A Comparison of Dothiepin versus Placebo in the Treatment of Pain in Rheumatoid Arthritis and the Association of Pain with Depression

Abstract

The effectiveness of dothiepin (a tricyclic anti-depressant) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis. Patients were classified as either 'depressed' or 'not depressed'. The week before, during and 2 weeks after the study, 600 mg ibuprofen was given orally three times daily to all patients. Compared with placebo, dothiepin produced a significant reduction in daytime pain by the end of the treatment period. The Hamilton rating scale in 'depressed' patients was significantly improved in patients given dothiepin. The Cassano-Castrogiovanni self-evaluation rating scale in both 'depressed' and 'not depressed' patients showed a tendency (not significant) to be improved following dothiepin treatment compared with placebo. These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood. Therapy with tricyclic anti-depressants, such as dothiepin, therefore, may determine an improvement of pain indexes besides having an anti-depressant effect.

Psychological factors and their relation to osteoarthritis pain

“…Tricyclic antidepressants have been demonstrated in small trials to be effective at reducing pain in rheumatoid arthritis patients(28-30), but have not achieved widespread use for treatment of that disease, given the development of disease-modifying drugs for that condition; at present there are no available disease-modifying treatments for OA. Three recent meta-analyses of anti-depressant treatment for fibromyalgia have all supported the likelihood of a modest effect on pain with tricyclics(31-33), but duloxetine has demonstrated a significant and repeated effect on tender points and measures of pain in randomized, controlled clinical trials(34, 35).…”

Guidelines for the use of antidepressants in painful rheumatic conditions

“…Only eight of these 15 trials were considered to meet the minimum standards in terms of methodological quality to demonstrate efficacy (Ash et al, 1999;Bird and Broggini, 2000;Frank et al, 1988;Ganvir et al, 1980;Grace et al, 1985;Koh et al, 1997;Macfarlane et al, 1986;Parker et al, 2003).These studies scored from 13 to 22 on a scale with a maximum of 28 (median quality score: 16.4). In almost all these trials, efficacy in the control of pain and symptoms was independent of the antidepressant effect (with the exception of Parker et al (2003) andSarzi Puttini et al (1988)), which included depressed patients). Thus, amitryptyline, trimipramine, dothiepine and paroxetine may have analgesic effects in patients with RA, and amitryptiline may be effective in reducing symptoms in AS.…”

Effect of Milnacipran on Pain in Patients with Rheumatoid Arthritis with Widespread Pain: A Randomized Blinded Crossover Trial

“…No studies have examined the effects of serotonin norepinephrine reuptake inhibitors (SNRIs) on pain in RA, although some have suggested that tricyclic antidepressants, which exert their effects via serotonin and norepinephrine, are effective (13–15). In addition, several studies have examined the role of SNRIs in chronic pain conditions associated with defects in central pain processing (e.g., fibromyalgia) (16–19).…”