Faculty Bibliography

Despite the widespread application of combined selective serotonin reuptake inhibitors (SSRI) and benzodiazepine treatment for panic disorder, there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy. Although the limited number of studies to date suggest a more rapid onset of benefit with combined treatment, this study is the first to address the critical question of whether continued combined treatment confers superior efficacy. This study is a randomized, double-blind, three-arm study in patients with panic disorder (n = 60), comparing the efficacy and safety of paroxetine and placebo (PP), paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase (PC-D), and ongoing combination treatment (PC-M). All treatment groups demonstrated significant improvement by endpoint. There was a significant advantage for the combined treatment groups early in treatment but, subsequently, outcome in all three groups was similar. A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered. The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout. Combined treatment with paroxetine and clonazepam resulted in more rapid response than with the SSRI alone, but there was no differential benefit beyond the initial few weeks of therapy. Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy.

Despite anecdotal reports suggesting that bupropion may be effective for panic disorder, both clinical lore and the results of one small controlled study suggest otherwise. There remains a paucity of systematic prospective data addressing this issue. Twenty outpatients meeting criteria for panic disorder with or without agoraphobia were entered in an 8 week, two center open-label flexible dose trial of bupropion SR. Treatment with bupropion SR resulted in a clinically and statistically significant mean reduction of 1 to 2 points in the primary outcome measure, the CGI Severity score, in both the intent to treat (ITT; t=4.36, df=19, p<0.001) and completer samples (t=3.89, df=13, p<0.002). Significant improvement was also noted in both completer and ITT samples for all other panic symptom measures, which included the Panic Disorder Severity Scale (PDSS), number of panic attacks in the past two weeks, and the proportion of time anticipatory anxiety was present. Although results may be influenced by the open nature of this trial, our findings suggest that bupropion SR may be effective for the treatment of panic disorder. Further controlled study of its efficacy for this condition are warranted.

OBJECTIVE: Quality of life in a treatment-seeking cohort of patients with social anxiety disorder was compared with that of patients with panic disorder who were matched for age, comorbid illnesses, and gender and with population-based norms. METHODS: The study participants were 33 patients with social anxiety disorder and 33 patients with panic disorder who had participated in clinical trials and who had completed the Medical Outcomes Study Short-Form-36 (SF-36) as part of a baseline evaluation. The patients did not have significant comorbid psychiatric disorders. Paired t tests were used to compare baseline scores on subscales of the SF-36 between the two cohorts. One-sample t tests were used to compare scores on subscales of the SF-36 with expectation scores based on 2,474 persons from the general population. RESULTS: Compared with the general population, the patients with social anxiety disorder had significantly greater impairment as measured by the SF-36 social functioning and mental health subscales. Subscale scores also indicated poorer emotional role functioning, but the difference was not significant. However, they were significantly less impaired than the patients with panic disorder in terms of physical functioning, physical role, and mental health. CONCLUSIONS: Patients with social anxiety disorder who do not have significant comorbid depression or anxiety are substantially impaired in quality of life, but to a lesser extent than patients with panic disorder, who suffer from both mental and physical impairments in quality of life.

BACKGROUND: Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [Am. J. Psychiatry 155 (1998) 1], despite a paucity of data systematically 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 prospective, 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.

BACKGROUND: The need for thyroid screening of patients presenting with panic disorder (PD), social phobia (SP) or generalized anxiety disorder (GAD) remains uncertain. METHODS: We examined thyroid histories and serum testing in 169 patients, 92 with PD, 48 with SP, and 29 with GAD. Combined prevalence rates of hyperthyroidism and hypothyroidism were compared with expected rates (2.7%) derived from the population based Whickham Survey. Data from previously published studies were also compared with these expected rates. RESULTS: In our sample, only 2/169 patients had thyroid dysfunction detected by serum testing, but 5/169 [1/92 (1%) with PD, 1/48 (2%) with SP, and 3/29 (10%) with GAD], all currently euthyroid, reported a history of thyroid disease. The rates were statistically significant only for GAD (10.4%; z = 2.56, p = 0.01). However, combining prior PD studies that examined both thyroid history and test results with our data also suggests significantly elevated rates of thyroid dysfunction (6.5%; z = 4.69, p < 0.0001). LIMITATIONS: As with previous data, the 95% confidence interval for our findings is broad, reflecting the instability of low rates of illness in relatively small samples. Further, methods for obtaining thyroid histories and tests were not uniform. CONCLUSIONS: Despite relatively low yields on serum testing, lifetime prevalence of thyroid dysfunction does appear elevated for GAD and PD, with minimal data addressing this issue for SP. The data support the need to query GAD and PD patients regarding thyroid history and perform serum testing in those without prior testing.

There is limited systematic data assessing alternate pharmacotherapy of social anxiety disorder in patients failing to tolerate or fully respond to initial treatment; no data specifically address the efficacy of citalopram in this scenario. We present a prospective open-label trial of citalopram in 10 patients with generalized social anxiety disorder, 6 of 10 of whom had not responded to or not tolerated a prior treatment intervention for the disorder. Citalopram, at a mean dose of 55 mg (SD+/-12.7 mg) was well tolerated, and patients improved significantly on all outcome measures. Results of this study suggest that citalopram may be a safe and effective treatment for generalized social anxiety disorder, including patients who have failed to tolerate or respond to a prior treatment trial.