Tricyclic antidepressants are probably the most commonly used adjuvant analgesics in the management of chronic pain. An adjuvant analgesic is a medication that is used to control pain despite that it is not designed for pain management. The tertiary amines (amitriptyline, imipramine, doxepin, and clomipramine) and the secondary amines (nortriptyline and desipramine) both have analgesic properties.
Amitriptyline is the prototype antidepressants used in this context. Clinical efficacy of tricyclics for neuropathic pain has been demonstrated by numerous well-controlled double blind clinical studies for both neuropathic and somatic pain. Clinical experiences, as well as the results from uncontrolled trials, generally support the analgesic effect and use in neuropathic pain syndromes. Clinicians have to be familiar with the possible side effects of amitriptyline, especially in elderly patients. These adverse effects include sedation, dry mouth, constipation, urinary retention, glaucoma, orthostatic hypotension and cardiac arrhythmias. Patients should be warned about the side effects before they start the medication. Amitriptyline should be avoided in patients with a history of heart disease (conduction disorders, arrhythmias or heart failure) and closed-angle glaucoma. Amitriptyline should be started at a relatively low dose (10 mg) at bedtime and slowly titrate up as tolerated. Most patients report improved sleep after taking amitriptyline. The onset of pain relief may precede the anticipated onset of antidepressant effects. In general, pain relief may be expected in 7 to 14 days. The dosage required for pain management is usually lower than for depression; 75 to 100mg at bedtime is often effective. If the patient cannot tolerate this dose, or is not a good candidate for amitriptyline, other tricyclics such as nortriptyline or desipramine may be considered. These secondary amines generally have less anticholinergic effects and, therefore, are better tolerated than the tertiary amines. However, their clinical efficacy is not as well established as that for amitriptyline.
The main advantage of the selective serotonin reuptake inhibitors is the favorable side-effect profile. However, selective serotonin reuptake inhibitors are clearly less effective than tricyclic antidepressants NNT (Number Needed to Treat to reach 50% pain relief): 6.7 vs. 2.4). Venlafaxine is a selective serotonin/noradrenaline reuptake inhibitor. Randomized controlled trials show good pain relief for painful polyneuropathy and also for neuropathic pain following treatment of breast cancer. Duloxetine, a newer selective serotonin/noradrenaline reuptake inhibitor, has also been demonstrated to have some analgesic effects in neuropathic pain. Bupropion, a noradrenergic compound, also has analgesic effects in neuropathic pain and often is activating. The latter effect can be particularly helpful in the hypoactive, depressed, sedated, or fatigued patients. However, bupropion is not significantly better than the placebo in the treatment of patients with non-neuropathic chronic low back pain. Trazodone (a serotonin-reuptake inhibitor as well as a postsynaptic serotonin receptor antagonist) does not appear to be effective for the treatment of chronic pain. Evidence for the efficacy of trazodone in treating insomnia is also very limited. The table below presents the tricyclic antidepressants most commonly used for pain management.