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February 2010

Second-Generation Antipsychotics: New Information
Second-generation antipsychotics differ from each other, offering options for patients.

Cognitive Effects of Antipsychotic Drugs: Are All Created Equal?
First- and second-generation antipsychotics appear comparable in their ability to lessen cognitive dysfunction associated with schizophrenia.

In Brief
Long-acting Injectable Olanzapine Approved in US; High-potency Cannabis May Increase Risk of Psychosis

Olanzapine and Sertraline Combined for Psychotic Depression
In a short-term trial, sertraline (Zoloft and others) combined with olanzapine (Zyprexa) was more efficacious than olanzapine plus placebo for psychotic depression in both young and elderly patients.

In Brief

February 2010

The US Food and Drug Administration approved an extended-release injectable suspension preparation of olanzapine (Zyprexa Relprevv) on December 11, 2009, for the treatment of schizophrenia in adults. It is a long-acting atypical antipsychotic for deep intramuscular gluteal injection. We reviewed this formulation last March (BTP 2009;32:9-10), noting concerns about a post-injection delirium sedation syndrome (PDSS), which occurs in 1.4% of patients and may result from a partial injection of olanzapine directly into the blood stream. PDSS resembles an olanzapine overdose and may include sedation, dizziness, confusion, slurred speech, altered gait, weakness, seizures, and unconsciousness. Patients should be observed for 3 hours following every injection. Like other antipsychotics, long-acting injectable olanzapine carries the warning of increased risk of death in elderly patients with dementia-related psychosis.

Recently, two large prospective epidemiological studies reported that cannabis use may increase the risk of psychosis (Henquet C, et al. Schizophr Bull 2005;31:608-612; Moore TH, et al. Lancet 2007;370:319-328). Di Forti and colleagues in the United Kingdom postulated that frequency of use and the potency of cannabis used may be moderating factors in this risk (Br J Psychiatry 2009;195:488-491). They compared cannabis use among 280 patients with a first episode of psychosis with 174 healthy controls. There was no statistically significant difference between the groups in whether they had ever taken cannabis or the age at first use. However, patients with psychosis were more likely to be current daily users and to have smoked cannabis for more than 5 years. In addition, among those who used cannabis, 78% of the cases group used high-potency cannabis compared with 37% of the control group. The main psychoactive component of cannabis is Δ9-tetrahydrocannabinol (Δ9-THC). Patients with a first episode of psychosis preferentially used the sinsemilla preparation of cannabis, which is estimated to contain between 12% and 18% Δ9-THC. By contrast, those in the control group were more likely to consume resin, which has an average Δ9-THC concentration of 3.4%. The authors conclude that these findings support the hypothesis that Δ9-THC is the active ingredient increasing the risk of psychosis and that potency and frequency may interact in further elevating the risk.

Heather S. Hopkins