Department of Rheumatology, Dryburn Hospital, North Road, Durham DH1 5TW, UK
SIR, We read with great interest the paper by Ash et al. [1], and would like to bring to readers' attention our own similar study, presented to the British Society of Rheumatology in 1989 [2].
One hundred and eighty-four patients with rheumatoid arthritis (RA), stable on second-line therapy, were screened for anxiety and depression using the Hospital and Depression scale (HAD); 91% (45%) met the entry requirements (HAD>7 on the subscales or >11 on the combined score), of whom 58 were recruited to receive dothiepin 75 mg or matched placebo for 6 weeks. Exclusions were as in the Ash et al. study, with the addition of patients with severely impaired hand function, who were unable to perform physical measurements (grip strength and finger joint circumference) unaided. These measurements, together with a diary of patients' assessments (visual analogue scale (VAS)) of duration of morning stiffness (EMS), mood, pain on waking, early evening and bedtime, and quality and duration of sleep (minutes), were done for all or part of the study. Assessments by investigators were done at baseline, 2 weeks (when the medication could be increased to 150 mg if the HAD score was still high), and 6 weeks, and were: global assessment score, a five-point scale of the clinical change in RA signs and symptoms; duration of EMS; and overall assessment of the study medication. The HAD scale was repeated at 2 and 6 weeks.
Our groups were well matched, with the exception of the initial HAD scores: group means for total HAD and the anxiety score were significantly higher (P<0.05) in the patients randomly selected to receive dothiepin; 11 patients withdrew (five on dothiepin, six on placebo). The mean HAD scores fell in both groups; within-treatment changes were highly significant (P<0.01) but between-group differences were not. Improvements at 2 weeks in mood, pain, sleep and grip strength occurred in both groups, but were more rapid in the treatment group. At 6 weeks, there was a significant improvement in the evening grip strength; mean pain scores fell in the dothiepin group but were consistent over time in the placebo group, although this did not reach significance owing to the higher entry scores in the dothiepin group.
Although the study of Ash et al. [1] was of slightly longer duration than ours (11 weeks on therapy), this was still not an accurate reflection of usual practice; long-term, low-dose tricyclic medication has now become an accepted part of chronic pain management. Their numbers were small at entry and had a high dropout rate (nearly half), reflecting the problems of high-dose tricyclics. We do not feel that they have acknowledged adequately the major placebo effect of regular frequent contact with health professionals, which, together with active patient participation (as in our study), was partly responsible for the high placebo response.
Ash et al. [1] maintained that few studies had examined the effects of antidepressants on mood in RA patients (they cited only four that were adequately controlled), specifically examined patients with depression, and included measures of anxiety and/or depression. Our study qualified on all three counts. We feel that the use of the HAD questionnaire as a screening tool in rheumatology clinics provides a quick and sensitive method of assessing undeclared psychological problems, and that treatment with tricyclic antidepressants or greater support improves both physical and psychological symptoms.
Notes
Correspondence to: A. J. Chuck.
Accepted 1 June 2000
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Department of Psychiatry, Ormskirk & District General Hospital, Wigan Road, Ormskirk, Lancashire L39 2JW and
1 Department of Psychiatry, University of Manchester, Rawnsley Building, Manchester Royal Infirmary, Oxford Road, Manchester M13, UK
WE would like to thank Chuck and co-authors for bringing the findings of their own study to our attention. We agree that the methods and findings of the two studies are broadly similar, other than that the mood assessment in our study included an observer-rated scale, the Hamilton Rating Scale for Depression (HRSD) in addition to a self-report scale (Hospital Anxiety and Depression Scale), and that the fall in pain scores observed in the study of Chuck et al. did not reach statistical significance. With the limited details of the trial presented in their letter it is not possible to speculate why our findings should have differed in this way.
It is of interest that both studies demonstrate improvement in mood ratings with time in both active drug and placebo groups, yet neither study was able to demonstrate a significant difference between drug and placebo groups, i.e. an antidepressant effect of dothiepin. We feel that this primarily reflects the relatively low threshold for severity of mood symptoms for entry into our study, and we presume that the same would hold for the study of Chuck et al. Severity of depressive symptoms is a predictor of response to antidepressant medication [1], and in our study the mean HRSD scores on entry (15.3 for dothiepin, 15.7 for placebo) were relatively low in comparison to those of psychiatric populations, although they were above the threshold for antidepressant effect.
We accept the comments of Chuck et al. that a drug trial lasting 11 weeks is not an accurate reflection of usual practice. However, this is a fairly typical duration of treatment for a placebo-controlled trial. It is possible that a more prolonged trial might demonstrate a significant effect of dothiepin on pain and depression since the placebo effects seen are likely to be short-lived.
Long-term low-dose tricyclic medication is becoming an accepted part of pain management. However, the approach to treatment of depression with antidepressants in subjects with rheumatoid arthritis remains distinct from that for analgesic augmentation. Doses of 150225 mg should be prescribed if the aim is to effectively treat depression in normal adults. This dose should be continued for at least 6 months after the mood has completely returned to normal. Medication should then be reduced and stopped over a period of 46 weeks unless continued analgesic augmentation is required, when it can be continued at doses of 2550 mg daily. We feel this is an important point, and clinicians should have clear in their mind what they aim to achieve by using antidepressants to avoid inadequate treatment of pain or depression.
We dispute the fact that we have failed to recognize adequately the importance of the placebo response in our subjects, and would direct attention to the last paragraph of our discussion, where we note the subjects included in this study would be likely to benefit from the detailed attention and sympathetic listening involved in repeated assessments ...
We fully endorse the view of Chuck et al. that the HADS questionnaire is a useful screening tool in rheumatology clinics to indicate where treatment of depression will reduce distress and improve quality of life, and may improve coping with physical symptoms.
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