Long-term maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia

BACKGROUND: There has been little systematic work done regarding the long-term treatment of panic disorders. The aim of the present study was to assess the 12-month cumulative risk of relapse specifically due to discontinuation of imipramine and to test the hypothesis that maintenance treatment with imipramine protects patients with panic disorder and agoraphobia from such reversals. METHOD: Following an acute-phase open trial with imipramine (2.25 mg/kg per day) involving 110 patients for 6 months, the 56 patients who were in stable remission, did not require additional treatment, and consented to be randomly assigned to double-blind maintenance (n = 29) or discontinuation (n = 27) conditions were followed up with planned assessments every 2 months during a 1-year period. There were no behaviorally oriented interventions or instructions at any time during the 18 months of the study. RESULTS: Maintenance treatment (1 relapse) and discontinuation (10 relapses) conditions had significantly different survival curves (Mantel-Cox statistic chi(2)1 = 10.47, P = .001). None of the additional 10 variables from demographic, clinical, and open-treatment domains considered in the proportional hazard model disrupted the significant relationship between experimental drug condition and relapse; other things being equal, a patient receiving imipramine maintenance was 92.5% lower in the hazard rate of relapse than a patient receiving placebo. CONCLUSION: The results confirm the very high degree of prophylactic effectiveness of maintenance imipramine treatment and demonstrate that relapse, although substantial, occurs in a minority of patients with panic disorder and agoraphobia who are in stable remission prior to treatment discontinuation.     

The effects of a subjective monitoring task in the physiological measure of genital response to erotic stimulation

Instrumentation has been developed which promises to further our understanding of the relationship between cognitive and physiological factors in the sexual arousal process. Past research has examined this relationship by continuous measurement of genital response, and discrete posttest measurement of subjective arousal. The self-report or cognitive lever allows individuals to rate feelings of arousal continuously throughout a stimulus interval by positioning a lever device along a calibrated scale. In this way, structural patterns of physiological and cognitive response can be examined. However, since attention has been shown to be an important cognitive operation in the processing of sexual stimuli, there is concern that this subjective measuring task may confound laboratory assessment by altering genital responsivity through distractive or possibly facilitative mechanisms. In order to test the methodological limitations of the cognitive lever, 14 male and female college students were exposed to duplicate viewings of erotic videotapes while alternately using and not using the self-report device. Results indicated that lever usage was not obtrusive in females, but was in males to the point of altering physiological response. In addition, the study took advantage of the continuous, concurrent measurements and examined patterns of convergence and divergence between the two. Results of correlational analyses indicated, in line with past research, that for men greater degrees of erection result in significantly higher subjective-objective agreement. Patterns for women as a group were much less clear, with only two significant correlations appearing. Finally, the limitations of the cognitive lever were discussed.This research was funded in part by VA Merit Review Research Grant 041-34-7119 and NIMH Grant MH33553.     

Sertraline in panic disorder: initial treatment versus switch strategy

The study explored whether there is differential efficacy for patients with panic disorder treated with sertraline initially (primary group) versus those switched (transfer group) after intolerance or nonresponse to imipramine in the context of the open 24-week treatment phase of a long-term maintenance/discontinuation study. Similar assessment and treatment procedures were used in the 2 groups and there were no concurrent cognitive behavioral interventions. A consistent pattern suggesting decreased efficacy for the transfer treatment group (n = 11, 68 +/- 25 mg/d) compared with the primary treatment group (n = 11, 70 +/- 25 mg/d) was found on response rates, univariate repeated measures analysis of variance and within group effect sizes in intent to treat, and completer samples. These preliminary findings concord well with clinical intuition but are contrary to findings in the treatment of depression. Replication studies seem warranted.     

Cost effectiveness of acute imipramine therapy versus two imipramine maintenance treatment regimens for panic disorder

OBJECTIVE: To examine the medical costs and effectiveness of acute treatment with imipramine versus acute treatment plus 2 different maintenance therapies for panic disorder. METHODS: A clinical decision model was constructed to estimate 18-month costs and outcomes associated with these treatment scenarios based on the medical literature and clinician judgment. The clinical parameters and outcomes for the model were derived from a series of systematic clinical trials with imipramine utilising uniform dosage procedures and validated response criteria. Costs were calculated based on standardised treatment regimens. The outcome measures were 18-month medical costs, quality-adjusted life years (QALYs) and costs per QALY gained. A sensitivity analysis was performed to explore the impact of treatment withdrawals on outcomes. STUDY PERSPECTIVE: US mental healthcare system. RESULTS: Over 18 months, the total costs (1997 values) and QALYs associated with half-dose maintenance therapy (imipramine 1.1 mg/kg/day) [$US3377; QALYs = 0.991] and full-dose maintenance therapy (imipramine 2.25 mg/kg/ day) [$US3361; QALYs = 0.991] were almost identical; both were cost saving compared with acute imipramine therapy (2.25 mg/kg/day) with no maintenance treatment ($US3691; QALYs = 0.979). Whether patients withdrawing from treatment were considered to have continued to respond to treatment or to have relapsed, the half-dose and full-dose maintenance treatments were still cost saving compared with acute treatment alone. CONCLUSIONS: The results indicate that imipramine maintenance treatment is cost effective compared with acute imipramine treatment for patients with panic disorder. The basic findings and conclusions are not affected after modifying model assumptions for clinical response in patients withdrawing from treatment.     

The relationship between panic disorder/agoraphobia and personality disorders

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.     

Correlates of DSM-III personality disorder in obsessive-compulsive disorder

Forty-three patients with primary obsessive-compulsive disorder (OCD) completed the Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to assess axis II personality disorders (PD) from DSM-III. Results showed that 53% of the patients received at least one PD diagnosis. The most frequent diagnoses were avoidant (30%), histrionic (26%), dependent (19%), and schizotypal (16%). Consideration of the personality traits irrespective of diagnostic category showed that in addition to avoidant and dependent personality characteristics, the sample had strong passive aggressive and compulsive tendencies and substantial histrionic, paranoid, and schizotypal traits. Patients exhibiting a greater number of personality traits were also significantly more symptomatic. However, anxiety, phobic, and obsessive-compulsive symptoms were not selected as unique predictors of any personality variables in the regression analyses. Rather, the most important correlate of PD in these patients consisted of dysphoric mood as assessed by the Beck Depression Inventory (BDI) and, to a lesser degree, younger age or shorter duration of illness. These findings do not support a specific link between OCD and PD in general and compulsive PD in particular.     

A comparison of DSM-III personality disorders in panic/agoraphobia and obsessive-compulsive disorder

One hundred eighty-seven patients meeting DSM-III criteria for panic disorder (161 with agoraphobia) and 51 patients meeting DSM-III criteria for obsessive-compulsive disorder (OCD) were assessed with the Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to assess axis II personality disorders and traits. The results showed that the personality profiles were similar between the two diagnostic groups and that the major personality characteristics identified in panic/agoraphobic patients, e.g., avoidant, dependent, histrionic, and borderline, were more pronounced in patients with OCD. These findings support our earlier suggestion of a nonspecific link between panic disorder/agoraphobia and personality disorder (PD)/traits.     

DSM-III personality disorders in obsessive-compulsive disorder: changes with treatment

Twenty-seven patients meeting DSM-III diagnostic criteria for obsessive-compulsive disorder (OCD) completed the Personality Diagnostic Questionnaire (PDQ; a self-rating scale designed to assess the axis II personality disorders [PDs] from the DSM-III) before and after 12 weeks of treatment with clomipramine. Treatment was accompanied with reduction on several personality variables, including the number of personality diagnoses assigned, the distribution of traits in the sample, and the number of items endorsed in each personality category. The data also showed that improvement in personality functioning was significantly greater in responders compared with nonresponders or partial responders. Further investigation of the relationship between personality and treatment outcome did not provide strong support for the notion that personality factors may have prognostic significance in the treatment of OCD. These findings suggest similarities and differences with panic/agoraphobia which are briefly discussed.