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Many antidepressants are known to cause adverse sexual effects. Bupropion is an antidepressant with fewer reported adverse sexual effects. Studies of sexual side effects are often confounded by psychiatric and medical conditions affecting sexual function. In this study, the effects of bupropion on subjective and objective sexual functioning were measured in healthy men. Thirteen men without psychiatric or medical illness completed a 2-week, placebo-controlled, double-blind, crossover trial of bupropion sustained-release 300 mg/day. Subjects had a 1-week washout period between trials. Sexual function was measured using a validated, self-administered questionnaire and the RigiScan, an instrument measuring nocturnal penile tumescence and rigidity. No differences were found in self-reported sexual function, number of erections, total erection time, or penile rigidity in subjects taking bupropion compared with those taking placebo or baseline. These findings support that bupropion does not have subjective adverse sexual side effects and does not affect nocturnal erections in healthy men.

A series of European Panic Forum meetings presented a unique opportunity to gather data on patients with panic disorder and their treatment. Data were collected on nearly 1200 panic disorder patients by means of a postal questionnaire. The survey gathered data on patient history, presentation, healthcare resources and management. The average patient was in their mid-thirties and had suffered panic disorder for a mean period of almost 5 years. In addition to panic disorder, many patients experienced comorbid depression, agoraphobia or generalized anxiety. Over half the patients were seen by a cardiovascular specialist prior to being seen by a psychiatrist, suggesting poor recognition of panic disorder in general practice. Almost 50 per cent of patients were treated with tricyclic antidepressants (TCAs), almost 60 per cent with selective serotonin reuptake inhibitors (SSRIs) and over 80 per cent with benzodiazepines. Of the drug treatments, SSRIs were considered to be markedly or moderately effective in 68 per cent of patients, compared with 59 per cent receiving benzodiazepines and 58 per cent receiving TCAs. Few patients received psychological interventions. In patients receiving combined treatment with either a benzodiazepine plus an antidepressant, or cognitive-behavioural therapy plus drug therapy, treatment was considered effective in 98–99 per cent of cases. © 1997 John Wiley & Sons, Ltd.

Epidemiologic data as well as data from treatment-seeking populations indicate that substance abuse disorders and other psychiatric disorders co-occur more commonly than would be expected by chance. In particular, substance abuse, especially cocaine abuse or dependence and alcoholism, is a far more common phenomenon in the population of patients with bipolar affective disorder than in the general population. National Institute of Mental Health Epidemiologic Catchment Area data indicate that bipolar affective disorder is the axis I disorder most likely to be associated with some form of substance abuse or dependence. Evidence from patient samples seeking treatment for substance abuse disorders as well as for psychiatric disorders suggests that clinical samples reflect similar patterns. There is evidence that bipolar patients with substance abuse have a worse course of illness. Diagnosing bipolar affective disorder in the face of substance abuse is difficult because the effects of drugs of abuse, particularly with chronic use, can mimic nearly any psychiatric disorder. At present, the data concerning a genetic link between bipolar affective disorder and substance abuse disorders are inconclusive. There are very few controlled data addressing either clinical features of, or specific treatment efforts with, this population. There is some theoretic rationale for the use of anticonvulsant, antikindling agents in this population, but no controlled studies have as yet been reported. In particular, a comparison of a mood-stabilizing agent, such as lithium, with an antikindling agent, such as valproate or carbamazepine, would be of theoretic and practical interest.

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 a50% 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.

Data from early studies of selective serotonin reuptake inhibitors have shown that these agents are effective in the treatment of social anxiety disorder (social phobia). This review highlights the outcomes of three large clinical trials of paroxetine in patients with social anxiety disorder. In two of the studies, patients received a flexible dose of paroxetine (20-50 mg/day) or placebo; the third trial was a fixed-dose study, in which patients received paroxetine 20, 40, or 60 mg/day, or placebo. A total of 861 subjects were randomized to treatment for 12 weeks, in centers across the U.S.A., Canada, Europe, and South Africa. The primary outcome measures were the Clinical Global Impressions (CGI) Global Improvement item and Liebowitz Social Anxiety Scale (LSAS) Total Score. In each of the studies, 45-66% of patients receiving paroxetine were rated as responders (very much or much improved on the CGI scale). Paroxetine treatment improved symptoms of social anxiety, as measured by the LSAS, compared with placebo. Differences between paroxetine and placebo groups were statistically significant and were clinically relevant within each study. In general, paroxetine was well tolerated. Paroxetine is effective for the treatment of social anxiety disorder. Based on the findings from these studies, a starting dose of 20 mg/day is recommended. The range of efficacy appears to be 20-50 mg/day for most patients.

Although panic attacks account for only a portion of the morbidity of panic disorder and panic attack frequency assessments are unreliable, studies of drug efficacy in panic disorder have generally used reduction in panic attack frequency as the primary measure of improvement. The authors studied the efficacy of fluoxetine treatment in panic disorder and measured the relative contributions of changes in symptoms to overall improvement.Patients with a diagnosis of panic disorder (N = 243) were randomly assigned to treatment with 10 or 20 mg/day of fluoxetine or placebo. Primary outcome measures were change in panic attack frequency and clinician-rated Clinical Global Impression improvement scores. Other assessments included a panic attack inventory, clinician-rated and patient-rated versions of the Panic and Phobic Disorder Change Scale, a phobia rating scale, the Hamilton Anxiety Rating Scale, the 21-item Hamilton Depression Rating Scale, and the Sheehan Disability Scale. Correlations were determined between outcomes in individual symptom domains and overall clinical outcome.Fluoxetine, particularly the 20-mg/day dose, was associated with more improvement than was placebo in patients with panic disorder across multiple symptom measures, including global improvement, total panic attack frequency, phobic symptoms, and functional impairment. Global improvement was most highly correlated with reductions in overall anxiety and phobic symptoms and least correlated with reduction in panic attacks. Fluoxetine treatment for panic disorder was well tolerated, with a safety profile consistent with that observed for fluoxetine in other disorders.These data provide support for the efficacy and safety of fluoxetine treatment in reducing panic attacks, phobic symptoms, anxiety, and depressive symptoms in patients with panic disorder. Reductions in panic attack frequency in subjects given either fluoxetine or placebo were less closely related to overall clinical improvement than reductions in phobic avoidance, anxiety, depressive symptoms, and functional impairment, suggesting that outcome measures in this disorder should be more broadly based.

The optimal assessment of treatment outcome for studies assessing the efficacy of treatments for panic disorder has been a controversial topic. A recent National Institute of Mental Health (NIMH)-sponsored consensus conference addressed this important topic, and a summary paper regarding assessment of essential elements of the disorder resulted. Among other conclusions, it was agreed that several different domains should be considered as essential. This article reviews three pivotal studies assessing the efficacy of paroxetine for the treatment of panic disorder, and evaluates these studies for inclusion of those variables considered essential. Additionally, some data were reanalyzed to determine the percentage of individuals in these studies who are unequivocal responders (i.e., were both panic-free and rated on global assessment as responders). A longer-term treatment and relapse study is also mentioned briefly.

Panic disorder and major depression frequently coexist in the clinical setting. Patients with overlapping symptoms of depression and panic disorder may have more severe symptoms, may require earlier treatment, earlier and more frequent hospitalization, and may have worse outcomes. In addition, such patients are at greater risk for suicide than those having either disorder alone. In light of the importance of these clinical consequences, the authors will review the available literature on the prevalence and prognosis of comorbid depression and panic disorder and will highlight the major clinical characteristics of panic disorder in depressed patients and the treatment strategies most often used.

A recently reported multinational, 8-week double-blind, placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam. We now report the results of a three-site, 6-week, double-blind, fixed-dose study comparing alprazolam 2 mg, alprazolam 6 mg, and placebo in 94 patients with panic disorder with or without agoraphobia. Both alprazolam treatment groups (6 mg and 2 mg) improved significantly more than did the placebo treatment group on most outcome measures. Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned, although the pattern of treatment response across measures suggested a dose effect. Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects, which may have contributed to the limited differences between groups at study end. The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder.

A recently reported multinational, 8-week double-blind, placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam. We now report the results of a three-site, 6-week, double-blind, fixed-dose study comparing alprazolam 2 mg, alprazolam 6 mg, and placebo in 94 patients with panic disorder with or without agoraphobia. Both alprazolam treatment groups (6 mg and 2 mg) improved significantly more than did the placebo treatment group on most outcome measures. Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned, although the pattern of treatment response across measures suggested a dose effect. Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects, which may have contributed to the limited differences between groups at study end. The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder.

Earlier reports indicated that phenelzine treatment may result in clinically significant reductions of vitamin B6 in some individuals. Sixteen subjects, ages 21-59 years (seven men, nine women) with panic disorder with or without agoraphobia were treated with an average of phenelzine 53.5 mg/day for an average of 10 weeks in an open treatment study. No significant effects on plasma levels of pyridoxal phosphate, the active form of vitamin B6, were discernible in this group, nor was there any clear relationship between pyridoxal phosphate levels and symptoms in the subgroup of five patients who did develop deficiency-type symptoms. Pyridoxine replacement had unclear effects in symptomatic patients.

We have previously reported that injection of dl-alphamethylparatyrosine methylester (AMPT) into the yolk sac of fertilized chicken eggs prior to incubation results in dose-related increases in the specific activity of tyrosine hydroxylase (TH) at 29 days postnatally. We now report that injection of 10.0 and 33.3 mg/kg of AMPT prior to incubation results in dose-related increases in acquisition rates of 2 operant responses. Between 1 and 3 weeks of postnatal age, we observed a dose-related decrease in latency to perform a detour response and, at 55-60 days of postnatal age, an increased rate of acquisition of a key peck response in an autoshaping paradigm. We could not discern any significant alteration in several measures of unconditioned behaviors in an open field situation at 3 weeks of postnatal age. Our data support the contention that early catecholamine (CA) depletion can produce long-term alterations in postnatal behavior.

This review surveys the literature in the area of predictors of response to antipsychotic drugs. Four general categories are presented and discussed: diagnosis as a predictor, clinical predictors, biological predictors, and pharmacological predictors. No single consistent predictor of response could be discerned; it appears that a variety of factors affect outcome and that several variables must be considered simultaneously. Based on the findings of this review, suggestions for improvements in clinical research design are made.

Fourteen patients who met DSM-III criteria for agoraphobia with panic attacks received 200 mg desipramine (DMI) per day for 12 to 16 weeks on an open basis. Seven of eight patients who responded had steady state plasma DMI levels greater than 125 ng/ml, while five of six nonresponders had DMI levels less than 125 ng/ml. Following increases in dosage sufficient to raise DMI levels to greater than 150 ng/ml, four nonresponders improved dramatically. Implications of these findings are discussed briefly.

This review surveys the literature in the area of predictors of response to antipsychotic drugs. Four general categories are presented and discussed: diagnosis as a predictor, clinical predictors, biological predictors, and pharmacological predictors. No single consistent predictor of response could be discerned; it appears that a variety of factors affect outcome and that several variables must be considered simultaneously. Based on the findings of this review, suggestions for improvements in clinical research design are made.

Earlier reports indicated that phenelzine treatment may result in clinically significant reductions of vitamin B6 in some individuals. Sixteen subjects, ages 21-59 years (seven men, nine women) with panic disorder with or without agoraphobia were treated with an average of phenelzine 53.5 mg/day for an average of 10 weeks in an open treatment study. No significant effects on plasma levels of pyridoxal phosphate, the active form of vitamin B6, were discernible in this group, nor was there any clear relationship between pyridoxal phosphate levels and symptoms in the subgroup of five patients who did develop deficiency-type symptoms. Pyridoxine replacement had unclear effects in symptomatic patients.