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Simon Collins, HIV i-Base
A study by Angela Dean from the University of Queensland and colleagues in the journal European Psychiatry has reported similar improvements in depression in patients using either methadone (MM) and buprenorphine (BM) as opiod substitution therapy (OST). [1]
This is important because this benefit of OST is not widely understood, or reported for methadone, and because early studies of buprenorphine emphasized it’s antidepressant effect as a potential advantage.
This was a sub-study of a much larger trial. [2] The authors studied the antidepressant affects in 54 patients who were part of a randomised controlled trial (with additional matched placebo) of daily 30mg MM syrup vs 4mg BM sublingual tablets in 405 heroin-dependent patients seeking opioid maintenance treatment. Doses were individually titrated based on patient assessment to optimise response.
Daily dosing occurred for 6 weeks, after which alternate day dosing began. Those on buprenorphine received double their previous daily dose (or increased to the maximum permitted dose of 32 mg) on alternate days and placebo on interposed days. Methadone patients received a corresponding increase in their placebo buprenorphine tablets to maintain the blind.
Baseline demographics included approximately 60% men, 40% women; age 30; 6-7 years heroin use (with a wide range); and 70-80% prior treatment for opiate dependence.
Depression was measured using the self-report Beck Depression Inventory (BDI) at baseline and after 3 months. Symptoms of depression significantly improved in both treatment groups over the study period (p<0.001) with no differences between groups (p=0.83). Neither previous duration of heroin use, nor dose levels of either drug were related to results on the depression score. These results are detailed in Table 1.
Table 1: Depression score results
With patients in the methadone group, a higher baseline depressive symptoms predicted higher symptoms at 3 months (p<0.01) and there was a significant relationship between adherence (as % of doses taken in last 30 days) and BDI at 3 months (p<0.05). Neither factor was significant for the buprenorphine group (p=0.38 and p=0.58 respectively).
The 9% of the study group using antidepressants had a smaller improvement in BDI scores but a modest but significant relationship between BDI scores and heroin use over the previous month.
This study therefore found no differential benefits of buprenorphine vs methadone on depressive symptoms. The high levels of depressive symptoms at treatment entry and subsequent improvement over time in both groups are consistent with other research. [3, 4]
However the authors also noted that given the small sample size, the power to detect group differences is low, and that that larger samples would be required in future studies. Other factors that could have impacted on the results, included differences in dosing and under-reporting of antidepressant use.
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Questions:
This is from 2004 – have other larger studies reported on this, or confirmed the findings?
Did the authors republish later when all 147 subjects had both baseline and 3 months – ie increasing the study power?
Double blind studies with methadone and buprenorphine are very difficult to do.
Certainly the antidepressant effect of methadone and buprenorphine are well recognised clinically, but few studies are designed study to document the effect. This study was designed to show that the antidepressant impact of buprenorphine may be an advantage over methadone, but by comparing both drugs in a randomised placebo-controlled study, the methadone effect was also clearly identified.
The cause-effect relationship is complicated. Clearly OST has an antidepressant effect, but is it the medication, or is it the cessation of all those psychosocial negative impacts of chaotic heroin use and the benefits of achieving some control over you life which is the antidepressant effect?
Alternatively it may just be the cessation of the rapid up-and-down cycles associated with regular heroin use. Maybe repeated low-grade withdrawal is a depressant, and preventing it, a powerful antidepressant?
Many questions, few answers.
References
1. Dean AJ et al. Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence. Short communication. European Psychiatry 19 (2004) 510–513.
2. Mattick RP et al. Buprenorphine versus methadone maintenance therapy: a randomized doubleblind trial with 405 opioid-dependent patients. Addiction 2003;98:441–52.
3. Rounsaville BJ et al. Diagnosis and symptoms of depression in opiate addicts: course and relationship to treatment outcome. Arch Gen Psych 1982; 39:151–6.
4. Strain EC et al. Early treatment time course of depressive symptoms in opiate addicts. J Nerv Ment Dis 1991;179: 215–21.
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