Dothiepin

Paper: The effects of dothiepin on subjects with rheumatoid arthritis
and depression

Authors: Ash, G, et al
Ref: Rheumatology. 1999;38:959-967.
Type: Prospective clinical study

Summary: Several studies have demonstrated that antidepressant drugs may have analgesic effects in rheumatoid arthritis (RA) patients, but the
mechanisms by which they achieve this effect are not clear. This study examined the effects of the antidepressant agent dothiepin on pain relief, depression, and anxiety, as well as other measures of RA activity, in female RA patients with depression.

Forty-eight female RA patients with depression and/or anxiety were randomized to receive either dothiepin (25 patients, up to 150 mg/day) or placebo (23 patients). Subjects were assessed at baseline and at 2, 4, 6, 10, and 12 weeks after commencement of the study. The Hospital Anxiety and Depression (HAD) scale was used to measure mood, the Hamilton Rating Scale (HRS) to assess depression, the visual analog scale to determine pain, and the Health Assessment Questionnaire (HAQ) to evaluate disability.

Erythrocyte sedimentation rate (ESR) was also determined as an objective measure of inflammation, the Ritchie Articular Index was used to assess disease activity clinically, and the duration of morning stiffness was also recorded.

In the dothiepin group, pain was significantly reduced by week 4 and continued through the end of the study at week 12. Depression (HRS) and HAD anxiety were reduced in both groups but did not differ significantly between the two groups. There was an interaction between dothiepin treatment and time in reducing pain, disability, and duration of morning stiffness. In the entire group, reductions in pain were highly
correlated with decreases in HAD depression, HAD anxiety, and HRS depression. The pattern of change in pain and anxiety/depression varied from one patient to another.

Patients taking dothiepin also experienced a nonsignificant decrease in Ritchie Index. ESR did not change significantly in either patient group, suggesting that dothiepin does not exert it effects on pain, disability, and morning stiffness by altering the inflammatory process.

"Dothiepin 150 mg daily is an effective analgesic for RA patients and may also have a beneficial effect on disability and the duration of early morning stiffness," wrote the authors. "In view of the time course of effect, we suggest that this effect is likely to be principally mediated by a direct analgesic mechanism similar to that suggested in
previous reviews."