Objective: To determine whether use of medications with potential depressive symptom side effects is associated with a higher level of depressive symptoms in adults with antidepressant-treated major depressive disorder (MDD).
Methods: The study was based on the 2013–2014, 2015–2016, and 2017–2018 National Health and Nutrition Examination Survey (NHANES)—a nationally representative cross-sectional survey of the US general population. In 885 adult participants from these NHANES cycles who reported receiving antidepressants for treatment of International Classification of Diseases, Tenth Revision, Clinical Modification MDD, the association between the number of medications with potential depressive symptom side effects and the level of depressive symptoms was assessed.
Results: A majority (66.7%, n = 618) of the participants with antidepressant-treated MDD used at least 1 non-psychiatric medication with potential depressive symptom side effects, and 37.3% (n = 370) used more than 1 such medication. The number of medications with depressive symptom side effects was significantly associated with lower odds of no to minimal depressive symptoms, defined as a Patient Health Questionnaire-9 (PHQ-9) score < 5 (adjusted odds ratio [AOR] = 0.75, 95% confidence interval [CI] = 0.64–0.87, P < .001), and higher odds of moderate to severe symptoms, defined as a PHQ-9 score ≥ 10 (AOR = 1.14, 95% CI = 1.004–1.29, P = .044). No such associations were found for medications without potential depressive symptom side effects.
Conclusions: Individuals treated for MDD frequently use non-psychiatric medications for comorbid medical conditions that are associated with an increased risk of depressive symptoms. In evaluating the response to antidepressant medication treatment, side effects of concomitantly used medications should be considered.
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Mojtabai R. Nonremission and time to remission among remitters in major depressive disorder: Revisiting STAR*D. Depress Anxiety. 2017;34(12):1123–1133. PubMedCrossRef
Nierenberg AA, Husain MM, Trivedi MH, et al. Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report. Psychol Med. 2010;40(1):41–50. PubMedCrossRef
Thase ME. The clinical, psychosocial, and pharmacoeconomic ramifications of remission. Am J Manag Care. 2001;7(suppl):S377–S385. PubMed
Trivedi MH, Rush AJ, Wisniewski SR, et al; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163(1):28–40. PubMedCrossRef
Judd LL, Paulus MJ, Schettler PJ, et al. Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness? Am J Psychiatry. 2000;157(9):1501–1504. PubMedCrossRef
Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 3rd ed. Am J Psychiatry. 2010;167(10):1.
Rush AJ, Aaronson ST, Demyttenaere K. Difficult-to-treat depression: a clinical and research roadmap for when remission is elusive. Aust N Z J Psychiatry. 2019;53(2):109–118. PubMedCrossRef
Masse-Sibille C, Djamila B, Julie G, et al. Predictors of response and remission to antidepressants in geriatric depression: a systematic review. J Geriatr Psychiatry Neurol. 2018;31(6):283–302. PubMedCrossRef
Mojtabai R, Amin-Esmaeili M, Spivak S, et al. Remission and treatment augmentation of depression in the United States. J Clin Psychiatry. 2021;82(6):21m13988. PubMedCrossRef
Zisook S, Johnson GR, Tal I, et al. General predictors and moderators of depression remission: a VAST-D report. Am J Psychiatry. 2019;176(5):348–357. PubMedCrossRef
Steffen A, Nübel J, Jacobi F, et al. Mental and somatic comorbidity of depression: a comprehensive cross-sectional analysis of 202 diagnosis groups using German nationwide ambulatory claims data. BMC Psychiatry. 2020;20(1):142. PubMedCrossRef
Gill D, Hatcher S. Antidepressants for depression in people with physical illness. Cochrane Database Syst Rev. 2000;(2):CD001312. PubMed
Cepeda MS, Reps J, Ryan P. Finding factors that predict treatment-resistant depression: results of a cohort study. Depress Anxiety. 2018;35(7):668–673. PubMedCrossRef
Godin O, Bennabi D, Yrondi A, et al; FondaMental Advanced Centers of Expertise in Resistant Depression (FACE-DR) Collaborators. Prevalence of metabolic syndrome and associated factors in a cohort of individuals with treatment-resistant depression: Results from the FACE-DR study. J Clin Psychiatry. 2019;80(6):19m12755. PubMedCrossRef
Chan KL, Cathomas F, Russo SJ. Central and peripheral inflammation link metabolic syndrome and major depressive disorder. Physiology (Bethesda). 2019;34(2):123–133. PubMedCrossRef
Gloger S, Vöhringer PA, Martínez P, et al. The contribution of early adverse stress to complex and severe depression in depressed outpatients. Depress Anxiety. 2021;38(4):431–438. PubMedCrossRef
Nelson J, Klumparendt A, Doebler P, et al. Childhood maltreatment and characteristics of adult depression: meta-analysis. Br J Psychiatry. 2017;210(2):96–104. PubMedCrossRef
Botts S, Ryan M. Depression. In: Tisdale JE, Miller DA, eds. Drug-Induced Diseases: Prevention, Detection, and Management. 3rd ed. American Society of Health-System Pharmacists; 2018:375–397.
Qato DM, Ozenberger K, Olfson M. Prevalence of prescription medications with depression as a potential adverse effect among adults in the United States. JAMA. 2018;319(22):2289–2298. PubMedCrossRef
Ried LD, Tueth MJ, Taylor MD, et al. Depressive symptoms in coronary artery disease patients after hypertension treatment. Ann Pharmacother. 2006;40(4):597–604. PubMedCrossRef
Patten SB, Francis G, Metz LM, et al. The relationship between depression and interferon beta-1a therapy in patients with multiple sclerosis. Mult Scler. 2005;11(2):175–181. PubMedCrossRef
National Center for Health Statistics. National Health and Nutrition Examination Survey. Cited June 20, 2017. https://www.cdc.gov/nchs/nhanes/
Chen TC, Clark J, Riddles MK, et al. National Health and Nutrition Examination Survey, 2015−2018: sample design and estimation procedures. Vital Health Stat. 2(184). Cited December 16, 2020. https://www.cdc.gov/nchs/data/series/sr_02/sr02-184-508.pdf
Kheshti R, Aalipour M, Namazi S. A comparison of five common drug-drug interaction software programs regarding accuracy and comprehensiveness. J Res Pharm Pract. 2016;5(4):257–263. PubMedCrossRef
Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–613. PubMedCrossRef
Huang FY, Chung H, Kroenke K, et al. Using the Patient Health Questionnaire-9 to measure depression among racially and ethnically diverse primary care patients. J Gen Intern Med. 2006;21(6):547–552. PubMedCrossRef
Andridge RR, Little RJ. A review of hot deck imputation for survey non-response. Int Stat Rev. 2010;78(1):40–64. PubMedCrossRef
Wiersema C, Oude Voshaar RC, van den Brink RHS, et al. Determinants and consequences of polypharmacy in patients with a depressive disorder in later life. Acta Psychiatr Scand. 2022;146(1):85–97. PubMedCrossRef
Mojtabai R, Olfson M. National trends in long-term use of antidepressant medications: results from the US National Health and Nutrition Examination Survey. J Clin Psychiatry. 2014;75(2):169–177. PubMedCrossRef
Judd LL, Akiskal HS, Maser JD, et al. Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse. J Affect Disord. 1998;50(2-3):97–108. PubMedCrossRef
Judd LL, Akiskal HS, Maser JD, et al. A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Arch Gen Psychiatry. 1998;55(8):694–700. PubMedCrossRef
Karp JF, Scott J, Houck P, et al. Pain predicts longer time to remission during treatment of recurrent depression. J Clin Psychiatry. 2005;66(5):591–597. PubMedCrossRef
Lauden A, Geishin A, Merzon E, et al. Higher rates of allergies, autoimmune diseases and low-grade inflammation markers in treatment-resistant major depression. Brain Behav Immun Health. 2021;16:100313. PubMedCrossRef
Kautzky A, Baldinger-Melich P, Kranz GS, et al. A new prediction model for evaluating treatment-resistant depression. J Clin Psychiatry. 2017;78(2):215–222. PubMedCrossRef
Rizvi SJ, Grima E, Tan M, et al. Treatment-resistant depression in primary care across Canada. Can J Psychiatry. 2014;59(7):349–357. PubMedCrossRef
Fishbain DA, Cole B, Lewis JE, et al. Does pain interfere with antidepressant depression treatment response and remission in patients with depression and pain? an evidence-based structured review. Pain Med. 2014;15(9):1522–1539. PubMedCrossRef
Sheng J, Liu S, Wang Y, et al. The link between depression and chronic pain: neural mechanisms in the brain. Neural Plast. 2017;2017:9724371. PubMedCrossRef
Burke NN, Finn DP, Roche M. Neuroinflammatory mechanisms linking pain and depression. Mod Trends Pharmacopsychiatry. 2015;30:36–50. PubMedCrossRef
Wang N, Shi M, Wang JY, et al. Brain-network mechanisms underlying the divergent effects of depression on spontaneous versus evoked pain in rats: a multiple single-unit study. Exp Neurol. 2013;250:165–175. PubMedCrossRef
Max MB, Wu T, Atlas SJ, et al. A clinical genetic method to identify mechanisms by which pain causes depression and anxiety. Mol Pain. 2006;2:1744-8069-2-14. PubMedCrossRef
Jackson JM, DeFor TA, Crain AL, et al. Validity of diabetes self-reports in the Women’s Health Initiative. Menopause. 2014;21(8):861–868. PubMedCrossRef
Okura Y, Urban LH, Mahoney DW, et al. Agreement between self-report questionnaires and medical record data was substantial for diabetes, hypertension, myocardial infarction and stroke but not for heart failure. J Clin Epidemiol. 2004;57(10):1096–1103. PubMedCrossRef