buprenorphine and Depressive-Disorder--Treatment-Resistant

Depression and post-traumatic stress disorder (PTSD) are leading causes of disability and loss of life by suicide. Currently, there are less than satisfactory medical solutions to treat these mental disorders. Here, we explore recent preclinical and clinical studies demonstrating the potential of using buprenorphine to treat major depressive disorder, treatment-resistant depression, and PTSD.. Bibliographic databases were searched to include preclinical and clinical studies demonstrating the therapeutic potential of buprenorphine and the involvement of the kappa opioid receptor (KOR) in mediating these effects.. Original clinical studies examining the effectiveness of buprenorphine to treat depression were mixed. The majority of participants in the PTSD studies were males and suffer from chronic pain and/or substance use disorders. Nonetheless, these recent studies and analyses established proof of concept warranting farther investigations. Additionally, KOR likely mediates the antidepressant and some of the anxiolytic effects of buprenorphine. Still, it appears that the full spectrum of buprenorphine's beneficial effects might be due to activity at other opioid receptors as well.. Pharmaceuticals' abilities to treat medical conditions directly relates to their ability to act upon the endogenous biological systems related to the conditions. Thus, these recent findings are likely a reflection of the central role that the endogenous opioid system has in these mental illnesses. Further studies are necessary to study the involvement of endogenous opioid systems, and specifically KOR, in mediating buprenorphine's beneficial effects and the ability to treat these medical conditions while minimizing risks for misuse and diversion.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Drug Combinations; Female; Humans; Male; Middle Aged; Naltrexone; Prospective Studies; Stress Disorders, Post-Traumatic; Young Adult

Numerous reports have suggested that buprenorphine may have antidepressant effects. Many individuals with depressive disorders don't respond to first-line treatment and are classified with treatment-resistant depression (TRD). Novel therapies for depression are required to better treat this population. This meta-analysis of randomized placebo-controlled trials sought to evaluate the potential antidepressant effects of buprenorphine as an adjunctive pharmacological treatment for individuals with TRD.. PubMed, Embase, CINAHL, Web of Science, and ClinicalTrials.gov databases were searched until June 2019 for original peer-reviewed reports of buprenorphine used for the treatment of depression. Standardized mean differences (SMD) were generated from random effects models. Risk of publication bias was assessed using a funnel plot. Potential sources of heterogeneity were explored in subgroup analyses.. In six studies that met inclusion criteria, depression symptom severity in individuals with TRD was not significantly decreased after an adjunctive intervention with buprenorphine when compared to placebo (SMD = -0.07, 95% CI: -0.21-0.06, p = 0.30). Five of the six studies utilized a combination of buprenorphine/samidorphan. In these studies, depression symptom severity was also not significantly reduced after intervention compared to placebo (SMD = -0.08, 95% CI: -0.21 - 0.05, p = 0.23).. Five included studies were performed by the same research group with significant conflicts of interest.. This meta-analysis did not reveal a significant reduction in depression symptom severity in individuals with TRD after an adjunctive intervention with buprenorphine when compared to placebo. However, more optimal doses of buprenorphine (2 mg/day) and longer treatment lengths should be explored.

Topics: Antidepressive Agents; Buprenorphine; Depression; Depressive Disorder, Treatment-Resistant; Humans

There is evidence that the endogenous opioid system in the brain plays an important role in mood regulation, and disturbances in its functioning may lead to the occurrence of depressive disorders. One of the drugs that affect the endogenous opioid system in the CNS is buprenorphine. The article is areview of the studies on the effectiveness of buprenorphine used as an augmentation of antidepressant treatment. The selection of articles was made by browsing the Medline and PubMed databases with the use of key words 'buprenorphine'and 'treatment of drug-resistant depression'. The analysis included thirty one studies. The results indicate that buprenorphine may be effective in drug-resistant depression in a similar manner as other augmentation strategies added to antidepressant treatment. Co-administration of buprenorphine and samidorphan may reduce the risk of addiction without losing the antidepressant effectiveness of buprenorphine. Further methodologically correct studies in this field are needed. In addition to being a partial agonist of the µ receptor, buprenorphine is also a potent antagonist of the kappa type opioid receptors. The antagonism of µ receptors alone does not cause antidepressant effects. Antagonism towards kappa receptors may cause antidepressant effects as well as reduce the severity of anhedonia. Depressed patients who do not respond to standard antidepressant treatment may have dysfunctions of the kappa receptor that are similar to opioid addicts.

Topics: Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Dose-Response Relationship, Drug; Humans

Treatment resistant depression (TRD) represents approximately 20% of all individuals receiving care for major depressive disorder. The opioidergic system is identified as a novel target which hitherto has not been sufficiently investigated in adults with TRD. The combination product buprenorphine + samidorphan is an opioid modulatory agent which has demonstrated replicated evidence of efficacy in TRD without abuse liability. Areas covered: Databases Pubmed, Google Scholar and clinicaltrials.gov were searched from inception through December 2017 for clinical trial information, pharmacokinetics, and pharmacodynamics of buprenorphine + samidorphan. Herein we provide a summary of the available information. Eight clinical trials were identified for inclusion, of the eight trials, five trials had available results and are included in detail in our review. Expert opinion: Buprenorphine + samidorphan has demonstrated efficacy in TRD. Extant evidence surrounding the safety and tolerability profile of buprenorphine + samidorphan does not identify any significant safety concerns. Additional studies are needed in order to assess the long-term safety and efficacy of this product.

Topics: Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Drug Combinations; Humans; Naltrexone; Treatment Outcome

Although several pharmacological options to treat depression are currently available, approximately one third of patients who receive antidepressant medications do not respond adequately or achieve a complete remission. Thus, novel strategies are needed to successfully address those who did not respond, or partially respond, to available antidepressant pharmacotherapy. Research findings revealed that the opioid system is significantly involved in the regulation of mood and incentives salience and may be an appropriate target for novel therapeutic agents. The present study aimed to systematically review the current literature about the use of buprenorphine (BUP) for major depression, treatment-resistant depression (TRD), non-suicidal self-injury (NSSI) behavior, and suicidal behavior. We investigated Pubmed and Scopus databases using the following keywords: "buprenorphine AND depression", "buprenorphine AND treatment resistant depression", "buprenorphine AND suicid*", "buprenorphine AND refractory depression". Several evidence demonstrate that, at low doses, BUP is an efficacious, well-tolerated, and safe option in reducing depressive symptoms, serious suicidal ideation, and NSSI, even in patients with TRD. However, more studies are needed to evaluate the long-term effects, and relative efficacy of specific combinations (e.g., BUP + samidorphan (BUP/SAM), BUP + naloxone (BUP/NAL), BUP + naltrexone) over BUP monotherapy or adjunctive BUP treatment with standard antidepressants, as well as to obtain more uniform guidance about the optimal BUP dosing interval.

Topics: Analgesics, Opioid; Buprenorphine; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Humans; Suicidal Ideation; Suicide Prevention

Current treatment strategies for depressive disorders have limited efficacy, leaving many patients unimproved or with significant residual symptoms. The development of additional treatments represent a significant unmet need for providers. Several lines of evidence suggest that the opioid system may be involved in regulation of mood and incentives salience. Intervention based on modifying central opioid receptors may represent a novel approach to treatment of depressive disorders among those unresponsive to accepted treatments.. We searched the English language literature using keywords: Buprenorphine AND Major Depression; Buprenorphine AND Bipolar Depression; Buprenorphine AND Affective Disorders.. Use of low dose buprenorphine as augmentation of pharmacotherapy for depression has shown promise in several reported studies. Effect size of available randomized controlled studies is comparable if not greater than most accepted augmentation strategies.. Review of available literature on the use of buprenorphine in individuals with treatment resistant depression demonstrated efficacy in the treatment of depressive disorders. Further prospective randomized controlled trials should be undertaken to evaluate the efficacy of buprenorphine as an adjunct for depression refractory to current pharmacotherapies.

Topics: Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Depressive Disorder, Treatment-Resistant; Humans; Treatment Outcome

Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ-opioid partial agonist, buprenorphine (BUP), and a potent μ-opioid antagonist, samidorphan (SAM), would demonstrate antidepressant activity without addictive potential. A placebo-controlled crossover study assessed the opioid pharmacodynamic profile following escalating doses of SAM co-administered with BUP in opioid-experienced adults. A subsequent 1-week, placebo-controlled, parallel-group study was conducted in subjects with MDD and an inadequate response to standard antidepressant therapy. This second study evaluated safety and efficacy of ratios of BUP/SAM that were associated with partial and with maximal blockade of opioid responses in the initial study. Pupillometry, visual analog scale assessments, and self-reported questionnaires demonstrated that increasing amounts of SAM added to a fixed dose of BUP resulted in dose-dependent reductions in objective and subjective opioid effects, including euphoria and drug liking, in opioid-experienced adults. Following 7 days of treatment in subjects with MDD, a 1 : 1 ratio of BUP and SAM, the ratio associated with maximal antagonism of opioid effects, exhibited statistically significant improvement vs placebo in HAM-D17 total score (p=0.032) and nearly significant improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score (p=0.054). Overall, BUP/SAM therapy was well tolerated. A combination of BUP and SAM showed antidepressant activity in subjects with MDD. Balanced agonist-antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders.

Topics: Adult; Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Cohort Studies; Cross-Over Studies; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Treatment Outcome; Young Adult

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.. 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.. 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.. 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.. ClinicalTrials.gov identifier: NCT01071538.

Topics: Age of Onset; Aged; Buprenorphine; Cognition; Depressive Disorder, Treatment-Resistant; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Quality of Life; Sleep; Treatment Outcome

Topics: Analgesics, Opioid; Animals; Anti-Anxiety Agents; Antidepressive Agents; Buprenorphine; Depressive Disorder, Treatment-Resistant; Humans; Hypoxia; Ketamine; Locomotion; Male; Rats; Rats, Wistar

Ketamine's rapid antisuicidal action has gathered significant clinical interest in treatment of depression though concerns exist that its actions occur through the Opioid pathway. A recent study additionally reported that Naltrexone blocks antisuicidal effects of Ketamine suggesting that its antisuicidal effects are also due to opioid mechanisms. We present a case of treatment refractory depression with recent suicide attempt and active suicidal ideations who was on an Opioid partial agonist, Buprenorphine, for management of pain. Patient responded to a trial of IV ketamine treatment with rapid improvement in suicidal thoughts. Patient's suicidal ideations decreased after first Ketamine treatment and resolved after second treatment while maintained on Buprenorphine. Our finding shows that Buprenorphine does not block Ketamine's effects on suicidal ideations and therefore Ketamine treatment could be provided safely in controlled environment to those with substance use disorders or with chronic pain while being maintained on Buprenorphine. Additionally, our case suggests that non-Opioid mechanisms may be involved in Ketamine's antidepressant effects and its response to suicidal ideations in those on Opioid partial agonists.

Topics: Antidepressive Agents; Buprenorphine; Depressive Disorder, Treatment-Resistant; Humans; Ketamine; Suicidal Ideation

Topics: Adult; Aged; Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Depressive Disorder, Treatment-Resistant; Female; Humans; Ketamine; Male; Methadone; Middle Aged; Naltrexone; Treatment Outcome

Topics: Adult; Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Drug Therapy, Combination; Female; Humans

The very strong relationship between suicide, depressive disorders, and substance use disorders is well recognized. Certain pain syndromes are significantly associated with suicide, irrespective of co-occurring medical or psychiatric diagnosis. Chronic pain, depression, substance use disorders, and suicide appear to involve overlapping neural pathways and brain regions that function in the processing of emotional and physical pain, as well as maintaining reward and anti-reward circuitry. In this article, we employ a clinical case to illustrate how various stressors disrupted the balance between pain and opioid-facilitated analgesia. This disruption resulted in excessive use of short-acting opioids to treat pain with ensuing allostatic overload and culmination in chronic suicidal ideation with a suicide attempt. Sublingual buprenorphine was selected to treat the opioid use disorder. We propose that the unique pharmacodynamics of this drug served to stabilize dysregulated neural circuits, neurotransmitters, and neuropeptides, allowing the mitigation of pain, assuaging opioid cravings, easing depression, and resolving suicidal ideation. To our knowledge, this is the first case report to describe the possible anti-suicidal effect of sublingual buprenorphine.

Topics: Administration, Sublingual; Allosteric Regulation; Analgesics, Opioid; Brain; Buprenorphine; Chronic Pain; Comorbidity; Depressive Disorder, Treatment-Resistant; Drug Interactions; Female; Humans; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Substance Abuse Treatment Centers; Suicidal Ideation; Suicide; Suicide Prevention; Suicide, Attempted