Use of antidepressant medication and risk of type 2 diabetes: Results from three cohorts of US adults

Department of Nutrition, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.
Diabetologia (Impact Factor: 6.67). 08/2011; 55(1):63-72. DOI: 10.1007/s00125-011-2268-4
Source: PubMed

ABSTRACT The results of several studies have suggested a potential positive association between use of antidepressant medication (ADM) and incident type 2 diabetes mellitus. We examined this association in three cohorts of US adults.
We followed 29,776 men in the Health Professionals Follow-up Study (HPFS, 1990-2006), 61,791 women in the Nurses' Health Study I (NHS I, 1996-2008) and 76,868 women in NHS II (1993-2005), who were free of diabetes mellitus, cardiovascular disease or cancer at baseline. The mean baseline ages for participants from the HPFS and NHS I and II were 56.4, 61.3 and 38.1 years, respectively. ADM use and other covariates were assessed at baseline and updated every 2 years. A time-dependent Cox proportional hazards model was used, and HRs were pooled together across the three cohorts.
During 1,644,679 person-years of follow-up, we documented 6,641 new cases of type 2 diabetes. ADM use was associated with an increased risk of diabetes in all three cohorts in age-adjusted models (pooled HR 1.68 [95% CI 1.27, 2.23]). The association was attenuated after adjustment for diabetes risk factors and histories of high cholesterol and hypertension (1.30 [1.14, 1.49]), and further attenuated by controlling for updated BMI (1.17 [1.09, 1.25]). Use of selective serotonin reuptake inhibitors and other antidepressants (mainly tricyclic antidepressants) were both associated with an elevated risk of diabetes, with pooled multivariate-adjusted HRs of 1.10 (1.00, 1.22) and 1.26 (1.11, 1.42), respectively.
The results suggest that ADM users had a moderately elevated risk of type 2 diabetes mellitus compared with non-users, even after adjustment for BMI.

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Available from: Michel Lucas, Sep 29, 2015
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    • "None of these studies included “no treatment” as a comparison group. It is possible that depression treatment may be delayed due to either competing demands of physical conditions [8-10] or watchful waiting due to adverse effects of antidepressants on incident diabetes and heart disease [11,12] or high rates of treatment failures and lack of robust evidence of depression treatment on chronic care outcomes [13,14]. In addition, the focus of these studies were on evaluating specific programs of collaborative care. "
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    ABSTRACT: Research on the impact of depression treatment on expenditures is nascent and shows results that vary from negative associations with healthcare expenditures to increased expenditures. However many of these studies did not include psychotherapy as part of the depression treatment. None of these studies included "no treatment" as a comparison group. In addition, no study has included a broad group of chronic physical conditions in studying depression treatment expenditures. We determined the association between depression treatment and short-term healthcare expenditures using a nationally representative sample of Medicare beneficiaries with chronic physical conditions and depression. In this retrospective cohort study, we examined the association between depression treatment in the baseline year and healthcare expenditures in the following year using data from 2000 through 2005 of the Medicare Current Beneficiary Survey (MCBS), a nationally representative survey of Medicare beneficiaries. Using the rotating panel design of MCBS, we derived five two-year cohorts: 2000--2001, 2001--2002, 2002--2003, 2003--2004, and 2004--2005. The study sample included 1,055 elderly Medicare beneficiaries aged 65 or over. We compared healthcare expenditures of no depression treatment group with depression treatment groups using t-tests. Linear regressions of log-transformed dollars were used to assess the relationship between depression treatment and healthcare expenditures after controlling for demographic, socio-economic, health status, lifestyle risk factors, year of observation and baseline expenditures. Compared to no depression treatment ($16,795), the average total expenditures were higher for those who used antidepressants only ($17,425) and those who used psychotherapy with or without antidepressants ($19,733). After controlling for the independent variables, antidepressant use and psychotherapy with or without antidepressants were associated with 20.2% (95% CI: 14.1-26.7%) and 29.4% (95% CI: 18.8-41.0%) increase in total expenditures, respectively. We observed that depression treatment was positively associated with inpatient, medical provider and prescription drug expenditures. Among the elderly Medicare beneficiaries with chronic physical conditions, depression treatment was associated with greater short-term healthcare expenditures. Future research needs to replicate these findings and also examine whether depression treatment reduces expenditures over a longer period of time.
    Journal of Negative Results in BioMedicine 10/2013; 12(1):15. DOI:10.1186/1477-5751-12-15 · 1.47 Impact Factor
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    • "Data from the Health Professionals Study (1990–2006), the Nurses’ Health Study (1996–2008), and Nurses’ Health Survey II (1993–2005) were pooled to assess the risk of diabetes associated with antidepressant use (26). These studies included 29,776 men and 138,659 women with a total of 1,644,679 person-years of follow-up. "
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    ABSTRACT: OBJECTIVE Antidepressant use has risen sharply over recent years. Recent concerns that antidepressants may adversely affect glucose metabolism require investigation. Our aim was to assess the risk of type 2 diabetes associated with antidepressants through a systematic review.RESEARCH DESIGN AND METHODS Data sources were MEDLINE, Embase, PsycINFO, The Cochrane Library, Web of Science, meeting abstracts of the European Association for the Study of Diabetes, American Diabetes Association, and Diabetes UK, Current Controlled Trials,, U.K. Clinical Research Network, scrutiny of bibliographies of retrieved articles, and contact with relevant experts. Relevant studies of antidepressant effects were included. Key outcomes were diabetes incidence and change in blood glucose (fasting and random).RESULTSThree systemic reviews and 22 studies met the inclusion criteria. Research designs included 1 case series and 21 observational studies comprising 4 cross-sectional, 5 case-control, and 12 cohort studies. There was evidence that antidepressant use is associated with type 2 diabetes. Causality is not established, but rather, the picture is confused, with some antidepressants linked to worsening glucose control, particularly with higher doses and longer duration, others linked with improved control, and yet more with mixed results. The more recent, larger studies, however, suggest a modest effect. Study quality was variable.CONCLUSIONS Although evidence exists that antidepressant use may be an independent risk factor for type 2 diabetes, long-term prospective studies of the effects of individual antidepressants rather than class effects are required. Heightened alertness to potential risks is necessary until these are complete.
    Diabetes care 10/2013; 36(10):3337-45. DOI:10.2337/dc13-0560 · 8.42 Impact Factor
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    • "All studies were published in the 2000s. The countries in which the studies had been conducted were as follows: the United States (n = 6),7,8,14,33-35) Netherlands (n = 1),11) the UK (n = 1),36) Finland (n = 1),9) Norway (n = 1),10) Australia (n = 1),37) and multiple countries (n = 1).13) We identified 15 eligible estimates from 3 nested case control articles,9,13,36) 6 retrospective cohort studies,8,10,11,14,33,35) and 3 prospective cohort studies.7,34,37) "
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    ABSTRACT: Epidemiologic studies have reported inconsistent findings regarding the association between the use of antidepressants and type 2 diabetes mellitus (DM) risk. We performed a meta-analysis to systematically assess the association between antidepressants and type 2 DM risk. We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library (through Dec 31, 2011), including references of qualifying articles. Studies concerning the use of tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), or other antidepressants and the associated risk of diabetes mellitus were included. Out of 2,934 screened articles, 3 case-control studies, 9 cohort studies, and no clinical trials were included in the final analyses. When all studies were pooled, use of antidepressants was significantly associated with an increased risk of DM in a random effect model (relative risk [RR], 1.49; 95% confidence interval [CI], 1.29 to 1.71). In subgroup analyses, the risk of DM increased among both SSRI users (RR, 1.35; 95% CI, 1.15 to 1.58) and TCA users (RR, 1.57; 95% CI, 1.26 to 1.96). The subgroup analyses were consistent with overall results regardless of study type, information source, country, duration of medication, or study quality. The subgroup results considering body weight, depression severity, and physical activity also showed a positive association (RR, 1.14; 95% CI, 1.01 to 1.28). A publication bias was observed in the selected studies (Egger's test, P for bias = 0.09). Our results suggest that the use of antidepressants is associated with an increased risk of DM.
    Korean Journal of Family Medicine 07/2013; 34(4):228-40. DOI:10.4082/kjfm.2013.34.4.228
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