The effects of dothiepin on subjects with rheumatoid arthritis and depression.
BACKGROUND
The relative importance of direct analgesic and antidepressant effects of antidepressant drugs in rheumatoid arthritis (RA) is not clear.


METHODS
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)].


RESULTS
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).


CONCLUSIONS
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.
Ash
G
G
Department of Psychiatry, Ormskirk and District General Hospital, Wigan Road, Ormskirk, Lancashire L39 2AZ, UK.
Dickens
C M
CM
Creed
F H
FH
Jayson
M I
MI
Tomenson
B
B
D000339:Affect / Q000187:drug effects; D000368:Aged; D000698:Analgesia; D000704:Analysis of Variance; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage*; D001007:Anxiety / Q000150:complications / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000523:psychology; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D004308:Dothiepin / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D010919:Placebos
D000929:Antidepressive Agents, Tricyclic; D010919:Placebos; D004308:Dothiepin