Antidepressants: Another weapon against chronic pain (2024)

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

  1. Kremer M, et al. Antidepressants and gabapentinoids in neuropathic pain: Mechanistic insights. Neuroscience. 2016; doi:10.1016/j.neuroscience.2016.06.057.
  2. Rosenquist EWK. Overview of the treatment of chronic non-cancer pain. https://www.uptodate.com/contents/search. Accessed June 23, 2019.
  3. Bates D, et al. A comprehensive algorithm for management of neuropathic pain. Pain Medicine. 2019; doi: 10.1093/pm/pnz075.
  4. Bonzon HT, et al. Essentials of Pain Medicine. 4th ed. Elsevier; 2018. https://www.clinicalkey.com. Accessed July 14, 2019.
  5. Daroff RB, et al. Disorders of peripheral nerves. In: Bradley's Neurology in Clinical Practice. 7th ed. Saunders Elsevier; 2016. https://www.clinicalkey.com. Accessed June 22, 2019.
  6. Brent DA. Antidepressants and suicidality. Psychiatric Clinics of North America. 2016; doi: 10.1016/j.psc.2016.04.002.

See also

  1. Chronic pain: Medication decisions
  2. Collecting Pennies Through the Pain
  3. Mayo Clinic Minute: Avoid opioids for chronic pain

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Antidepressants: Another weapon against chronic pain (2024)

FAQs

What antidepressant is good for 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.

Does wellbutrin help with chronic pain? ›

Seventy-three percent, or 30 of the patients reported their pain was improved or much improved after six weeks of bupropion therapy, whereas 90 percent claimed their pain became worse or remained unchanged while receiving the placebo. sem*nchuk recommended additional larger scale studies to confirm the results.

What medication stops pain signals to the brain? ›

Tricyclic antidepressants, such as amitriptyline (Elavil), doxepin (Sinequan), and nortriptyline (Pamelor). These drugs are prescribed for pain at doses lower than are effective for depression. Serotonin–norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta) and venlafaxine (Effexor).

What are the newest most effective antidepressants? ›

The Newest Antidepressants Offering Hope
  • Gepirone (Exxua) FDA Approved in 2023 – An Antidepressant Breakthrough. ...
  • Esketamine (Spravato) FDA Approved in 2019 – A Revolutionary Nasal Spray Medication. ...
  • Brexanolone (Zulresso) FDA Approved in 2019 – Addressing Postpartum Depression.
Mar 26, 2024

What is the drug of choice in the management of chronic pain? ›

What drug is commonly prescribed for chronic pain? Doctors commonly prescribe cyclooxygenase (COX) inhibitors to treat chronic pain syndromes. Several categories of COX inhibitors are available, including: nonsteroidal anti-inflammatory drugs (NSAIDs)

What is the best medicine for extreme pain? ›

Ten best painkillers in the United States
  • Vicodin (hydrocodone-combination)
  • Percocet (oxycodone with acetaminophen)
  • OxyContin (oxycodone HCL)
  • Acetaminophen with codeine.
  • Morphine sulfate.
  • Fentanyl.
  • OxyContin.
  • Methadone.

What SSRI is best for neuropathic pain? ›

Among SSRIs, paroxetine (Paxil) and citalopram (Celexa) have shown modest effectiveness in people with a neuropathic pain condition.

Which is better Wellbutrin or Cymbalta? ›

Cymbalta has an average rating of 6.3 out of 10 from a total of 1885 ratings on Drugs.com. 53% of reviewers reported a positive effect, while 30% reported a negative effect. Wellbutrin XL has an average rating of 7.5 out of 10 from a total of 485 ratings on Drugs.com.

How does Cymbalta help with pain? ›

Scientists believe that by increasing levels of serotonin and nor-epinephrine in the body, duloxetine can calm pain signals and provide pain relief.

What stops nerve pain immediately? ›

Lidocaine or capsaicin may help ease neuropathic pain. You can apply these creams, ointments or patches directly to the affected areas. Nerve blocks. These injections can provide temporary pain relief.

What is the strongest drug for nerve pain? ›

Studies have shown that gabapentin, pregabalin, amitriptyline, duloxetine, and venlafaxine are the most effective nerve pain medications. Opioid painkillers, such as tramadol, are some of the strongest drugs available for pain control. However, they come with a high risk of addiction.

How do you rewire your brain to stop pain? ›

The following techniques can help you take your mind off the pain and may help to override established pain signals.
  1. Deep breathing. ...
  2. Eliciting the relaxation response. ...
  3. Meditation with guided imagery. ...
  4. Mindfulness. ...
  5. Yoga and tai chi. ...
  6. Positive thinking.
Apr 11, 2015

What is the world's strongest antidepressant? ›

The most effective antidepressant compared to placebo was the tricyclic antidepressant amitriptyline, which increased the chances of treatment response more than two-fold (odds ratio [OR] 2.13, 95% credible interval [CrI] 1.89 to 2.41).

What is the hardest antidepressant to come off of? ›

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are the most likely antidepressants to cause withdrawal symptoms. Listed according to their risk of causing withdrawal, they include: With a high risk of withdrawal: Desvenlafaxine (Khedezla, Pristiq)

What is the new antidepressant in 2024? ›

FDA Greenlights Exxua™ (Gepirone): A Promising New Antidepressant for 2024. Exxua represents a promising new antidepressant for Major Depressive Disorder (MDD) with a unique mechanism of action targeting the glutamatergic system.

What is the best medication for chronic muscle pain? ›

Nonsteroidal anti-inflammatory drugs, known as NSAIDs

These medications are commonly used for arthritis and pain resulting from muscle sprains, strains, back and neck injuries, or menstrual cramps. Generic (brand) names. Ibuprofen (Advil, Motrin IB, others); naproxen sodium (Aleve); others.

What antidepressant is also an anti-inflammatory? ›

SSRIs and SNRIs are some of the most commonly applied drugs during pharmacotherapy of recurrent depressive disorders. The anti-inflammatory and anti-oxidative effect may be one of the potential mechanisms of action of SSRIs and SNRIs.

What can I take for chronic body pain? ›

If over-the-counter drugs do not provide relief, your doctor may prescribe stronger medications, such as muscle relaxants, anti-anxiety drugs (such as diazepam [Valium]), antidepressants (like duloxetine [Cymbalta] for musculoskeletal pain), prescription NSAIDs such as celecoxib (Celebrex), or a short course of ...

What is the best antidepressant for joint pain? ›

Common antidepressants used for orthopedic pain relief include:
  • Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft).
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine (Cymbalta) and venlafaxine (Effexor XR).
Jun 27, 2023

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