TY - JOUR
T1 - Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults
AU - Karp, Jordan F.
AU - Butters, Meryl A.
AU - Begley, Amy E.
AU - Miller, Mark D.
AU - Lenze, Eric J.
AU - Blumberger, Daniel M.
AU - Mulsant, Benoit H.
AU - Reynolds, Charles F.
N1 - Funding Information:
Author affiliations: Department of Psychiatry, Western Psychiatric Institute and Clinic (Drs Karp and Reynolds); Department of Psychiatry, University of Pittsburgh School of Medicine (Drs Butters, Miller, and Mulsant and Ms Begley); Department of Behavioral and Community Health Sciences, Graduate School of Public Health, University of Pittsburgh (Dr Reynolds), Pittsburgh, Pennsylvania; Department of Psychiatry, Washington University, St Louis, Missouri (Dr Lenze); and Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada (Drs Blumberger and Mulsant). Potential conflicts of interest: Dr Karp receives medication supplies from Reckitt Benckiser and Pfizer for investigator-initiated trials. Dr Butters has served as a consultant for GlaxoSmithKline. Dr Lenze has received research support from Forest, Johnson & Johnson, Roche, and Lundbeck, as well as (medications only) Pfizer, Corcept, and Bristol-Myers Squibb. Dr Blumberger received research funding from a Canadian Institutes of Health Research Industry Partnered (Brainsway Ltd.) operating grant, the Campbell Family Research Institute, and the Temerty Centre for Therapeutic Brain Intervention. Dr Mulsant has received financial support during the past 36 months from the National Institute of Mental Health and the Canadian Institutes for Health Research and pharmaceutical supplies from Bristol-Myers Squibb, Eli Lilly, and Pfizer for his National Institutes of Health (NIH)–sponsored research. Dr Mulsant has also received reimbursement for travel expenses from Roche and owns stock in General Electric. Dr Reynolds has received pharmaceutical support for NIH-sponsored research studies from Bristol-Myers Squibb, Forest, Pfizer, and Eli Lilly; has received grants from NIH, Patient Centered Outcomes Research Institute, Commonwealth of Pennsylvania, John A. Hartford Foundation, National Palliative Care Research Center, University of Pittsburgh Medical Center Endowment in Geriatric Psychiatry, and American Foundation for Suicide Prevention; and has served on the American Association for Geriatric Psychiatry editorial review board. Dr Reynolds has received an honorarium as a speaker from MedScape/WebMD and is the coinventor (licensed intellectual property) of Psychometric Analysis of the Pittsburgh Sleep Quality Index, and his NIH-funded research is supported by the following grants: P60 MD000207, P30 MH090333, UL1RR024153, UL1TR000005. Ms Begley and Dr Miller report no potential conflict of interest. Funding/support: Supported in part by National Institutes of Health grants AG033575 (Dr Karp), P30 MH090330 (Dr Reynolds), MH083660 (Drs Reynolds, Lenze, and Mulsant), MH072947 (Dr Butters), and KL2 RR024154 (Steven Reis, MD) and the Brain and Behavior Research Foundation (formerly known as NARSAD) (Dr Karp). Reckitt Benckiser provided medication supplies for this investigator-initiated trial. Role of the sponsor: Reckitt Benckiser was not involved in any aspect of the design or conduct of this clinical trial. The authors are grateful for their support. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
Publisher Copyright:
© 2014 Physicians Postgraduate Press, Inc.
PY - 2014/8/1
Y1 - 2014/8/1
N2 - 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. Treatmentemergent 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.
AB - 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. Treatmentemergent 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.
UR - http://www.scopus.com/inward/record.url?scp=84908351930&partnerID=8YFLogxK
U2 - 10.4088/JCP.13m08725
DO - 10.4088/JCP.13m08725
M3 - Article
C2 - 25191915
AN - SCOPUS:84908351930
SN - 0160-6689
VL - 75
SP - e785-e793
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
IS - 8
ER -