Abstract
S.M. Razali and C.I. Hasanah, Department of Psychiatry, School of Medical Sciences, Universiti Sains Malaysia, Malaysia:
Recently, there have been arguments about the cost-effectiveness of newer antidepressants as compared with tricyclic antidepressants (TCAs); the consensus opinion was favourable for tricyclics [1], [2], [3]. We, in a developing country, would like to share our experience with other colleagues regarding the use of conventional antidepressants. We do not have much exposure to newer antidepressants. We have used cyclic antidepressants routinely in our daily practice because the selective serotonin re-uptake inhibitors (SSRIs) are not easily available.
We have completed a short clinical trial to assess the efficacy and safety profile of cyclic anti-depressants. The trial involved 82 consecutively depressed outpatients aged below 60 years, attending the psychiatric clinic of the Universiti Hospital (USM) for the first time. They had fulfilled the DSMIII-R [4] diagnostic criteria for depressive illness. To be included in the study, they had to have a minimum baseline Hamilton Depressive Rating Scale (HDRS) [5] score of 16 and were safe to be managed at home (i.e. not a high suicidal risk). The attending psychiatrists did the initial assessment. They also selected the type and initial dose of antidepressants based on clinical judgement. The choices of antidepressants were amitriptyline, imipramine, dothiepin and maprotiline. The SSRIs are not available as a standard drug and any patients that required SSRIs or needed their substitution were dropped from the study.
All of the patients were followed up by their respective psychiatrists. The maximum daily dose of antidepressants allowed was 175 mg of imipramine or equivalent for 8 week's trial. The highest effective dose was clinically determined from the patients' improvement and ability to tolerate the side effect. Response to the treatment was defined by the reduction of more than 50% of the HDRS score or attaining the minimum score of 12 or below. The daily drug intake checklist monitored drug compliance. Patients with poor compliance or those manipulating the checklist were dropped from the study. The patients were assessed by independent psychiatrists who were blind to the dose and type of medication at the end of 8 weeks. The interrater reliability using the HDRS was satisfactory and continuously checked throughout the study.
Out of 82 selected patients, 75 completed 8 weeks' clinical trial. Those defaulting follow-up and who had poor compliance were dropped from the study. The baseline of the HDRS score ranged from 16 to 29 with a mean of 20.2 (SD == 3.9). Of the 75 patients who had completed the trial, 68 were tolerating cyclic anti-depressants; only seven (9%) patients required SSRIs and were dropped from the study. Forty-nine (65%) patients improved with TCAs and the other 11 (15%) were effectively treated with tetracyclic anti-depressants (maprotoline). The most popular choice of antidepressants was dothiepin (newer T C A s). However, eight (11%) patients did not respond to the treatment regime at the end of 8 weeks and required higher doses of antidepressants.
Since the majority of the patients could tolerate cyclic antidepressants, especially the newer TCAs that have a better side-effect profile, it seems that the routine first line treatment with SSRIs in this country at current prices is not cost-effective. The cost of treatment with 100 mg of fluvoxamine (the cheapest of the SSRIs on the market) daily is four and 31 times higher than the cost of 75 mg dothiepin and the equivalent dose of amitriptyline, respectively. The comparison with fluoxetine is even more frightening because a tablet of 20 mg fluoxetine costs 2.2 times more than a tablet of 100 mg fluvoxamine. The situation in other developing countries in the South-East Asia is similar. The SSRIs are too expensive and out of reach of the majority of the population who always get free treatment from government hospitals. Our finding is in line with Woods and Rizzo's [6] suggestion that it appears more cost-effective to reserve SSRIs for patients who are not responding adequately to initial treatment with TCAs.