Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults

Abstract

Objective: To describe the clinical effect and safety of low-dose buprenorphine, a κ-opioid receptor antagonist, for treatment-resistant depression (TRD) in midlife and older adults.

Method: In an 8-week open-label study, buprenorphine was prescribed for 15 adults aged 50 years or older with TRD, diagnosed with the Structured Clinical Interview for DSM-IV, between June 2010 and June 2011. The titrated dose of buprenorphine ranged from 0.2-1.6 mg/d. We assessed clinical change in depression, anxiety, sleep, positive and negative affect, and quality of life. The Montgomery-Asberg Depression Rating scale (MADRS) served as the main outcome measure. Tolerability was assessed by documenting side effects and change in vital signs, weight, and cognitive function. Clinical response durability was assessed 8 weeks after discontinuation of buprenorphine.

Results: The mean dose of buprenorphine was 0.4 mg/d (mean maximum dose = 0.7 mg/d). The mean depression score (MADRS) at baseline was 27.0 (SD = 7.3) and at week 8 was 9.5 (SD = 9.5). A sharp decline in depression severity occurred during the first 3 weeks of exposure (mean change = -15.0 [SD = 7.9]). Depression-specific items measuring pessimism and sadness indicated improvement during exposure, supporting a true antidepressant effect. Treatment-emergent side effects (in particular, nausea and constipation) were not sustained, vital signs and weight remained stable, and executive function and learning improved from pretreatment to posttreatment.

Conclusion: Low-dose buprenorphine may be a novel-mechanism medication that provides a rapid and sustained improvement for older adults with TRD. Placebo-controlled trials of longer duration are required to assess efficacy, safety, and physiologic and psychological effects of extended exposure to this medication.

Trial registration: ClinicalTrials.gov identifier: NCT01071538.

Figure 1

Individual subject trajectories for MADRS total score, reported sadness, and pessimistic thoughts. Note: Group mean trajectories included as bold line. Sample size indicated at each time point. Total MADRS graph shows telephone assessment of depression symptoms at week 16 done to assess durability of the antidepressant effect.

Figure 2

Individual subject trajectories for positive and negative affect, anxiety, sleep and the mental and physical components of the SF-36. Note: Group mean trajectories included as bold line. Sample size indicated at each time point. Circle symbol indicates subject had only one observation.