OBJECTIVE This study sought to determine the short- and long-term effects of focused cognitive therapy for  panic disorder . METHOD Thirty-three psychiatric out patients with the DSM-III diagnosis of panic disorder were r and omly assigned to either 12 weeks of individual , focused cognitive therapy or 8 weeks of brief supportive psychotherapy based on principles of client-centered therapy . The patients who received supportive psychotherapy were subsequently given the opportunity to cross over to cognitive therapy for 12 weeks . Patients were rated for panic and depression before therapy , after 4 and 8 weeks of therapy , and at 6-month and 1-year follow-up . RESULTS Clinician ratings and self-ratings of panic frequency and intensity indicated that the focused cognitive therapy group achieved significantly greater reductions in panic symptoms and general anxiety after 8 weeks of treatment than did the group that received brief supportive psychotherapy . At 8 weeks , 71 % of the cognitive therapy group were panic free , compared to 25 % of the psychotherapy group . Moreover , 94 % of the psychotherapy patients elected to cross over to 12 weeks of cognitive therapy . At 1-year follow-up , 87 % of the group that received cognitive therapy only and 79 % of the group that crossed over into cognitive therapy remained free of panic attacks . CONCLUSIONS Focused cognitive therapy offers a promising nonpharmacological alternative for the treatment of panic disorder Delivering psychotherapy by videoconference could significantly increase the accessibility of empirically vali date d treatments . The aim of this study was to compare the effectiveness of cognitive-behavior therapy ( CBT ) for panic disorder with agoraphobia ( PDA ) when the therapy is delivered either face-to-face or by videoconference .  A sample of 21 participants was treated either face-to-face or by videoconference . Results showed that CBT delivered by videoconference was as effective as CBT delivered face-to-face . There was a statistically significant reduction in all measures , and the number of panic-free participants among those receiving CBT by videoconference was 81 % at post-treatment and 91 % at the 6-month follow-up . None of the comparisons with face-to-face psychotherapy suggested that CBT delivered by videoconference was less effective . These results were confirmed by analyses of effect size . The participants reported the development of an excellent therapeutic alliance in videoconference as early as the first therapy session . The importance of these results for treatment accessibility is discussed . Hypotheses are proposed to explain the rapid creation of strong therapeutic alliances in videoconferencing 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 We explored a causal sequence between panic and avoidance to provide recommendations for psychotherapy , pharmacotherapy , and their combination in treating agoraphobia . We produced a two-way [ ( imipramine hydrochloride vs placebo ] by [ office-based behavioral therapy vs in vivo exposure ] ) design by amalgamating two studies . We assessed agoraphobic patients for panic and avoidance at these time points : baseline ( week 0 ) , midcourse ( week 13 ) , and termination ( week 26 ) . The causal sequence model was tested by path analysis . Imipramine was superior to placebo in lowering panic and avoidance at both postbaseline time points . Exposure was superior to office-based treatment in lowering avoidance only at week 13 . Exposure appeared to produce quicker improvement of avoidance than office-based therapy , but relapse occurred if this improvement was not supported by medication . Exposure did not benefit panic . We believe patients should be informed that imipramine is superior to exposure in inducing a panic-free state . Exposure without imipramine is of benefit only in reducing avoidance , but adding imipramine to exposure is necessary for panic control and substantially improves exposure and exposure maintenance BACKGROUND Exposure to external phobic cues is an effective therapy for  panic/agoraphobia  but the value of exposure to interoceptive cues is unclear . AIMS R and omised controlled comparison in panic/agoraphobia of the effects of ( a ) external , ( b ) interceptive or ( c ) combined external and interoceptive self-exposure to ( d ) control subjects . METHOD Eighty out- patients were r and omised to a control group or to one of three forms of self-exposure treatment ( external , interoceptive , or combined ) . Each treatment included seven sessions over 10 weeks and daily self-exposure homework . Assessment s were at pre- and post-treatment and up to 1 year post-entry . Assessors remained blind during treatment . RESULTS The three self-exposure groups improved significantly and similarly at post-treatment and up to 1-year followup , and significantly more than did the control subjects . Rates of improvement on main outcome measures averaged 60 % at post-treatment and 77 % at follow-up . CONCLUSIONS The three methods of self-exposure were equally effective in reducing panic and agoraphobic symptoms in the short- and long-term Background : Previous studies have suggested that physical exercise can reduce symptoms for subjects suffering from panic disorder ( PD ) . The efficacy of this intervention has so far not been compared to an established psychotherapy , such as cognitive behaviour therapy ( CBT ) . Assessment of controlled long-term effects and the clinical significance of the treatment are also lacking . Aim : To compare physical exercise to CBT as treatment for PD , and assess controlled long-term and clinical ly significant effects . Method : PD- patients were r and omized to either three weekly sessions of physical exercise ( n = 17 ) , or one weekly session of CBT ( n = 19 ) . Both treatments ran for 12 weeks , were manualized and administered in groups . Patients were assessed twice before the start of treatment , at post-treatment and at 6 and 12 months thereafter . Primary outcome - measures consisted of the Mobility Inventory ( MI ) , the Agoraphobia Cognitions Question naire ( ACQ ) and the Body Sensations Question naire ( BSQ ) . Results : A two-way repeated measures MANOVA of these measures demonstrated a significant effect of time , F(16 , 544 ) = 7.28 , p < .01 , as well as a significant interaction effect , F(16 , 544 ) = 1.71 , p < .05 , in favour of CBT . This finding was supported by the assessment of clinical ly significant changes of avoidant behaviour and of treatment-seeking one year later . Conclusion : Group CBT is more effective than group physical exercise as treatment of panic disorder , both immediately following treatment and at follow-up assessment Major depressive disorder is associated with considerable morbidity , disability , and risk for suicide . Treatments for depression most commonly include antidepressants , psychotherapy , or the combination . Little is known about predictors of treatment response for depression . In this study , 681 patients with chronic forms of major depression were treated with an antidepressant ( nefazodone ) , Cognitive Behavioral Analysis System of Psychotherapy ( CBASP ) , or the combination . Overall , the effects of the antidepressant alone and psychotherapy alone were equal and significantly less effective than combination treatment . Among those with a history of early childhood trauma ( loss of parents at an early age , physical or sexual abuse , or neglect ) , psychotherapy alone was superior to antidepressant monotherapy . Moreover , the combination of  psychotherapy and pharmacotherapy was only marginally superior to  psychotherapy  alone among the childhood abuse cohort . Our results suggest that psychotherapy may be an essential element in the treatment of patients with chronic forms of major depression and a history of childhood trauma BACKGROUND In 2001 , the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments ( CANMAT ) partnered to produce evidence -based clinical guidelines for the treatment of depressive disorders .  A revision of these guidelines was undertaken by CANMAT in 2008 - 2009 to reflect advances in the field . This article , one of five in the series , review s new studies of psychotherapy in the acute and maintenance phase of MDD , including computer-based and telephone-delivered psychotherapy . METHODS The CANMAT guidelines are based on a question -answer format to enhance accessibility to clinicians . Evidence -based responses are based on up date d systematic review s of the literature and recommendations are grade d according to the Level of Evidence , using pre-defined criteria . Lines of Treatment are identified based on criteria that included evidence and expert clinical support . RESULTS Cognitive-Behavioural Therapy ( CBT ) and Interpersonal Therapy ( IPT ) continue to have the most evidence for efficacy , both in acute and maintenance phases of MDD , and have been studied in combination with antidepressants . CBT is well studied in conjunction with computer-delivered methods and bibliotherapy . Behavioural Activation and Cognitive-Behavioural Analysis System of Psychotherapy have significant evidence , but need replication . Newer psychotherapies including Acceptance and Commitment Therapy , Motivational Interviewing , and Mindfulness-Based Cognitive Therapy do not yet have significant evidence as acute treatments ; nor does psychodynamic therapy . LIMITATIONS Although many forms of psychotherapy have been studied , relatively few types have been evaluated for MDD in r and omized controlled trials . Evidence about the combination of different types of psychotherapy and antidepressant medication is also limited despite widespread use of these therapies concomitantly . CONCLUSIONS CBT and IPT are the only first-line treatment recommendations for acute MDD and remain highly recommended for maintenance . Both computer-based and telephone-delivered psychotherapy -- primarily studied with CBT and IPT -- are useful second-line recommendations . Where feasible , combined antidepressant and CBT or IPT are recommended as first-line treatments for acute MDD BACKGROUND Psychotherapy of " pure " dysthymic disorder remains understudied . This article reports outcomes of an acute r and omized trial of 94 subjects treated for 16 weeks with either interpersonal psychotherapy ( IPT ) , brief supportive psychotherapy ( BSP ) , sertraline , or sertraline plus IPT .  METHODS Recruited by clinical referral and advertising , subjects met DSM-IV criteria for early onset dysthymic disorder , with no episode of major depression in the prior six months . They were r and omly assigned to one of four 16-week treatments , with options for crossover or continuation treatment . Results were analyzed from the intention-to-treat sample by ANCOVA , controlling for baseline depressive severity . RESULTS Subjects improved in all conditions over time , with the cells including sertraline pharmacotherapy showing superiority over psychotherapy alone for response and remission . Response rates were 58 % for sertraline alone , 57 % for combined treatment , 35 % for IPT , and 31 % for BSP . LIMITATIONS The study was underpowered and may have employed too " active " a control condition . Follow-up data were unobtainable . CONCLUSIONS In this acute trial for " pure " dysthymic disorder , sertraline with or without IPT showed advantages relative to IPT and BSP . Method ological difficulties may have limited differential outcome findings . This study bolsters a small but growing literature on the treatment of dysthymic disorder , suggesting that pharmacotherapy may acutely benefit patients more than psychotherapy Panic disorder with agoraphobia ( PD/AG ) is a prevalent mental disorder featuring a substantial complex genetic component . At present , only a few established risk genes exist . Among these , the gene encoding monoamine oxidase A ( MAOA ) is noteworthy given that genetic variation has been demonstrated to influence gene expression and monoamine levels . Long alleles of the MAOA-uVNTR promoter polymorphism are associated with PD/AG and correspond with increased enzyme activity . Here , we have thus investigated the impact of MAOA-uVNTR on therapy response , behavioral avoidance and brain activity in fear conditioning in a large controlled and r and omized multicenter study on cognitive behavioral therapy ( CBT ) in PD/AG . The study consisted of 369 PD/AG patients , and genetic information was available for 283 patients . Carriers of the risk allele had significantly worse outcome as measured by the Hamilton Anxiety scale ( 46 % responders vs 67 % , P=0.017 ) . This was accompanied by elevated heart rate and increased fear during an anxiety-provoking situation , that is , the behavioral avoidance task . All but one panic attack that happened during this task occurred in risk allele carriers and , furthermore , risk allele carriers did not habituate to the situation during repetitive exposure . Finally , functional neuroimaging during a classical fear conditioning paradigm evidence d that the protective allele is associated with increased activation of the anterior cingulate cortex upon presentation of the CS+ during acquisition of fear . Further differentiation between high- and low-risk subjects after treatment was observed in the inferior parietal lobes , suggesting differential brain activation patterns upon CBT . Taken together , we established that a genetic risk factor for PD/AG is associated with worse response to CBT and identify potential underlying neural mechanisms . These findings might govern how psychotherapy can include genetic information to tailor individualized treatment approaches Two years after completion of a controlled outcome study of treatments for panic disorder with agoraphobia , patients were revisited and interviewed about their complaints . In the initial study , four treatments had been compared : ( i ) fluvoxamine combined with exposure ; ( ii ) placebo medication plus exposure ; ( iii ) psychological panic management plus exposure : and ( iv ) exposure alone . Comparison of the results at post‐test had revealed superior efficacy of fluvoxamine combined with exposure over the other three treatments in reducing agoraphobic avoidance . The current naturalistic follow‐up study investigated the long‐term efficacy of the treatments with regard to abatement of complaints and reduced dem and for further treatment . In addition , we examined whether patients were able to taper off the study medication without a recurrence of complaints . In total , 71 of the 76 patients of the original trial ( 93 % ) were interviewed . Comparison of the mean level of psychopathology at follow‐up revealed no difference between the original treatment groups . The effect in the fluvoxamine plus exposure group was maintained , but was no longer superior , due to further improvements in the other treatment groups . Most patients received additional treatment during the follow‐up period , usually because the 12 treatment sessions in the controlled study had yielded insufficient improvement . There was a trend for patients who received the fluvoxamine plus exposure treatment to require less aftercare than those who received the other treatments . Finally , almost 50 % of the patients who had received medication in the original trial were able to taper off the use of fluvoxamine without a recurrence of complaints 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 In spite of excessive fear during a panic attack , studies have found no or little evidence for an activation of cortisol during natural panic attacks . Whether this phenomenon is related to psychopathology or outcome of psychotherapy is unknown . In this study , 10 patients with panic disorder and agoraphobia were treated with cognitive behavioural therapy including 3 in-vivo exposures ( flooding ) to individual phobic situations . Before , during and after exposure , the level of subjective fear was assessed and blood was collected simultaneously . Cortisol and ACTH were analysed from plasma . Ten matched healthy control subjects went through the same procedure . Fear and stress hormones during exposure were compared in patients and controls as well as related to therapy outcome at the end of therapy and 2 follow-ups in patients . Results showed that the concentrations of cortisol and ACTH did not significantly increase during exposure . Patients ' cortisol concentrations were higher than those of controls at baseline and during exposure , while ACTH concentrations were comparable before and during exposure , and even lower than those of controls at recovery . Cortisol concentrations were moderately but consistently correlated to therapy outcome , i.e. patients with least cortisol release during exposure profited least from therapy . The study showed that a lack of stimulation of the HPA system at repeated confrontation with the phobic situation was related to therapeutic outcome . Mechanisms of action via the influence of cortisol on extinction learning or the inhibition of central excitatory neurotransmission are conceivable OBJECTIVE To test the hypothesis that intensive multimodal psychosocial intervention ( that includes academic assistance and psychotherapy ) combined with methylpheni date significantly enhances the academic performance and emotional status of children with attention-deficit/hyperactivity disorder ( ADHD ) compared with methylpheni date alone and with methylpheni date combined with nonspecific psychosocial treatment ( attention control ) . METHOD One hundred three children with ADHD ( ages 7 - 9 ) , free of conduct and learning disorders , who responded to short-term methylpheni date were r and omized for 2 years to receive one of three treatments : ( 1 ) methylpheni date alone , ( 2 ) methylpheni date plus psychosocial treatment that included academic remediation , organizational skills training , and psychotherapy as well as parent training and counseling and social skills training , or ( 3 ) methylpheni date plus attention control treatment . Children 's function was assessed through academic testing , parent ratings of homework problems , and self-ratings of depression and self-esteem . RESULTS No advantage was found on any measure of academic performance or emotional status for the combination treatment over methylpheni date alone and over methylpheni date plus attention control . Significant improvement occurred across all treatments and was maintained over 2 years . CONCLUSIONS In stimulant-responsive young children with ADHD without learning and conduct disorders , there is no support for academic assistance and psychotherapy to enhance academic achievement or emotional adjustment . Significant short-term improvements were maintained over 2 years BACKGROUND Traditional combination strategies of cognitive-behavior therapy plus pharmacotherapy have met with disappointing results for anxiety disorders . Enhancement of cognitive-behavior therapy with d-cycloserine ( DCS ) pharmacotherapy represents a novel strategy for improving therapeutic learning from cognitive-behavior therapy that remains untested in panic disorder . METHOD This is a r and omized , double-blind , placebo-controlled augmentation trial examining the addition of isolated doses of 50 mg d-cycloserine or pill placebo to brief exposure-based cognitive-behavior therapy .  R and omized participants were 31 out patients meeting DSM-IV criteria for panic disorder with or without agoraphobia , who were offered five sessions of manualized cognitive-behavior therapy emphasizing exposure to feared internal sensations ( interoceptive exposure ) but also including informational , cognitive , and situational exposure interventions . Doses of study drug were administered 1 hour before cognitive-behavior therapy sessions 3 to 5 . The primary outcome measures were the Panic Disorder Severity Scale ( PDSS ) and Clinicians ' Global Impressions of Severity . RESULTS Results indicated large effect sizes for the additive benefit of d-cycloserine augmentation of cognitive-behavior therapy for panic disorder . At posttreatment and 1 month follow-up , participants who received d-cycloserine versus placebo had better outcomes on the PDSS and global severity of disorder and were significantly more likely to have achieved clinical ly significant change status ( 77 % vs. 33 % ) . There were no significant adverse effects associated with DCS administration . CONCLUSIONS This pilot study extends support for the role of d-cycloserine in enhancing therapeutic learning from exposure-based cognitive-behavior therapy and is the first to do so in a protocol emphasizing exposure to feared internal sensations of anxiety in panic disorder OBJECTIVE Major depression occurs with generalized anxiety disorder and panic disorder in up to 60 % of psychiatric and primary care patients . This comorbidity has been associated with greater severity of depression , poorer psychosocial functioning , and poorer treatment outcomes in psychiatric sample s. This study examined the clinical outcomes for depressed primary care patients with and without a lifetime anxiety disorder . METHOD A total of 157 primary care patients who met criteria for major depression were r and omly assigned to st and ardized interpersonal psychotherapy or pharmacotherapy with nortriptyline and were assessed at baseline and at 4 and 8 months on severity of depression , psychosocial functioning , and health-related functioning . RESULTS Depressed patients with a comorbid anxiety disorder presented with significantly more psychopathology and tended to prematurely terminate treatment more frequently than patients with major depression alone . Both st and ardized depression-specific treatments were effective for depressed patients with and without a comorbid generalized anxiety disorder , although time to recovery was longer for the former . Patients with lifetime panic disorder showed poor recovery in response to psychotherapy or pharmacotherapy . CONCLUSIONS St and ardized psychotherapy and pharmacotherapy are effective for patients with major depression with and without a generalized anxiety disorder . However , the longer time to recovery for the former group and lack of response to these treatments by patients with lifetime panic disorder suggest that primary care physicians should carefully assess history of anxiety disorder among depressed patients so as to select a proper intervention OBJECTIVE To compare the efficacy of antidepressants with that of antidepressants plus psychotherapy ( " combined therapy " ) in the treatment of depression . METHODS 6 month r and omised clinical trial of  antidepressants ( N=84 ) and  combined therapy ( N=83 ) in ambulatory patients with Major Depression and a 17-item HDRS baseline score of at least 14 points . The antidepressant protocol provides for three successive steps in case of intolerance or inefficacy : fluoxetine , amitriptyline and moclobemide . The combined therapy condition consists , in addition to pharmacotherapy , of 16 sessions of Short Psychodynamic Supportive Psychotherapy .  Efficacy is assessed using the 17-item HDRS , the CGI of Severity and of Improvement , the depression subscale of the SCL-90 , and the Quality of Life Depression Scale . The data analysis is conducted on three sample s : the intention-to-treat sample , the per protocol sample and the observed cases sample . RESULTS After r and omisation , 32 % of the patients refused the proposed pharmacotherapy while 13 % refused the proposed combined therapy . In 24 weeks , 40 % of the patients who started with the pharmacotherapy stopped medication ; 22 % of those receiving the combined therapy did so . The difference in success rates is statistically significant , favouring combined therapy , in 23 % , 31 % and 62 % of the patients after 8 , 16 and 24 weeks of treatment , respectively . At week 24 , the mean success rate is 40.7 % in the pharmacotherapy group and 59.2 % in the combined therapy group . CONCLUSION Patients found combined treatment significantly more acceptable , they were significantly less likely to drop out of combined therapy and , ultimately , significantly more likely to recover .  Combined therapy is preferable to pharmacotherapy in the treatment of ambulatory patients with major depression Background : Nonresponsiveness to therapy is generally acknowledged , but only a few studies have tested switching to psychotherapy . This study is one of the first to examine the malleability of treatment-resistant patients using acceptance and commitment therapy ( ACT ) .  Methods : This was a r and omized controlled trial that included 43 patients diagnosed with primary panic disorder and /or agoraphobia ( PD/A ) with prior unsuccessful state-of-the-art treatment ( mean number of previous sessions = 42.2 ) . Patients were treated with an ACT manual administered by novice therapists and followed up for 6 months . They were r and omized to immediate treatment ( n = 33 ) or a 4-week waiting list ( n = 10 ) with delayed treatment ( n = 8) . Treatment consisted of eight sessions , implemented twice weekly over 4 weeks . Primary outcomes were measured with the Panic and Agoraphobia Scale ( PAS ) , the Clinical Global Impression ( CGI ) , and the Mobility Inventory ( MI ) . Results : At post-treatment , patients who received ACT reported significantly more improvements on the PAS and CGI ( d = 0.72 and 0.89 , respectively ) than those who were on the waiting list , while improvement on the MI ( d = 0.50 ) was nearly significant . Secondary outcomes were consistent with ACT theory . Follow-up assessment s indicated a stable and continued improvement after treatment . The dropout rate was low ( 9 % ) . Conclusions : Despite a clinical ly challenging sample and brief treatment administered by novice therapists , patients who received ACT reported significantly greater changes in functioning and symptomatology than those on the waiting list , with medium-to-large effect sizes that were maintained for at least 6 months . These proof-of-principle data suggest that ACT is a viable treatment option for treatment-resistant PD/A patients . Further work on switching to psychotherapy for nonresponders is clearly needed OBJECTIVE To establish the long-term effectiveness of 3 treatments for DSM-IV panic disorder with or without agoraphobia :  cognitive-behavioral therapy ( CBT ) , pharmacotherapy using a selective serotonin reuptake inhibitor ( SSRI ) , or the combination of both ( CBT + SSRI ) . As a secondary objective , the relationship between treatment outcome and 7 predictor variables was investigated . METHOD Patients were enrolled between April 2001 and September 2003 and were r and omly assigned to treatment . Academic and nonacademic clinical sites participated . Each treatment modality lasted 1 year . Pharmacotherapists were free to choose between 5 SSRIs currently marketed in The Netherl and s. Outcome was assessed after 9 months of treatment ( posttest 1 ) , after discontinuation of treatment ( posttest 2 ) , and 6 and 12 months after treatment discontinuation ( follow-up 1 and follow-up 2 ) . RESULTS In the sample ( N = 150 ) , 48 % did not suffer from agoraphobia or suffered from only mild agoraphobia , while 52 % suffered from moderate or severe agoraphobia . Patients in each treatment group improved significantly from pretest to posttest 1 on the primary outcome measures of level of anxiety ( P < .001 ) , degree of coping ( P < .001 ) , and remitter status ( P < .001 ) , as well as on the secondary outcome measures of depressive symptomatology ( P < .001 ) , and from pretest to posttest 2 for health-related quality of life ( P < .001 ) . Gains were preserved from posttest 2 throughout the follow-up period . Some superiority of CBT + SSRI and SSRI as compared with CBT was observed at posttest 1 . However , at both follow-ups , differences between treatment modalities proved nonsignificant . Client satisfaction appeared to be high at treatment endpoint , while patients receiving CBT + SSRI appeared slightly ( P < .05 ) more satisfied than those receiving CBT only . CONCLUSIONS No fall-off in gains was observed for either treatment modality after treatment discontinuation . SSRIs were associated with adverse events . Gains produced by CBT were slower to emerge than those produced by CBT + SSRI and SSRI , but CBT ended sooner . TRIAL REGISTRATION Netherl and s Trial Register ( www.trialregister.nl ) Identifier : IS RCT N8156869 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 Background This naturalistic open label follow-up study had three objectives :1 ) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment2 ) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia.3 ) To observe paroxetine 's  tolerability over a 24 month period . Methods 143 patients with panic disorder ( PD ) , with or without agoraphobia , successfully finished a short-term ( ie 12 week ) trial of paroxetine treatment . All patients then continued to receive paroxetine maintenance therapy for a total of 12 months . At the end of this period , 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase . The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored , as in the first group , for another year while medication-free . The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a r and omized manner . Results Only 21 of 143 patients ( 14 % ) relapsed during the one year medication discontinuation follow-up phase . There were no significant differences in relapse rates between the patients who received intermediate-term ( up to 12 months ) paroxetine and those who chose the long-term course ( 24 month paroxetine treatment ) . 43 patients ( 30.1 % ) reported sexual dysfunction . The patients exhibited an average weight gain of 5.06 kg . All patients who eventually relapsed demonstrated significantly greater weight increase ( 7.3 kg ) during the treatment phase . Conclusions The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation . Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment BACKGROUND It is a common view that psychodynamic treatment does not help much to ameliorate the symptoms of panic and agoraphobia . The effects of an insight-oriented treatment on central anxiety symptoms are the subject of the present controlled study . METHODS Forty patients with severe panic and agoraphobia were admitted to an inpatient anxiety treatment program . Most of the patients had been treated by pharmacological means unsuccessfully . The patients were r and omly assigned to pure client-centered therapy or to additional behavioral exposure treatment . Client-centered and behavioral agoraphobia manuals were used . The patients were examined on admission , at discharge and at 3 , 6 , and 12 months follow-up for panic ( Structured Clinical Interview for DSM III-R -- SCID ) , anxiety ( Hamilton Anxiety Scale ) , agoraphobia ( SCID , Fear Survey Schedule ) , and depressive ( Hamilton Depression Scale ) symptoms . RESULTS Both client-centered treatment and a combination with exposure treatment reduced panic , avoidance and depressive symptoms significantly . For a short period the combined treatment was superior in patients ' coping actively with anxiety and improving agoraphobic symptoms . However , at 1-year follow-up there was no further difference in the reduction of anxiety and depressive symptoms . CONCLUSIONS The results are discussed with regard to the combination of these forms of therapy and to widespread skepticism about the efficacy of insight-oriented treatment Objective : Combined treatment with interpersonal psychotherapy ( IPT ) and antidepressants ( ADs ) has been found more effective than single pharmacotherapy in patients with major depression and concomitant borderline personality disorder ( BPD ) . The aim of our study is to investigate whether combined treatment with a modified version of IPT is still superior to ADs when treating patients with a single diagnosis of BPD . Method : Fifty-five consecutive out patients with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision , diagnosis of BPD were enrolled . They were r and omly assigned to 2 treatment arms for 32 weeks : fluoxetine 20 to 40 mg per day plus clinical management ; and fluoxetine 20 to 40 mg per day plus IPT adapted to BPD ( IPT-BPD ) . Eleven patients ( 20 % ) discontinued treatment owing to noncompliance . Forty-four patients completed the treatment period . They were assessed at baseline , and at week 16 and 32 with : a semi-structured interview for demographic and clinical variables ; Clinical Global Impression Scale ( CGI-S ) ; Hamilton Depression Rating Scale ( HDRS ) ; Hamilton Anxiety Rating Scale ( HARS ) ; Social and Occupational Functioning Assessment Scale ( SOFAS ) ; BPD Severity Index ( BPD-SI ) ; and a question naire for quality of life ( Satisfaction Profile [ SAT-P ] ) . A univariate general linear model was performed with 2 factors : duration and type of treatment . P values of less than 0.05 were considered significant . Results : Remission rates did not differ significantly between subgroups . Duration , but not type of treatment , had a significant effect on CGI-S , HDRS , SOFAS , and total BPD-SI score changes . Combined therapy was more effective on the HARS ; the items : interpersonal relationships , affective instability , and impulsivity of BPD-SI ; and the factors : psychological functioning and social functioning of SAT-P. Conclusions : Combined therapy with adapted IPT was superior to fluoxetine alone in BPD patients , concerning a few core symptoms of the disorder , anxiety , and quality of life OBJECTIVES Depression in older patients contributes to personal suffering and family disruption and increases disability , medical morbidity , mortality , suicide risk , and healthcare utilization . The majority of clinical trials of antidepressant treatments are conducted in younger patients . For this reason , clinicians often have to extrapolate from studies in population s that do not present the same problems as older patients . For example , older patients often have serious coexisting medical conditions that may contribute to the depression and complicate the choice of treatment . Older patients as a rule need to be on many medications , some of which may contribute to depression and /or interact with antidepressants . Finally , older adults metabolize medications slowly and are more sensitive to side effects than younger patients . Because of these complexities , we conducted a consensus survey of expert opinion on the pharmacotherapy of depressive disorders in older patients to address clinical questions not definitively answered in the research literature . METHOD After review ing the literature and convening a work group of experts , we prepared a written survey with 64 questions that asked about 857 options . 618 of the options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For the other options , the experts were asked to write in answers ( e.g. , average doses ) or to check a box to indicate their preferred answer . We sent the survey to 50 national experts on geriatric depression , all of whom completed it . Consensus on each option was defined as a nonr and om distribution of scores by chi-square " goodness-of-fit " test . We assigned a categorical rank ( first line/preferred choice , second line/alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables indicating preferred treatment strategies were then developed for key clinical situations . RESULTS The expert panel reached consensus on 89 % of the options rated on the 9-point scale . The experts stress the importance of identifying coexisting medical conditions that may be contributing to the depression or complicate treatment . For unipolar nonpsychotic major depression , the preferred strategy is an antidepressant ( selective serotonin reuptake inhibitor [ SSRI ] or venlafaxine XR preferred ) plus psychotherapy . For unipolar psychotic major depression , the treatment of choice is an antidepressant ( SSRI or venlafaxine XR ) plus one of the newer atypical antipsychotics . Electroconvulsive therapy is also first line . For dysthymic disorder or persistent milder depression , the experts recommend combining an antidepressant ( SSRIs preferred ) and psychotherapy . If the patient has a comorbid medical condition ( e.g. , hypothyroidism ) that is contributing to the depression , the experts recommend treating both the depression and the medical condition from the outset . The SSRIs were the top-rated antidepressants for all types of depression . Among them , the experts gave the highest ratings for efficacy and tolerability to citalopram and sertraline . Paroxetine was another first-line option , and fluoxetine was rated high second line . The preferred psychotherapy techniques for treating depression in older patients are cognitive-behavioral therapy , supportive psychotherapy , problem-solving psychotherapy , and interpersonal psychotherapy . The experts also give strong support to including appropriate psychosocial interventions ( e.g. , psychoeducation , family counseling , visiting nurse services ) in the treatment program . The majority of experts would continue treatment with antidepressant medication for at least 1 year if a patient has had a single episode of severe unipolar major depression , for 1 - 3 years for a patient who has had 2 such episodes , and for longer than 3 years if there is a history of 3 or more episodes . CONCLUSIONS The experts reached a high level of consensus on the appropriateness of including both antidepressant medication , specifically SSRIs , and nonpharmacological modalities in treatment plans for severe depression . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide direction for addressing common clinical dilemmas in older individuals . They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions . Nonetheless , the guidelines can not address the complexities involved in the care of each individual patient and can be most helpful in the h and s of experienced clinicians CONTEXT Panic disorder ( PD ) may be treated with drugs , psychosocial intervention , or both , but the relative and combined efficacies have not been evaluated in an unbiased fashion . OBJECTIVE To evaluate whether drug and psychosocial therapies for PD are each more effective than placebo , whether one treatment is more effective than the other , and whether combined therapy is more effective than either therapy alone . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted in 4 anxiety research clinics from May 1991 to April 1998 . PATIENTS A total of 312 patients with PD were included in the analysis . INTERVENTIONS Patients were r and omly assigned to receive imipramine , up to 300 mg/d , only ( n=83 ) ; cognitive-behavioral therapy ( CBT ) only ( n=77 ) ; placebo only ( n=24 ) ; CBT plus imipramine ( n=65 ) ; or CBT plus placebo ( n=63 ) . Patients were treated weekly for 3 months ( acute phase ) ; responders were then seen monthly for 6 months ( maintenance phase ) and then followed up for 6 months after treatment discontinuation . MAIN OUTCOME MEASURES Treatment response based on the Panic Disorder Severity Scale ( PDSS ) and the Clinical Global Impression Scale ( CGI ) by treatment group . RESULTS Both imipramine and CBT were significantly superior to placebo for the acute treatment phase as assessed by the PDSS ( response rates for the intent-to-treat [ ITT ] analysis , 45.8 % , 48.7 % , and 21.7 % ; P=.05 and P=.03 , respectively ) , but were not significantly different for the CGI ( 48 . 2 % , 53.9 % , and 37.5 % , respectively ) . After 6 months of maintenance , imipramine and CBT were significantly more effective than placebo for both the PDSS ( response rates , 37.8 % , 39.5 % , and 13.0 % , respectively ; P=.02 for both ) and the CGI ( 37.8 % , 42.1 % , and 13.0 % , respectively ) . Among responders , imipramine produced a response of higher quality . The acute response rate for the combined treatment was 60.3 % for the PDSS and 64.1 % for the CGI ; neither was significantly different from the other groups . The 6-month maintenance response rate for combined therapy was 57.1 % for the PDSS ( P=.04 vs CBT alone and P=.03 vs imipramine alone ) and 56.3 % for the CGI ( P=.03 vs imipramine alone ) , but not significantly better than CBT plus placebo in either analysis . Six months after treatment discontinuation , in the ITT analysis CGI response rates were 41.0 % for CBT plus placebo , 31.9 % for CBT alone , 19.7 % for imipramine alone , 13 % for placebo , and 26.3 % for CBT combined with imipramine . CONCLUSIONS Combining imipramine and CBT appeared to confer limited advantage acutely but more substantial advantage by the end of maintenance . Each treatment worked well immediately following treatment and during maintenance ; CBT appeared durable in follow-up . JAMA . 2000;283:2529 - BACKGROUND This 12-week , placebo-controlled study was carried out to compare the relative efficacy of paroxetine , clomipramine , and cognitive therapy in the treatment of DSM-III-R-defined panic disorder with or without agoraphobia . METHOD After a 3-week single-blind , placebo run-in period , 131 patients were r and omly assigned to receive double-blind medication or 12 sessions of cognitive therapy based on the model of Clark . Efficacy assessment s included the daily panic attack diary , the Clinical Global Impression scale , the Patient Global Evaluation , the Hamilton Rating Scale for Anxiety , the Marks-Sheehan Phobia Scale , the Montgomery-Asberg Depression Rating Scale , and the Sheehan Disability Scale . RESULTS Comparisons with placebo revealed significant superiority of paroxetine ( 20 - 60 mg/day ) and clomipramine ( 50 - 150 mg/day ) on nearly all outcome measures . On most measures , paroxetine also showed higher efficacy than cognitive therapy . With few exceptions , cognitive therapy did not differ significantly from placebo . The number of subjects becoming panic-free ( 66 % ) was higher and the onset of action was faster in the paroxetine-treated group . Treatment with cognitive therapy yielded the highest drop-out rate ( 26 % ) . CONCLUSION In this short-term study assessing treatment of panic disorder and agoraphobia , paroxetine and clomipramine were consistently superior to pill placebo , whereas cognitive therapy was superior on only a few measures Background Transdiagnostic Cognitive Behavior Therapy ( TCBT ) manuals delivered in individual format have been reported to be just as effective as traditional diagnosis specific CBT manuals . We have translated and modified the “ The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders ” ( UP-CBT ) for group delivery in Mental Health Service ( MHS ) , and shown effects comparable to traditional CBT in a naturalistic study . As the use of one manual instead of several diagnosis-specific manuals could simplify logistics , reduce waiting time , and increase therapist expertise compared to diagnosis specific CBT , we aim to test the relative efficacy of group UP-CBT and diagnosis specific group CBT . Methods / design The study is a partially blinded , pragmatic , non-inferiority , parallel , multi-center r and omized controlled trial ( RCT ) of UP-CBT vs diagnosis specific CBT for Unipolar Depression , Social Anxiety Disorder and Agoraphobia/Panic Disorder . In total , 248 patients are recruited from three regional MHS centers across Denmark and included in two intervention arms . The primary outcome is patient-ratings of well-being ( WHO Well-being Index , WHO-5 ) , secondary outcomes include level of depressive and anxious symptoms , personality variables , emotion regulation , reflective functioning , and social adjustment . Assessment s are conducted before and after therapy and at 6 months follow-up . Weekly patient-rated outcomes and group evaluations are collected for every session . Outcome assessors , blind to treatment allocation , will perform the observer-based symptom ratings , and fidelity assessors will monitor manual adherence . Discussion The current study will be the first RCT investigating the dissemination of the UP in a MHS setting , the UP delivered in groups , and with depressive patients included . Hence the results are expected to add substantially to the evidence base for rational group psychotherapy in MHS . The planned moderator and mediator analyses could spur new hypotheses about mechanisms of change in psychotherapy and the association between patient characteristics and treatment effect . Trial registration Clinical trials.gov NCT02954731 . Registered 25 October BACKGROUND R and omized clinical trials indicate a benefit from combining medications with cognitive behavioral therapy ( CBT ) relative to medication alone for panic disorder . Using an as-treated analysis , we evaluated whether the addition of CBT enhanced outcomes for panic disorder relative to medications alone in the primary -care setting . METHOD Primary -care patients with panic disorder reported on their receipt of CBT and medications over the 3 months following baseline assessment . The degree to which outcomes for those who used anti-panic medications were enhanced by the receipt of at least one component of CBT was analyzed using a propensity score model that took into account observable baseline patient characteristics influencing both treatment selection and outcomes . RESULTS The addition of CBT result ed in statistically and clinical ly significant improvements at 3 months on anxiety sensitivity , social avoidance , and disability . Also , patients receiving CBT in the first 3 months of the study were more improved at 12 months than patients who took medications only during the first 3 months of the study . CONCLUSIONS The clinical utility of the findings are discussed in terms of the importance of primary -care physicians encouraging their panic disorder patients to receive CBT as well as medications The efficacy of tricyclics and benzodiazepines in the short term ( approximately 2 - 4 months ) treatment of panic disorder is well demonstrated , but efficacy over the longer term is not considered established . The present study provided systematic data from a double blind comparison of maintenance therapy ( up to 8 months ) of panic disorder with or without agoraphobia with alprazolam , imipramine , or placebo in 181 patients who had responded to the same regimen in a r and omized 8-week treatment trial . All three groups had improved during the first 2 months ( active treatments more than placebo and about equal to each other ) , and all maintained or extended their improvement over the next 6 months without any significant change in dose . More than twice as many alprazolam and imipramine than placebo patients ( 15 % ) remained in treatment for the full 8 months and did slightly better on symptom measures than the remaining placebo patients . Both medications were well tolerated during the maintenance period . The data suggest sustained efficacy and safety of imipramine and alprazolam over an extended period . More specifically , they suggest that tolerance does not develop to the therapeutic effects of either drug Previous research on the treatment of out patients with bulimia nervosa has focused on two treatment strategies : ( 1 ) drug therapy , primarily using tricyclic antidepressants , and ( 2 ) psychotherapy , often employing behavioral and cognitive behavioral techniques . We report here the short-term treatment outcome of a 12-week comparison trial of bulimic out patients who were r and omly assigned to one of four treatment cells : ( 1 ) imipramine hydrochloride treatment , ( 2 ) placebo treatment , ( 3 ) imipramine treatment combined with intensive group psychotherapy , and ( 4 ) placebo treatment combined with intensive group psychotherapy . All three active treatment cells result ed in significant reductions in target-eating behaviors and in a significant improvement in mood relative to placebo treatment . However , the results also suggested that the amount of improvement obtained with the intensive group psychotherapy component was superior to that obtained with antidepressant treatment alone . The addition of antidepressant treatment to the intensive group psychotherapy component did not significantly improve outcome over intensive group psychotherapy combined with placebo treatment in terms of eating behavior , but did result in more improvement in the symptoms of depression and anxiety
After the acute phase treatment , as long as the drug was continued , the superiority of the combination over either monotherapy appeared to persist .
BACKGROUND Panic disorder can be treated with pharmacotherapy , psychotherapy or in combination , but the relative merits of combined therapy have not been well established .
OBJECTIVES To review evidence concerning short- and long-term advantages and disadvantages of combined psychotherapy plus antidepressant treatment for panic disorder with or without agoraphobia , in comparison with either therapy alone .