Are Antidepressants Effective for Chronic Pain Conditions?

Arthritis and Fibromyalgia Patients May Be Prescribed Antidepressants

Depressed woman on sofa.
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It's not uncommon for patients with chronic pain diseases and conditions, such as rheumatoid arthritis, lupus, fibromyalgia, and neuropathic pain to experience depression. Patients with chronic physical problems have higher rates of lifetime major depression. Pain and depression are often comorbidities. That said, it's not uncommon for patients with chronic pain conditions to be prescribed antidepressants.

While antidepressants are primarily prescribed to elevate the mood of clinically depressed patients by affecting neurotransmitters in the brain, antidepressants may also be prescribed as a primary treatment for chronic pain, anxiety disorders, or sleep disorders. The precise mechanism of how antidepressants work to manage pain is largely unknown. Various mechanisms may play a role. It is generally thought that antidepressants have an effect on serotonin and norepinephrine, especially along descending spinal pain pathways. Antidepressants may also work through histamine receptors or sodium channels. 

Selective Serotonin Reuptake Inhibitors (SSRIs)

Some of the more commonly prescribed antidepressants are Selective Serotonin Reuptake Inhibitors (SSRIs). These include, Prozac (fluoxetine), Lexapro (escitalopram), Celexa (citalopram), Zoloft (sertraline), and Paxil (paroxetine).

As the name suggests, SSRIs target the neurotransmitter (brain chemical) serotonin and the goal is to keep serotonin in the brain longer.

They are effective medications for many patients and side effects are usually moderate or tolerable.

Dual Inhibitors (also called Serotonin and Norepinephrine Reuptake Inhbitors or SNRIs)

There are other antidepressants that target two neurotransmitters (e.g., serotonin and norepinephrine), called dual inhibitors or SNRIs.

According to rheumatologist Scott J. Zashin MD, "Both classes of antidepressants (SSRIs and dual inhibitors) help control fatigue and pain associated with fibromyalgia or chronic pain syndromes, although the dual inhibitors may be even more effective in terms of pain relief."

Dr. Zashin further explained, "Cymbalta (duloxetine) and Effexor (venlafaxine) are considered SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), also referred to as dual inhibitors." Cymbalta was approved by the FDA for the treatment of fibromyalgia in 2008 and for chronic musculoskeletal pain in 2010. Common side effects associated with SNRIs include, nausea, loss of appetite, anxiety, headache, insomnia, and tiredness.

Tricyclic Antidepressants

Tricyclic antidepressants were considered the standard treatment for depression before SSRIs were developed. Tricyclic antidepressants (e.g., Elavil [amitriptyline]) are given in low doses to help patients fall asleep and obtain the restorative non-REM sleep. In low doses taken on a regular basis, tricyclic antidepressants may also help decrease pain. Due to numerous side effects (e.g., blurred vision, weight gain, sleepiness), in the dose required to treat depression, they are seldom used for that indication.

Norepinephrine and Dopamine Reuptake Inhibitors (NDRIs)

NDRIs are another type of antidepressant. Bupropion (brand names Wellbutrin or Zyban) is an NDRI. Common side effects include, agitation, nausea, headache, loss of appetite, insomnia, and increased blood pressure.

Combined Reuptake Inhibitors and Receptor Blockers

Combined Reuptake Inhibitors and Receptor Blockers include Desyrel (Trazadone), Remeron (Mirtazpine), and Serzone (Nefazodone). This type of antidepressant should not be taken by people with a history of liver problems. There are a number of possible side effects you should discuss with your doctor.

Drowsiness, dry mouth, nausea, and dizziness are some of the more common side effects.

Monoamine Oxidase Inhibitors (MAO Inhibitors)

MAO Inhibitors are older antidepressants that are not widely used to treat depression or other conditions. They are used for select patients. MAO Inhibitors (e.g., Nardil [Phenelzine]) require dietary restrictions and they are associated with significant side effects.

Warnings Surround the Use of Antidepressants

The use of antidepressants is not without warnings. The FDA states that adults should be observed for increased depression or suicidal thoughts or behavior during the first few months of treatment or following a change in medication dosage. Patients should immediately contact their doctor if depression symptoms worsen or if suicidal thoughts or behavior increase. Patients should be aware of all potential side effects and report changes to their doctor.


Sodium channel blockade may contribute to the analgesic efficacy of antidepressants. The Journal of Pain. 2007 Apr;8(4):315-24. December 15, 2006.

Managing Chronic Pain and Depression in Arthritis. Michael Clark, M. Johns Hopkins Arthritis Center. October 13, 2011.

Pain, Pain, Go Away. Psychiatry MMC. Sansone and Sansone. December 2008.

Antidepressants: Definitive Guide.Peter F. Ullrich Jr., M.D. 11/6/2005.

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