Antidepressants should be first-line approach for nerve tissue pain

July 19, 2005

New reviews of previous studies confirm that older-style antidepressants, as well as anticonvulsant drugs, can help ease the disabling pain caused by nerve tissue damage.

Often felt as a burning, tingling or stabbing sensation, neuropathic pain can result from nerve injuries or from conditions including chronically high blood sugar, complications from shingles or some cancer treatments.

For many years antidepressants, which are believed to work by dampening pain signals, have been the first-line drugs for neuropathic pain. "It is usual to start with an antidepressant like amitriptyline, and if this fails then try an anticonvulsant," says Phil Wiffen, a researcher at Churchill Hospital in Oxford, England. "The results of these meta-analyses suggest this is probably still the best approach to take."

Wiffen led several systematic evidence reviews on the effect of various antidepressants and anticonvulsives on pain, appearing in the current issue of the Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Wiffen and Tiina Saarto, M.D., analyzed 50 trials of 19 antidepressants, which involved more than 2,500 study participants. They found that tricyclic anti-depressants, particularly amitriptyline, can help ease the two most common types of neuropathic pain: from diabetes and shingles. The researchers recommend more studies of the effects of other antidepressants such as the newer selective serotonin reuptake inhibitors (SSRIs) and selective Norepinephrine Reuptake Inhibitors (SNRIs), as well as alternative medicines such as St. John's Wort, before they can be recommended for neuropathic pain.

These results on tricyclics may be encouraging but "antidepressants do not cure or totally eliminate all pain," says Dennis C. Turk, Ph.D., at the University of Washington.

"The amount of pain reduction is moderate at best. Typically the pain reduction averages around 40 percent in 50 percent of treated patients," Turk says. "This means that a significant proportion of patients do not obtain even moderate reductions in pain and even those who do continue to experience significant pain."

The findings on anticonvulsants are similarly both encouraging and sobering. Originally developed to treat epilepsy, anticonvulsants have been used to treat pain since the 1960s, and are believed to work by quieting abnormal firings of nerves in the brain and central nervous system.

Anticonvulsant drugs currently used for neuropathic pain are: carbamazepine, gabapentin, clonazepam, gabapentin, lamotrigine, oxcarbazepine, phenytoin, valproate and, most recently, pregabalin.

To evaluate the effectiveness of carbamazepine, Wiffen and colleagues examined 12 studies, which included more than 400 participants. "There is evidence to show that carbamazepine is effective but trials are small," write Wiffen and colleagues.

Gabapentin is a newer drug that is becoming so popular that it has reaped more than $2 billion in yearly sales in recent years, mostly for neuropathic pain treatment. After examining 15 studies of gabapentin that consisted of nearly 1,500 participants, the researchers found its effectiveness to be comparable to carbamazepine.

Gabapentin has fewer side effects than carbamazepine so it may be a good choice for some, but it's more expensive, and cheaper treatments are equally effective.

"Gabapentin is not superior to carbamazepine," Wiffen says. "It works, but so do carbamazepine and tricyclic antidepressants, which are far more affordable.

In their general analysis of anticonvulsants, Wiffen and colleagues examined 23 trials consisting of more than 1,000 patients. These results of these studies were conflicting, suggesting the need for more studies of the effectiveness of each anticonvulsant, along with comparison studies of anticonvulsants and antidepressants, according to the researchers.

"The evidence here does not support the use of anticonvulsants as first-line remedies," write Wiffen and colleagues, adding that tricyclic antidepressants should be the first choice.

Turk says the newer antidepressants, the SSRIs and SNRIs - are worth trying even though the jury is still out on their effectiveness for neuropathic pain, but the side effects are more manageable.

"Neuropathic pain can be extremely severe, disabling, and recalcitrant to treatment," Turk says. "It is therefore reasonable to try patients on antidepressants and combinations of antidepressants with other drugs in what has come to be known as 'rational polypharmacy.'"
Health Behavior News Service: 202-387-2829 or
Interviews: Contact Phil Wiffen at 44-186-522-5762 or
To receive a full copy of the review or to arrange an interview with an author, contact Julia Lampam at 44-124-377-0668 or

Wiffen P, Collins S. et al. Anticonvulsant Drugs for Acute and Chronic Pain; Saarto T & Wiffen, PJ. Anitdepressants for Neuropathic Pain; Wiffen PJ, McQuay HJ, Moore RA. Carbamazepine for Acute and Chronic Pain; Wiffen PJ, McQuay HJ, Moore RA. Gabapentin for Acute and Chronic Pain (Reviesw) The Cochrane Database of Systematic Reviews 2005, Issue 3

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit for more information.

Center for Advancing Health

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