This article is one in a series on Medications for Pain. What are your choices? How do various medications work? What are the pros and cons? How about side effects?

Antidepressants are medications originally used to treat depression or anxiety, and which are also good for pain. Within this class, there are:

• Tricyclic antidepressants (TCAs), which include Amitriptyline (Elavil) and Nortriptyline.
• SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors), which include Cymbalta, Effexor (specifically at higher doses), and Savella.
• SSRIs (Selective Serotonin Reuptake Inhibitors), which include Zoloft, Prozac, Lexapro, etc.

It’s important to know that antidepressants work for pain even if you’re not depressed or anxious. They have an independent pain-reducing effect. So if your physician recommends an antidepressant, that doesn’t mean that your pain is all in your head, or that you’re just anxious or depressed.

That being said, anxiety and depression often go along with chronic pain, unfortunately. So if that’s true for you, a good thing about these medications is that they also help depression, anxiety and PTSD (Post Traumatic Stress Disorder; PTSD can occur if there was a traumatic cause to your pain, such as a car or work accident). As well, because sedation is a common side effect of some antidepressants, they can help the sleep disturbance that accompanies pain.

Effect of Antidepressants: All antidepressants work to change neurotransmitters in the brain. Neurotransmitters are those chemicals by which nerves communicate with one another. TCAs and SNRIs increase both serotonin and norepinephrine, while SSRIs only increase serotonin. TCAs also affect many other chemical systems, so can cause many other side effects such as dry mouth, constipation, sedation, and cardiac and blood pressure effects.

It seems that the combination of serotonin and norepinephrine effect is what’s crucial in decreasing pain.

Medical Studies:

• TCAs: Out of 126 studies of TCAs for pain, 95% of the studies showed that TCAs were effective for reducing pain.
• SNRIs: Out of 10 studies, 100% showed that SNRIs were effective.
• SSRIs: Of 39 studies, 33% showed that SSRIs were effective.

So again, this demonstrates that the medications which affect both serotonin and norepinephrine work best at helping with pain.

Uses of Antidepressants: Let’s look at some examples of these medications for specific pain disorders. Cymbalta is FDA-approved to treat the pain that can accompany diabetes, called Diabetic Peripheral Neuropathy. Savella is approved for Fibromyalgia. Paxil is helpful for chronic daily headache and migraines. We do know that SSRIs are generally not helpful for neuropathic (nerve) pain.

Common Side Effects:

• TCAs: sedation, constipation, weight gain; less often heart arrhythmia, decreased blood pressure
• SNRIs: nausea, sedation
• SSRIs: headache, nausea