Antidepressants

What are Antidepressants?

While antidepressants weren't originally designed to treat neuropathic pain, they have become one of the most common medications for pain management.

How do they work?

How antidepressants relieve pain is not completely understood. It is known that antidepressants alter neurotransmitter activity; it is thought that that this is the mechanism through which pain is modified. Different classes of antidepressants affect different neurotransmitters, including acetylcholine, norepinephrine, serotonin or combinations.

Pain relief, however, isn’t necessarily immediate and may take weeks to begin. One-third of patients diagnosed with neuropathic pain report moderate (or better) relief of pain with the use of antidepressants. In many cases, the dose used for pain relief may be lower than the dose typically used for treating depression. As a common side effect of antidepressants, somnolence (or drowsiness) may improve the ability to sleep in patients. Similarly, they may be a good choice if you are suffering from both depression and chronic neuropathic pain.

What kinds are there?

• Tricyclic antidepressants (TCAs) 
  Examples: amitriptyline, nortriptyline, desipramine and imipramine
  TCAs are one of the most commonly used antidepressants for pain management. TCAs are most often prescribed in lower doses than would be prescribed for managing depression. In these low doses, side effects are mild but may include: blurred vision, drowsiness, weight gain, constipation, problems with heart rhythm and difficulty urinating.  
  
  
• Serotonin and norepinephrine reuptake inhibitors (SNRIs)
  Examples: venlafaxine and duloxetine 
  Like TCAs, SNRIs are thought to work on more than one neurotransmitter system. These types of 'dual action' antidepressants are considered first-line medication treatments for neuropathic pain. In addition, depression can sometimes develop in patients diagnosed with chronic pain. In these instances, SNRIs may be effective for treating both depression and pain. Side effects for SNRIs may include nausea, insomnia, restlessness, drowsiness, diarrhea or constipation, or excessive sweating.  
  
  
• Selective serotonin reuptake inhibitors (SSRIs)
  Examples:  paroxetine and fluoxetine
  SSRIs aren’t thought to be useful in treating pain directly. However, they can be effective in treating pain-related depression and some SSRIs are thought to boost the effects of some TCAs (so-called 'combination treatment'). Side effects of SSRI use are similar to SNRIs. 

Related evidence

Lunn MPT, Hughes RAC, Wiffen, PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. The Cochrane Collaboration. 2014 Jan 3. doi: 10.1002/14651858.CD007115.pub3

Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. The Cochrane Collaboration. 2012 Aug 15. doi:10.1002/14651858.CD005454.pub2#sthash.zFMuncTW.dpuf