February 2007

Acupuncture for Depression: Missing the Point
Depression-specific acupuncture was no better than nonspecific acupuncture for patients with major depression.

Adjunctive Galantamine in Schizophrenia
Galantamine (formerly Reminyl, currently Razadyne) added to risperidone (Risperdal) treatment for schizophrenia patients offered some benefits.

Adverse Effects of Erectile Dysfunction Drugs
Drugs for erectile dysfunction, such as sildenafil (Viagra) and vardenafil (Levitra), may worsen sleep apnea and can cause seizures.

Deep brain stimulation decreased obsessive compulsive symptoms in 10 patients.

Clozapine for Treatment-Resistant Schizophrenia
Clozapine (Clozaril and others) was superior to other second-generation antipsychotics for treatment-resistant patients with schizophrenia.

In Brief
Rasagiline Approved for Treatment of Parkinson's Disease; Paliperidone Approved for Treatment of Schizophrenia; PCOS Reversed When Valproate Discontinued.

Antipsychotics and New MIs
A large study suggests that antipsychotic drugs do not increase the risk of a new myocardial infarction (heart attack).

Take Ziprasidone with Food
Adequate absorption of ziprasidone is promoted by taking it with a meal that contains at least 30% fat.

Clozapine for Treatment-Resistant Schizophrenia

February 2007

For most people who suffer from schizophrenia, antipsychotic drugs may provide improvement but are hardly a cure (BTP 2006;29:50-52). In a recent study by Lambert et al, only 12.8% of patients with schizophrenia met their criteria for remission after 2 years.1 Worse still, up to a third of patients derive little benefit at all from these drugs.2 Clozapine (Clozaril and others) has long been considered the most efficacious, albeit most toxic, antipsychotic. Lewis and others present data from a study in the United Kingdom of clozapine versus other second-generation agents in treatment-resistant schizophrenia.3

Investigators enrolled 136 adult patients with schizophrenia who had been poorly responsive to at least two antipsychotic drugs. Subjects were assigned at random to treatment either with clozapine or another second-generation antipsychotic selected by the managing clinicians. The choices were risperidone (Risperdal, 3 to 8 mg/day), olanzapine (Zyprexa, 10 to 30 mg/day), quetiapine (Seroquel, 300 to 750 mg/day), or amisulpride* (600 to 800 mg/day), and raters were blinded.

The study could not demonstrate a significantly greater improvement in quality of life for patients taking clozapine versus the other agents. However, clozapine did show a statistically significant advantage in the positive and negative syndrome scale as well as a trend towards causing fewer extrapyramidal effects. At 12 weeks, participants taking clozapine reported their mental health as significantly better than those receiving the other drugs.

Second-generation antipsychotics appear somewhat more tolerable than first-generation agents, and they cause few cases if any of tardive movement disorders. But there is little evidence that they are superior in efficacy to the first generation. By contrast to other second-generation agents, clozapine does seem to offer enhanced efficacy, particularly for treatment-resistant patients. However, it can cause serious and sometime life-threatening adverse effects.

*Not available in the United States.

1Lambert M, Schimmelmann BG, Naber D, Schacht A, Karow A, Wagner T, Czekalla J: Prediction of remission as a combination of symptomatic and functional remission and adequate subjective well-being in 2960 patients with schizophrenia. J Clin Psychiatry 2006;67:1690-1697.

2Conley RR, Buchanan RW: Evaluation of treatment-resistant schizophrenia. Schizophr Bull 1997;23:663-674.

3Lewis SW, Barnes TR, Davies L, Murray RM, Dunn G, Hayhurst KP, Markwick A, Lloyd H, Jones PB: Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Schizophr Bull 2006;32:715-723.