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Letter to the Editor

A Prospective Study of Antidepressant Adherence and Suicidal Ideation Among Adults

Fady Henein, MD; Deepak Prabhakar, MD, MPH; Edward L. Peterson, PhD; L. Keoki Williams, MD, MPH; and Brian K. Ahmedani, PhD

Published: November 17, 2016

A Prospective Study of Antidepressant Adherence and Suicidal Ideation Among Adults

To the Editor: Previous studies1-3 examining the link between antidepressant medication and suicidal ideation among youth have been inconclusive. Earlier studies demonstrated an association leading to the US Food and Drug Administration’s black box warning,1 but more recent studies4 have suggested an inverse association, such that antidepressants may reduce suicide risk. Additionally, most studies2 among adults suggest that antidepressants decrease suicidal ideation during the immediate period following initiation. Nevertheless, little research has examined long-term suicidal ideation associated with continued antidepressant therapy. It is not known whether risk varies by level of adherence or by the class of antidepressant medication. The current study examined whether antidepressant adherence was associated with a higher or lower likelihood of suicidal ideation among adults with depression.


Methods. This study included 344 patients with a clinical diagnosis of major depressive disorder (ICD-9 criteria) and no self-reported suicidal ideation at baseline. All patients received antidepressant treatment from clinical providers within a single, large health system and were members of the affiliated health plan. This membership allowed complete capture of health care utilization and pharmacy records. To ensure long-term medication use, patients were required to fill a prescription for a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) before, during, and after the 1-year observation period.

Prospective surveys querying suicidal thoughts and depressive symptoms, using the 9-item Patient Health Questionnaire (PHQ-9),5 were administered at baseline and after 1 year of observation (March 2013 and March 2014, respectively). Suicidal thoughts were assessed via item 9 of the PHQ-9, which has been shown to predict suicidal behavior.6 An item 9 score ≥ 1 (self-harm thoughts for at least several days the prior 2 weeks) was used to indicate suicidal thoughts. Pharmacy claims were used to calculate a continuous measure of medication availability.7 Continuous measure of medication availability estimates adherence by using the total medication days’ supply to determine the proportion of days that the medication could have been taken as directed. Logistic regression prospectively measured antidepressant adherence and suicidal ideation (yes-no), with adjustment for baseline depression severity and demographic factors. Analyses were stratified by class.

Results. Overall, 344 patients filled an antidepressant at all 3 required time points (ie, before, during, and after the 1-year observation time). This included 243 patients who filled an SSRI and 144 who filled an SNRI during each period, with 43 individuals filling prescriptions for both medication classes. Patient demographic characteristics are shown in Table 1. Baseline depression severity scores averaged approximately 7, indicating mild depressive symptoms. On average, patients were adherent to their antidepressant medication an estimated 85% of days. As shown in Table 1, greater adherence to antidepressants overall was associated with a lower likelihood of suicidal ideation at 1-year follow-up, even after adjustment (odds ratio [OR] = 0.61, P = .047). Adherence to SSRIs was also independently associated with a lower likelihood of suicidal ideation (OR = 0.52, P = .025), but the association did not persist for SNRIs (OR = 0.61, P = .140).

Table 1

Click figure to enlarge


This prospective study suggests that adherence to antidepressants may prevent suicidal ideation in adults with major depressive disorder. While the magnitude and direction of association was similar for SNRIs, this subgroup analysis did not reach statistical significance, a likely result of the smaller sample size and lower power. Overall, our findings extend prior research indicating that short-term antidepressant treatment reduces suicidal ideation among adults.2 This study also underscores the importance of adherence to long-term treatment for depression. However, physicians should consider the observational nature of this study and the generalizability of a single health system’s experience when making treatment decisions. While our findings support a beneficial role for antidepressant therapy in reducing or preventing suicidal ideation in adults, additional research is needed to replicate the results.


1. Mann JJ, Emslie G, Baldessarini RJ, et al. ACNP Task Force report on SSRIs and suicidal behavior in youth. Neuropsychopharmacology. 2006;31(3):473-492. PubMed doi:10.1038/sj.npp.1300958

2. Gibbons RD, Brown CH, Hur K, et al. Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012;69(6):580-587. PubMed doi:10.1001/archgenpsychiatry.2011.2048

3. Coupland C, Hill T, Morriss R, et al. Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database. BMJ. 2015;350:h517. PubMed doi:10.1136/bmj.h517

4. Lu CY, Zhang F, Lakoma M, et al. Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study. BMJ. 2014;348:g3596. PubMed doi: 10.1136/bmj.g3596

5. 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. PubMed doi:10.1046/j.1525-1497.2001.016009606.x

6. Simon GE, Rutter CM, Peterson D, et al. Does response on the PHQ-9 Depression Questionnaire predict subsequent suicide attempt or suicide death? Psychiatr Serv. 2013;64(12):1195-1202. PubMed doi:10.1176/

7. Steiner JF, Prochazka AV. The assessment of refill compliance using pharmacy records: methods, validity, and applications. J Clin Epidemiol. 1997;50(1):105-116. PubMed doi:10.1016/S0895-4356(96)00268-5

Fady Henein, MDa

Deepak Prabhakar, MD, MPHa

Edward L. Peterson, PhDb

L. Keoki Williams, MD, MPHc,d

Brian K. Ahmedani, PhDa,d

aBehavioral Health Services, bPublic Health Sciences, cDepartment of Internal Medicine, and dCenter for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan

Author contributions: All authors have contributed to and have approved the final submitted manuscript.

Potential conflicts of interest: None.

Funding/support: The project was supported by grants from the Fund for Henry Ford Hospital and the National Institutes of Health (R01MH103539).

Role of the sponsor: The funding agency had no role in the design and conduct of the study; collection, management, analysis, and interpretation of data; or preparation, review, or approval of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Disclaimer: Each author had full access to the data and takes responsibility for the integrity of the data and accuracy of the data analysis.

Published online: November 17, 2016.

Prim Care Companion CNS Disord 2016;18(6):doi:10.4088/PCC.16l01935

© Copyright 2016 Physicians Postgraduate Press, Inc.

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