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.

Long-Acting Injectable Risperidone Often Discontinued

July 2010

Soon after antipsychotic drugs were introduced in the 1950s, it became apparent that many patients who required long-term treatment with these agents stopped taking them and lost any benefit they may have experienced. Years later, fluphenazine (Prolixin and others) and then haloperidol (Haldol and others) became available in long-acting injectable preparations. Ostensibly, this mode of delivery would enhance adherence to antipsychotic regimens by freeing patients from having to take medication by mouth every day. Among second-generation antipsychotics, risperidone (Risperdal and others), paliperidone (Invega), and olanzapine (Zyprexa) are now available in long-acting injectable preparations (marketed in the United States as Risperdal Consta, Invega Sustenna, and Zyprexa Relprevv, respectively).

Long-acting injectable risperidone (LAIR) entered the market in 2003. Clinicians hoped it would simultaneously provide the benefits associated with second-generation antipsychotics and the advantages of an assured-delivery system that required an injection only once every few weeks. Mohamed and coauthors recently examined LAIR treatment length for patients with schizophrenia in the Department of Veterans Affairs (VA) health care system throughout the United States.1

Researchers evaluated the records of almost 12,000 patients diagnosed with schizophrenia who had new prescriptions for antipsychotic medications within the first 2 months of fiscal year 2006. Clozapine (Clozaril and others) looked best overall for continued treatment. It had the lowest termination rate in the first 30 days, while LAIR had the highest. Over the course of a year, 84.8% of clozapine patients were still receiving prescriptions for it versus a 1-year continuation rate of 54.3% for the 280 patients who were prescribed LAIR (the third lowest), and only 33.4% for patients prescribed aripiprazole (Abilify). At 18 to 24 months, clozapine still had the best continuation rate with 77.1%, aripiprazole had the worst (27.7%), and LAIR was the third lowest (44.6%). Oral first-generation antipsychotics had an 18-to-24-month continuation rate of 57.9%; olanzapine, 55.0%; and oral risperidone, 49.5%. Ziprasidone (Geodon) had no statistically significant difference in likelihood of discontinuation compared with LAIR.

Why did clozapine have such a low discontinuation rate? Patients obviously dislike the need for regular blood tests. Yet a majority of these VA patients apparently felt that clozapine's advantages outweighed its disadvantages.

And why was discontinuation so common with LAIR? Dr Mohamed's group acknowledges that the cohort of patients treated with LAIR may be those who are more likely to discontinue medications or drop out of treatment prematurely, which conceivably could have biased the data. Nonetheless, it is clear that if patients (or family members) don't like a treatment, they will probably discontinue it. Finding a proper role for long-acting antipsychotics, including risperidone, remains a work in progress.

1Mohamed S, Rosenheck R, Harpaz-Rotem I, Leslie D, Sernyak MJ: Duration of pharmacotherapy with long-acting injectable risperidone in the treatment of schizophrenia. Psychiatr Q 2009;80:241-249.