Side-effects of antipsychotic medication and health-related quality of life in schizophrenia Introduction Side-effects are a crucial component of drug acceptability and adherence. The methodological problems involved in identifying them are consid- erable but rarely taken into account. There are two key issues concerning the identification of drug- related side-effects – the attribution of particular manifestations to the drug in question, and the standing of reported ÔsubjectiveÕ side-effects. The attribution of side-effects to a drug is associated with a number of problems and biases. In clinical practice, five sources of difficulty can be identified: the patient, the disease, the drug, the doctor and the available data on the drugÕs side- effect profile. Each of these potential problems and Bebbington PE, Angermeyer M, Azorin J-M, Marwaha S, Marteau F, Toumi M. Side-effects of antipsychotic medication and health-related quality of life in schizophrenia. Objective: This analysis used data from the large (n = 1208) European Schizophrenia Cohort to examine the association between subjective side-effects of antipsychotic medication and the Mental and Physical Composite Scores (MCS; PCS) of the SF-36 scale. Method: Relationships between the subjective evaluation of side- effects identified from the Subjective Side-Effects Scale and the adjusted mean score on the PCS and MCS were examined. Where appropriate, these associations of subjective side-effects were compared with those of the same side-effects measured objectively. Results: In this study, subjective side-effects of antipsychotic medication were linked either to both the PCS and the MCS or, in a few instances, to neither. Subjective evaluations of sexual side-effects were associated only with the MCS, those of sialorrhoea only with the PCS. Objective ratings of extrapyramidal side-effects were related neither to PCS nor to MCS. Conclusion: These data suggest that side-effects, whether subjective or objective, may need to be considered individually in relation to their impact on quality of life. P. E. Bebbington 1 , M. Angermeyer 2 , J.-M. Azorin 3 , S. Marwaha 4 , F. Marteau 5 , M. Toumi 6 1 Department of Mental Health Sciences, UCL, London, UK, 2 Department of Psychiatry, University of Leipzig, Leipzig, Germany, 3 SHU Psychiatrie Adultes, Hôpital Sainte Marguerite, Marseille, France, 4 Department of Mental Health Sciences, University College London, London, UK, 5 Global Outcomes and HTA Management, Lundbeck SAS, Paris, France and 6 Department MA2D, University of Lyon I, Lyon, France Key words: schizophrenia; quality of life; side-effects Paul Bebbington, Department of Mental Health Sciences, UCL, 67–73 Riding House Street, 2nd Floor, Charles Bell House, London W1W 7EJ, UK. E-mail: p.bebbington@ucl.ac.uk Significant outcomes • In this study, subjective evaluations of the side-effects of antipsychotic medication tended to be associated with both physical and mental components of quality of life, or with neither. • Sexual side-effects were associated only with the Mental Composite Scores (MCS), sialorrhoea only with the Physical Composite Scores (PCS). Weight gain was not associated with either the PCS or the MCS. • Individual side-effects of medication cannot be assumed to affect patient quality of life; they must be assessed separately for their impact on physical and mental aspects of quality of life. Limitations • The use of baseline data cannot examine effects over time or permit causal inference. • Multivariate analyses were conducted on a dataset restricted by missing data. Acta Psychiatr Scand 2009: 119 (Suppl. 438): 22–28 All rights reserved DOI: 10.1111/j.1600-0447.2008.01310.x Copyright Ó 2008 The Authors Journal Compilation Ó 2008 Blackwell Munksgaard ACTA PSYCHIATRICA SCANDINAVICA 22