Biomedical subjects
Publications and source records attributed to M Mavissakalian.
There are few controlled studies of combined behavioral-pharmacological treatments of agoraphobia with panic. This review of the empirical evidence from studies using exposure in vivo as the behavioral modality and imipramine as the pharmacological agent suggests that these treatments have mutually potentiating effects in this disorder.
Several issues remain to be ascertained beyond the acute response to imipramine hydrochloride in patients with panic disorder. Study 1 consisted of a prospective, systematic characterization of half-dose 12-month maintenance in patients with panic disorder with agoraphobia who had shown marked and stable response to 6 months of acute-phase treatment with imipramine. Study 2 assessed the 6-month cumulative relapse rate following discontinuation of acute-phase imipramine treatment in a comparable sample of patients. The same assessment battery was used in both studies, and the integrity of experimental drug conditions was verified by plasma drug level determinations. In contrast to the high relapse rate following discontinuation of acute-phase treatment, none of the patients showed relapse or had sustained worsening in panic or phobia measures during the half-dose maintenance period. The results underscore the importance of pharmacological prophylaxis and provide empirical guidelines for a successful low-dose maintenance regimen for patients with panic disorder and agoraphobia who respond markedly to imipramine.
OBJECTIVE: This study was designed to assess and compare the differential relapse rates of patients with panic disorder and agoraphobia after discontinuation of acute treatment (6 months) or acute plus maintenance treatment (18 months) with imipramine. METHOD: Sixteen patients with panic disorder and agoraphobia who had shown marked and stable response to 6 months of acute imipramine treatment and a comparable group of 14 patients who had been in remission during an additional year of half-dose imipramine maintenance treatment entered a 3-month, double-blind discontinuation study followed by a 3-month drug-free period. Assessments of the patients were made according to operationalized response/relapse criteria, and plasma drug concentrations were monitored. RESULTS: Survival analysis revealed significantly different cumulative probabilities of continued response 6 months after discontinuation of imipramine treatment between the patients who had received only acute treatment and those who had received acute and maintenance treatment. CONCLUSIONS: The results support the hypothesis that successful imipramine maintenance treatment of patients with panic and agoraphobia can have protective effects against relapse, at least in the first 6 months after the maintenance treatment period.
Psychophysiological process and outcome phenomena were analyzed to examine differential temporal patterns within and across cognitive, behavioral and physiologically-based treatments of agoraphobia. Eighty-eight severe and chronic agoraphobics with panic attacks (DSM-III) were randomly assigned to one of three treatments: Paradoxical Intention, Graduated Exposure or Progressive Deep Muscle Relaxation Training. Protocol therapists, whose treatment integrity was objectively monitored, conducted 12 two-hour weekly sessions. All subjects received programmed practice instructions concurrent with their primary treatment. Analyses revealed numerous significant reductions on in vivo psychophysiological measures for the relaxation condition, a few improvements for the exposure treatment and no effects for the paradoxical intention modality. The mediating role of pretreatment physiological reactivity in treatment outcome and follow-up status was examined and revealed no significant associations. Synchrony-desynchrony patterns were found to vary widely according to both treatment phase and the time interval between assessments. No between-group differences were observed on the proportion of synchronizers. However, synchronizers exhibited superior outcome and follow-up compared to desynchronizers on all domains except the physiological measures. Conceptual, methodological and clinical implications of these findings are discussed with recommendations for future research.
This selective review of the relationship between panic disorder/agoraphobia and DSM-III personality disorders points to a preponderance of dependent, avoidant, and histrionic features and reveals a certain degree of covariation between severity of Axis I disorder and personality functioning. However, the link between panic/agoraphobia and Axis II disorders does not appear to be specific because (1) general features such as neuroticism, stress, dysphoric mood, and interpersonal sensitivity, rather than duration and severity of panic attacks and phobias, emerge as unique predictors or determinants of personality disorder; and (2) similar personality profiles are obtained in a heterogenous population of psychiatric outpatients or patients with social phobia, obsessive-compulsive disorder, and major depression.
Thirty-eight patients who had panic disorder with agoraphobia completed 8 weeks of treatment with imipramine followed by 8 weeks of treatment with imipramine combined with behavior therapy consisting of self-directed exposure. Sixty-three percent (24) of the patients responded markedly to this cost-effective combined pharmacologic and behavioral approach. Results also revealed that most of the improvement in panic occurred during the first 8 weeks of treatment when imipramine treatment alone was used, whereas improvement in severity, anxiety, depression, and phobias, in particular, continued to be significant between midtreatment and end of study. Further analysis revealed that improvement in phobic anxiety and avoidance in the first 8 weeks of treatment, rather than improvement in panic, predicted final outcome. Implications of these findings on the complex issue of differential antipanic and antiphobic effects of imipramine are briefly discussed.
The clinical significance of the effects of pharmacotherapy and the relationship between plasma tricyclic concentrations and outcome in 33 obsessive-compulsive disorder (OCD) patients who completed 10 weeks of treatment with clomipramine (239.4 +/- 57.0 mg/day) were analyzed. Results revealed that at the end of treatment, OCD symptoms had decreased to a subclinical level in 15 (47%) patients and that nearly 33 percent of the sample was virtually symptom free. However, 1 out of 4 patients failed to improve. Analysis of plasma levels (clomipramine 169.9 +/- 102.1 ng/ml; N-desmethylclomipramine 379.0 +/- 160.6 ng/ml) revealed that responders had significantly higher clomipramine levels and a trend toward lower desmethylclomipramine/clomipramine ratios. A significant degree of correlation was also obtained between plasma levels of clomipramine, but not N-desmethylclomipramine, and post-treatment outcome measures.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Analyses in 44 agoraphobic patients given single-blind placebo over a two-week period, without the customary confound of instructions of exposure to phobic situations, replicated previous findings of a weak placebo response in that there were statistically, but not clinically, significant reductions in panic and phobic symptoms. Further analyses of a representative subsample of 10 patients who continued to receive placebo revealed that the placebo response was maintained and even increased at the end of 10 weeks when 20% to 30% of the patients could be classified as marked responders on key panic and phobic measures. Results also revealed an interesting observation that most of the improvement in panic, anxiety, and depression occurred early whereas improvement in phobic measures was more gradual and increased significantly over time. Implications for clinical research are briefly discussed.
One hundred and one patients meeting DSM-III criteria for agoraphobia with panic rated their avoidance of 21 situations. Factor analysis of the ratings revealed five factors: two that were purely agoraphobic, involving travel or transportation and shopping; one that was agoraphobic but with social features; another that was agoraphobic with claustrophobic features; and a somewhat heterogeneous factor. The results were compared with an earlier analysis by Johnston, Johnston, Wilkes, Burns & Thorpe (1984) of ratings of the same situations and with the Fear Questionnaire of Marks & Mathews (1979).
Explore the source record for details and available documents.
This paper presents two sets of data that suggests a weak but specific placebo response in agoraphobia. First, analyses in 20 agoraphobic patients given single-blind placebo over a 2-week period, without the customary confound of instructions for exposure to phobic situations, revealed a statistically significant reduction in panic and phobic symptoms. However, symptoms remained in the moderate to severe range and functioning was virtually unchanged. Second, comparisons between six agoraphobic patients receiving double-blind placebo and six others receiving "no pills," matched for age, sex and exposure treatment, revealed a significant placebo effect over an 8-week period. Implications for clinical research are briefly discussed.
Thirty-seven patients participating in a controlled treatment study with imipramine were classified as high or low depressed simultaneously on two depression measures. Analysis of variance by 2 (high-low depressed) X 2 (high-low imipramine dosage) groupings revealed significant dose but no depression main effects. The greater dose effect observed in the low depressed group and the greater response rates found among high-dose patients with low initial depression strongly suggest that the beneficial effect of imipramine in agoraphobia was not primarily antidepressant in nature.
Eleven patients with panic disorder or agoraphobia with panic attacks completed an 8-week single-blind trial of trazodone (300 mg/day) without concurrent behavioral instructions. The measures of change included ratings of generalized and panic anxiety, phobias, and depression and a behavioral avoidance test, which were administered during a baseline period of placebo administration and at 4 and 8 weeks of the trial. There was significant improvement on all symptom dimensions, which suggests that trazodone may have specific antipanic and antiphobic actions and underscores the importance of serotonergic mechanisms in these anxiety disorders.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Sixty-two agoraphobic patient who had completed a controlled study of therapist-assisted in vivo exposure (flooding) and imipramine were assessed 1 month, 6 months, 1 year, and 2 years later. Overall, improvement during treatment was maintained throughout follow-up. At 1 month but not subsequently, imipramine and flooding had significant effects on central measures of agoraphobia. Patients who were marked treatment responders had a favorable clinical course and did not experience secondary depression, unlike patients who had not responded markedly to treatment. These findings suggest that treatments which evoke maximum therapeutic benefit initially are likely to foster long-term maintenance and reduce subsequent depressive sequelae.