Anti-Depressant Medication Used to Treat Low Back Pain

While several classes of anti-depressants have been used successfully in the treatment of a variety of pain syndromes, the literature most strongly supports the analgesic efficacy of the tricyclics (anti-depressant drug). Amitriptyline (a type of anti-depressant) has been investigated as an analgesic more than the other anti-depressant agents and appears to be the most popular anti-depressant analgesic in the clinical setting. Migraine headaches, neuropathic pain associated with diabetic neuropathy, and postherpetic neuralgia have been found to respond favorably to anti-depressant administration.

These agents have also been found to alleviate the pain associated with musculoskeletal conditions such as fibromyalgia, rheumatoid arthritis, and osteoarthritis. Anti-depressants have been successfully utilized in the treatment of cancer pain. In the cancer population, when administered concurrently with an anti-depressant, opioid agents may be used at a reduced dose and with a diminished incidence of side effects.

The analgesic abilities of anti-depressants were once felt to be related to the alleviation of the depression, which can often accompany persistent pain, but several anti-depressants have been found to reduce pain symptoms in patients not experiencing co-morbid depression. These agents are now believed to have primary analgesic abilities, which are most likely related to their effects on monoamines in endogenous pain pathways. The efficacy of both serotonin and norepinephrine selective anti-depressants would suggest that effects on pathways which involve either of these transmitters might contribute to analgesia. Other suggested mechanisms of analgesia involve the antihistamine properties of some agents, increased endorphin secretion, and an increased density of cortical calcium channels.

In a study of 44 patients admitted for low back pain, Jenkins et al compared treatment with oral imipramine (Tofranil®), 25-mg t.i.d. (three times per day), with placebo over a four-week period. After treatment, no significant difference in improvement in straight leg raising, pain and stiffness assessments, nor psychological testing was noted between the two study groups. In those individuals with apparent discogenic pain, imipramine treated patients demonstrated greater improvement in pain and stiffness, but this was not found to be statistically significant. No significant difference in side effects was noted between the two groups.

In a study of 48 patients with chronic low back pain, treatment with imipramine was compared to placebo. Seven of the patients included were determined clinically depressed according to standard criteria. Patients completed Beck depression questionnaires at both the initial and final visits. Depression score improvements, while not statistically significant, were noted in those patients who benefited from imipramine treatment. Individuals treated with imipramine did demonstrate a significant improvement in both limitations of work and restrictions in normal activities. Anticholinergic side effects were associated with a 10% dropout rate.

In a review of the literature on anti-depressants in the treatment of chronic low back pain, Egbunike et al concluded that the most consistent responses were found with doxepin (Sinequan®) and desipramine at doses above 150-mg daily. Some studies may have failed to demonstrate a response secondary to inadequate dosing. Other anti-depressants were found less effective in providing analgesia. In several studies reviewed, while improvements in depression were observed, poor correlations were noted between analgesic effects and changes in the severity of depression. The relationship between pain relief and anti-depressant effect remains unclear.

Dosage
Tricyclic anti-depressants (TCAs) produce analgesia at lower dosages than are typically prescribed for the treatment of depression. The starting dose of the tricyclics should be low. Initial daily dosing of amitriptyline should be 10-mg in elderly patients and 25-mg in younger individuals. Every two to three days an increment in dosing equal to the initial starting dose can be made until adequate analgesia is achieved or adverse effects develop.

The typical effective daily dose of amitriptyline ranges from 50- to 150-mg, although doses as low as 10-25-mg can be helpful in some patients. As the TCA half-life is generally long and sedation is a common side effect, single nighttime dosing can be prescribed. Some patients report better pain relief and less morning drowsiness with divided daily dosing. Those studies, which have investigated the analgesic efficacy of selective serotonin reuptake inhibitors (SSRIs), have typically involved dosages similar to those prescribed in the management of depression, 20- to 40-mg of fluoxetine or paroxetine. Further research is needed in order to clarify the relationship between dosage and analgesia with the serotonin specific agents.

Adverse Effects
The occurrence of serious adverse effects resulting from antidepressant administration is low. These complications would be rare at the generally lower dosages utilized in the treatment of pain. While cardiac side effects are uncommon, tricyclics are contraindicated in those individuals with heart failure or serious cardiac conduction abnormalities. Orthostatic hypotension is the most frequent cardiovascular adverse effect, and the elderly are particularly at risk. The sedating effect often observed with anti-depressant use can be beneficial as patients with pain often demonstrate diminished daytime functioning from inadequate sleep.

Anticholinergic side effects such as dry mouth, blurred vision, and urinary retention are more likely with amitriptyline use than with other TCAs. These effects are also less likely at the lower dosages used for analgesia. Nortriptyline and desipramine have been found to induce fewer anticholinergic side effects and are less sedating.

While anti-depressants have been demonstrated as useful adjuncts in the treatment of pain, their analgesic mechanism remains unclear. Initial dosing should be low and then slowly increased to minimize side effects. When taken at night, the sedating properties of these agents can be beneficial in those pain patients experiencing difficulty with sleep.

Reference:
Malanga GA, et al. Pharmacologic Treatment of Low Back Pain. In Physical Medicine and Rehabilitation State of the Art Reviews, Philadelphia, Hanley and Belfus Vol.13, No.3, October, 1999