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  • Michele Curatolo

Do antidepressants reduce pain or not?

Patients with chronic pain are frequently proposed to take an antidepressant. Why would and antidepressant relieve pain?
As a patient with chronic pain, you may wonder why you are proposed an antidepressant

This blog is mainly conceived to inform patients about the use of antidepressants for pain. Any health care professional is welcome to provide their patients with this link, if deemed useful.

As a patient with chronic pain who has been proposed to take an antidepressants, you have likely asked your health care professional or yourself:

  • Why would an antidepressant reduce my pain?

  • I do not have depression, so why am I proposed an antidepressant?

  • My depression is caused by my pain, so why am I not treated primarily for my pain?

  • Does my doctor think my pain is all in my head?

Antidepressants act on pain pathways

The sites and mechanisms of action of antidepressants and not fully understood, but we know that antidepressants increase the efficiency of the pain inhibitory system. This system is physiologically active in everyone, also in individuals without pain. The inhibitory system serves different functions. For instance, it allows to escape danger after a major injury, such as during a battle or after a car accident. Without this protective mechanism, the pain could prevent the injured person from surviving the event. Two chemicals in the brain, serotonin and noradrenalin, contribute to the pain inhibitory system, and their concentration is increased by antidepressants. This is one of the explanations why antidepressants may help patients with pain, independent of depression.

Brain areas that are implicated in pain and depression talk to each other

Several studies using advanced brain MRI have identified areas of the brain associated with pain perception and mood disorder. Although centers of these areas are anatomically different, connections and cross-talks between the two have been revealed. This supports the knowledge that pain and depression influence each other, likely in a bi-directional way, meaning that pain increases depression and depression increases pain. It is therefore logical to treat the depression, even if its primary cause is the pain. Importantly, the presence of depression reduces the chances of success of pain treatments, such as procedures (learn more here).

More broadly, pain management should not exclusively focus on treatments that primarily reduce pain sensation. In fact, treatment of sleep disorder, psychological distress and disability may promote pain reduction and increase the chances of successful pain treatment, as explained here. Not doing so will greatly hamper your improvement.

If your health care professional proposes an antidepressant, it is not because they think the pain "is all in your head", or "made up".

Do antidepressants really work?

Yes, but:

  • In a subset of patients

  • Mostly producing partial (but valuable) pain relief

  • Not uncommonly at costs of side-effects, which are however reversible

  • Not all antidepressants are effective for pain, meaning that some of them improve depression, but not pain

A very recent study found 26 systematic reviews that made a total of 42 comparisons between antidepressants and placebo, for 22 pain conditions (see here to know more about placebo). Antidepressants were efficacious in 11 comparisons. For the other 31 comparisons, antidepressants "were either not efficacious (five comparisons) or the evidence was inconclusive (26 comparisons)". However, we need to consider that the studies tested the efficacy in comparison with placebo. Even if part or the majority of the effect of antidepressants is due to placebo, this is a desired effect for the reasons explained here. Nevertheless, the findings of the review confirm that antidepressants can help some, but not the majority of patients.

To summarize:

  • Antidepressants can relieve pain independent of the presence of depression

  • Only part of patients benefit

  • Side effects are common, but reversible after stopping the medication

  • Not all antidepressants are effective for pain - If you are currently taking an antidepressant for your depression and have no pain relief, discuss with your health care professional the option to switch to another antidepressant that is known to reduce pain

  • If your health care professional proposes an antidepressant for pain, they do not think that your pain "is all in your head", or "made up" - so be open

  • The medication alone will unlikely make a significant difference if other dimensions are not addressed: sleep, physical function, and psychosocial issues, among others

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