Antidepressants provide analgesia for many pain conditions.
First line drugs for fibromyalgia; neuropathic pain conditions, such as diabetic neuropathic pain, and postherpetic neuralgia.
Used as prophylactic treatment of migraine and tension-type headaches.
Multiple studies have also demonstrated that drugs that increase the bioavailability of both serotonin and norepinephrine, the SNRI, provide much more analgesia than do drugs that affect only one neurotransmitter, such as the SSRIs.
Tricyclic antidepressants (TCAs) are the oldest of the SNRIs.
Guidelines on neuropathic pain recommend the TCAs as first-line drugs, and more recently elevated the newer SNRIs to this same level.
SNRIs include duloxetine (Cymbalta), venlafaxine (Effexor), desvenlafaxine (Pristiq), and milnacipran (Savella).
Duloxetine and milnacipran are the only SNRIs that are FDA approved as analgesics.
Analgesic properties of venlafaxine are also supported by multiple studies.
Duloxetine is currently the only drug approved by the FDA for the treatment of depression and pain.
Studies have confirmed the analgesic effects of venlafaxine and duloxetine in patients with diabetic neuropathic pain, postherpetic neuralgia, and fibromyalgia, and for prophylaxis of migraine and tension-type headache.
Duloxetine is beneficial for osteoarthritic pain and low back pain, and studies on milnacipran are essentially limited to fibromyalgia.
TCAs are at least as efficacious analgesics as venlafaxine, duloxetine, or milnacipran.
The potential for analgesic effects with the TCAs needs to be weighed against their adverse-effect profile of anticholinergic effects, with dry mouth, constipation, and difficulty urinating and may be associated with problems with cognition, and sedation.
Nortriptyline and desipramine have less anticholinergic and antihistaminic effects than the more widely used amitriptyline.
TCAs are also associated with the risk of impaired cardiac conduction.
The above adverse effects limit use of TCAs in the elderly.