Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial Diana D. Cardenas a, * , Catherine A. Warms a , Judith A. Turner a,b , Helen Marshall a , Marvin M. Brooke c , John D. Loeser d a Department of Rehabilitation Medicine, Box 356490, University of Washington, Seattle, WA 98195, USA b Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, USA c Good Samaritan Hospital, Puyallup, WA 98371, USA d Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA Received 6 August 2001; received in revised form 15 November 2001; accepted 29 November 2001 Abstract Chronic pain in persons with spinal cord injury (SCI) is a difficult problem for which there is no simple method of treatment. Few randomized controlled trials of medications for pain in persons with SCI have been conducted. This study was designed to determine whether amitriptyline, a tricyclic antidepressant, is efficacious in relieving chronic pain and improving pain-related physical and psychosocial dysfunction in persons with SCI. Eighty-four participants with SCI and chronic pain were randomized to a 6-week trial of amitriptyline or an active placebo, benztropine mesylate. All pre- and post-treatment assessments were conducted by evaluators blind to the allocation. Regression analyses were conducted to examine whether there was a medication group effect on the primary (average pain intensity) and secondary outcome measures. No significant differences were found between the groups in pain intensity or pain-related disability post- treatment, in either intent-to-treat analyses or analyses of study completers. These findings do not support the use of amitriptyline in the treatment of chronic pain in this population, but we cannot rule out the possibility that certain subgroups may benefit. q 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. Keywords: Chronic pain; Spinal cord injury; Amitriptyline 1. Introduction Although tricyclic antidepressants (TCAs) have long been used to treat chronic pain in persons with spinal cord injury (SCI), clinical studies are limited. In a meta-analysis of 39 controlled trials (Onghena and Van Houdenhove, 1992), antidepressants were found to be beneficial in the treatment of chronic pain; however, only one of the clinical trials focused on SCI pain (Davidoff et al., 1987). This study, the only controlled trial of an antidepressant in the treatment of pain associated with SCI, failed to show signif- icant pain relief with trazodone, a heterocyclic antidepres- sant that, unlike TCAs, selectively inhibits serotonin and norepinephrine reuptake in a ratio of 25:1 (Davidoff et al., 1987). Suggestive evidence that at least some antidepressant medications may be effective in relieving pain in SCI patients comes from several studies that demonstrated the efficacy of antidepressant medication in relieving peripheral neuropathic pain (Langohr et al., 1982; Kvinesdal et al., 1984; Max et al., 1987, 1988; Kishore-Kumar et al., 1990; Lynch et al., 1990; Sindrup et al., 1990). Similarities between central pain states and peripheral neuropathic pain include the character of the pain, the sensory abnorm- alities, and the poor response to analgesic drugs (Leijon and Boivie, 1989). According to Leijon and Boivie (1989) the most commonly used medications to treat central pain are antidepressants. Their study of central pain demonstrated significant post-stroke pain relief with amitriptyline compared with placebo (Leijon and Boivie, 1989). In a case report of a woman with SCI, a combination of amitrip- tyline and carbamazepine was more effective in relieving dysesthetic pain than was either drug alone (Sandford et al., 1992). Others have recommended TCAs specifically for pain associated with SCI (Donovan et al., 1982; Farkash and Portenoy, 1986), but these recommendations are based on case reports. Given the similarities between central and peripheral neuropathic pain conditions, and the preva- lence of central pain problems in SCI (Siddall et al., 1999; Turner et al., 2001), there is reason to believe that treatments effective for peripheral neuropathic pain may be effective Pain 96 (2002) 365–373 0304-3959/02/$20.00 q 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. PII: S0304-3959(01)00483-3 www.elsevier.com/locate/pain * Corresponding author.