N. L. S. Potts

Treatment of Social Phobia With Clonazepam and Placebo

Clonazepam and placebo were administered in a double-blind pilot study to 75 outpatients with social phobia. The mean maximum dose of clonazepam was 2.4 mg/day at endpoint (range, 0.5 to 3 mg). Treatment was continued for up to 10 weeks. The results of an intent-to-treat analysis indicated superior effects of clonazepam on most measures. Response rates for clonazepam and placebo were 78.3 and 20.0%. Drug effects were apparent on performance and generalized social anxiety, on fear and phobic avoidance, on interpersonal sensitivity, on fears of negative evaluation, and on disability measures. Significant differences were evident by week 1, 2, or 6, depending upon the rating scale used. Clonazepam was well tolerated in general, although unsteadiness and dizziness were more severe and persistent than was the case for placebo subjects.

The Brief Social Phobia Scale: a psychometric evaluation.

The Brief Social Phobia Scale (BSPS) is an observer-rated scale designed to assess the characteristic symptoms of social phobia, using three subscales-fear, avoidance, and physiological arousal-which may be combined into a total score. Each of 18 BSPS items is anchored to a 5-point rating scale. Psychometric evaluation of the BSPS in a sample of 275 social-phobia patients yielded a high level of reliability and validity. Test-retest reliability was excellent, as was internal consistency. The fear and avoidance subscales demonstrated highly significant correlations with remaining item totals; however, the physiological subscale did not. The BSPS also demonstrated significant relationships with other established scales that assess anxiety and disability, and it proved sensitive to treatment effects in a trial of a 5-HT3 antagonist and placebo. Factor analysis yielded six meaningful factors. We conclude that the BSPS provides a reliable, valid, and sensitive measure for the evaluation of social phobia.

Magnetic resonance imaging in social phobia

Recent studies have implicated dopamine and the basal ganglia circuits in the pathophysiology of social phobia. Twenty-two patients who met DSM-III-R criteria for social phobia and 22 age- and sex-matched control subjects underwent magnetic resonance imaging (MRI). MRI was performed with a 1.5 Tesla General Electric Signa System. No statistically significant difference was demonstrated between social phobia patients and normal control subjects in respect to total cerebral, caudate, putamen, and thalamic volumes. Although this study failed to demonstrate any specific cerebral structure abnormalities in patients with social phobia, it did reveal an age-related reduction in putamen volumes in patients with social phobia that was greater than that seen in controls. This age-related reduction in putamen volumes in patients with social phobia was not correlated with the severity of their illness.

Discontinuation of clonazepam in the treatment of social phobia.

Patients with social phobia who responded well to 6 months of open-label treatment with clonazepam were assigned to receive either continuation treatment (CT) with clonazepam for another 5 months, or to undergo discontinuation treatment (DT) using a clonazepam taper at the rate of 0.25 mg every 2 weeks, with double-blind placebo substitution. Clinical efficacy was compared between the CT and DT groups using three different social phobia scales. Benzodiazepine withdrawal symptoms were also measured. Relapse rates were 0 and 21.1% in the CT and DT groups, respectively. Subjects in the CT group generally showed a more favorable clinical response at midpoint and/or endpoint, although even in the DT group clinical response remained good. With respect to withdrawal symptoms, the rates were low in both groups (12.5% for CT and 27.7% for DT) with no real evidence suggesting significant withdrawal difficulties. At the end of 11 months of treatment with clonazepam, however, a more rapid withdrawal rate was associated with greater distress. This study offers preliminary evidence to suggest that continuation therapy with clonazepam in the treatment of social phobia is safe and effective, producing a somewhat greater clinical benefit than a slow-taper discontinuation regime. However, even in the DT group, withdrawal symptoms were not found to be a major problem. The study can be taken as supportive of benefit for longterm clonazepam treatment in social phobia, as well as being compatible with a reasonably good outcome after short-term treatment and slow taper.

Cognitive performance on the Alzheimer's disease assessment scale : effect of education

The cognitive subscale of the Alzheimers Disease Assessment Scale (ADAS-Cog) is used to monitor disease progression and treatment efficacy in clinical trials of Alzheimers disease (AD). Using data from a 12-week drug trial, we retrospectively studied the effect of education on ADAS-Cog performance in a group of 444 patients with AD. The effect of education was statistically significant on baseline ADAS-Cog total scores. This effect remained statistically significant after controlling for age, gender, and dementia severity. Education effects were also statistically significant at week 12 for ADAS-Cog total and 10 of 11 subitem scores in 138 AD patients in the placebo arm of the trial. Post hoc analysis showed that non-high school graduates performed worse than those with greater educational levels across a broad range of cognitive domains. Our results, in conjunction with reports linking lower educational level with a higher risk for AD, suggest that educational level of patients be given consideration in the design and interpretation of cognitive tests in AD drug trials.

The neurobiology of social phobia.

Studies in the neurobiology of social phobia have used neuroendocrine, naturalistic and chemical challenges, pharmacological probes, neurotransmitter system measures, peripheral receptor binding and magnetic resonance measures. Studies of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes have been largely unrevealing; adrenaline, carbon dioxide, caffeine and yohimbine tests have provided mixed results; probe studies using L-dopa, clonidine and fenfluramine have provided some evidence of post-synaptic serotonergic abnormality; studies on platelet and lymphocyte binding have failed to distinguish social phobia from other groups; magnetic resonance imaging and magnetic resonance spectroscopy studies suggest possible differences between patients with social phobia and healthy controls in respect of dopamine, serotonin and second-messenger function. In aggregate, these studies have provided some neurobiological basis for separating social phobia from panic disorder and non-psychiatric healthy controls.

NSAIDs and cognition in Alzheimer's disease

To the Editor: Recent studies have suggested a neuroprotective influence for nonsteroidal anti-inflammatory drugs (NSAIDs). [1-4] The Rotterdam Study, [1] the Canadian Study of Health and Aging, [2] and a co-twin control study [3] found that anti-inflammatory treatments were associated with a reduced risk of Alzheimers disease (AD). The Honolulu Heart Program study found that concurrent aspirin use was associated with superior cognitive scores in nondemented subjects. [4] We studied 444 AD subjects selected for a multicenter clinical trial to test the hypothesis that concurrent NSAID …

Social phobia : biological aspects and pharmacotherapy

1. Social phobia is one of the anxiety disorders that until recently, had not been thoroughly investigated. 2. Social phobia is a relatively common anxiety disorder that appears to have a genetic basis. 3. There are certain physiological aspects of social phobia that separate it from the other anxiety disorders. 4. Support for a dopaminergic abnormality related to social phobia is supported by investigation studies and pharmacotherapy. 5. There are a number of studies reporting success in the treatment of social phobia with medications.