An evaluation of the anti-aggressive effects of olanzapine in chronic psychotic patients

Context

Recent studies have demonstrated that clozapine (CLZ), a novel antipsychotic, effectively reduces aggressive and violent behavior in patients with schizophrenia. However, the exact neurobiology of aggression remains unclear. Several receptor systems have been linked with violence, in particular serotonergic and noradrenergic. The selective effects of clozapine on serotonin and noradrenaline (or dopamine) receptors may partially explain its anti-aggressive properties.

Olanzapine (OLZ) shares a similar pharmacology with clozapine. Both are potent antagonists of 5-HT2A, 2C, 3, 6. In contrast, these agents have different affinities for the 5-HT7 receptors, with olanzapine being less potent. At dopamine receptors, namely D1-4 , olanzapine is consistently more potent than clozapine. Olanzapine is less potent at a-adrenergic receptors. The clinical impact of these pharmacologic similarities and differences has not yet been evaluated with respect to aggression and violence among patients with chronic psychotic disorders.

Objectives

To determine if OLZ  effectively reduces aggressive or violent behavior in patients suffering from chronic psychotic disorders.

Setting

A Canadian psychiatric care teaching hospital.

Design

This was a retrospective, mirror image chart review.  Sixty-five inpatients of the Nova Scotia Hospital’s Rehabilitation and Forensic units, diagnosed with a chronic psychotic disorder, who had received OLZ therapy for >30 days were selected. Time spent in seclusion, prn medication use and behavioral problems were recorded over six months prior to and seven months following the initiation of OLZ treatment.  Time spent in seclusion was the primary endpoint. Similar data were collected from 30 patients treated with CLZ for >30 days as a means to validate our methods and results.

Main Outcome Measures

The primary endpoint was the time the patients spent in seclusion.

Results

Time spent in seclusion decreased non-significantly by 10.5 ± 56.3 hours/30 days (n=33, p=0.14) after starting OLZ therapy. There was a significant improvement in non-compliance (-0.77 ± 2.53 incidents/30 days, n=65, p=0.02), use of prn benzodiazepines (-35.90 ± 141.51 mg equivalents/30 days, n=65, p=0.045), use of prn chloral hydrate (-537.21 ± 2057.89 mg chloral hydrate/30 days, n=65, p=0.04), overall prn medication use (-3.24 ± 7.75 days prn given/30days, n=57, p=0.004), and overall behavioral incidents (-10.76 ± 9.45, n=65, p=0.026). The reduction in agitation (-6.30 ± 25.63 incidents/30 days, p=0.052, n=65) and verbal aggression (-1.57 ± 6.54 incidents/30 days, p=0.057, n=65) with OLZ treatment trended towards significance. Findings of reduced seclusion time, prn medication use and behavioural incidents with CLZ were consistent with findings of other investigators and provide validation for our methods.

Conclusions

Switching to OLZ was associated with a significant reduction in overall behavior problems, and specifically non-compliance.  PRN benzodiazepine and overall prn medication use also decreased significantly. Time spent in seclusion, agitation and physical aggression decreased non-significantly. Major limitations include regression to the mean bias and uncertainty around point estimates related to the small sample.  As far as we are aware this is the first specific examination of the anti-aggressive effects of OLZ in chronic psychosis, other than through sub-factor analysis of the Positive and Negative Symptoms Scale in prospective RCTs. This information is complementary as it reflects real-world use of OLZ in this population. Similar studies to ours that address the anti-aggressive effects of CLZ have been published.

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