Psychopharmacology of schizophrenia: The Future Looks Bleak.

INTRODUCTION: More than half a century after the introduction of effective pharmacotherapy for the illness, in most patients schizophrenia remains a chronic, relapsing condition with poor long-term outcomes. METHODS: We examine the pharmacological treatment of schizophrenia from different perspectives to understand why there have not been significant advances, and to consider what the future might hold in store. RESULTS: We argue that the treatment of schizophrenia addresses the phenotype and not the cause; that the causes may not be treatable even if identifiable; that secondary prevention approaches involving treating the phenotype before full-fledged illness develops have, so far, not yielded promising results; and that shifting the focus of treatment from dopamine to other neurotransmitter systems is merely a tertiary prevention approach which will not reverse the extensive structural and functional pathology of schizophrenia. CONCLUSIONS: We believe that, given the current state of our knowledge of the illness, the future of the pharmacotherapy of schizophrenia looks bleak.

Familial vulnerability to an unusual cognitive adverse effect of topiramate: Discussion of mechanisms.

BACKGROUND: Some patients experience cognitive disturbances with topiramate. CASE HISTORIES: A 19-year-old bipolar woman and her 46-year-old mother with paranoid personality disorder both used topiramate (25-50 mg/day) off-label for weight loss. Both women suffer from learning disorders, and both are excessively sensitive to the sedative adverse effects of psychotropic medications. RESULTS: Within days of starting topiramate, the women began to exhibit troublesome word- and phrase-repetition and word substitution, both occurring only in their written expression. The symptoms were associated with mild sedation, persisted during two weeks of topiramate treatment, and remitted days after topiramate was withdrawn. DISCUSSION: The presence of the learning disorders and the sensitivity to the sedative adverse effects of drugs may explain why cognitive adverse effects, known to occur with topiramate, developed at the low dose of 25-50 mg/day. The proclivity of topiramate to affect language functions and a possible familial vulnerability herein may explain why the women explained similar, language-specific symptoms. An investigation of topiramate-induced cognitive impairments in family members with epilepsy may throw light on the subject.

Quality outcomes management: Veterans Affairs case study.

During the last decade, the Department of Veterans Affairs (VA) has made major strides in enhancing quality of medical, surgical, and mental health care for veterans. These improvements have been achieved through the will and commitment of VA leadership and by changes in the administrative structure, such as through the creation of Veteran Integrated Service Networks and patient care service lines, the use of state-of-the-art technology for electronic health records, implementation of high-value preventative and chronic disease management performance measures, and the ability to track their effectiveness. Parallel with these changes, the quality of mental heath care in the VA has also improved, as have mental health education and research.

Modafinil for remitted bipolar depression with hypersomnia.

OBJECTIVE: To report 2 cases of bipolar disorder with recent depression in remission with prominent residual hypersomnia, responding well to the addition of the psychostimulant modafinil. CASE SUMMARIES: Two patients with bipolar disorder with recent depressive episodes in remission are presented. Despite the absence of prominent depressive symptoms, both patients had significant hypersomnia, with scores ranging from 15 to 20 (maximum 24) on the Epworth Sleepiness Scale. The addition of modafinil to their medication regimen resulted in a decrease in hypersomnia and improvement in their level of functioning. DISCUSSION: This is the first report (MEDLINE search, October 7, 2003) demonstrating the use of modafinil in the treatment of hypersomnia in bipolar disorder while mood symptoms were in remission. Hypersomnia frequently occurs in depressive episodes and can be disabling when severe. The patients had optimal mood stabilization with mood stabilizers and antidepressants, but continued to experience excessive daytime sleepiness. Conventional stimulants were not considered because of the risk of triggering mania. The addition of the selective psychostimulant modafinil resulted in significant improvement in the hypersomnia, with improvement in functioning. No adverse effects or mood changes were noted. CONCLUSIONS: Modafinil may be a well-tolerated and effective alternative to conventional stimulants in the treatment of hypersomnia, especially in bipolar disorder, where there is considerable risk of switch to mania with stimulant medications. Modafinil may be useful even when depressive symptoms are not prominent.