My SSRI antidepressant doesn’t work for me anymore. Why not?

Response from Mark Pollack, MD:

Your doctor has prescribed an SSRI (serotonin selective reuptake inhibitor) for your anxiety disorder or depression (or both), but you feel you aren’t responding adequately to your treatment.

Mark Pollack, MDConsider these issues: 
•    Your prescribed dose may be too low.
•    You may not have been taking it long enough to achieve a full response.
•    Side effects may prevent you from taking adequate doses.



SSRIs (Selective Serotonin Reuptake Inhibitors)

Generic names How they work
citalopram, escitalopram, fluoxetine, paroxetine, sertraline
Relieves symptoms by blocking the reabsorption, or reuptake, of serotonin by certain nerve cells in the brain. This leaves more serotonin available, which enhances neurotransmission—the sending of nerve impulses—and improves mood. SSRIs are “selective” because they affect only serotonin and not other neurotransmitters.

While the SSRIs work in similar ways, they’re not identical because they differ in their chemical structure and in their potency. And for reasons we do not yet fully understand, some patients may respond better to one SSRI than another.

Another Issue

Now some intriguing research suggests another potential cause for why SSRIs may not be effective in some cases. Recent evidence suggests that nonsteroidal anti-inflammatory agents (NSAIDs) taken with SSRIs may reduce their effectiveness.

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)

Generic names How they work
aspirin, celecoxib, diclofenac, diflunisal, etodolac, ibuprofen, indomethacin, ketoprofen,  ketorolac,  nabumetone, naproxen, oxaprozin, piroxicam, salsalate, sulindac, tolmetin Used primarily to treat inflammation, mild to moderate pain, and fever, NSAIDs block the enzymes and reduce prostaglandins throughout the body that promote these symptoms.

According to one theory, depression may be related to the body’s inflammatory responses. Called the cytokine hypothesis, this theory is based on observations that some cytokines, or the chemicals released as part of inflammation, help regulate serotonin and other neurotransmitters. Reducing inflammation, the NSAIDs negate the effects of the SSRIs, which increase levels of these chemicals.

Talk to your doctor if you take SSRIs and NSAIDs, and do not stop taking either medication. Learn about discontinuing medications. Ask if your use of NSAIDs — long-term or occasional — might be affecting your response to your SSRI antidepressant.

Mark Pollack, MD, is the Grainger Professor and Chairman, Department of Psychiatry, Rush University Medical Center

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