dothiepin-hydrochloride and Arthritis--Rheumatoid

Several studies have shown that 20 to 66.2% of patients with rheumatoid arthritis have associated psychiatric comorbidity especially depression. Dothiepin hydrochloride is a well-established and effective antidepressant in patients with depressive symptoms of varying severity and co-existing anxiety. To document the efficacy and tolerability of dothiepin hydrochloride in the management of major depressive disorder (MDD) in rheumatoid arthritis patients a phase IV, open, single arm, prospective study was initiated with dothiepin hydrochloride in the dose of 75 mg/day, duration of therapy was 6 weeks. Twenty-five rheumatoid arthritis patients suffering from co-morbid MDD completed the 6-week dothiepin hydrochoride treatment and were considered for final analysis. There was significant reduction (p < 0.05) in mean HAM-D scores at week 2 (13.92 +/- 5.45), week 4 (9.28 +/- 4.13) and week 6 (5.72 +/- 3.26) compared to baseline (21.64 +/- 5.93). There was significant reduction (p < 0.05) in mean HAM-A scores at week 2 (6.52 +/- 3.34), week 4 (4.0 +/- 2.25) and week 6 (2.76 +/- 1.59) compared to baseline (10.68 +/- 3.68). The global impression of efficacy at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as marked and moderate improvement in 20 (80%) and 5 patients (20%) respectively. Only 2 patients reported dry mouth as an adverse event in the study. The overall assessment of tolerability at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as good and fair in 19 (76%) and 6 patients (24%) respectively. Dothiepin hydrochloride was found to be an effective and well-tolerated drug in the management of MDD and anxiety in patients suffering from rheumatoid arthritis.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Depressive Disorder; Developing Countries; Dose-Response Relationship, Drug; Dothiepin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; India; Male; Maximum Tolerated Dose; Middle Aged; Patient Satisfaction; Prospective Studies; Risk Assessment; Severity of Illness Index; Single-Blind Method; Treatment Outcome

Topics: Antidepressive Agents, Tricyclic; Arthritis, Rheumatoid; Depressive Disorder; Dothiepin; Humans; Treatment Outcome

The relative importance of direct analgesic and antidepressant effects of antidepressant drugs in rheumatoid arthritis (RA) is not clear.. Forty-eight female out-patients with RA, with depression and/or anxiety, were entered into a double-blind, placebo-controlled study of dothiepin in doses up to 150 mg daily to assess the effects on mood [Hospital Anxiety and Depression (HAD) scale and Hamilton Rating Scale (HRS) for Depression], pain [visual analogue scale (VAS)] and disability [Health Assessment Questionnaire (HAQ)].. Repeated measures multivariate analysis of variance revealed that treatment had a significant effect on pain (F(d.f. 1,39) =5.7, P=0.02). There were further interaction effects between treatment and time on pain (F(d. f. 3,117) =3.3, P=0.03), disability (F(d.f. 3,117)=4.2, P=0.008) and duration of early morning stiffness (F(d.f. 3,117) =3.3, P=0.03). Depression (HRS) was considerably reduced in both the dothiepin and placebo groups, and there was no significant difference between groups. Post hoc analyses using analysis of covariance revealed that, in the dothiepin group, pain was significantly reduced by week 4 and remained so at week 12. Disability scores and duration of early morning stiffness were consistently lower in the dothiepin group, although differences failed to reach statistical significance at any follow-up assessment. In the group as a whole, reductions in pain were highly significantly correlated with reductions in HAD depression (r =0.63, P<0.0005), HAD anxiety (r=0.46, P=0.001) and HRS depression (r=0.37, P=0.01).. Dothiepin is effective in relieving pain, disability and reducing the duration of early morning stiffness in out-patients with RA. Although there is a general association between pain reduction and improved anxiety and depression, the analgesic effect of dothiepin is independent of its antidepressant effect. Individual variation is considerable and further research should try to identify mechanisms of interaction between the antidepressant and analgesic effects of treatment in different patient groups.

Topics: Affect; Aged; Analgesia; Analysis of Variance; Antidepressive Agents, Tricyclic; Anxiety; Arthritis, Rheumatoid; Depression; Dothiepin; Double-Blind Method; Female; Humans; Middle Aged; Pain; Placebos