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What are Antidepressants?

Several drugs that were originally shown to be effective in treating depression can also be used to treat chronic pain. Not all antidepressants work to treat pain, and when antidepressants do work to treat pain, it is not because they are treating depression. Individuals with chronic pain without depression are just as likely to experience an improvement in pain when they are given these drugs as are individuals with both depression and chronic pain.

In addition to chronic pain, these drugs can also be used to treat depression and anxiety.

How do Antidepressants work?

The antidepressants that are most useful in treating chronic pain are those that raise levels of two different brain chemicals or neurotransmitters – serotonin and norepinephrine. Antidepressants that mainly increase serotonin are called Selective Serotonin Reuptake Inhibitors (SSRIs) whereas the antidepressants that increase both serotonin and norepinephrine are called Serotonin Norepinephrine Reuptake Inhibitors (SNRIs). The latter SNRI drugs that increase both serotonin and norepinephrine are often better at treating pain than the SSRI drugs that only increase serotonin.

The reason that these drugs can be used to treat pain is that serotonin and norepinephrine levels in certain brain regions help the body to inhibit pain. When levels of serotonin and norepinephrine are low in certain brain regions, the nervous system becomes more sensitive to pain. Similarly, when serotonin and/or norepinephrine are low in other brain regions, this causes depression or anxiety. Because serotonin and norepinephrine are involved in both pain and in depression/anxiety, the same drug can be used to treat both conditions. Thus although these drugs are often labelled as antidepressants, these drugs are directly improving pain and mood separately; not by indirectly improving pain by making depression better.

What are the names of some Antidepressants that are used to treat chronic pain?

SSRIs - Fluoxetine (Prozac) - Paroxetine (Paxil) - Sertraline (Zoloft) - Citalopram (Celexa) - Es-citalopram (Lexapro) - Fluvoxamine (Luvox) - Volazodone (Viibrid) - Vortioxetine (Brintellix)

SNRIs - Duloxetine (Cymbalta, Irenka). This is the antidepressant that has the best evidence for treating many types of chronic pain (e.g., neuropathic pain, fibromyalgia, osteoarthritis, low back pain) - Milnacipran (Savella). This drug is approved for use in fibromyalgia. - Venlafaxine (Effexor, Effexor XR) - Atomoxetine (Strattera) - Desvenlafaxine (Pristiq, Khedezla) - Levomilnacipran (Fetzima) - Tramadol (Ultram, Ultracet)


Some of the more common side effects of antidepressants include:

  • Nausea, constipation, diarrhea, stomach pain, upset stomach, throwing up, or feeling less hungry. These side effects are often worst when the person first starts taking the drug, and get better over a few days to weeks. These side effects are often improved by taking the drugs with food.
  • Headache
  • Dry mouth
  • Trouble sleeping
  • Feeling dizzy, sleepy, tired, or weak
  • Sweating a lot
  • Weight change (both gain or loss)
  • Problems with sex

Some less common but more serious side effects of antidepressants include:

  • Increased risk of suicide. Drugs like these may increase the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take antidepressants need to be watched closely – especially when they first start taking these drugs. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • Allergic reactions. Several different types of serious allergic reactions can occur in response to these drugs.
  • Serotonin syndrome. This is a rare but very serious syndrome associated with taking drugs that increase serotonin. Symptoms include agitation, confusion, changes in balance, flushing, palpitations, shivering or shaking, fever, headache and even seizures.

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