What Are Antidepressants?

Antidepressants are one of the most common prescription medications the world over. While many think of them only for treating depression, antidepressants for pain are becoming more commonly prescribed. Many people with chronic pain suffer from depression, but antidepressants for pain can ease symptoms whether or not there is underlying depression.

The pain relieving properties of antidepressants for pain are not very well understood. They may increase neurotransmitters, or chemical messengers, in the brain and spinal cord that decrease pain signals. Antidepressant pain-relieving effects are not immediate and may take several weeks to provide maximum benefit. Many people report moderate pain relief from antidepressants. Anti-seizure medications can be added to antidepressants if pain relief is incomplete.

Antidepressants are used to treat other psychiatric disorders, too, such as:

  • Generalized anxiety disorder
  • Social anxiety disorder
  • Obsessive-compulsive disorder (OCD)
  • Anorexia
  • Bulimia

Managing Pain With Antidepressants

Antidepressants are another weapon in your fight against chronic pain. They are an integral part of treatment for many chronic pain conditions.

Classes of antidepressants include:

  • Monoamine oxidase inhibitors (MAOIs)
  • Atypical antidepressants
  • Tricyclic antidepressants (TCAs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Norepinephrine-dopamine reuptake inhibitors (NDRIs)

All classes of antidepressants are not equally effective in the treatment of chronic pain. The two classes of antidepressants for pain that stand out are the TCAs and SNRIs. Examples of TCAs include:

  • Amitriptyline (Elavil)
  • Imipramine (Tofranil)
  • Nortriptyline (Pamelor)
  • Trimipramine (Surmontil)

Examples of SNRIs include:

  • Duloxetine (Cymbalta)
  • Cenlafaxine (Effexor XR)
  • Desvenlafaxine (Pristiq)
  • Milnacipran (Savella)

How do antidepressants for pain work?

Both TCAs and SNRIs increase levels of the brain neurotransmitters serotonin and epinephrine. These may block pain signals. Only the SNRI antidepressants duloxetine and milnacipran have been approved by the Food and Drug Administration (FDA) for the treatment of pain.

Chronic pain has two basic categories—neuropathic and nociceptive. Neuropathic pain is caused by nerve damage. Nociceptive pain is caused by damage to body tissue. Duloxetine has been approved for the treatment of neuropathic pain, nociceptive pain, and fibromyalgia.

Fibromyalgia is a chronic pain condition characterized by widespread musculoskeletal pain. Milnacipran has been approved for the treatment of fibromyalgia.

Although not FDA-approved for the treatment of pain, tricyclic antidepressants (TCAs) have a large body of literature supporting their use for treating chronic pain. The TCA with the most support for its use in the treatment of chronic pain is amitriptyline (Elavil).

Other classes of antidepressants, besides tricyclics, may also be helpful in the management of chronic pain. Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine, duloxetine, and milnacipran can be used to treat fibromyalgia. Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine and fluoxetine can also relieve pain and may be able to boost the pain-killing effects of some tricyclic antidepressants.

Antidepressants For Pain | PainDoctor.com

What conditions can I take antidepressants for? 

The pain involved in the following may be responsive to antidepressant drugs:

Treatment of diabetic peripheral neuropathic pain is difficult. Currently, there is only one antidepressant with an FDA indication for its treatment—duloxetine.

Chronic low back pain and chronic painful osteoarthritis are frequently treated with antidepressants. Duloxetine also has an FDA indication for the management of chronic musculoskeletal pain.

Fibromyalgia is another condition leading to chronic pain. Currently only two medications have an FDA indication for the treatment of fibromyalgia—duloxetine and milnacipran.

Antidepressants For Pain Side Effects

No matter the cause of chronic pain, there are several guidelines when using antidepressants for pain medication:

  • Psycho-education, clearly understanding that there is substantial evidence for the use of antidepressants in the treatment of chronic pain
  • Awareness of drug-drug interactions and always talking to your doctor about them fully
  • That you may have to slowly increase the antidepressant dose, or titrate, for it to take effect
  • Careful management of side effects can prevent risks (as explained below)
  • Always work closely with your doctor when stopping or reducing your use of antidepressants for pain

Some of the most common adverse side effects of antidepressants are:

  • Weight gain
  • Sexual dysfunction
  • Sleep issues
  • Anxiety
  • Agitation
  • Dry mouth
  • Headache or migrine
  • Nausea
  • Difficulty urinating
  • Drowsiness

Mayo Clinic lists some further side effects related to specific types of antidepressants. A Pain Doctor post also lists common antidepressants side effects.

Another concern of antidepressant usage is the chance of increased suicidal thoughts or actions. Thoughtful and immediate management of common adverse effects can lead to increased compliance in patients. In other words, patients will take the medication as directed by their physicians.

How to manage side effects

You and your doctor will work closely to manage your side effects. These preventative strategies may include:

  • Starting at a lower dose, titrating slower, giving dose at bedtime, or giving dose after food
  • Working on weight management, frequent weight measurements, and consultations with a nutritionist to avoid weight gain
  • Decreasing dose of antidepressant (if possible) or switching class of antidepressant (if appropriate) is sexual dysfunction occurs
  • If insomnia occurs, trying AM dosing and trazodone for persistent symptoms
  • If drowsiness occurs, consider PM dosing, no daytime naps, sleep hygiene advice, and switching class of antidepressant
  • Managing anxiety by lowering antidepressant dosage and a one to two week limited course of a benzodiazepine such as diazepam (Valium), alprazolam (Xanax), or lorazepam (Ativan)

Always follow your doctor’s advice closely to reduce pain and decrease your chance of side effects.


Antidepressants are primarily used to treat depression, but they can also be an integral part of the management of varied chronic pain conditions.

There are several classes of antidepressants that can reduce pain. The classes of antidepressants that have the best track record treating chronic pain are the tricyclic antidepressants (TCAs) and SNRIs. Selective serotonin reuptake inhibitors (SSRIs) do not work as well as TCAs and SNRIs.

Antidepressants have common adverse effects, which can be minimized by timely diagnosis and management. Additional ongoing clinical trials will help shed light on treating chronic pain with antidepressants.

To learn more about how antidepressants for pain can help you, talk to a pain specialist. You can find a pain doctor in your area by clicking the button below or looking for one in your area by using the tips here: https://paindoctor.com/pain-management-doctors/.

Find Your Pain Doctor


  1. Greist JH, Greeden JF, Jefferson JW, Grivedi MH. Depression and pain. J Clin Psychiatry. 2008; 69 (12): 1970-1978.
  2. Park HJ, Wiffen PJ. Antidepressants for neuropathic pain. Korean J Pain. 2010; 23 (2): 99-108.
  3. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. J Neurol Neurosurg Psychiatry. 2010; 81 (12): 1372-1373.
  4. Ursini F, Pipicelli G, Grembiale RD. Efficacy and safety of duloxetine in fibromyalgia. Clin Ter. 2010; 161 (4): 391-395.
  5. Skliarevski V, Desaiah D, Liu-Seifert H et al. Efficacy and safety of duloxetine in patients with chronic low back pain. Spine. 2010; 35 (13): 578-585.
  6. Chwieduk CM, McCormack PL. Milnacipran: in fibromyalgia. Drugs. 2010; 70 (1): 99-108.
  7. Hamer M, Batty GD, Marmot HG, Singh-Manoux A, Kivimaki M. Anti-depressant medication use and C-reactive protein: results from two population-based studies. Brain Behav Immun. 2011; 25 (1): 168-173.
  8. Chappell AS, Ossanna MJ, Liu-Seifert H et al. Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee paon: a 13-week, randomized, placebo-controlled trial. Pain. 2009; 146 (3): 253-260.