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July 2010

Omega-3 Fatty Acids and Exercise for Psychosis?
Omega-3 fatty acid supplementation and exercise are relatively benign interventions that might prevent symptoms and improve outcome in patients with or at high risk of developing chronic psychotic disorders.

Long-Acting Injectable Risperidone Often Discontinued
In a study of patients with schizophrenia in the US Department of Veterans Affairs health care system, clozapine (Clozaril and others) had the highest continuation rate over 1 to 2 years, while long-acting injectable risperidone (Risperdal Consta) was discontinued by over half of patients for whom it was prescribed.

Can Molindone Help with Weight Loss?
Molindone (Moban) may produce modest benefits for weight loss in patients taking antipsychotics but carries the risk of long-term movement disorders and is no longer available in the United States.

In Brief
Depression Care Initiative Reduces Suicide Rate to Zero; Ecstasy Decreases Serotonin Transporter Binding in Brain Regions Associated with Memory

Adjunctive Aspirin Reduces Schizophrenia Symptoms
Preliminary data suggest aspirin might reduce schizophrenia symptoms through its anti-inflammatory properties.

Torsade de Pointes and Ziprasidone
The second case of torsade de pointes following ziprasidone (Geodon) overdose reported in the medical literature involved multiple risk factors for triggering the life-threatening ventricular arrhythmia.

Omega-3 Fatty Acids and Exercise for Psychosis?

July 2010

Last year, we discussed treatments for patients at ultra-high risk of developing psychotic disorders (BTP 2009;32:10-12). In theory, successful early intervention should ensure a better lifetime outcome. But as a recent review noted, it is by no means clear what is optimal preventive treatment, and the best wisdom appears to be a stepped approach, beginning with the least hazardous interventions.1 Amminger and coworkers in Australia note findings of reduced long-chain omega-3 and omega-6 polyunsaturated fatty acids in patients with schizophrenia, which suggests that dysfunctional fatty acid metabolism may contribute to causing the disorder.2 Controlled trials of omega-3 supplementation in people with schizophrenia, however, have yielded equivocal results. Because omega-3 fatty acids appear to lack adverse effects and are generally beneficial to health, Amminger and colleagues conducted a randomized placebo-controlled trial to determine their effectiveness in preventing psychosis, reducing other psychiatric symptoms, and improving function in those with a subthreshold psychotic disorder.

In a study funded by the Stanley Foundation, 81 individuals deemed at ultra-high risk of developing a psychotic disorder were given 1.2 g/day of omega-3 polyunsaturated fatty acids or placebo for 12 weeks, followed by 40 weeks of monitoring—for a total study of 12 months. By the end of 1 year, psychosis had developed in 11 (27.5%) of the 40 placebo subjects versus only 2 (4.9%) of the 41 subjects in the omega-3 group (P = .007). Furthermore, omega-3 fatty acids significantly reduced positive, negative, and general symptoms and improved functioning to a significantly greater degree than placebo. The incidence of adverse effects did not differ between omega-3 fatty acids and placebo.

The incorporation of omega-3 fatty acids into cell membranes alters membrane fluidity and receptor responses, which might account for their presumed therapeutic benefits. In addition, omega-3 fatty acids may interact with dopaminergic and serotonergic systems, possibly modulating receptor-coupled arachidonic acid release. They are also believed to have neuroprotective properties.

An independent study evaluated exercise in the treatment of schizophrenia. Pajonk and coauthors observed that hippocampal volume is lower than expected in patients with schizophrenia and that exercise stimulates hippocampal plasticity.3 With public and foundation funding, researchers studied 24 male patients with chronic schizophrenia attending a day hospital program or an outpatient clinic and 8 healthy matched controls. Subjects were randomized to an aerobic exercise training program (cycling) or a control condition (playing table football) for 3 months. Hippocampal volume increased following exercise training—12% in patients and 16% in healthy subjects. Patients not in the exercise group showed no change in hippocampal volume. For all subjects in the exercise group, changes in hippocampal volume were correlated with improvement in aerobic fitness, measured by change in maximum oxygen consumption. For patients with schizophrenia, improvement in test scores for short-term memory was correlated with change in hippocampal volume.

Omega-3 fatty acid supplementation appears to be a benign intervention and, in fact, may improve cardiovascular and metabolic indices. Exercise, subject to reasonable cautions, also is beneficial to health. Both may have a role to play in preventing and improving outcome in patients with chronic psychotic disorders. Further research will be welcome in this developing area.

1McGorry PD, Nelson B, Amminger GP, Bechdolf A, Francey SM, Berger G, Riecher-Rössler A, Klosterkötter J, Ruhrmann S, Schultze-Lutter F, Nordentoft M, Hickie I, McGuire P, Berk M, Chen EY, Keshavan MS, Yung AR: Intervention in individuals at ultra high risk for psychosis: A review and future directions. J Clin Psychiatry 2009;70:1206-1212.

2Amminger GP, Schäfer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, Mackinnon A, McGorry PD, Berger GE: Long-chain α-3 fatty acids for indicated prevention of psychotic disorders: A randomized, placebo-controlled trial. Arch Gen Psychiatry 2010;67:146-154.

3Pajonk FG, Wobrock T, Gruber O, Scherk H, Berner D, Kaizl I, Kierer A, Müller S, Oest M, Meyer T, Backens M, Schneider-Axmann T, Thornton AE, Honer WG, Falkai P: Hippocampal plasticity in response to exercise in schizophrenia. Arch Gen Psychiatry 2010;67:133-143.