Treating SSRI Resistant Depression

When your antidepressant medication does not work, should you switch to a different medication from the same class or should you try an antidepressant medication that has a different mechanism of action? This is the question asked by researchers in a new report scheduled for publication in Biological Psychiatry on April 1st.


Papakostas and colleagues compared two strategies for treating symptoms of major depressive disorder that do not respond to treatment with a selective serotonin reuptake inhibitor (SSRI) antidepressant: either switching to a second SSRI or to a non-SSRI antidepressant. Some common SSRI antidepressants are fluoxetine (Prozac), citalopram (Celexa) and sertraline (Zoloft), while examples of a few common non-SSRI antidepressants are venlafaxine (Effexor) and buproprion (Wellbutrin, Zyban). The authors combined 4 studies comparing these two types of treatment strategies and performed a meta-analysis on the pooled data.


Dr. George I. Papakostas, corresponding author on this project, explains the results: "Switching from a selective serotonin reuptake inhibitor to a drug with a different mechanism of action was found to be slightly more effective and slightly less-well tolerated than switching to a non-SSRI drug." Looking at the findings from a clinical perspective, the advantage in effectiveness means that 22 depressed people would need to be switched to treatment with a non-SSRI for one additional person to obtain relief from their symptoms.


John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, adds that this result "may be related to the fact that while somewhat different, the medications evaluated in this report all acted on the monoamine systems of the brain." Because of the particular design of this study, the authors explain that "subsequent studies examining whether differences in efficacy between these two treatments exist for specific subpopulations, symptoms, or symptom clusters are warranted." Dr. Krystal concludes that while this advantage could be important, "there continues to be a pressing need to introduce new antidepressant medications that target novel brain mechanisms."


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