When Antidepressants Fail, Dose Increase May Be a Less Effective Response


From Psychiatry Adviser: In a study published in the Journal of Clinical Psychiatry, the investigators did not recommend increasing antidepressant dosage in response to treatment failure, after analyses of dose increase regimens appeared to reveal insignificant changes in effect size.

Some surveys have demonstrated that a dose increase is the prevailing reaction to a lack of response to antidepressant treatment. Other common recommended practices include switching to a different antidepressant, combining two or more antidepressants, or augmenting treatment with antipsychotics.

The investigators identified 9 studies comprising 1273 adult patients via the CENTRAL, PubMed, Embase, and PsycINFO databases. They included randomized, controlled trials in which patients with unipolar depression who had not responded to antidepressant treatment were assigned to dose increase schedules or continued-dose control groups. All studies examined selective serotonin reuptake inhibitors, with 1 study also reporting on maprotiline.

Compared with a continued dose in accordance with a patient’s initial prescription, an increased dose was not shown to be more effective, with a negligible standardized mean difference of 0.053 (95% CI, −0.143 to 0.248). In a similar fashion, secondary outcome analyses found a nonsignificant odds ratio of 1.124 for antidepressant response and depression remission.

Article →

Support MIA

MIA relies on the support of its readers to exist. Please consider a donation to help us provide news, essays, podcasts and continuing education courses that explore alternatives to the current paradigm of psychiatric care. Your tax-deductible donation will help build a community devoted to creating such change.

Select Payment Method
Personal Info

Credit Card Info
This is a secure SSL encrypted payment.

Billing Details

Donation Total: $20


  1. Psychiatrists do like to max out dosages, even in under 18’s and off-label, before trying something else. Its in direct contradiction to most guidelines and the pharmacological evidence on response curves of uptake reinhibition. Thats before you even think about the evidence on feeble efficacy. They are literally making it up as they go along in the belief that they are at least “doing something” and its reckless.