There are several types of antidepressants, including:

• Selective serotonin and norepinephrine reuptake inhibitors (SSNRIs). Increase the availability of mood-regulating neurotransmitters serotonin and norepinephrine in the brain. The U.S. Food and Drug Administration (FDA) has approved one SSNRI, duloxetine (Cymbalta),  for relief of painful diabetic peripheral neuropathy. This is the only antidepressant specifically approved by the agency to treat pain. It is one of only two drugs approved to treat diabetic neuropathy, the other being an anticonvulsant.
  
  
• Tricyclic antidepressants (TCAs). Increase the availability of serotonin, norepinephrine and (to a lesser extent) dopamine in the brain.
  
  
• Selective serotonin reuptake inhibitors (SSRIs). Increase the availability of serotonin in the brain.
  
  
• Monoamine oxidase inhibitors (MAOIs). Increase the concentration of chemicals that transmit data between nerves in specific regions of the brain, which may lead to increased cognitive functioning.
  
  
• Serotonin modulators. Block the reuptake of serotonin.
  
  
• Norepinephrine-serotonin modulators. Block certain receptors that accept serotonin and norepinephrine.

TCAs and SSNRIs are known to relieve pain, even in patients who do not suffer from depression. Several TCAs appear to provide roughly the same levels of pain relief, with some subtle variations. Typically, the type of antidepressant prescribed to a patient will depend on the patient’s overall health and susceptibility to side effects.

The most commonly prescribed antidepressant for pain relief, amitriptyline, is also the most sedating of the tricyclics, which may be beneficial in patients who are having problems sleeping.  However, it is associated with a higher incidence of side effects than the other TCAs. Other TCAs commonly prescribed to treat pain include desipramine (Norpramin, Pertofrane) and nortriptyline (Aventyl, Pamelor), which are less sedating than amitriptyline.

In addition to duloxetine, SSNRIs include venlafaxine (Effexor). It appears to provide pain relief at a similar level to that provided by duloxetine.

Lithium, which is prescribed primarily to treat bipolar disorder (manic depression), is also sometimes used in the treatment of cluster headaches.