Risperidone versus pimozide in Tourette's disorder: a comparative double-blind parallel-group study.

BACKGROUND: The treatment of Tourette's disorder with classical neuroleptics is limited by their side effects. Risperidone is a new efficacious antipsychotic with a low propensity for extrapyramidal side effects. To establish risperidone's therapeutic potential in Tourette's disorder, we studied the safety and efficacy of risperidone in comparison with pimozide in patients with Tourette's disorder diagnosed according to DSM-III-R. METHOD: In a 12-week, multicenter, double-blind, parallel-group study, 26 patients were treated with risperidone (mean daily dose = 3.8 mg), and 24 patients were treated with pimozide (mean daily dose = 2.9 mg). RESULTS: There was significant improvement of tics with respect to the Tourette's Symptom Severity Scale (TSSS) for both groups. Forty-one patients completed the study. At endpoint, 54% (14/26) of the risperidone patients and 38% (9/24) of the pimozide patients had only very mild or no symptoms on the global severity rating of the TSSS. Both treatment groups had improved significantly at endpoint in regard to Global Assessment of Functioning and Clinical Global Impressions scale outcomes. Symptoms of anxiety and depressive mood improved significantly from baseline in both groups. Obsessive-compulsive behavior improvement reached significance only in the risperidone group. Although the severity of extrapyramidal side effects was low in both groups, fewer patients in the risperidone group reported extrapyramidal side effects (N = 4) compared with the pimozide group (N = 8). Depression, fatigue, and somnolence were reported as the most prominent side effects in both treatment groups. CONCLUSION: Both drugs were efficacious and well tolerated in patients with Tourette's disorder. Risperidone may become the first-line drug in the treatment of Tourette's disorder owing to a more favorable efficacy and tolerability profile.

Neuropsychiatry of hypersexuality.

Relatively few studies of the psychobiology of hypersexuality have been undertaken. Nevertheless, the literature does suggest the possibility of a neurobiology of hypersexuality. Three cases of hypersexual behavior are presented in the context of neuropsychiatric disorders, and the literature on this phenomenon is briefly reviewed. These case studies and the literature provide evidence that different brain systems may play a role in this disorder. Frontal lesions may be accompanied by disinhibition, including impulsive hypersexual response to external cues, while striatal lesions may be accompanied by repetitive triggering of internally generated response patterns. Temporal-limbic lesions may be accompanied by disturbances in sexual appetite itself, including change in the direction of sexual drive. These case studies demonstrate that a neurobiology of hypersexuality may prove of some heuristic value in the clinic. However, further research is required to consolidate the literature in this area.

A risk-benefit assessment of pharmacotherapy for anxiety disorders in children and adolescents.

Few pharmacotherapy trials have been undertaken in young people with anxiety disorders. Of those conducted, few are placebo-controlled or blinded, and often sample size is small, making interpretation of the data difficult. Case report and uncontrolled trial data generally support the efficacy of pharmacotherapy in many of the anxiety disorders seen in young people. However, most attempts to confirm these impressions in controlled trials have not been as encouraging. Further controlled studies in larger, diagnostically homogeneous samples are needed. At present, the decision as to whether or not to use medication in this patient population must be made on clinical grounds. Evidence is accumulating to suggest that anxiety disorders in young people can become chronic and cause at least moderate functional impairment in some individuals. This possibility has to be weighed against the potential for adverse effects of many of the drugs used clinically. Serious adverse effects appear only in a minority of patients; however, there does not seem to be a reliable method of predicting which patients might be at risk. Benzodiazepines are used to treat anxious children, notwithstanding concerns about dependence, behavioural disinhibition, cognitive impairment and mood changes. The tricyclic antidepressants (TCAs) are generally well tolerated, but their effects on cardiac conduction at higher plasma concentrations are well documented and there have been sporadic reports of sudden death associated with their use in children. Toxicity in overdose is an added concern. The use of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors in children and adolescents is widespread, but few rigorous supportive trials have been conducted. The occurrence of both potentially serious adverse effects and other less serious, but troublesome, adverse effects and a possible discontinuation syndrome may complicate the use of these agents in younger patients. However, their relative safety in overdose and the apparent reversibility of adverse effects may favour their use over the TCAs. Other drugs used in this setting include buspirone and beta-blockers. No controlled trials are available at this time, but their adverse effect profiles appear to be relatively favourable and further study is warranted, given the promising nature of the uncontrolled data. The reversible monoamine oxidase inhibitors may be useful in younger anxious patients, but controlled data are needed. The decision to use pharmacotherapy should be made after consideration of multiple factors, and firm recommendations for the use of drug therapy in anxiety disorders in children and adolescents await more rigorous data.