Antidepressants: Another weapon against chronic pain

Antidepressants are a mainstay in the treatment of many chronic pain conditions — even when depression isn't a factor.

By Mayo Clinic Staff

Some of the more effective and commonly used medications for chronic pain are drugs that were developed to treat other conditions. Although not specifically intended to treat chronic pain, antidepressants are a mainstay in the treatment of many chronic pain conditions, even when depression isn't recognized as a factor.

Types of pain relieved

Antidepressants seem to work best for pain caused by:

  • Arthritis
  • Nerve damage from diabetes (diabetic neuropathy)
  • Nerve damage from shingles (postherpetic neuralgia)
  • Nerve pain from other causes (peripheral neuropathy, spinal cord injury, stroke, radiculopathy)
  • Tension headache
  • Migraine
  • Facial pain
  • Fibromyalgia
  • Low back pain
  • Pelvic pain
  • Pain due to multiple sclerosis

The painkilling mechanism of these drugs still isn't fully understood. Antidepressants may increase neurotransmitters in the spinal cord that reduce pain signals. But they don't work immediately.

You may feel some relief from an antidepressant after a week or so, but maximum relief may take several weeks. People generally experience moderate pain relief from antidepressants.

Medications from other drug classes with distinct mechanisms of pain relief (such as anticonvulsants) may be used in combination with antidepressant class medications if pain relief with antidepressants is incomplete.

Antidepressants are classified based on their chemical structure and how they work. One of the most effective groups of antidepressants for pain is known as the tricyclics.

Tricyclic antidepressants

Tricyclic antidepressants are the most common type of antidepressant used for pain. They include:

  • Amitriptyline
  • Nortriptyline (Pamelor)
  • Protriptyline (Vivactil)
  • Doxepin (Silenor)
  • Imipramine (Tofranil)
  • Clomipramine (Anafranil)
  • Desipramine (Norpramin)

Side effects of tricyclic antidepressants

Side effects of tricyclic antidepressants may include:

  • Blurred vision
  • Drowsiness
  • Dry mouth
  • Nausea
  • Lightheadedness on standing up due to a drop in blood pressure (orthostatic hypotension)
  • Weight gain
  • Difficulty thinking clearly
  • Constipation
  • Difficulty urinating
  • Heart rhythm problems
  • Problems having sexual intercourse

To reduce or prevent side effects, your doctor will likely start you at a low dose and slowly increase the amount. Most people are able to take tricyclic antidepressants, particularly in low doses, with only mild side effects. The doses that are effective for pain are generally lower than the doses used for depression.

Other antidepressants that may help

Other classes of antidepressants have become more popular because they have fewer side effects. These drugs may also be used to help relieve chronic pain:

  • Serotonin and norepinephrine reuptake inhibitors (SNRIs). Some SNRIs, such as venlafaxine (Effexor XR), duloxetine (Cymbalta, Drizalma Sprinkle), milnacipran (Savella) and desvenlafaxine (Pristiq), may help relieve chronic pain. People with chronic pain often develop depression along with their chronic pain. Venlafaxine and duloxetine offer the advantage of being effective for depression and anxiety at the same dosages useful for treating pain.

    Venlafaxine can cause drowsiness, insomnia or elevated blood pressure, and may worsen heart problems. Duloxetine can cause side effects, such as drowsiness, insomnia, nausea, dry mouth, dizziness, constipation or excessive sweating.

    Milnacipran is used to relieve fibromyalgia pain and can cause side effects such as nausea and drowsiness. However, it has shown only limited effectiveness in relieving other types of pain.

  • Selective serotonin reuptake inhibitors (SSRIs). SSRIs, which include drugs such as paroxetine (Paxil) and fluoxetine (Sarafem, Prozac), may help relieve certain types of pain, but there's a lack of evidence that they help alleviate nerve pain.

    SSRIs may boost the painkilling effects of some tricyclic antidepressants by increasing the levels of tricyclic antidepressants in your blood. If your doctor prescribes both medications, they should be used with caution. If you have any concerns, talk with your doctor.

    SSRIs generally don't work as well as tricyclic antidepressants for pain, but they often produce fewer side effects. Fluoxetine can cause certain side effects, such as insomnia and dizziness.

It's important to note that antidepressant medications are associated with a slightly increased risk of suicidal thoughts or actions. Talk to a doctor or counselor promptly if you feel depressed or suicidal.

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Sept. 07, 2019