Buprenorphine Linked to Greater Reduction in Opioid Use Compared to Methadone


BUP associated with lower likelihood of any opioid use among participants with mood disorders, without mental disorder, compared to MET.

Yih-Ing Hser, Ph.D

Yih-Ing Hser, Ph.D

A recent study investigated differences in reduction in opioid use treated by either buprenorphine-naloxone (BUP) or methadone (MET) in adults with comorbid opioid use disorder (OUD) and mental disorders.

Investigators, led by Yih-Ing Hser, Ph.D., UCLA Integrated Substance Abuse Programs, found adults with OUD and mental disorders had greater reduction in opioid use with buprenorphine compared to treatment with methadone.

As mental disorders in patients with OUD are common, investigators noted a need to incorporate complex factors involved in influencing outcomes of medication treatment for OUD (MOUD).


Before the findings, investigators hypothesized OUD patients with mood disorder would have better outcomes after buprenorphine treatment, citing its antidepressant effects, compared to patients treated with methadone.

The study used data from a multi-site, prospective study that randomized 1269 participants with DSM-IV opioid dependence from 9 federal opioid treatment clinics during 2006 – 2009.

Patients received either BUP or MET for 24 weeks. After the medication period, patients were referred or transferred to community treatment program, or were tapered off medication over ≤8 weeks.

In addition, 3-year follow-up assessments were conducted with 1080 participants during 2011 – 2016.

The Starting Treatment with Agonist Replacement Therapies (START) was a Phase IV study to compare the effects of BUP and MET on liver function and served as the parent study.

Of the 1080 patients in long-term follow up, 797 completed follow-up Interview One (Visit 1), 728 completed Interview Two (Visit 2), which included a structured psychiatric interview (723 participants completed the psychiatric interview), and 647 completed Interview Three (Visit 3).

A total of 597 participants had relevant data for the present secondary analysis.

The study outcome measure included the number of days of using opioids per month during the follow-up period, while the percentage of follow-up months with opioid use was calculated as the number of follow-up months with at least one day of opioid use divided by the total number of follow-up months

Investigators used the Mini-International Neuropsychiatric Interview (MINI), a 17-module assessment of psychiatric disorders, to define lifetime mood disorders, including major depressive episode, (hypo)manic episode, and a mood disorder with psychotic symptoms.

In addition, they complied 3 groups based on the mood disorder diagnosis as mood diroder (bipolar, major depressive disorder), mental disorder other than mood disorder (anxiety disorder, antisocial personality disorder), and no mental disorder.

They used medication treatment (BUP, MET, no treatment) in the follow-up as a time-varying predictor.

Investigators used a zero-inflated poission (ZIP) mixed model with 2 portions, including logistic regression for modeling a repeated dichotomous outcome (1 for any use, 0 for no use) and a Poission regression for modeling repeated-count outcome (number of days using opioids each month).


After data collection, the team found 50.6% of the study participants had mood disorder, 19.1% had mental disorder other than mood disorder, and 30.3% did not have any comorbid mental health diagnoses. No difference in demographics were found at baseline.

There were no differences in opioid found during the follow-up period in the 3 mental disorder groups.

The team found opioid use during the follow-up had a significant reduction by BUP (OR, 0.12; 95% CI, 0.07-0.21 for any use; risk ratio (RR), 0.77; 95% CI, 0.66-0.89 for days of use)

A reduction in opioid-use by MET (OR, 0.33; 95% CI, 0.25 - 0.45 for any use; RR, 0.78; 95% CI, 0.72 - 0.84 for days of use) was found in patients with no mood disorder.

Further, BUP was associated with a lower likelihood of opioid use (OR, 0.52; 95% CI, 0.36 - 0.74) among patients with a mood disorder, in participants without mental disorder (OR, 0.37; 95% CI, 0.21 - 0.66).

It was also associated with fewer number of days using opioids (RR, 0.37; 95% CI, 0.25-0.56) among participants with other mental disorders.

In addition, the poission ZIP model showed that injection use (RR, 4.15; 95% CI, 1.44 – 11.94) and randomization to BUP versus MET (RR 3.14; 95% CI, 1.20 – 8.19) were associated with an increased number of opioid use days.

However, both treatments were associated with reduced opioid use among participants without mental disorder in BUP (RR 0.77, 95% CI, 0.66-0.89) and in MET (RR 0.78, 95% CI, 0.72-0.84).

As well, opioid use was reduced in participants with mood disorder in BUP (RR, 0.80; 95% CI, 0.73-0.88) and in MET (RR, 0.72; 95% CI, 0.68-0.76) compared with those not receiving any MOUD treatment.

In addition, only participants on BUP showed significant reduction of opioid use days among participants with comorbid mental disorders other than mood disorders (RR, 95% CI: 0.38, 0.25-0.56; P <0.001) compared with those without treatment.


Investigators concluded among adults with comorbid OUD and mental disorders, treatment with BUP had a greater reduction in opioid use in comparison to treatment with MET.

They also noted that regardless of mental health condition type, treatment with either BUP or MET led to less opioid use than participants not treated with MOUD.

“Strategies to expand access to and engagement in all types of MOUD, especially BUP, and to retain OUD patients in MOUD are essential to address OUD and comorbid mental health complications,” investigators wrote.

The study, “Long-term Follow-up Assessment of Opioid Use Outcomes among Individuals with Comorbid Mental Disorders and Opioid Use Disorder Treated with Buprenorphine or Methadone in a Randomized Clinical Trial,” was published online in Addiction.

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