Higher SSRI Doses Linked to Greater Risk for Self-Harm in Youth

Summary and Comment |
May 5, 2014

Higher SSRI Doses Linked to Greater Risk for Self-Harm in Youth

  1. Peter Roy-Byrne, MD

In depressed individuals aged 24 years and younger, the rate of self-harm was greatest in the 3 months after initiating higher versus modal doses.

  1. Peter Roy-Byrne, MD

Although studies have shown increased risks for suicidal ideation and attempts with selective serotonin reuptake inhibitors (SSRIs) in patients aged ≤24, the effect of dose on these risks has not been examined. Now, researchers have compared risks for deliberate self-harm after initiation of citalopram, fluoxetine, or sertraline for depression at high versus modal dose. Analyses were based on observational data on 162,625 patients (age range, 10–64) from a large claims database.

High- and modal-dose groups were propensity-matched on multiple demographic, illness severity, and suicide history variables. Patients changing doses were censored from analyses. Among patients aged ≤24 or younger, subsequent risk for self-harm was twice as great in those started on high (18% of patients) than on modal doses. Most events occurred in the first 90 days. In patients aged >25, dose had no effect on self-harm risk. Among young patients in the modal-dose group, the risk was similar before and after antidepressant initiation. Results were unchanged in analyses excluding treatment-naive patients and those without suicide histories.


This study suggests that clinicians treating young, depressed patients should begin SSRIs at lower doses. Unfortunately, as editorialists note, the study did not examine below-modal starting doses, nor did it compare treated patients with those not initiating antidepressants. Also, the effect of dose escalation was not explored. Although the authors feel that before-and-after analyses are limited and less valid than the method they chose, the finding that self-harm events did not increase after modal-dose SSRI initiation suggests that dose may indeed be an important factor. Despite the propensity method, there may still be unmeasured characteristics of patients started on higher doses that placed them at risk for both higher-dose selection and worse suicidality outcomes.

Editor Disclosures at Time of Publication

  • Disclosures for Peter Roy-Byrne, MD at time of publication Equity Valant Medical Solutions Grant / research support NIH-NIDA; NIH-NIMH Editorial boards Depression and Anxiety; UpToDate Leadership positions in professional societies Anxiety Disorders Association of America (Ex-Officio Board Member); Washington State Psychiatric Society (President-Elect)


Reader Comments (2)

SCOTT JOSEPH Physician, Psychiatry, Adult Inpatient State Hospital

SSRIs can cause akathisia and GI problems. One should go at a reasonable pace with increasing dose, especially as results of this will NOT be rapid---i.e., 2-6 week average response lag anyway.

Richard Thornton, M.D. Physician, Obstetrics/Gynecology, Retired

My aging brain tells me that were I still prescribing, I would charge the most reliable and available person to give the prescribed dose. The patient could be given charge of his medication later when dosage and side effects and clincal progress warrented.

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