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To the Editor: Although the efficacy of antipsychotic drugs for the treatment of psychotic disorders is well established, there is still considerable debate about how these drugs should be dosed. Numerous considerations must be made in decisions about dosage, including the patient's mental status, medical history, age, concurrent medications, smoking status, and tolerance for side effects (1). Guidelines are therefore necessarily broad and largely at the discretion of the prescriber.

In a recent study of dosing in a heterogeneous psychiatric outpatient population (2), we observed that 32% of patients were treated with antipsychotics at dosages classified as “excessive,” because they exceeded by 1.5 times the designated daily dose (DDD) defined by the World Health Organization. To better understand this potential concern, we compared dosing of patients treated by psychiatrists and those treated by general practitioners, because these professionals may differ in their dosing strategies (3). We therefore expanded our analysis to compare prescription patterns of the two groups, as well as characteristics of the prescribers themselves. The patient population and methods were described previously (2); the protocol was approved by the University of British Columbia Research Ethics Board. A total of 406 patients, who provided written informed consent, were recruited from community mental health teams in Vancouver, British Columbia, between October 2005 and October 2006. Antipsychotic dosing was compared by converting to chlorpromazine equivalent (CE) doses, because we have shown that DDDs are unreliable predictors of extrapyramidal symptoms (4). Data about prescribers were obtained through the British Columbia Medical Association. Statistical analyses included chi square tests and analysis of variance.

A total of 323 patients (164 men and 159 women) were prescribed antipsychotics by a psychiatrist, and 83 were prescribed these agents by a general practitioner. The two patient groups did not differ by sex or psychiatric diagnosis. Mean±SD ages indicated that the group treated by a psychiatrist was older by three years (49.4±12.4 and 46.3±10.4, respectively, p<.05). The types of antipsychotic medication prescribed were similar between groups, with the exception of clozapine; psychiatrists were more than eight times as likely as general practitioners to prescribe this drug (9.9% and 1.2%, p<.01). Notably, dosing was significantly greater for patients treated by a general practitioner than by a psychiatrist (CE=212±14 mg versus 167±7 mg, p<.05). A possible corollary of this was that use of anticholinergic agents (a proxy for extrapyramidal symptoms) was almost twice as high among patients treated by a general practitioner (24% and 13%, p<.01).

Characteristics of the prescribers themselves (N=76) were examined. Compared with psychiatrist prescribers, the general practitioner prescribers were more likely to have completed their medical degree locally within the province (p<.001) and five years earlier (p<.005). None of the general practitioners in the study was a physician with a university affiliation, compared with 49% of the psychiatrists (p<.001).

The reasons for the difference in excessive dosing between the prescriber groups are uncertain; however, excessive dosing is associated with less awareness of drug treatment algorithms among prescribers and lower adherence to them (5). Further study is therefore needed to determine whether these or similar factors account for higher antipsychotic drug dosing by general practitioners.

Dr. Barr is affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics and the other authors are with the Department of Psychiatry, all at the Faculty of Medicine, University of British Columbia, Vancouver, Canada.

Acknowledgments and disclosures

This research was supported by a grant from the Canadian Institutes of Health Research. The authors thank Joy Johnson and Johnny Su for assistance.

Dr. Honer has received research funds from, acted as a consultant to, or served on an advisory board for Pfizer, AstraZeneca, Janssen, Novartis, and Insilico. Dr. Procyshyn has served on advisory boards for Pfizer, AstraZeneca, Janssen, and Bristol-Myers Squibb. The other authors report no competing interests.

References

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2 Procyshyn RM , Honer WG , Wu TK , et al.: Persistent antipsychotic polypharmacy and excessive dosing in the community psychiatric treatment setting: a review of medication profiles in 435 Canadian outpatients. Journal of Clinical Psychiatry 71:566–573, 2010 Crossref, MedlineGoogle Scholar

3 Hartung DM , Wisdom JP , Pollack DA , et al.: Patterns of atypical antipsychotic subtherapeutic dosing among Oregon Medicaid patients. Journal of Clinical Psychiatry 69:1540–1547, 2008 Crossref, MedlineGoogle Scholar

4 Barr AM , Honer WG , Johnson JL , et al.: A comparison of antipsychotic drug-defined daily doses versus chlorpromazine equivalent doses in patients with or without extrapyramidal motor symptoms. Journal of Clinical Psychopharmacology 30:741–743, 2011 CrossrefGoogle Scholar

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