Bupropion-SR in treatment of social phobia.

A 12-week, open label flexible dosing study was conducted to evaluate the efficacy of bupropion-SR in the treatment of generalized social phobia. The primary outcome measures include the Clinical Global Impression of Improvement (CGI-I) and the Brief Social Phobia Rating Scale (BSPS). A total of 18 subjects were enrolled. Five of the ten subjects who completed all 12 weeks were considered as responders. Response to treatment was defined as a CGI-I score of 1 or 2, ("much improved" or "very much improved," respectively) and a > 50% decrease in BSPS score. The final doses for the completers ranged between 200 and 400 mg/day (mean 366 +/- 68 mg/day). The medication was generally well tolerated. Findings from this open-label trial suggest that bupropion-SR may be useful in treating generalized social phobia.

Evaluation of the efficacy, safety and physiological effects of fluvoxamine in social phobia.

There is no US Food and Drug Administration (FDA) approved treatment for social phobia although data suggest efficacy for several drug classes, including beta-blockers, benzodiazepines, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors (SSRIs). The SSRIs are particularly attractive due to their favourable tolerance and safety profile. An open label trial of fluvoxamine was conducted to evaluate its efficacy and safety in the treatment of social phobia (DSM-III-R) and to assess physiological changes that may accompany treatment. Fifteen non-depressed patients, aged 22-44 years (mean 31.6 years), entered the study. A 5-min performance task (public speaking simulation) preceded and concluded the active treatment period. Cardiovascular monitoring was performed during this time and blood sampled for plasma cortisol and steady-state plasma fluvoxamine concentration (at week 7). Ten patients (5 men and 5 women) completed an active 6 week treatment period of flexible dosing (50-150 mg/day). Five patients failed to complete the study due to drowsiness (n = 2), nausea (n = 1), or were lost to follow-up (n = 2). Analysis of clinical ratings indicated a statistically significant decrease in all scales from baseline to week 7 at the conclusion of the active treatment period. Clinical benefits were still evident at follow-up 1 week after drug discontinuation. Neither physiological effects nor plasma drug concentration correlated with clinical change. Fluvoxamine appeared to be effective and well tolerated in completers. Randomized clinical trials are needed to further demonstrate the efficacy of fluvoxamine in the treatment of social phobia.

Once-weekly dosing of fluoxetine in the maintenance of remission in panic disorder.

BACKGROUND: Fluoxetine and its active metabolite norfluoxetine have long half-lives of 4-6 days and 4-16 days, respectively. We postulated that, owing to the long elimination half-life, patients diagnosed with panic disorder might be maintained on fluoxetine taken once a week, after being treated initially with daily doses of fluoxetine. METHOD: Ten patients with DSM-III-R panic disorder were treated openly with fluoxetine, 20-40 mg daily. Once panic free, these patients were switched to once-weekly dosing of fluoxetine, and dosage was titrated as needed. RESULTS: All 10 patients successfully switched to once-weekly dosing. One patient reported recurrence of panic attacks 18 months after the switch. After a brief treatment for 4 weeks with benzodiazepines and daily fluoxetine, the patient was once again maintained on once-weekly dosing when rechallenged. Patients have been maintained in a panic-free state for up to 26 months with a single weekly dose of fluoxetine ranging from 10 to 60 mg. The medication was well tolerated. CONCLUSION: Fluoxetine at doses ranging from 10 to 60 mg administered once weekly appears to be effective maintenance treatment for patients with panic disorder who were initially treated successfully with daily fluoxetine. A once-weekly regimen may allow for considerable cost savings and may serve as a convenient alternative method for treating panic disorder.

Abnormal peripheral benzodiazepine receptor density associated with generalized social phobia.

BACKGROUND: Peripheral benzodiazepine receptors (PBRs) are involved in regulating stress responses. Abnormally low numbers of platelet PBRs have been found in patients with panic disorder, posttraumatic stress disorder, and generalized anxiety disorder, but not in patients with obsessive-compulsive disorder (OCD) or major depressive disorder (MDD). The purpose of this study was to evaluate the PBR density on platelets from patients with generalized social phobia (GSP). METHODS: The density (Bmax) and dissociation constant (Kd) of platelet PBRs was determined for 53 medication-free patients with GSP and an equal number of control subjects (NC). RESULTS: The GSP group was found to have a significantly lower PBR Bmax than the NC group (GSP = 2764 +/- 1242 vs. NC = 4327 +/- 1850 fmol/mg protein, df = 1,100, F = 22.7, p = .00001). CONCLUSIONS: GSP shares this PBR abnormality with some other anxiety disorders but not with OCD or MDD. PBRs may play a role in the pathophysiology of some anxiety disorders.

Plasma pyridoxal phosphate in anxiety disorders.

One hundred and eighty-nine subjects with either generalized anxiety disorder, panic disorder, or obsessive-compulsive disorder were evaluated for plasma pyridoxal phosphate (PLP) levels and compared with normal controls. There was no difference in plasma PLP levels between the anxiety disorder groups and normal controls. Low levels of plasma PLP were found in 42% of the controls. Our results suggest that previous reports of low PLP levels in psychiatric patients are unlikely to be significant in the etiology of the psychiatric disorders.

Preliminary report: placebo-controlled, double-blind study of the clinical and metabolic effects of desipramine in panic disorder.

Fifty-six males and females with panic disorder with or without agoraphobia participated in a 12-week, placebo-controlled treatment study of the efficacy of desipramine (DMI). Twenty-six of 28 patients receiving DMI completed the study; 17 of 28 placebo (PBO) recipients completed 12 weeks. Patients receiving DMI responded significantly better than did PBO recipients as measured by Hamilton Anxiety Scale (HAM-A) and global phobia ratings, with a trend toward greater global improvement, but no between-group differences on panic attack frequency were discerned. By Week 12, 22 of 26 (85%) DMI patients were panic-free; 13 of 17 (76%) PBO patients were panic-free. Resting metabolic rate (RMR) was tested on a subset of the patients. Patients receiving DMI showed no effects on RMR or thyroid indices but lost a significant amount of weight; the PBO recipients exhibited no weight loss or RMR effects. In this study, the high PBO response rate obscured treatment group differences on some measures. This study underscores the need for placebo comparisons in treatment studies. In summary, DMI appears to be an effective treatment for panic disorder. DMI appears to have little effect on RMR; a slight but significant weight loss was observed in the DMI but not PBO group.