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Antidepressant Use and Mortality in Finland Antidepressant use and mortality in Finland: a register-linkage study from a nationwide cohort Jari Haukka, Martti Arffman, Timo Partonen, Sinikka Sihvo, Marko Elovainio, Jari Tiihonen, Jouko Lönnqvist, Ilmo Keskimäki To cite this version: Jari Haukka, Martti Arffman, Timo Partonen, Sinikka Sihvo, Marko Elovainio, et al.. Antidepressant use and mortality in Finland: a register-linkage study from a nationwide cohort. European Journal of Clinical Pharmacology, Springer Verlag, 2009, 65 (7), pp.715-720. 10.1007/s00228-009-0616-9. hal-00534942 HAL Id: hal-00534942 https://hal.archives-ouvertes.fr/hal-00534942 Submitted on 11 Nov 2010 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Eur J Clin Pharmacol (2009) 65:715–720 DOI 10.1007/s00228-009-0616-9 PHARMACOEPIDEMIOLOGY AND PRESCRIPTION Antidepressant use and mortality in Finland: a register-linkage study from a nationwide cohort Jari Haukka & Martti Arffman & Timo Partonen & Sinikka Sihvo & Marko Elovainio & Jari Tiihonen & Jouko Lönnqvist & Ilmo Keskimäki Received: 8 September 2008 /Accepted: 8 January 2009 /Published online: 5 March 2009 # Springer-Verlag 2009 Abstract Findings Current AD use was associated with a lowered Background It is generally acknowledged that depressed all-cause mortality (RR=0.18, 95% CI=0.18–0.19) com- patients need specific attention during the first weeks after pared with those who filled one previous prescription only. initiation of antidepressant (AD) treatment because of the There was no difference in suicide mortality when any increased risk of suicide. current antidepressant usage was compared to the one- Methods The study population consisted of all individuals prescription group. Current SSRI usage was associated with residing in Finland from 1999 to 2003 who had purchased a lower risk of suicide compared to the one-prescription or prescribed antidepressant at least once but had no preceding other antidepressant groups (RR 0.47, 0.38–0.59). antidepressant prescription. Data sources were the National Interpretation Current AD treatment is associated with Prescription Register, the Causes of Death Register, Census decreased all-cause mortality rates in patients who have Data of Statistics Finland, and the National Care Register. ever had AD treatment. Follow-up started at the first purchase and ended at the end of 2003 or death. Data on prescriptions were used to Keywords Antidepressant . Suicide . Mortality . SSRI construct contiguous treatment periods of follow-up time. Life-table analysis with Poisson regression was used to estimate risk ratios (RR) of antidepressant use with respect Introduction to all-cause mortality and to deaths from suicide. It is acknowledged that depressed patients should be monitored intensively during the first weeks after initiation of antidepressant (AD) treatment because of temporarily increased risk of suicide [1]. However, the temporal * : : : : J. Haukka ( :) M. Arffman: T. Partonen S. Sihvo evolution of mortality and suicide risk after discontinuation M. Elovainio J. Lönnqvist I. Keskimäki of AD treatment remains unknown. Based on ecological National Institute for Health and Welfare, Helsinki, Finland evidence, the increased use of AD and especially of e-mail: [email protected] selective serotonin re-uptake inhibitors (SSRI) is associated M. Arffman with decreased rate of suicides [2–6]. e-mail: [email protected] Still, concerns have been raised about the potential connection between antidepressant use and suicidal behav- J. Tiihonen ior. This has been studied using meta-analysis, case-control Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, studies, ecological studies, and observational cohort stud- Kuopio, Finland ies. A meta-analysis based on drug company data from placebo-controlled, randomized trials indicated that in- J. Lönnqvist creased risk of suicide and self-harm caused by SSRIs Department of Psychiatry, University of Helsinki and Helsinki University Central Hospital, cannot be ruled out [7], but on the other hand analysis of Helsinki, Finland FDA reports showed no difference in suicide risk between 716 Eur J Clin Pharmacol (2009) 65:715–720 antidepressant-treated and placebo-treated depressed sub- purchased from a pharmacy are registered by the Social jects in controlled trials [8]. Insurance Institution. The linking of these registers is A retrospective cohort study with a total of 57,361 possible because every individual residing in Finland has patients and follow-up time of 120 days concluded that the a unique personal identification number. observed connection between suicidal behavior and pre- Construction of the study population began by identify- scription of SSRIs is due to confounding by indication [9]. ing all people who had reimbursed antidepressant prescrip- UK General Practice Research Database (GPRD) was used tions from 1999 to 2003, using the database of the National in a matched case-control study that compared risk of Social Insurance Institution. The study population consists suicidal behavior among users of four antidepressant drugs of new antidepressant users and hence patients with [10]. In a nested case-control study, the adjusted odds ratio antidepressant purchases in the preceding 5 years were of suicide was 0.57 [95% confidence interval (95% CI) excluded. Prescription data contained the personal identifi- 0.26–1.25] in people prescribed SSRIs compared with those cation number, date of purchase, anatomic therapeutic code prescribed tricyclic antidepressants [11]. In a case-control (ATC), and amount purchased as defined daily doses study of an elderly population (66 years and older) in (DDD) [20]. Prescription data also included information Canada, SSRI therapy was associated with increased risk of on all antipsychotic drug (ATC code N05) prescriptions, suicide during the month following its initiation [12]. In an while data on prescriptions during the 5 previous years ecological study of association between use of antidepres- were used as background variable. sants and suicide rate in Finland, increased use of Statistics Finland provided socioeconomic background antidepressants was associated with a decline in suicide variables for the study population by record linkage using rate [13]. Similarly, the fall in suicide rates in Norway was the unique personal identification numbers. The following associated with the increased sales of non-TCA antidepres- background variables were used in analyses: sex, age at sants [14]. An aggregated data analysis of National Vital the beginning of follow-up (10–14, 15–19, 20–29, 30–39, Statistics from the U.S. Centers for Disease Control and 40–49, 50–59, 60–69, 70–79, and over 80 years), socio- Prevention showed that a higher number of tricyclic economic status (non-manual employee, manual employee, antidepressants (TCA) was associated with higher suicide farmer, other entrepreneur, student, other, or unknown), rates compared with SSRI use [15]. marital status (married, other), employment status An observational, individual-level register linkage study (employed, 0–6 months unemployed, 7–12 months unem- of 15,390 patients with previous attempted suicide showed ployed, retired, or other outside of workforce), education that treatment of any antidepressant was associated with level (basic level, secondary or higher), family net income increased risk of attempted suicide and, at the same time, quintile, living alone (yes, no), time since start of follow-up decreased risk of completed suicide and death [16]. A recent (first antidepressant prescription in days), and calendar year study based on the GPRD with 219,088 patients concluded (1999–2003). that there is excess risk of suicide associated with use of In addition, information on hospitalizations was obtained venlafaxine, which is probably due to the higher burden of from the Care Register for Health. The following dichot- suicide risk among venlafaxine users [17]. A register-based omous variables for each individual were constructed, study from Denmark showed lower rate of suicides for those based on hospitalizations during the previous 5 years: who continued antidepressant use compared to those who hospital-treated attempted suicide, alcohol-dependence di- purchased once (rate ratio 0.31, 95% CI 0.26–0.36) [18]. On agnosis (ICD-10 starting with F1), schizophrenia, schizo- the other hand, a longitudinal register study from Finland typal and delusional disorder (F2), mood disorder (F3), and demonstrated that lower socio-economic groups received the personality disorder (F6). Causes and date of death were lowest levels of treatment despite evidence of their increased obtained from the Causes of Death Register of Statistics prevalence of depression and suicide [19]. Finland. Cause of death was classified as suicide (ICD-10 The aim of this study was to investigate, in a nation-wide X60*-X84) or all other causes. Follow-up of the individual cohort of antidepressant users, how the risk of suicide and was started at the first purchase of antidepressant medica- all-cause
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