Medication for Attention-Deficit/Hyperactivity Disorder and Risk for Depression: A Nationwide Longitudinal Cohort Study

Published:February 23, 2016DOI:



      Attention-deficit/hyperactivity disorder (ADHD) is associated with high rates of psychiatric comorbidity, including depression. However, it is unclear whether ADHD medication increases or decreases the risk for depression.


      We studied all individuals with a diagnosis of ADHD born between 1960 and 1998 in Sweden (N = 38,752). We obtained data for prescription of ADHD medication, diagnosis of depression and other psychiatric disorders, and sociodemographic factors from population-based registers. The association between ADHD medication and depression was estimated with Cox proportional hazards regression.


      After adjustment for sociodemographic and clinical confounders, ADHD medication was associated with a reduced long-term risk (i.e., 3 years later) for depression (hazard ratio = 0.58; 95% confidence interval, 0.51–0.67). The risk was lower for longer duration of ADHD medication. Also, ADHD medication was associated with reduced rates of concurrent depression; within-individual analysis suggested that occurrence of depression was 20% less common during periods when patients received ADHD medication compared with periods when they did not (hazard ratio = 0.80; 95% confidence interval, 0.70–0.92).


      Our study suggests that ADHD medication does not increase the risk of later depression; rather, medication was associated with a reduced risk for subsequent and concurrent depression.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Faraone S.V.
        • Sergeant J.
        • Gillberg C.
        • Biederman J.
        The worldwide prevalence of ADHD: Is it an American condition?.
        World Psychiatry. 2003; 2: 104-113
        • Pliszka S.R.
        Comorbidity of attention-deficit/hyperactivity disorder with psychiatric disorder: An overview.
        J Clin Psychiatry. 1998; 59: 50-58
        • Angold A.
        • Costello E.J.
        • Erkanli A.
        J Child Psychol Psychiatry. 1999; 40: 57-87
        • Barkley R.A.
        Major life activity and health outcomes associated with attention-deficit/hyperactivity disorder.
        J Clin Psychiatry. 2002; 63: 10-15
        • Dalsgaard S.
        • Ostergaard S.D.
        • Leckman J.F.
        • Mortensen P.B.
        • Pedersen M.G.
        Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: A nationwide cohort study.
        Lancet. 2015; 385: 2190-2196
        • Daviss W.B.
        A review of co-morbid depression in pediatric ADHD: Etiology, phenomenology, and treatment.
        J Child Adolesc Psychopharmacol. 2008; 18: 565-571
        • Daviss W.B.
        • Birmaher B.
        • Diler R.S.
        • Mintz J.
        Does pharmacotherapy for attention-deficit/hyperactivity disorder predict risk of later major depression?.
        J Child Adolesc Psychopharmacol. 2008; 18: 257-264
        • Waxmonsky J.
        Assessment and treatment of attention deficit hyperactivity disorder in children with comorbid psychiatric illness.
        Curr Opin Pediatr. 2003; 15: 476-482
        • Chirdkiatgumchai V.
        • Xiao H.
        • Fredstrom B.K.
        • Adams R.E.
        • Epstein J.N.
        • Shah S.S.
        • et al.
        National trends in psychotropic medication use in young children: 1994-2009.
        Pediatrics. 2013; 132: 615-623
        • Bolanos C.A.
        • Barrot M.
        • Berton O.
        • Wallace-Black D.
        • Nestler E.J.
        Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood.
        Biol Psychiatry. 2003; 54: 1317-1329
        • Carlezon Jr, W.A.
        • Mague S.D.
        • Andersen S.L.
        Enduring behavioral effects of early exposure to methylphenidate in rats.
        Biol Psychiatry. 2003; 54: 1330-1337
        • van der Marel K.
        • Bouet V.
        • Meerhoff G.F.
        • Freret T.
        • Boulouard M.
        • Dauphin F.
        • et al.
        Effects of long-term methylphenidate treatment in adolescent and adult rats on hippocampal shape, functional connectivity and adult neurogenesis.
        Neuroscience. 2015; 309: 243-258
        • Lafay-Chebassier C.
        • Chavant F.
        • Favreliere S.
        • Pizzoglio V.
        • Perault-Pochat M.C.
        • French Association of Regional Pharmacovigilance Centers
        Drug-induced depression: A case/non case study in the French Pharmacovigilance Database.
        Therapie. 2015; 70: 425-432
        • Kim J.
        • Kim M.
        • Ha J.H.
        • Jang J.
        • Hwang M.
        • Lee B.K.
        • et al.
        Signal detection of methylphenidate by comparing a spontaneous reporting database with a claims database.
        Regul Toxicol Pharmacol. 2011; 61: 154-160
        • Biederman J.
        • Monuteaux M.C.
        • Spencer T.
        • Wilens T.E.
        • Faraone S.V.
        Do stimulants protect against psychiatric disorders in youth with ADHD? A 10-year follow-up study.
        Pediatrics. 2009; 124: 71-78
        • Staikova E.
        • Marks D.J.
        • Miller C.J.
        • Newcorn J.H.
        • Halperin J.M.
        Childhood stimulant treatment and teen depression: Is there a relationship?.
        J Child Adolesc Psychopharmacol. 2010; 20: 387-393
        • Bangs M.E.
        • Emslie G.J.
        • Spencer T.J.
        • Ramsey J.L.
        • Carlson C.
        • et al.
        • Atomoxetine ADHD and Comorbid MDD Study Group
        Efficacy and safety of atomoxetine in adolescents with attention-deficit/hyperactivity disorder and major depression.
        J Child Adolesc Psychopharmacol. 2007; 17: 407-420
        • Fredriksen M.
        • Halmoy A.
        • Faraone S.V.
        • Haavik J.
        Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: A review of controlled and naturalistic studies.
        Eur Neuropsychopharmacol. 2013; 23: 508-527
      1. U.S. Food and Drug Administration (2005): Public health advisory: Suicidal thinking in children and adolescents being treated with Strattera (atomoxetine). Available at: Accessed October 5, 2015.

        • Jensen P.S.
        • Arnold L.E.
        • Swanson J.M.
        • Vitiello B.
        • Abikoff H.B.
        • Greenhill L.L.
        • et al.
        3-year follow-up of the NIMH MTA study.
        J Am Acad Child Adolesc Psychiatry. 2007; 46: 989-1002
        • Ray W.A.
        Population-based studies of adverse drug effects.
        N Engl J Med. 2003; 349: 1592-1594
        • Ludvigsson J.F.
        • Otterblad-Olausson P.
        • Pettersson B.U.
        • Ekbom A.
        The Swedish personal identity number: Possibilities and pitfalls in healthcare and medical research.
        Eur J Epidemiol. 2009; 24: 659-667
        • Wettermark B.
        • Hammar N.
        • Fored C.M.
        • Leimanis A.
        • Otterblad Olausson P.
        • Bergman U.
        • et al.
        The new Swedish Prescribed Drug Register—opportunities for pharmacoepidemiological research and experience from the first six months.
        Pharmacoepidemiol Drug Saf. 2007; 16: 726-735
        • Chang Z.
        • Lichtenstein P.
        • D’Onofrio B.M.
        • Sjolander A.
        • Larsson H.
        Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication: A population-based study.
        JAMA Psychiatry. 2014; 71: 319-325
        • Lichtenstein P.
        • Halldner L.
        • Zetterqvist J.
        • Sjolander A.
        • Serlachius E.
        • Fazel S.
        • et al.
        Medication for attention deficit-hyperactivity disorder and criminality. 2012; 367: 2006-2014
        • Chen Q.
        • Sjolander A.
        • Runeson B.
        • D’Onofrio B.M.
        • Lichtenstein P.
        • Larsson H.
        Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: Register based study.
        BMJ. 2014; 348: g3769
        • Chang Z.
        • Lichtenstein P.
        • Halldner L.
        • D’Onofrio B.
        • Serlachius E.
        • Fazel S.
        • et al.
        Stimulant ADHD medication and risk for substance abuse.
        J Child Psychol Psychiatry. 2014; 55: 878-885
        • Hechtman L.
        • Abikoff H.
        • Klein R.G.
        • Weiss G.
        • Respitz C.
        • Kouri J.
        • et al.
        Academic achievement and emotional status of children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment.
        J Am Acad Child Adolesc Psychiatry. 2004; 43: 812-819
        • Faraone S.V.
        • Wilens T.E.
        Effect of stimulant medications for attention-deficit/hyperactivity disorder on later substance use and the potential for stimulant misuse, abuse, and diversion.
        J Clin Psychiatry. 2007; 68: 15-22
        • Corp S.A.
        • Gitlin M.J.
        • Altshuler L.L.
        A review of the use of stimulants and stimulant alternatives in treating bipolar depression and major depressive disorder.
        J Clin Psychiatry. 2014; 75: 1010-1018
        • Lavretsky H.
        • Reinlieb St, M.
        • Cyr N.
        • Siddarth P.
        • Ercoli L.M.
        • Senturk D.
        Citalopram, methylphenidate, or their combination in geriatric depression: A randomized, double-blind, placebo-controlled trial.
        Am J Psychiatry. 2015; 172: 561-569
        • Gibbons R.D.
        • Amatya A.K.
        • Brown C.H.
        • Hur K.
        • Marcus S.M.
        • Bhaumik D.K.
        • et al.
        Post-approval drug safety surveillance.
        Annu Rev Public Health. 2010; 31: 419-437
        • Larsson H.
        • Ryden E.
        • Boman M.
        • Langstrom N.
        • Lichtenstein P.
        • Landen M.
        Risk of bipolar disorder and schizophrenia in relatives of people with attention-deficit hyperactivity disorder.
        Br J Psychiatry. 2013; 203: 103-106
        • Fazel S.
        • Wolf A.
        • Chang Z.
        • Larsson H.
        • Goodwin G.M.
        • Lichtenstein P.
        Depression and violence: A Swedish population study.
        Lancet Psychiatry. 2015; 2: 224-232
        • Scheffler R.M.
        • Hinshaw S.P.
        • Modrek S.
        • Levine P.
        The global market for ADHD medications.
        Health Aff (Millwood). 2007; 26: 450-457
        • Zoega H.
        • Furu K.
        • Halldorsson M.
        • Thomsen P.H.
        • Sourander A.
        • Martikainen J.E.
        Use of ADHD drugs in the Nordic countries: A population-based comparison study.
        Acta Psychiatr Scand. 2011; 123: 360-367
        • Cortese S.
        • Holtmann M.
        • Banaschewski T.
        • Buitelaar J.
        • Coghill D.
        • Danckaerts M.
        • et al.
        Practitioner review: Current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents.
        J Child Psychol Psychiatry. 2013; 54: 227-246

      Linked Article

      • Can Medication Effects Be Determined Using National Registry Data? A Cautionary Reflection on Risk of Bias in “Big Data” Analytics
        Biological PsychiatryVol. 80Issue 12
        • Preview
          Stimulant and nonstimulant medications are recommended as part of attention-deficit/hyperactivity disorder (ADHD) treatment, based on the best available evidence of their costs and benefits (1). At the same time, some important clinical questions remain to be definitively resolved. This is because of both limitations in the scope of previous trials and, in some cases, their methodological and design weaknesses. Added to this, a degree of skepticism exists, in some quarters, concerning the veracity of the ADHD medication evidence base as a whole, because of the potentially distorting effect of pharmaceutical industry involvement in trials.
        • Full-Text
        • PDF