Safety, Tolerability, and Clinical Effect of Low-Dose Buprenorphine for Treatment-Resistant Depression in Midlife and Older Adults

Abstract

Objective Describe the clinical effect and safety of low-dose buprenorphine, a kappa-opioid receptor antagonist, for treatment-resistant depression (TRD) in mid-life and older adults. Method Using an open-label protocol, buprenorphine was prescribed for 15 adults age 50 and older with TRD, diagnosed with the SCID for DSM-IV, between 6/2010-6/2011. The titrated dose of buprenorphine ranged from 0.2 mg-1.6 mg/day. We assessed clinical change in depression, anxiety, sleep, positive and negative affect, and quality of life. Tolerability was assessed by documenting change in vital signs, weight, cognitive function, and side effects. Clinical response durability was assessed 8 weeks after discontinuation of the buprenorphine. Results The average dose of buprenorphine was 0.4 mg/day (average maximum dose = 0.7 mg/day). The average depression score (MADRS) at baseline was 27.0 (SD=7.3); and at week 8, 9.5 (SD=9.5). There was a sharp decline in depression severity during the first three weeks of exposure (mean delta=−15.0 (SD=7.9)). Depression-specific items tapping pessimism and sadness improved 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 pre- to post-treatment. 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 physiological and psychological effects of extended exposure to this medication.

Eight-Milligram Single Dose of Buprenorphine as an Expeditious Treatment for Severe Suicidal Ideation: A Case Report

“…Therefore, it is a suitable treatment choice for refractory depression, anxiety, self-injurious behaviors, and suicidal ideation (6,7,(14)(15)(16)(17). In the present report, we observed that 8 mg of buprenorphine had a rapid effect on the reduction and cessation of suicidal thoughts and depression.…”

“…Overall, buprenorphine reduces physiological and subjective responses to social stressors, including social rejection (14). In this regard, Karp et al demonstrated the effectiveness of lowdose buprenorphine for treatment-resistant depression in older adults (17). Norelli et al also successfully treated severe self-injurious behaviors with buprenorphine (16).…”

Coexistence of Chronic Pain and Depression: A Short Review with a Focus on the Antidepressant Effect of Tramadol and Buprenorphine

“…Clinical and pre-clinical studies have demonstrated the efficacy of buprenorphine and its novel analogues in the pharmacotherapy Review Danuta Szkutnik-Fiedler of depression [3,[71][72][73][74][75][76]. Ahmadi et al [73] suggest that a single high-dose of buprenorphine provides a safe, speedy and straightforward means of depression, especially in patients who are opioid dependent.…”

“…Almatroudi et al [75] also showed that co-administration of buprenorphine with naltrexone in CD-1 mice produced an antidepressant-like response in behaviours in both the forced swim test and novelty-induced hypophagia task what means that this combination represents a novel approach, to the treatment of depression. According to a study by Karp et al [71], buprenorphine provides rapid and sustained improvement for older adults with treatment-resistant depression. A low-dose of buprenorphine sharply decreased major depression severity during the first three weeks of treatment.…”

Dynorphin, Dysphoria, and Dependence: the Stress of Addiction

“…A more 'out of the box approach' is to take advantage of "creative" pharmacology. Buprenorphine is not only a mu partial agonist, but is a potent kappa antagonist having antidepressant activity (Karp et al, 2014). A recent open label clinical trial by Alkermes demonstrated that the nonselective KOR antagonist buprenorphine when combined with a mu opioid antagonist significantly reduced depressive symptoms in a population of individuals having treatment resistant depression (E. Ehrich, Kappa-2015 conference proceedings).…”