title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01071538.
authors.affiliation: WPIC, 3811 O'Hara St, Pittsburgh, PA 15213 karpjf@upmc.edu.
authors.forename: Jordan F
authors.initials: JF
authors.lastname: Karp
authors.forename: Meryl A
authors.initials: MA
authors.lastname: Butters
authors.forename: Amy E
authors.initials: AE
authors.lastname: Begley
authors.forename: Mark D
authors.initials: MD
authors.lastname: Miller
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lenze
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Blumberger
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reynolds
mesh_terms: D017668:Age of Onset; D000368:Aged; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D012890:Sleep / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D009292:Narcotic Antagonists; D002047:Buprenorphine