Treatment of agoraphobia with group exposure in vivo and imipramine. Treatment of phobias. I. Comparison of imipramine hydrochloride and placebo. Comparison of Fluvoxamine alone, Fluvoxamine and cognitive psychotherapy and psychotherapy alone in the treatment of panic disorder in Kelantan--implications for management by family doctors. Do selective serotonin re-uptake inhibitors enhance the efficacy of very brief cognitive behavioral therapy for panic disorder? A pilot study. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. Clomipramine treatment and behaviour therapy with agoraphobic women. Imipramine and brief therapists-aided exposure in agoraphobics having self-exposure homework. Paroxetine in the treatment of panic disorder. A randomised, double-blind, placebo-controlled study. Randomised placebo-controlled trial of moclobemide, cognitive-behavioural therapy and their combination in panic disorder with agoraphobia. Treatment of panic disorder with agoraphobia: comparison of fluvoxamine, placebo, and psychological panic management combined with exposure and of exposure in vivo alone. Overcoming resistance to exposure in panic disorder with agoraphobia. Combined pharmacological and behavioral treatment for agoraphobia. The Galway Study of Panic Disorder. I: Clomipramine and lofepramine in DSM III-R panic disorder: a placebo controlled trial. Agoraphobia: relative and combined effectiveness of therapist-assisted in vivo exposure and imipramine. Personality disorder and social anxiety predict delayed response in drug and behavioral treatment of panic disorder. Pharmacological treatment of agoraphobia: imipramine versus imipramine with programmed practice. Does brief dynamic psychotherapy reduce the relapse rate of panic disorder? Agoraphobia: behavioral and pharmacological treatments, preliminary outcome, and process findings. A randomized, double-blind, placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitive-behavioral therapy alone.
Seventy-six white agoraphobic women, 21 to 45 years old, were treated with combined group exposure in vivo and imipramine or placebo in a randomized double-blind study. A majority of the patients in both the placebo and imipramine groups showed moderate to marked improvement. However, imipramine therapy was significantly superior to placebo therapy on three of the four reported measures of improvement: primary phobia, spontaneous panic, and global improvement. There was a negative correlation between depression and outcome; ie, the more depressed patients fared worse on several outcome measures than those who were less depressed. A comparison of these patients with agoraphobic women previously treated with imipramine and imaginal desensitization showed a superiority of exposure in vivo midway in treatment, but no significant difference between the two groups at the completion of therapy. In a controlled-outcome study of phobias, 218 adult phobic patients (147 women and 71 men) received a course of 26 weekly treatment sessions that consisted of behavior therapy (BT) and imipramine hydrochloride, BT and placebo, or supportive psychotherapy and imipramine. The BT consisted of systematic desentization using fantasy and assertiveness training. Patients were classified as agoraphobic, mixed phobic, or simple phobic. Although the conditions of most patients in each group showed moderate to marked improvement, the effects of imipramine were significantly superior to those of placebo in patients with spontaneous panic attacks, ie, patients with agoraphobia or mixed phobia. In patients with simple phobia, who do not experience spontaneous panic, there was not a significant difference between imipramine and placebo. This study clearly distinguished those phobic patients who experienced spontaneous panic from those who did not in terms of pharmacologic benefits. This paper reports the result of a brief therapy attempt at treating panic in a busy outpatient psychiatric clinic. The patients were cases of panic referred from the various outpatient clinics within the hospital complex. The patients were divided into three groups at random using one of three modalities of treatment, i.e. cognitive behaviour therapy (CBT), CBT and Fluvoxamine (FVX), and FVX alone. The therapy was aimed for a maximum of nine sessions after which the patients were to be discharged. There were 14 patients in each group. The results show that all the groups were similar in the severity and scores pre treatment but after the different types of treatment there was a significant difference among them. The FVX alone group, showed significant improvement from the pretreatment levels but did not show as much improvement as the other groups and the mean score was only 9.07 after nine sessions. The best group was the CBT in combination with FVX. This indicates that the best way to treat panic is to combine drug treatment and psychological treatment. It is also shown from the study that the combination group requires less FVX than the FVX alone group. This finding has implications for the treatment of panic at the family physician clinic. 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 randomized 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 materials. 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. 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.
                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.
                Randomized, double-blind, placebo-controlled clinical trial conducted in 4 anxiety research clinics from May 1991 to April 1998.
                A total of 312 patients with PD were included in the analysis.
                Patients were randomly 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.
                Treatment response based on the Panic Disorder Severity Scale (PDSS) and the Clinical Global Impression Scale (CGI) by treatment group.
                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.
                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;283:2529-2536 The separate and combined effects of clomipramine hydrochlorzide and behaviour therapy on agoraphobic symptoms were investigated in a 28-week placebo-controlled double-blind clinical trial. One hundred and eight women diagnosed as agoraphobic were randomly assigned to one of four treatment conditions: clomipramine alone, behaviour therapy alone, clomipramine and behaviour therapy or placebo. Sixty women completed the assigned treatment. Clomipramine was prescribed in weekly increments to a maximum of 300 mg per day, with a mean dosage at week 8 of 94.6 mg per day. Behaviour therapy focused on graded in vivo exposure therapy. Assessments of patients were performed at six points prior to and during the trial and included standardized questionnaires, daily diaries and a Behavioral Approach Test. Significant main effects for both clomipramine and behaviour therapy on 15 and 12 of the dependent measures respectively were found but no interaction of treatments emerged. Forty-five chronic agoraphobics were randomly assigned to treatment by placebo or imipramine in doses up to 200 mg/day for 28 weeks. All patients also had systematic self-exposure homework with an instruction manual. In addition, half of each drug group had therapist-aided exposure and half had therapist-aided relaxation, each totalling three hours. Patients in both drug groups improved substantially and maintained their gains for one year of follow-up. Imipramine had no significant therapeutic effect despite satisfactory plasma levels and significant drug side effects. Patients' low initial Hamilton depression scores might explain the absence of any drug effect. Antidepressants may be ineffective for agoraphobics who have normal mood. Brief therapist-aided exposure improved phobias and panics to a significant but limited extent, and is a useful adjuvant to self-exposure homework, which can be a powerful therapeutic agency by itself. This study compared the efficacy and tolerability of paroxetine with placebo in the treatment of panic disorder.
                After three weeks of placebo, patients received 12 weeks of treatment with paroxetine (20, 40, or 60 mg) or placebo, and finally two weeks of placebo. Dosages were adjusted according to efficacy and tolerability. Standardised cognitive therapy was given to all patients. The primary measure of outcome was reduction in the number of panic attacks.
                Analysis of the results showed statistically significant differences in favour of paroxetine between the two treatment groups in two out of the three primary measures of outcome, i.e. 50% reduction in total number of panic attacks and number of panic attacks reduced to one or zero over the study period. For the third measure of outcome, the mean change in the total number of attacks from baseline, there was a positive trend in favour of paroxetine. The results of the primary measures of outcome were strongly supported by the results of the secondary efficacy measures of outcome. In addition, paroxetine, at all doses, was very well tolerated.
                Paroxetine plus cognitive therapy was significantly more effective than placebo plus cognitive therapy in the treatment of panic disorder. 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.
                To demonstrate that moclobemide and cognitive-behavioural therapy (CBT) are effective singly and more effective in combination.
                Fifty-five patients were randomly assigned to an eight-week treatment of: moclobemide plus CBT; moclobemide plus clinical management ('psychological placebo'); placebo plus CBT; or placebo plus clinical management.
                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.
                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. 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.
                Ninety-six patients were randomly 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 standardized multitask behavioral avoidance test, and continuous monitoring of panic attacks. Seventy-six patients completed the study.
                All four treatments were effective and resulted 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.
                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. The issue of panic disorder resistant to treatment (whether pharmacological or psychological) has attracted little research attention, despite its clinical frequency and importance. The aim of this study was to compare three treatment modalities, namely exposure alone (E), exposure associated with imipramine (EI) and cognitive therapy supplementing exposure (EC), in a sample of 21 patients with DSM-IV panic disorder and agoraphobia, who failed to respond to a first standard course of individual behavioural treatment based on exposure in vivo. Treatments were administered according to a cross-over, controlled design (E-EI-EC, EI-EC-E, EC-E-EI). Twelve of the 21 patients achieved remission (panic-free status) during the trial. In 8 cases this occurred after exposure alone (E) and in two cases each after the other treatments (EI and EC). The results revealed a significant effect of the factor time on a number of variables, and the superiority of exposure alone compared to other treatment modalities with regard to some variables. These findings suggest that long-term behavioural treatment based on exposure may be necessary in some patients, and may induce clinical remission. However, patients who do not respond to exposure show poor tolerance of and compliance with pharmacological treatment, and are unlikely to achieve remission with imipramine or cognitive therapy, even though this may occur in individual cases. nan Among 79 volunteer, unpaid, family doctor-referred psychiatric out patients with DSM III-R panic disorder, with and without agoraphobia, 66 completed a six week placebo-controlled trial of lofepramine versus clomipramine and 57 survivors were followed up for 6 months. All subjects received one hour per week concurrent behavioural counselling in the acute phase. Of 13 dropouts in the first 3 weeks, 9 (of 27) were on clomipramine, 2 (of 26) were on lofepramine and 2 (of 26) were on placebo. The high (30%) early dropout from the clomipramine group was largely due to medication intolerance. Both drugs were superior to placebo by the end of week 6 on several standard rating scales but not on panic attack frequency. No significant differences in efficacy were found between the two drugs tested to the end of 6 months. No tendency for relapse was noted in the three months following taper-off of medication from week 12 to week 24. The study provides evidence that both drugs, in the dosages used, are superior to placebo in the acute phase of panic disorder in treatment-naive subjects concurrently receiving appropriate psychotherapy. Sixty-two chronically agoraphobic patients completed a controlled study to assess the effects of 1) imipramine up to 200 mg/day (mean = 130 mg/day), 2) 12 weekly therapist-assisted in vivo exposure sessions (flooding), and 3) imipramine plus flooding. The control group received systematic therapeutic instructions for self-directed in vivo exposure (programmed practice). Clinical measures of global severity, phobia, panic, anxiety, depression, and behavioral performance tests were administered before treatment and at Weeks 4, 8, and 12 of treatment. Results revealed significant improvement in all groups on all measures over the course of treatment; almost a third of the control patients showed marked improvement. Imipramine had significant effects on improvement of phobias and markedly increased clinical response rates in patients receiving 150-200 mg/day. Less chronicity and severity of condition also predicted better clinical outcome. Flooding had limited effects above and beyond programmed practice, and no imipramine-flooding interactions effects were found. The aim of this study was to analyze the impact of pretreatment characteristics and personality disorders on the onset of response in the treatment of panic disorder.
                The data of 73 out-patients with panic disorder who had completed at least 6 weeks of a randomized trial of 24 weeks of either paroxetine only or paroxetine combined with cognitive group-therapy were analyzed in a Cox proportional hazards model.
                The likelihood of having responded to treatment (defined by a CGI rating of improvement) was more than twice as high for patients without a personality disorder or social phobia than for Patients with a personality disorder or social phobia.
                We suggest that patients with these characteristics do benefit from prolonged treatment, and they may profit from an additional treatment focused on social anxiety. Eighteen agoraphobic patients with randomly assigned to 12 week treatment with imipramine (I) or imipramine and programmed in-vivo exposure practice (I+BT) to investigate the contribution of behavioural instructions to the clinical effects of pharmacotherapy. Significantly greater improvement on phobic measures was found in the I+BT group compared to the I group. Differences were less marked on measures of panic and anxiety. The results suggest that imipramine possesses an antiphobic effect which can be substantially enhanced with programmed practice. Controlled large-scale investigations of the pharmacological and instructional effects of the phamacotherapy of agoraphobia are needed for a definitive evaluation of the specific antiphobic effect of antidepressant drugs. 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.
                Patients with panic disorder (defined by DSM-III-R) were randomized 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.
                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.
                The addition of brief dynamic psychotherapy to treatment with clomipramine significantly reduces the relapse rate of panic disorder compared with clomipramine treatment alone. nan Both cognitive-behavioral therapy and treatment with selective serotonin reuptake inhibitors (SSRIs) have proved to be effective in the treatment of panic disorder. The present study examined the effects of paroxetine added to continued cognitive-behavioral therapy in patients who were unsuccessfully treated with initial cognitive-behavioral therapy alone.
                161 patients with panic disorder with or without agoraphobia (DSM-IV criteria) underwent a manual-guided cognitive-behavioral therapy of 15 sessions. Forty-three unsuccessfully treated patients from this group were included in a double-blind, placebo-controlled, next-step treatment study consisting of continued cognitive-behavioral therapy plus adjunctive paroxetine at a dose of 40 mg/day or continued cognitive-behavioral therapy plus placebo.
                Overall, patients in the cognitive-behavioral therapy plus paroxetine condition improved significantly on agoraphobic behavior (p < .05) and anxiety discomfort (p < .01), whereas patients in the cognitive-behavioral therapy plus placebo condition did not. Effect sizes in the cognitive-behavioral therapy plus paroxetine condition ranged from 1.0 to 1.8 and in the cognitive-behavioral therapy plus placebo condition, from 0.4 to 1.0.
                Patients with panic disorder who are unsuccessfully treated with initial cognitive-behavioral therapy may benefit from the addition of an SSRI as a second treatment modality. The importance of timely evaluation of treatment results is emphasized.
Either combined therapy or psychotherapy alone may be chosen as first line treatment for panic disorder with or without agoraphobia, depending on patient preference.