Do Analgesics Interfere with Efficacy of Selective Serotonin Reuptake Inhibitors?

Jonathan Silver, MD

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This elegant translational study connects the observations in a rodent depression model with possible clinical response to antidepressants. SSRIs (but not noradrenergic antidepressants) increase cytokines, which increase p11, resulting in the antidepressant response. NSAIDs (and acetaminophen) inhibit the step-activating cytokines. Clinically, worse antidepressant response is associated with analgesic use. Further research is needed, including prospective studies of various antidepressant types and studies of other possible etiologies – e.g., putatively NSAID-lowered plasma levels of SSRIs or a greater likelihood that depression will be refractory to treatment in patients with pain. Meanwhile, clinicians should carefully evaluate their depressed patients' analgesic use; it may be one reason for poor response. For patients requiring analgesics, clinicians may wish to consider non-SSRIs.

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