buprenorphine and Depressive-Disorder--Major

Depressive disorders are common. Many patients with major depression do not achieve remission with available treatments. Buprenorphine has been raised as a potential treatment for depression as well as suicidal behavior but may pose certain risks.. A meta-analysis comparing the efficacy, tolerability, and safety of buprenorphine (or combinations such as buprenorphine/samidorphan) versus control in improving symptoms in patients with depression. Medline, Cochrane Database, PsycINFO, Excerpta Medica Database and The Cumulative Index to Nursing and Allied Health Literature were searched from inception through January 2, 2022. Depressive symptoms were pooled using Hedge's g with 95% Confidence Intervals (CI). Tolerability, safety, suicide outcomes were summarized qualitatively.. 11 studies (N = 1699) met inclusion criteria. Buprenorphine had a small effect on depressive symptoms (Hedges' g 0.17, 95%CI: 0.05-0.29). Results were driven by six trials of buprenorphine/samidorphan (N = 1,343, Hedges's g 0.17, 95%CI: 0.04-0.29). One study reported significant improvement in suicidal thoughts (Least Squares Mean Change: -7.1, 95%CI: -12.0 - 2.3). Most studies found buprenorphine was well-tolerated with no evidence of abuse behavior or dependency.. Buprenorphine may have a small benefit for depressive symptoms. Future research should clarify the dose response relationship between buprenorphine and depression.

Topics: Buprenorphine; Depression; Depressive Disorder, Major; Humans

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

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

Research concerning psychiatric issues relating to opioid drugs currently focuses primarily on their role in reinforcing addictive behaviors, given the recent proliferation of lethal abuse of illicit opiates in the United States and around the world. In contrast, this article will review the mechanism of action of opioids in affective disorders and the available evidence and potential for their use, especially in the treatment of resistant major depression. Buprenorphine is the opioid derivative of special interest; we review this and other opioid derivatives, highlighting the growing role of opioids in treating depressive illnesses and other related psychopathologies.

Topics: Analgesics, Opioid; Animals; Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Humans; United States

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

Mammalian brains contain at least 7 primal emotional systems--Seeking, Rage, Fear, Lust, Care, Panic and Play (capitalization reflects a proposed primary-process terminology, to minimize semantic confusions and mereological fallacies). These systems help organisms feel affectively balanced (e.g. euthymic) and unbalanced (e.g. depressive, irritable, manic), providing novel insights for understanding human psychopathologies. Three systems are especially important for understanding depression: The separation distress (Panic) system mediates the psychic pain of separation distress (i.e. excessive sadness and grief), which can be counteracted by minimizing Panic arousals (as with low-dose opioids). Depressive dysphoria also arises from reduced brain reward-seeking and related play urges (namely diminished enthusiasm (Seeking) and joyful exuberance (Play) which promote sustained amotivational states). We describe how an understanding of these fundamental emotional circuits can promote the development of novel antidepressive therapeutics--(i) low-dose buprenorphine to counteract depression and suicidal ideation emanating from too much psychic pain (Panic overarousal), (ii) direct stimulation of the Seeking system to counteract amotivational dysphoria, and (iii) the discovery and initial clinical testing of social-joy-promoting molecules derived from the analysis of the Play system.

Topics: Analgesics, Opioid; Animals; Antidepressive Agents; Bipolar Disorder; Brain; Buprenorphine; Deep Brain Stimulation; Depression; Depressive Disorder, Major; Emotions; Humans; Oligopeptides; Panic; Play and Playthings; Reward; Suicidal Ideation

Individuals treated for opioid use disorder (OUD) have high rates of psychiatric disorders potentially diminishing treatment outcomes. We examined long-term treatment experiences and outcomes by type of psychiatric disorder among participants who participated in the Starting Treatment with Agonist Replacement Therapies (START) study and its follow-up study.. We categorized the 593 participants who completed the Mini-International Neuropsychiatric Interview (MINI) during the START follow-up study into four mutually exclusive groups to indicate current psychiatric diagnosis: 1) bipolar disorder (BPD; n = 51), 2) major depressive disorder (MDD; n = 85), 3) anxiety disorder (AXD; n = 121), and 4) no comorbid mental disorder (NMD; n = 336). We compared participants' baseline characteristics and treatment outcomes.. Groups with mental disorders had worse substance use outcomes and poorer psychosocial functioning than the NMD group. Participants with BPD had significantly more self-reported days using opioids (Mean: 8.6 for BPD vs. 3.4 days for NMD, p < 0.01) and heroin (Mean: 6.4 for BPD vs. 2.0 for MDD, 3.1 days for NMD, p < 0.05) in the 30 days prior to the final interview. Compared to patients without mental disorders, patients with MDD spent more time engaged with OUD pharmacotherapy during the ∼16-month period between MINI and final interview (mean: 71.6 % vs. 50.6 %; p < 0.001).. Our results show that treatment outcomes in individuals with OUD vary by psychiatric comorbidity groups, which supports the need for mental health assessment and treatment for psychiatric conditions in the context of pharmacotherapy for patients with OUD.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Comorbidity; Depressive Disorder, Major; Follow-Up Studies; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

The endogenous opioid system is thought to play an important role in the regulation of mood. Buprenorphine/samidorphan (BUP/SAM) combination is an investigational opioid system modulator for adjunctive treatment of major depressive disorder (MDD). To confirm results from early studies, we report the efficacy and safety of BUP/SAM as adjunctive treatment in patients with MDD and an inadequate response to antidepressant therapy (ADT) in FORWARD-4 and FORWARD-5: two phase 3, randomized, double-blind, placebo-controlled studies that utilized the same sequential parallel-comparison design. Efficacy was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). FORWARD-5 achieved the primary endpoint and demonstrated that adjunctive BUP/SAM 2 mg/2 mg was superior to placebo (average difference change from baseline to week 3 through end of treatment [EOT] in MADRS-6 and -10 versus placebo: -1.5, P = 0.018; -1.9, P = 0.026, respectively). FORWARD-4 did not achieve the primary endpoint (change from baseline in MADRS-10 at week 5 versus placebo: -1.8, P = 0.109), although separate analyses showed significant treatment differences at other timepoints using traditional, regulatory-accepted endpoints such as reduction in MADRS-10 at EOT. The pooled analysis of the two studies demonstrated consistently greater reduction in MADRS-10 scores from baseline for BUP/SAM 2 mg/2 mg versus placebo at multiple timepoints including EOT and average change from baseline to week 3 through EOT (-1.8, P = 0.010; -1.8, P = 0.004, respectively). The overall effect size (Hedges' g) in the pooled analyses for MADRS-10 change from baseline to EOT was 0.22. Overall, BUP/SAM was generally well tolerated, with most adverse events (AEs) being mild or moderate in severity. The most common AEs, occurring in ≥5% of patients in the BUP/SAM 2 mg/2 mg treatment group, which was more frequently than the placebo group, included nausea, constipation, dizziness, vomiting, somnolence, fatigue, and sedation. There was minimal evidence of abuse, and no evidence of dependence or opioid withdrawal by AEs or objective measures. This report describes adjunctive BUP/SAM 2 mg/2 mg combination, a therapy with a novel opioidergic mechanism of action, as a potential new treatment option for patients with MDD who have an inadequate response to currently available ADT.

Topics: Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naltrexone; Treatment Outcome

Buprenorphine/samidorphan (BUP/SAM; ALKS 5461) is an investigational opioid system modulator for the adjunctive treatment of patients with major depressive disorder (MDD), who did not respond adequately to prior antidepressant therapy (ADT). FORWARD-2, an open-label extension study, assessed long-term safety and tolerability of adjunctive BUP/SAM treatment in these patients. Patients from four short-term trials and de novo patients were enrolled; all had confirmed MDD and a current major depressive episode lasting 2-24 months. Patients were treated with an established ADT for ≥8 weeks before receiving sublingual, adjunctive BUP/SAM 2 mg/2 mg for up to 52 weeks. Safety (primary objective) was assessed via adverse events (AEs), the Columbia-Suicide Severity Rating Scale, and the Clinical Opiate Withdrawal Scale (COWS). Exploratory evaluation of efficacy was done using the Montgomery-Åsberg Depression Rating Scale (MADRS). Of 1485 patients, 50% completed the study and 11% discontinued due to AEs. AEs of nausea, headache, constipation, dizziness, and somnolence, each occurred in ≥10% of patients. There was no evidence of increased suicidal ideation or behavior. Euphoria-related AEs were uncommon (1.2%). Following abrupt BUP/SAM discontinuation, "drug withdrawal" AEs were infrequent (0.4%), and the incidence of COWS categorical worsening after abrupt drug discontinuation was low (6.5%). Improvements in mean MADRS scores were maintained until study end, suggesting durability of antidepressant effect in patients continuing treatment. BUP/SAM was generally well tolerated, with a low risk of abuse and an AE profile consistent with those seen in placebo-controlled studies. Withdrawal reports were uncommon and of limited clinical impact.

Topics: Adult; Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naltrexone; Psychiatric Status Rating Scales; Treatment Outcome

To examine the impact of different doses of buprenorphine on depression symptoms in opioid dependent inpatient over a three-day interval, using a randomized clinical trial design (RCT).. Patients were randomized and assigned to three groups.. Forty males who were admitted to an inpatient psychiatric unit and who fulfilled the DSM-5 criteria for both opioid dependence and major depressive disorder.. Patients randomly received 32 mg, 64 mg, or 96 mg of buprenorphine as a single high dose. Out of 40 patients, 11 (27.5%) received 32 mg, 14 (35%) received 64 mg and 15 (37.5%) received 96 mg of buprenorphine. We conducted medical precautional measures, including cardiovascular and respiratory monitoring.. Depression was measured by the Beck Depression Inventory (BDI). All patients completed the three-day treatment duration. The results showed a significant reduction in depression symptoms within each of the three groups (p = 0.00), although there was no significant difference in depression outcome across the groups (p = 0.90).. The results suggest that a single high dose of buprenorphine could provide a safe, simple and speedy means of depression improvement. A single high dose of buprenorphine can be used as medication that supplies a fast and maintained treatment for major depressive disorder in patients who are opioid dependent. Placebo-controlled trials of longer periods and larger sample sizes are needed to test ability and safety, as well as the physiological and psychological impact of extended exposure to this drug.

Topics: Adult; Buprenorphine; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Time Factors; Treatment Outcome; Young Adult

Buprenorphine is usually administered to treat opioid use disorder and pain syndromes. This research presents the first study regarding the effectiveness of different singly administered high doses of buprenorphine (a partial opioid agonist (of μ-opioid receptors), a potent opioid antagonist (of κ-receptors) and a partial agonist of nociception receptors) in reducing suicidal ideation in acutely depressed people with co-morbid opiate dependence. It follows small studies that suggest that ultra-low-dose buprenorphine may be useful in reducing suicidal ideation. The goal of this study was to describe the outcome of different doses of buprenorphine on suicidal opioid-dependent patients over a 3-day interval, by conducting a randomized clinical trial.. Fifty-one suicidal male inpatients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for both opioid dependence and major depressive disorder were randomized to three groups (n = 17 per group) to receive a single, sublingual dose of buprenorphine (32 mg, 64 mg, or 96 mg). Out of 51 participants, there were 47 patients; 16 (34.04%) received 32 mg, 17 (36.17%) received 64 mg, and 14 (29.78%) received 96 mg of sublingual buprenorphine. They were evaluated by using psychometric assessment of the Beck Scale for Suicidal Ideation (BSSI) and interviews based on DSM-5 criteria. A placebo group was not included because of the high probability of severe withdrawal without active pharmacological treatment. The study was conducted with appropriate precautions and monitoring of respiratory and cardiovascular measures. The medication was administered while the patients were in moderate opiate withdrawal, as indicated by the presence of four to five withdrawal symptoms. A structured clinical interview was conducted, and urine toxicology testing was performed.. Patients completed the 3-day trial course. The outcomes illustrated a significant reduction in BSSI scores within each of the three groups, p < 0.01., but no difference in results between the groups, p = 0.408.. The results suggest that a single high dose of buprenorphine could rapidly treat suicidal ideations. A single high dose of buprenorphine may be a main-mechanism medication that gives a rapid treatment for suicidal opioid-dependent patients. Placebo-controlled trials are required to measure the safety and the physiological and psychological effects of this medication.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Comorbidity; Depressive Disorder, Major; Double-Blind Method; Humans; Iran; Male; Opioid-Related Disorders; Substance Withdrawal Syndrome; Suicidal Ideation; Time Factors; Treatment Outcome

Major depressive disorder has been associated with dysregulation of the endogenous opioid system. The authors sought to determine whether opioid modulation achieved through administration of ALKS 5461, a combination of a μ- and κ-opioid partial agonist, buprenorphine, and a μ-opioid antagonist, samidorphan, would exhibit antidepressant activity in patients with major depression.. A multicenter, randomized, double-blind, placebo-controlled, two-stage sequential parallel comparison design study was conducted in adults with major depression who had an inadequate response to one or two courses of antidepressant treatment. Participants were randomly assigned to receive adjunctive treatment with 2 mg/2 mg of buprenorphine/samidorphan (the 2/2 dosage group), 8 mg/8 mg of buprenorphine/samidorphan (the 8/8 dosage group), or placebo. Antidepressant effect was measured based on change from baseline to the end of 4 weeks of treatment on the 17-item Hamilton Depression Rating Scale (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Clinical Global Impressions severity scale (CGI-S).. Compared with the placebo group, there were significantly greater improvements in the 2/2 dosage group across the three depression outcome measures (HAM-D: -2.8, 95% CI=-5.1, -0.6; MADRS: -4.9, 95% CI=-8.2, -1.6; CGI-S: -0.5, 95% CI=-0.9, -0.1). There was also evidence of improvement in the 8/8 dosage group, although it did not achieve statistical significance. Overall, the buprenorphine/samidorphan combinations were well tolerated, and there was no evidence of opioid withdrawal on treatment discontinuation.. The buprenorphine/samidorphan combination is a novel and promising candidate for treatment of major depressive disorder in patients who have an inadequate response to standard antidepressants.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Treatment Outcome; Young Adult

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

Topics: Adult; Aged; Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Treatment Outcome

The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2+/-8.9, 177 males-29 females) were applicants to a long-term buprenorphine treatment program (mean doses 7.9+/-0.42 mg). Aim of the study was to evaluate dual diagnosis variables possibly influencing retention rate and abstinence from illicit drugs. The patients were divided into 5 subgroups on the basis of dual diagnosis: group 1: major depression (MD) 29.61%; group 2: generalized anxiety (GAD) (11.2%); group 3: personality disorders (PD), antisocial-borderline (21.84%); group 4: schizophrenia (SC)(6.3%); group 5: substance use disorder without overt psychiatric comorbidity (SUD) (31.1%). Group 1 patients affected by MD showed the highest retention rate at 12 months (72.1%) in comparison with the other groups of patients: group 2 GAD (39.1%), group 3 PD (17.8%), group 4 SC (7.7%) and group 5 SUD, without comorbidity (45.3%) (p=0.006, p<0.001, p<0.001, p=0.002). Similarly, at 12 months, the patients affected by MD showed less risk of illicit opioid use (16.4%) than those affected by GAD (34.8%), PD (42.2%), SC (53.8%) and SUD without comorbidity (34.4%) (p=0.06, p=0.003, p=0.008, p=0.017). When evaluated on the whole sample, retention rate was not influenced by dose. In contrast, the higher BUP doses were associated with less risk of illicit opioid use, than lower doses (p<0.001). Multivariate analysis and factor analysis showed a greater association of outcome measures (retention rate and negative urines rate) with comorbid diagnosis (depression) (respectively 0.64) than with buprenorphine doses (respectively 0.54). Our data need to be interpreted with caution because of the retrospective methodology applied to a clinical non-experimental setting. BUP seems to be more effective in opioid-dependent patients affected by depression, probably due to the kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety. High doses of BUP appear to predict a better outcome, in terms of negative urines, but not in terms of retention.

Topics: Adult; Anxiety; Buprenorphine; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Heroin Dependence; Humans; Male; Multivariate Analysis; Narcotics; Personality Disorders; Retrospective Studies; Schizophrenia; Time Factors; Treatment Outcome

Depression is common among patients who abuse both opiates and cocaine, and its treatment has had mixed success. This study compares buprenorphine-maintained patients with lifetime major depressive disorder (MDD, N = 53) with those never depressed (ND, N = 96) on cocaine and opiate-free urines during a 12-week outpatient double-blind, placebo-controlled, randomized clinical trial. The 149 subjects were assigned to four groups: 1) desipramine (DMI) + contingency management (CM); 2) DMI + noncontingency management (NCM); 3) placebo + CM; and 4) placebo + NCM. Depression assessments included Hamilton Depression Rating Scale, Center for Epidemiological Studies Depression Inventory, and Structured Clinical Interview for DSM-IV interview for diagnosis of lifetime MDD. Urine toxicologies were performed thrice weekly and the CES-D was performed monthly. The MDD group had a larger proportion of females (45% vs 21%, P = 0.02) and were more likely to be married (13.2% vs 7.3%, P = 0.02) than the ND group. Treatment retention did not vary by depression status. Hierarchical Linear Modeling found that depressive symptoms decreased comparably across the four treatment groups. Although participation in CM improved drug-free urines more for patients with MDD than for the ND group (Z = 2.44, P = 0.01), treatment with DMI was significantly more efficacious for the ND group than for the MDD group (Z = -2.89, P = 0.003). These results suggest that patients with MDD may respond better to behavioral treatments such as CM than to desipramine plus buprenorphine. The ND cocaine-abusing, opiate-dependent patients may be more responsive to the anticraving effects of DMI.

Topics: Adult; Aged; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Depressive Disorder, Major; Desipramine; Diagnosis, Dual (Psychiatry); Double-Blind Method; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Prognosis; Psychiatric Status Rating Scales; Treatment Outcome

Norbuprenorphine interferences were observed in urine drug testing LC-MS-MS confirmation methods used to assess patient compliance with prescribed buprenorphine for chronic pain and opioid use disorder. The interferences were observed in the norbuprenorphine MS-MS transitions, m/z 414.4/83.1 and 414.4/187.2, at and near the norbuprenorphine retention time at multiple laboratories using different sample preparation procedures and chromatographic conditions. When the interferences were present, a norbuprenorphine result could not be reported. Upon investigation, the interferences were correlated with prescribed quetiapine (Seroquel, Seroquel XR), a second-generation antipsychotic medication approved for the treatment of schizophrenia, bipolar disorder and more recently as an adjunct treatment for major depressive disorder. In addition to the approved indications, quetiapine is prescribed off-label for other conditions including insomnia and anxiety disorders. Off-label prescribing has increased in recent years, thereby exacerbating this analytical issue. Here, we present the study of four quetiapine metabolites found to have significant direct or potential interferences in norbuprenorphine quantitation. The four metabolites were putatively identified as two hydroxyquetiapine acids differing in the site of hydroxylation and a quetiapine sulfoxide acid diastereomer pair. As a result of this study, interference-free norbuprenorphine MS-MS transitions, m/z 414.4/340.2 and 414.4/326.1, were found that were selective for norbuprenorphine while maintaining an acceptable 10 ng/mL lower limit of quantitation.

Topics: Buprenorphine; Chromatography, Liquid; Depressive Disorder, Major; Humans; Quetiapine Fumarate; Tandem Mass Spectrometry

Using a mobile research facility, we enrolled 141 opioid users from a neighborhood of Philadelphia, an urban epicenter of the opioid epidemic. Nearly all (95.6%) met DSM-5 criteria for severe opioid use disorder. The prevalence of HIV infection (8.5%) was more than seven times that found in the general population of the city. Eight of the HIV-positive participants (67.0%) reported receiving antiretroviral treatment but almost all of them had unsuppressed virus (87.5%). The majority of participants (57.4%) reported symptoms consistent with major depressive disorder. Severe economic distress (60.3%) and homelessness were common (57%). Polysubstance use was nearly universal, 72.1% had experienced multiple overdoses and prior medication for opioid use disorder (MOUD) treatment episodes (79.9%), but few currently engaged in addiction care. The prevalence, multiplicity and severity of chronic health and socioeconomic problems highlight consequences of the current opioid epidemic and underscore the urgent need to develop integrated models of treatment.. Utilizando un Centro de Investigación Móvil, inscribimos a 141 usuarios de opioides del vecindario de Filadelfia, un epicentro urbano de la epidemia de opioides. Casi todos (95,6%) cumplieron con los criterios del DSM-5 para el trastorno del uso severo del consumo de opioides. La prevalencia de la infección de VIH (8,5%) fue másﹶ de 7 veces superior a las encontrada en la población general de la ciudad. Ocho de los participantes con VIH positivo (67,0%) reportaron haber recibido tratamiento antirretroviral pero casi todos tuvieron virus no suprimido (87,5%). La mayoría de los participantes (57,4%) informaron síntomas compatibles con el Desorden Depresivo Mayor. La angustia severa por lo económico (60,3%) y las personas sin hogar fueron comunes (57%). El uso de múltiples sustancias fue casi universal, el 721% había experimentado múltiples sobredosis y previos medicamentos para el tratamiento del trastorno por consumo de opioides (MOUD) (79,9%), pero muy pocos estaban comprometidos con la atención a las adicciones. La prevalencia, la multiplicidad y la seriedad de los problemas de salud crónica y los problemas socioeconómicos destacan las consecuencias de la actual epidemia de opioides y subrayan la urgente necesidad de desarrollar nuevos modelos de tratamiento integrados.

Topics: Analgesics, Opioid; Buprenorphine; Depression; Depressive Disorder, Major; HIV Infections; Humans; Opiate Alkaloids; Opioid Epidemic; Opioid-Related Disorders; Philadelphia

Approximately two-thirds of major depressive disorder (MDD) patients do not respond adequately to current therapies. BUP/SAM (ALKS 5461), a combination of buprenorphine (BUP) and samidorphan (SAM), is a novel opioid system modulator in development as an adjunct treatment for MDD. Using a rat strain (Wistar Kyoto rat) that is predisposed to stress and has an inadequate response to selective serotonin reuptake inhibitors (SSRIs), we investigated the effect of BUP and SAM, individually and in combination, in established nonclinical assays used to study antidepressants (the forced swim test, FST) and anxiolytics (marble burying test). As opioids and their receptors are expressed in mesocorticolimbic regions of the brain, we analyzed extracellular concentrations of dopamine, serotonin, and/or their metabolites in brain areas associated with mood and motivation. BUP alone and in combination with SAM significantly reduced immobility in the FST. Similarly, the BUP/SAM combination significantly reduced immobility in SSRI (escitalopram)-treated rats. BUP/SAM also decreased burying behavior. SAM attenuated BUP-induced changes of extracellular levels of serotonin and dopamine in the medial prefrontal cortex and nucleus accumbens shell. The latter suggests that the addition of SAM to BUP may limit activation of the mesolimbic dopamine reward pathway and thereby reduce BUP's reinforcing properties. SAM alone had no effect on neurochemistry or immobility in the FST. Collectively, these data indicate that opioid system modulation may offer an alternative mechanism that does not rely on enhanced serotonergic neurotransmission in neurocircuits associated with antidepressant and anxiolytic activity in nonclinical models.

Topics: Analgesics, Opioid; Animals; Antidepressive Agents; Behavior, Animal; Buprenorphine; Citalopram; Depressive Disorder, Major; Dopamine; Drug Combinations; Drug Therapy, Combination; Male; Models, Animal; Motor Activity; Naltrexone; Rats; Rats, Inbred WKY; Serotonin; Swimming

Buprenorphine is currently being studied for treatment-resistant depression because of its rapid effect, relative safety, and unique pharmacodynamics. To understand the neural impact of buprenorphine in depression, we examined acute limbic and reward circuit changes during an intervention with low-dose buprenorphine augmentation pharmacotherapy. Mid and late-life adults with major depression (N = 31) who did not completely respond to an adequate trial of venlafaxine were randomized to augmentation with low-dose buprenorphine or matching placebo. We investigated early neural changes using functional magnetic resonance imaging (fMRI) from pre-randomization to 3 weeks using both an emotional reactivity task and a gambling task. We tested if: 1) there were significant neural changes acutely per intervention group, and 2) if acute neural changes were associated with depressive symptom change over 8 weeks using both the total score and the dysphoria subscale of the Montgomery Asberg Depression Rating Scale. Participants in both the buprenorphine and placebo groups showed similar changes in depressive symptoms. Neither the emotional reactivity nor gambling task resulted in significant neural activation changes from pre-randomization to 3-weeks. In both groups, increases in rostral anterior cingulate (rACC) and ventromedial prefrontal cortex (vmPFC) activation during the emotional reactivity task were associated with overall symptom improvement. In the buprenorphine but not the placebo group, increased activation in left anterior insula (aINS) and bilateral middle frontal gyrus (MFG) was associated with improvement on the dysphoria subscale. Activation changes in the reward task were not associated with buprenorphine. This is the first study to show an association between acute neural changes during emotion reactivity and changes in depression severity with buprenorphine treatment.

Topics: Aged; Antidepressive Agents; Brain; Buprenorphine; Depression; Depressive Disorder, Major; Double-Blind Method; Emotions; Female; Humans; Magnetic Resonance Imaging; Male; Reward

A combination of buprenorphine (BUP) and samidorphan (SAM) at a 1:1 (mg/mg) fixed-ratio dose is being investigated as an adjunctive treatment of major depressive disorder (BUP/SAM, ALKS 5461). Both [

Topics: Animals; beta-Arrestins; Buprenorphine; Cell Line; CHO Cells; Cricetulus; Depressive Disorder, Major; Drug Combinations; GTP-Binding Proteins; HEK293 Cells; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid, delta; Receptors, Opioid, mu

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

The study aimed to determine patterns of major depression (MD) across 36 months, and the relationship to outcomes for the treatment of heroin dependence. As part of a longitudinal cohort study, 429 heroin users were interviewed at 36 month follow-up. MD declined from 23.8% at baseline to 8.2% at 36 months. Females were more likely to have MD at both baseline (31.1 vs. 19.8) and 36 months (11.9 vs. 6.1%). Those with MD at baseline were significantly more likely to be diagnosed with MD at a follow-up interview (40.2 vs. 15.9%) and at 36 months (14.7 vs. 6.1%). Antidepressant use did not decrease across 36 months amongst either gender. Baseline MD was not related to treatment exposure across 36 months. There were large and significant declines in drug use and drug-related problems, and improvements in physical health with no group differences evident at 36 months. Despite improvements in global mental health, at both baseline and 36 months those with MD at baseline had significantly lower SF12 mental health scores. It was concluded that, with the exception of depression, the prognosis of depressed heroin users is not worse than that of non-depressed users.

Topics: Adolescent; Adult; Buprenorphine; Cohort Studies; Comorbidity; Crime; Depressive Disorder, Major; Drug Overdose; Female; Health Status; Health Status Indicators; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Methadone; Middle Aged; Narcotics; Needle Sharing; New South Wales; Prognosis; Substance Abuse, Intravenous; Suicide, Attempted; Treatment Outcome; Young Adult

Amongst people on opioid maintenance treatment (OMT), chronic hepatitis C (HCV) is common but infrequently treated. Numerous barriers, including misuse of alcohol may limit efforts at anti-viral treatment. The aim of this study was to define barriers, including alcohol misuse, to the effective treatment of HCV amongst OMT recipients. Ninety-four OMT patients completed the 3-item Alcohol Use Disorders Identification Test (AUDIT-C). A semi-structured interview was used in 53 subjects to assess alcohol use in detail, psychological health, discrimination and access to HCV treatment. Feasibility of brief intervention for alcohol misuse was assessed. Of the screening participants, 73% reported they were HCV positive. Of the detailed interview participants, 26% reported no drinking in the past month, but 53% scored 8 or more on AUDIT and 42% exceeded NHMRC drinking guidelines. Twenty subjects received brief intervention and among 17 re-interviewed at one month, alcohol consumption fell by 3.1 g/day (p = 0.003). Severe or extremely severe depression, stress and anxiety were found in 57%, 51% and 40% of interviewees respectively. Episodic heavy drinking, mental health problems, perceived discrimination, limited knowledge concerning HCV were all common and uptake of HCV treatment was poor. Brief intervention for alcohol use problems was acceptable to OMT patients, and warrants further study.

Topics: Adolescent; Adult; Alcoholism; Antiviral Agents; Anxiety Disorders; Australia; Buprenorphine; Comorbidity; Cross-Sectional Studies; Depressive Disorder, Major; Drug Therapy, Combination; Female; Follow-Up Studies; Health Knowledge, Attitudes, Practice; Health Services Accessibility; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Male; Mass Screening; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Patient Acceptance of Health Care; Patient Satisfaction; Psychotherapy, Brief; Substance Abuse, Intravenous

The current study aimed to describe the characteristics (demographics, drug use, mental and physical health) of entrants to treatment for heroin dependence in three treatment modalities; and to compare these characteristics with heroin users not in or seeking treatment. Participants were 825 current heroin users recruited from Sydney, Adelaide and Melbourne: 277 entering methadone/buprenorphine maintenance treatment (MT), 288 entering detoxification (DTX), 180 entering drug-free residential rehabilitation (RR) and 80 not in treatment (NT). Treatment entrants were generally long-term heroin users with previous treatment experience. The majority of the sample (55%) were criminally active in the month preceding interview. Injection-related health problems (74%) and a history of heroin overdose (58%) were commonly reported. There were high degrees of psychiatric co-morbidity, with 49% reporting severe psychological distress, 28% having current major depression, 37% having attempted suicide and 42% having a lifetime history of post-traumatic stress disorder. Personality disorders were also prevalent, with 72% meeting criteria for antisocial personality disorder and 47% screening positive for borderline personality disorder. Striking similarities were noted between the non-treatment and treatment groups in length of heroin use career, drug use and treatment histories.

Topics: Adult; Australia; Buprenorphine; Comorbidity; Crime; Demography; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Female; Health Status; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Methadone; Narcotics; Patient Acceptance of Health Care; Residential Treatment; Severity of Illness Index; Stress Disorders, Post-Traumatic; Suicide; Treatment Outcome

To determine the lifetime and recent histories of attempted suicide among entrants to treatment for heroin dependence in three treatment modalities and a non-treatment comparison group; and to ascertain factors associated with a recent history of attempted suicide.. Cross-sectional structured interview.. Sydney, Australia.. Six hundred and fifteen current heroin users: 201 entering methadone/buprenorphine maintenance (MT), 201 entering detoxification (DTX), 133 entering drug free residential rehabilitation (RR) and 80 not in treatment (NT).. A lifetime history of attempted suicide was reported by 34% of subjects, 13% had attempted suicide in the preceding year and 5% had done so in the preceding month. Females were more likely to have lifetime (44% versus 28%) and 12 month (21% versus 9%) suicide attempt histories. The 12 month prevalence of attempted suicide among treatment groups ranged between 11% (MT, NT) and 17% (RR). Factors associated with recent suicide attempts were: being an RR entrant, female gender, younger age, less education, more extensive polydrug use, benzodiazepine use, recent heroin overdose, Major Depression, current suicidal ideation, Borderline Personality Disorder (BPD)and Post-Traumatic Stress Disorder.. Recent suicidal behaviour is a major clinical problem for heroin users, and for females and RR entrants in particular. An essential adjunct to treatment for heroin dependence is routine screening for depression and suicidal ideation, with the provision of appropriate treatment where needed.

Topics: Adolescent; Adult; Age Factors; Ambulatory Care; Antisocial Personality Disorder; Borderline Personality Disorder; Buprenorphine; Cross-Sectional Studies; Depressive Disorder, Major; Drug Overdose; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Mass Screening; Methadone; Middle Aged; Narcotics; Needle-Exchange Programs; New South Wales; Outcome and Process Assessment, Health Care; Patient Admission; Rehabilitation Centers; Risk Factors; Sex Factors; Stress Disorders, Post-Traumatic; Substance Abuse, Intravenous; Suicide, Attempted

A sample of 535 entrants to opioid dependence treatments across three treatment modalities were administered a structured interview to ascertain the prevalence of non-injecting heroin use. Ten per cent of participants had used heroin primarily by smoking/inhaling in the month preceding interview, and 9% had used heroin and other drugs exclusively by non-injecting routes. Non-injectors were younger (25.3 vs. 29.5 years), had higher levels of education (10.6 vs. 10.0 years), were more likely to be employed (33 vs. 18%) and had lower levels of recent crime (31 vs. 56%). They also had shorter heroin using careers (5.1 vs. 9.9 years), fewer symptoms of dependence (5.1 vs. 5.6), had been enrolled in fewer previous treatment episodes (3.3 vs. 11.5) and had less extensive lifetime (8.0 vs. 9.1 drug classes) and recent (3.6 vs. 4.9) polydrug use. Non-injectors were substantially less likely to report lifetime (13% vs. 58%) or recent (2% vs. 29%) heroin overdoses. There were no differences between the general physical and psychological health of the two groups. While non-injectors had a lower level of post-traumatic stress disorder (29% vs. 34%), there were no differences in levels of major depression, attempted suicide, antisocial personality disorder, or borderline personality disorder. A substantial minority of Australian treatment entrants are now using heroin exclusively by non-injecting routes. While this group is younger, and has substantially reduced risk of overdose and blood borne virus transmission, the physical and psychological health of non-injectors mirrors that of injectors.

Topics: Administration, Inhalation; Adolescent; Adult; Antisocial Personality Disorder; Borderline Personality Disorder; Buprenorphine; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Overdose; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Methadone; Middle Aged; Narcotic Antagonists; Residential Treatment; Suicide, Attempted

Topics: Analgesics, Opioid; Buprenorphine; Depressive Disorder, Major; Humans; Receptors, Opioid; Receptors, Opioid, mu; Treatment Outcome