Cognitive performance on the Alzheimer's Disease Assessment Scale: effect of education.

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is used to monitor disease progression and treatment efficacy in clinical trials of Alzheimer's 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.

Treatment of social phobia with benzodiazepines.

Although social phobia is a common and highly treatable anxiety disorder, the majority of social phobics do not receive treatment. Without intervention, it is unlikely that patients will attain significant relief from the symptoms and disability associated with the disease. The authors review the results of studies concerning the use of high-potency benzodiazepines in the treatment of social phobia. These studies, which include open trials as well as a double-blind, placebo-controlled evaluation of clonazepam, have demonstrated clinical efficacy and suggest a therapeutic role for this drug class in the treatment of social phobia. Developmental work with the Davidson Brief Social Phobia Scale is described, along with predictors of treatment outcome for clonazepam and placebo and relapse data upon discontinuation of both treatments. Finally, the authors discuss general issues concerning the relapse of patients upon drug discontinuation, the long-term use of benzodiazepines, and other important issues concerning the use of these agents for the treatment of social phobia.

The role of nuclear magnetic resonance imaging in psychiatric research.

Magnetic resonance imaging (MRI) has become an important tool in the investigation of cerebral abnormalities associated with psychiatric illnesses. There are a number of benefits of investigating psychiatric illness with MRI, which is superior to computed tomography scanning. MRI has been used to study neurologic deficits seen in schizophrenia, affective disorders, dementia, and more recently, anxiety disorders. Magnetic resonance spectroscopy offers a new investigational technique that adds functional information to the structural changes seen with standard MRI scanning. This review highlights the current data in living human subjects that demonstrate structural changes in psychiatric disorders using MRI, including recent studies of the anxiety disorders.

Long-term treatment of social phobia with clonazepam.

Twenty-six socially phobic outpatients were treated with clonazepam for the relief of symptoms. At evaluation, which took place after an average of 11.3 months of continuous treatment, 22 (84.6%) patients showed good improvement and 4 (14.4%) showed no improvement or were not recovered. The dose declined over time, from a peak mean of 2.1 mg/day to a mean of 0.94 mg/day at follow-up. Side effects are described, along with individual case descriptions that illustrate important aspects of the use of benzodiazepines for the treatment of social phobia.

Levels of urinary free cortisol in social phobia.

Levels of urinary free cortisol were measured in 10 patients with social phobias and in 15 age- and sex-matched normal controls. No differences were found either in cortisol levels or in the ratio of free cortisol to creatinine. These nonsignificant differences between groups do not necessarily rule out the possibility that the hypothalamic-pituitary-adrenal axis may be altered in individuals with social phobia.

The Brief Social Phobia Scale.

An observer measure of social phobic symptoms, referred to as the Brief Social Phobia Scale, consists of 11 items, 7 evaluating commonly feared or avoided situations and 4 additional items measuring autonomic distress. Symptoms represented by the scale items are found frequently in social phobia, and the instrument demonstrates acceptable interrater and test-retest reliability, internal consistency, concurrent validity against other measures of social phobia, and the ability of patients to change as a result of treatment. It can also detect differences between active treatment and placebo treatment. A comparison of the sensitivity of this scale with other scales in detection of size of effect also is presented.

Magnetic resonance spectroscopy in social phobia: preliminary findings.

Proton localized magnetic resonance spectroscopy was studied in 20 social phobics and 20 age- and sex-matched controls. Stimulated Echo Acquisition Mode volume element localization was used with chemical shift imaging. Choline and creatine signal-to-noise ratios (SNRs) were significantly lower in social phobia than in controls in subcortical, thalamic, and caudate areas. In the social phobic group, N-acetylaspartate (NAA) SNR was significantly lower in cortical and subcortical regions, and ratios of NAA to other metabolites were lower in social phobia. Choline, creatine, and NAA SNRs were inversely correlated to total social phobia and fear symptoms, as measured by the Brief Social Phobia Scale, in the thalamic and noncortical gray areas. In a small number of patients who received clonazepam, posttreatment SNRs generally increased relative to baseline. Our results suggest a promising place for magnetic resonance spectroscopy in social phobia and also indicate potential pharmacodynamic uses of this technique.

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.

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.

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.

Long-Term Use of Benzodiazepines: Implications and guidelines.

Problems associated with physical dependence and abuse of benzodiazepines by a small percentage of patients have reduced their popularity from the most commonly prescribed psychoactive drug in the 1970s to being prescribed for mainly short periods. Patients who benefit from long-term benzodiazepine use are nearly ignored by the medical community as a whole. This article details what patient population can improve from long-term benzodiazepine therapy, the risks and benefits of treatment, and how to select appropriate candidates.

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.

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.