Rates of 5 Common Antidepressant Side Effects Among New Adult and Adolescent Cases of Depression: A Retrospective US Claims Study



      Antidepressants are the first-line treatment for depression, yet medication-related side effects may be associated with antidepressant discontinuation before reaching a period of exposure believed to result in effectiveness. There is a gap in knowledge of the prevalence of side effects across commonly prescribed antidepressants and the effect of the type of antidepressant on the likelihood of side effects in real-world clinical practice.


      The aim of this study was to estimate and compare the prevalence of headaches, nausea or vomiting, agitation, sedation, and sexual dysfunction among patients diagnosed with depression who initiated monotherapy across different classes of antidepressants and to estimate the effect of the type of antidepressant on the likelihood of each of the 5 side effects.


      A retrospective cohort of patients aged ≥13 who were newly diagnosed with depression and began antidepressant monotherapy was created using LifeLink managed care claims from 1998 to 2008. Antidepressant groups included selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), bupropion, phenylpiperazine, and tetracyclic antidepressants. Prevalence of headache, nausea or vomiting, agitation, sedation, and sexual dysfunction were compared across antidepressant groups. Propensity-adjusted Cox proportional hazards regression was used to estimate the likelihood of each of the 5 side effects for each antidepressant group compared with SSRIs, adjusted for demographic, clinical, and treatment characteristics.


      The study cohort included 40,017 patients (3617 adolescents, aged 13–18 years, and 36,400 adults, aged ≥19 years; mean age = 45 years; 67% female) with a new episode of depression who were initiated on antidepressant monotherapy within 30 days of diagnosis (SSRI [66%], bupropion [14%], SNRI [12%], other [8%]). The most common side effects were headache (up to 17/1000 person-months of therapy in adults and adolescents) and nausea (up to 7.2/1000 in adults, 9.3/1000 in adolescents). Relative to adults receiving SSRIs, adults receiving SNRIs had a higher risk of nausea (hazard ratio [HR] = 1.26; 95%CI,1.05–1.51). Adults (HR = 0.78; 95% CI, 0.62–0.96) and adolescents (HR = 0.43; 95% CI, 0.21–0.87) taking bupropion were less likely to experience headaches compared with adults and adolescents, respectively, taking an SSRI. Adolescents receiving a tetracyclic were more likely to experience headaches than adolescents receiving an SSRI (HR = 3.16; 95%CI, 1.13–8.84).


      Prevalence and risk of the 5 side effects varied across types of antidepressants for both adults and adolescents. Results from this study were consistent with prior clinical trials, suggesting that variation in side effect profiles exists in a more generalized managed care population.

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        • Kessler R.C.
        • Walters E.E.
        Epidemiology of DSM-III-R major depression and minor depression among adolescents and young adults in the National Comorbidity Survey.
        Depress Anxiety. 1998; 7: 3-14
        • Kessler R.C.
        • Berglund P.
        • Demler O.
        • et al.
        The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).
        JAMA. 2003; 289: 3095-3105
        • Murray C.J.
        • Lopez A.D.
        Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study.
        Lancet. 1997; 349: 1436-1442
        • Glaser M.
        Annual Rx survey.
        Drug Topics. 1997; 141: 45-53
        • Barbui C.
        • Percudani M.
        • Barbui C.
        • Percudani M.
        Epidemiological impact of antidepressant and antipsychotic drugs on the general population.
        Curr Opin Psychiatry. 2006; 19: 405-410
        • Valuck R.
        Selective serotonin reuptake inhibitors: a class review.
        Pharmacy and Therapeutics. 2004; 29: 234-243
        • Libby A.M.
        • Orton H.D.
        • Valuck R.J.
        Persisting decline in depression treatment after FDA warnings.
        Arch Gen Psychiatry. 2009; 66: 633-639
        • Gartlehner G.
        • Hansen R.
        • Thieda P.
        • et al.
        Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Agency for Healthcare Research and Quality, Rockville, Md2007
        • Lin E.
        • Korff M.V.
        • Katon W.M.
        • et al.
        The role of the primary care physician in patients' adherence to antidepressant therapy.
        Med Care. 1995; 33: 67-74
        • Maddox J.C.
        • Levi M.
        • Thompson C.
        The compliance with antidepressants in general practice.
        J Psychopharmacol. 1994; 8: 48-52
        • Bull S.A.
        • Hu X.H.
        • Hunkeler E.M.
        • et al.
        Discontinuation of use and switching of antidepressants: influence of patient-physician communication.
        JAMA. 2002; 288: 1403-1409
        • Bondolfi G.
        • Aubry J.M.
        • Golaz J.
        • et al.
        A stepwise drug treatment algorithm to obtain complete remission in depression: a Geneva study.
        Swiss Med Wkly. 2006; 136: 78-85
        • Gartlehner G.
        • Hansen R.A.
        • Carey T.S.
        • et al.
        Discontinuation rates for selective serotonin reuptake inhibitors and other second-generation antidepressants in outpatients with major depressive disorder: a systematic review and meta-analysis.
        Int Clin Psychopharmacol. 2005; 20: 59-69
        • Goethe J.W.
        • Woolley S.B.
        • Cardoni A.A.
        • et al.
        Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.
        J Clin Psychopharmacol. 2007; 27: 451-458
        • Bull S.A.
        • Hunkeler E.M.
        • Lee J.Y.
        • et al.
        Discontinuing or switching selective serotonin-reuptake inhibitors.
        Ann Pharmacother. 2002; 36: 578-584
        • Kroenke K.
        • West S.L.
        • Swindle R.
        • et al.
        Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: A randomized trial.
        JAMA. 2001; 286: 2947-2955
        • Brambilla P.
        • Cipriani A.
        • Hotopf M.
        • Barbui C.
        Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and newer antidepressants: a meta-analysis of clinical trial data.
        Pharmacopsychiatry. 2005; 38: 69-77
        • Cipriani A.
        • Barbui C.
        • Brambilla P.
        • et al.
        Are all antidepressants really the same?.
        J Clin Psychiatry. 2006; 67: 850-864
        • MacGillivray S.
        • Arroll B.
        • Simon H.
        • et al.
        Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis.
        BMJ. 2003; 326: 1014-1017
        • Omori I.M.
        • Watanabe N.
        • Nakagawa A.
        • et al.
        Efficacy, tolerability and side-effect profile of fluvoxamine for major depression: meta-analysis.
        J Psychopharmacol. 2009; 23: 539-550
        • IMS Inc.
        LifeLink Health Plan Claims Data Users Guide & Data Dictionary.
        (Watertown, MA)September 2008
        • National Committee for Quality Assurance
        HEDIS Volume 2: Technical Specifications.
        National Committee for Quality Assurance, Washington, DC2004
        • Scholle S.H.
        NCQA behavioral health measurement efforts.
        J Manag Care Pharm. 2005; 11: S9-S11
        • Libby A.M.
        • Brent D.A.
        • Morrato E.H.
        • et al.
        Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs.
        Am J Psychiatry. 2007; 164: 884-891
        • Morrato E.H.
        • Dodd S.
        • Oderda G.
        • et al.
        Prevalence, utilization patterns, and predictors of antipsychotic polypharmacy: experience in a multistate Medicaid population, 1998–2003.
        Clin Ther. 2007; 29: 183-195
        • Valuck R.
        • Libby A.M.
        • Orton H.D.
        • et al.
        Spillover effects on treatment of adult depression in primary care after the FDA advisory on risk of pediatric suicidality with SSRIs.
        Am J Psychiatry. 2007; 164: 1198-1205
        • Sullivan P.W.
        • Valuck R.
        • Saseen J.
        • MacFall H.M.
        A comparison of the direct costs and cost effectiveness of serotonin reuptake inhibitors and associated adverse drug reactions.
        CNS Drugs. 2004; 18: 911-932
        • Malone D.
        • Billups S.
        • Valuck R.
        • Carter B.
        Development of a chronic disease indicator score using a Veterans Affairs Medical Center medication database.
        J Clin Epidemiol. 1999; 52: 551-557
        • Rosner B.
        Fundamental of Biostatistics.
        Brooks/Cole, Pacific Grove, Calif2000
        • Rosenbaum P.
        • Rubin D.
        Reducing bias in observational studies using subclassification on the propensity score.
        J Am Stat Assoc. 1984; 79: 516-524
        • Braitman L.E.
        • Rosenbaum P.R.
        Rare outcomes, common treatments: analytic strategies using propensity scores.
        Ann Intern Med. 2002; 137: 693-695
        • Collett D.
        Modeling Survival Data in Medical Research.
        Chapman & Hall, London, UK1994
        • Cipriani A.
        • Furukawa T.A.
        • Salanti G.
        • et al.
        Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis.
        Lancet. 2009; 373: 746-758
        • Rascati K.
        • Godley R.
        • Pham H.
        Evaluation of resources used to treat adverse events of selective serotonin reuptake inhibitor use.
        J Manag Care Pharm. 2001; 7: 402-406
        • Whooley M.A.
        • Simon G.E.
        Managing depression in medical outpatients.
        N Engl J Med. 2000; 343: 1942-1950
      1. Baciu A. Stratton K. Burke S. The Future of Drug Safety: Promoting and Protecting the Health of the Public. Institute of Medicine of the National Academies, National Academies Press, Washington, DC2006
      2. Public law 110-85: Food and Drug Administration Amendment Act of 2007.
        (Accessed January 11, 2011)
        • Nadkarni P.M.
        Drug safety surveillance using de-identified EMR and claims data: issues and challenges.
        J Am Med Inform Assoc. 2010; 17: 671-674