How antipsychotics work: The patients’ perspective Romina Mizrahi, R. Michael Bagby, Robert B. Zipursky, Shitij Kapur * Centre for Addiction and Mental Health-CAMH, Toronto, Ontario, Canada M5T 1R8 Department of Psychiatry, Faculty of Medicine, University of Toronto, Canada Accepted 1 March 2005 Available online 23 May 2005 Abstract Background: While much is known about the neuropharmacology and objective efficacy of antipsychotics, little is known about how these drugs act on psychosis from the patients’ perspective. Most previous studies of the patient’s perspective have focused on drug tolerability and acceptability—rather than their effects on psychosis per se. Methods: The authors examined how antipsychotics work from a patient’s perspective by analyzing their responses to a subjective questionnaire. Ninety-one patients with schizophrenia (cross-sectional component) and eight neuroleptic naı ¨ve patients (before and after treatment, longitudinal component) participated. The patients’ responses to the questionnaire were analyzed using Principal Component Analysis (PCA) and general linear models. Results: Analysis of the patients’ responses showed that from their perspective the drugs were substantially more effective in: ‘‘help deal, help stop thinking, and make the symptoms not bother’’ rather than ‘‘take away’’ or ‘‘change my mind’’. This differentiation was clear in the raw data and was supported by a formal PCA. Two underlying factors – the first termed detachment and second eradication –explained 71% of the variance in the patients’ perspective on how antipsychotics work for them. Neuroleptic naı ¨ve patients, who had no prior exposure, expected drugs to help with both detachment and eradication, but, changed their mind with just 6 weeks of experience with the medications. Conclusions: From the patients’ perspective the action of antipsychotics is best characterized by a detachment from symptoms—rather than an eradication or elimination of symptoms. They have more wide-ranging expectations prior to antipsychotic exposure, but, even 6 weeks of exposure is sufficient to change their mind in favor of detachment. This finding is consistent with some of the very earliest ideas that antipsychotics produced a state of ‘‘indifference’’ and is also consistent with the more recent, neurobiologically informed notions that antipsychotics work by dampening the salience of psychotic symptoms. D 2005 Elsevier Inc. All rights reserved. Keywords: Antipsychotics; Mechanism of action; Patient’s perspective 1. Introduction Since the serendipitous discovery of chlorpromazine almost half a century ago, advances in psychopharmacology, cognitive neuroscience and functional brain imaging techni- ques have allowed us to probe deeper into the objective actions of antipsychotic drugs. Studies at a neuropharmaco- logical level have implicated a critical role for the dopamine system, though other receptors have also been implicated (Kapur and Mamo, 2003; Kapur and Seeman, 2001; Meltzer, 1999). Cognitive explanations have focussed on the action of the drugs on information processing or cognitive processes such as sensory motor gating (Geyer et al., 2001; Goldberg and Weinberger, 1996; Kumari and Sharma, 2002; Oranje et al., 2002; Stip, 1996). In addition, neuroimaging studies have drawn attention to the receptors where the drugs act and the regions where they change metabolism (Adolphs, 2003; Farde et al., 1988; Kapur et al., 2000; Nordstrom et al., 1993). 0278-5846/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2005.03.001 Abbreviations: ANT, attitudes towards medication treatment; DAI, Drugs Attitude Inventory; MARS, the Medication Adherence Rating Scale; M.I.N.I., Mini-International Neuropsychiatric Interview; PANSS, Positive and Negative Syndrome Scale; PCA, Principal Component Analysis; PETiT, Personal Evaluations of Transitions in Treatment; IQ, intelligence quotient; WAIS, Wechsler Adult Intelligence Scale. * Corresponding author. Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada M5S 2S1. Tel.: +1 416 979 6890; fax: +1 416 260 4206. E-mail address: shitij _ kapur@camh.net (S. Kapur). Progress in Neuro-Psychopharmacology & Biological Psychiatry 29 (2005) 859 – 864 www.elsevier.com/locate/pnpbp