Abstract
Tardive dyskinesia (TD) may occur in never-medicated patients with psychotic illness, indicating the existence of non-medication, possibly disease-related, causes. We tested the hypothesis that, independent of the antipsychotic-induced rise in prolactin, the incidence of TD would be associated with the incidence of prolactin-related sexual disturbances (PRSD), which would be suggestive of a common pathology involving multiple dopamine tracts. Simple, global measures of TD and PRSD (loss of libido, amenorrhea, gynaecomastia, impotence, and galactorrhea) were rated in a prospective, observational European Health Outcomes Study (SOHO). New onset of TD and new onset of PRSD at 3, 6, and 12 months was analyzed in a risk set of 4263 patients using a Cox proportional hazard model yielding adjusted hazard ratios (aHR). Incidence of TD was significantly and linearly comorbid with the incidence of PRSD in both men and women. Compared to those with no PRSD, the risk for TD was 2.0 (95% CI: 1.1, 3.7) with one PRSD, 2.4 (95% CI: 1.3, 4.5) with two PRSD, and 3.6 (95% CI: 1.1, 11.8) with three PRSD. Associations were stronger in those who only had received prolactin-sparing medications (aHR per unit PRSD increase=2.0, 95% CI: 1.2, 3.3) than in those who only had received prolactin-raising medications (aHR=1.3, 95% CI: 0.9, 1.9). In people with schizophrenia, TD and PRSD show comorbidities that are independent of antipsychotic-induced alterations in plasma prolactin. This may suggest a shared, pandopaminergic pathological mechanism associated with schizophrenia itself, rather than only a medication effect.
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Acknowledgements
The SOHO study has the financial support of Eli Lilly and Company Limited. DE Tenback was formerly employed by Eli Lilly and Company. The study was an initiative of Eli Lilly, and designed with the help of an international panel of experts in the area of psychosis. Although Eli Lilly did have input into the design and conduct of the study, it did not have any input in the analysis or reporting of the current analyses. The authors had unlimited access to the data. The views expressed are the authors' own. We thank the SOHO study group for their contributions.
The SOHO Study Group: Jean-Pierre Lepine, Hôpital Fernand Widal, Paris, France; Martin Knapp, LSE Health and Social Care, London School of Economics, Centre for the Economics of Mental Health, Institute of Psychiatry, London, UK; Isabelle Gasquet, Hopital Paul Brousse, Villejuif, France; Jordi Alonso, Health Services Research Unit, Institut Municipal d'Investigacio Medica, University of Barcelona, Barcelona, Spain; Josep Maria Haro, Research and Development Unit, Sant Joan de Déu-SSM, St Boi, Barcelona, Spain; Cees J Slooff, Department of Psychotic Disorders, Mental Health Centre Drenthe, Assen, The Netherlands.
Disclosure of competing interest: Diederik Tenback is a member of the Dutch advisory board for Lilly and Bristol-Myers Squibb (BMS) and a former employee of Eli Lilly and Company (Lilly). He received research support from Lilly. Peter van Harten is a speaker for Lilly, Pfizer Inc (Pfizer), AstraZeneca and Janssen-Cilag. Cees Slooff is a speaker or member of the Dutch advisory board for Lilly and BMS. Jim van Os is a speaker or member of the advisory board for Lilly, BMS, Janssen-Cilag and AstraZeneca. He received grant or research support from Lilly, GSK, BMS and AstraZeneca. Jean-Pierre Lepine is a speaker or member of the advisory board for Lilly, GlaxoSmithKline Inc. (GSK), Pfizer, Pierre Fabre Laboratories and Wyeth. He received grant or research support from Lilly, GSK and Pfizer. Martin Knapp has no financial interests to disclose.
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Tenback, D., van Harten, P., Slooff, C. et al. Tardive Dyskinesia in Schizophrenia is Associated with Prolactin-Related Sexual Disturbances. Neuropsychopharmacol 31, 1832–1837 (2006). https://doi.org/10.1038/sj.npp.1301044
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DOI: https://doi.org/10.1038/sj.npp.1301044
