Effectiveness of antipsychotic treatments in community cohort after first hospitalisation for schizophrenia

A Finnish study has examined the association between prescribed antipsychotic drugs and outcome in schizophrenia or schizoaffective disorder in community patients.

The study which involved 2230 consecutive adults hospitalised for the above mentioned conditions, measured the following parameters:

• Rates of discontinuation of drugs
• Rates of rehospitalisation
• Mortality associated with monotherapy with the 10 most commonly used antipsychotic drugs.

To obtain crude relative risks, these incidence figures for all drugs were compared with the incidence figures for haloperidol. The following findings were reported:

• The most commonly used initial drug was risperidone, followed by olanzapine, clozapine, oral perphenazine, thioridazine, chlorpromazine, chlorprothixene, haloperidol, perphenazine depot, and levomepromazine.

• Initial use of clozapine (adjusted relative risk 0.17, 95% CI, 0.10 to 0.29), perphenazine depot (0.24, 0.13 to 0.47), and olanzapine (0.35, 0.18 to 0.71) were associated with the lowest rates of discontinuation for any reason vs oral haloperidol.

• The most commonly used antipsychotic drug during the entire follow-up period was olanzapine, followed by clozapine, risperidone, oral perphenazine, thioridazine, perphenazine depot, chlorprothixene, chlorpromazine, haloperidol, and levomepromazine.

• During an average follow-up of 3.6 years, there were 84 deaths and 4640 cases of rehospitalisation; current use of perphenazine depot (0.32, 0.22 to 0.49), olanzapine (0.54, 0.41 to 0.71), and clozapine (0.64, 0.48 to 0.85) were associated with the lowest risk of rehospitalisation.

• Use of haloperidol was associated with a poor outcome among women.

• Mortality was raised in patients not taking antipsychotics (12.3, 6.0 to 24.1) and the risk of suicide was high (37.4, 5.1 to 276).

The study concluded from these findings that “effectiveness of first and second generation antipsychotics varies greatly in the community. Patients treated with perphenazine depot, clozapine, or olanzapine have a substantially lower risk of rehospitalisation or discontinuation (for any reason) of their initial treatment than do patients treated with haloperidol. Excess mortality is seen mostly in patients not using antipsychotic drugs.”

Link to Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/bmj.38881.382755.2Fv1  

Varenicline for smoking cessation shown to be effective in trials

Source: JAMA 2006; 296: 47-55, 5-63, 64-71, 94-5

Three trials published this week show that varenicline, an investigational drug in late-stage development, is more effective than placebo in helping smoking cessation. Varenicline is a partial agonist at the alpha4-beta2 nicotinic acetylcholine receptor, which appears to be significant in reinforcing the effects of nicotine, and it therefore may both relieve the symptoms of nicotine withdrawal and reduce the reinforcing effects of continued use. The three trials describe its effects compared to placebo and bupropion s/r (two trials).

Two very similar multi-centre, randomised, double-blind, placebo-controlled trials compare varenicline with s/r bupropion and placebo. They involved 1,025 and 1,027 adult smokers wishing to quit who were generally healthy and had less than three months smoking abstinence in the previous year. Participants were randomised to treatment with varenicline, s/r bupropion, or placebo in a 1:1:1 ratio for twelve weeks, with 40 weeks follow-up. Primary outcome was four-week continuous abstinence from smoking for weeks 9 to 12 of the study period; prolonged abstinence to four months and twelve months were secondary outcomes. Analysis of the results on an intention-to-treat basis showed that both active drugs were superior to placebo, and varenicline was superior to s/r bupropion (continuous abstinence rates for weeks 9-12 - about 18%, 44%, and 30% respectively across the two studies, P < 0.001). Both study drugs were fairly well tolerated, with the most common adverse effects being nausea for varenicline and insomnia for s/r bupropion. The authors of these studies conclude that varenicline is more effective than placebo and bupropion for smoking cessation, and is safe.

The third study investigated the effects of a further twelve-week maintenance course of varenicline in 1,210 people who had stopped smoking after an initial twelve-week course of open-label varenicline. They were randomised to a further twelve weeks treatment with either varenicline or placebo with follow-up to 52 weeks: primary outcome was continued abstinence over weeks 13 to 24, and weeks 13 to 52. in this study, continued abstinence was greater in the active group compared to the placebo group for both weeks 13-24 (70.5% vs. 49.6%, P < 0. 001) and 13-52 (43.6% vs. 36.9%, P < 0.02). No difference in adverse effects was reported during this period. The authors conclude that smokers who achieved abstinence after initial twelve weeks treatment with varenicline were more likely to remain abstinent with an additional twelve weeks treatment.

An accompanying editorial discusses the studies: the author notes some limitations of the results, but considers them promising.

Link to Editorial: http://jama.ama-assn.org/cgi/content/extract/296/1/94

Response to third antidepressive drug after two fail is unlikely?

Source: Am J Psychiatry 2006; 163: 1123-5, 1161-72

A randomised controlled trial found that neither nortriptyline nor mirtazapine was particularly effective in patients who had already failed treatment with two other drug regimens. There is limited evidence on the best treatment in depressed patients who fail on two regimens, and this trial aimed to clarify previous small studies suggesting that mirtazapine or nortriptyline may be effective. It was the continuation of a study that previously identified effective options for second step therapy (the STAR*D trial) and involved 235 adults with major depressive disorder who had not responded to or tolerated the initial treatment regimens. They were randomised on an open-label basis (to mimic clinical practice and allow 'vigorous' dosing) to treatment with either mirtazapine (up to 60 mg/day, n=114) or nortriptyline (up to 200 mg/day, n=121). Study duration was 14 weeks, and primary outcome was remission based on a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HAM-D).

Remission rates were low for both treatments - 19.8% for nortriptyline and 12.3% for mirtazapine (difference not statistically significant). There were also no significant differences in secondary outcomes measured. Based on their results, the authors conclude that switching to a third monotherapy antidepressive regimen as third-step treatment in major depression is associated with a low response rate of less than 20%, with no significant difference between the two drugs studied. An accompanying editorial discusses the study.

Link to Abstract: http://intl-ajp.psychiatryonline.org/cgi/content/abstract/163/7/1161

Boletín de Actualización en Neuropsicofarmacología (BAN)
Editor: Luis I. Mariani
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Número de Suscriptos: 928 
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