buprenorphine and Stress-Disorders--Post-Traumatic

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

Posttraumatic stress disorder (PTSD) and opioid use disorder (OUD) may be associated with poor outcomes in rural areas where access to mental health services and opioid agonist treatment (OAT) is limited. This study examined the characteristics associated with a history of PTSD among a sample of individuals seeking buprenorphine treatment for OUD in Vermont, the second-most rural state in the US. Participants were 89 adults with OUD who participated in one of two ongoing randomized clinical trials examining the efficacy of an interim buprenorphine dosing protocol for reducing illicit opioid use during waitlist delays to OAT. Thirty-one percent of participants reported a history of PTSD. Those who did (PTSD+; n = 28) and did not (PTSD-; n = 61) report a history of PTSD were similar on sociodemographic and drug use characteristics. However, the PTSD+ group was less likely to have received prior OUD treatment compared to the PTSD- group (p = .02) despite being more likely to have a primary care physician (p = .009) and medical insurance (p = .002). PTSD+ individuals also reported greater mental health service utilization, more severe psychiatric, medical and drug use consequences, and greater pain severity and interference vs. PTSD- individuals (ps < 0.05). These findings indicate that a history of PTSD is prevalent and associated with worse outcomes among individuals seeking treatment for OUD in Vermont. Dissemination of screening measures and targeted interventions may help address the psychiatric and medical needs of rural individuals with OUD and a history of PTSD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Longitudinal Studies; Opiate Substitution Treatment; Opioid-Related Disorders; Stress Disorders, Post-Traumatic; Vermont

Large randomized trials have found that behavioral therapy for opioid use disorder (e.g., Individual Drug Counseling, Cognitive Behavioral Therapy for Opioid Use Disorder) does not improve buprenorphine maintenance outcomes, on average, for individuals with opioid use disorder. However, recent studies indicate that certain subgroups of patients may benefit from the addition of behavioral therapy to buprenorphine. In particular, people with more complex and severe psychosocial needs may benefit from the addition of behavioral therapy for opioid use disorder.. In this study, we conducted a secondary analysis of a large, multi-site randomized trial (N = 357) of buprenorphine maintenance with and without individual Opioid Drug Counseling (ODC) for the treatment of opioid use disorder. We hypothesized that participants with posttraumatic stress disorder (PTSD) would benefit from the addition of ODC.. Logistic regression models indicated a significant PTSD by treatment condition interaction. Specifically, 67% of those with PTSD had a successful opioid use disorder treatment outcome when they were assigned to receive both ODC and buprenorphine, compared to a 36% response rate among those who received buprenorphine alone.. Although these results require replication, our findings provide initial indication that ODC is an important complement to buprenorphine maintenance treatment for people with co-occurring PTSD and opioid use disorder.

Topics: Analgesics, Opioid; Buprenorphine; Counseling; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmaceutical Preparations; Stress Disorders, Post-Traumatic

Topics: Buprenorphine; Humans; Infusion Pumps, Implantable; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Stress Disorders, Post-Traumatic; United States; United States Food and Drug Administration

Opioid use disorder (OUD) rates are high among veterans. PTSD is also prevalent among veterans; those with comorbidity have worse outcomes than those without comorbidity. This study assessed buprenorphine retention rates in veterans initiating OUD treatment, comparing veterans without PTSD to veterans with PTSD who were receiving versus not receiving concurrent trauma treatment.. This retrospective chart review examined consecutive referrals to buprenorphine maintenance (N = 140). PTSD diagnosis was identified by chart review and retention was defined as continuous buprenorphine maintenance 6-months post-admission. Logistic regression analyses compared buprenorphine retention for veterans without PTSD and PTSD-diagnosed veterans who received concurrent trauma treatment to a reference group of PTSD-diagnosed veterans who did not receive trauma treatment. Models adjusted for opioid type, age, and service-connected status.. Sixty-seven (47.9%) buprenorphine-seeking veterans carried a PTSD diagnosis; only 31.3% (n = 21) received trauma treatment while in buprenorphine maintenance, with 11.9% (n = 8) receiving evidence-based psychotherapy for PTSD. Among PTSD-diagnosed veterans who received trauma treatment, 90.5% (n = 19/21) were in buprenorphine maintenance at 6-months, compared to 23.9% (n = 11/46) of PTSD-diagnosed veterans without trauma treatment, and 46.6% (n = 34/73) of veterans without PTSD. In the full model, veterans with trauma treatment had 43.36 times greater odds of remaining in buprenorphine treatment than the reference group.. Most PTSD-diagnosed veterans in buprenorphine treatment were not receiving trauma treatment. Those receiving concurrent trauma treatment had better retention, suggesting OUD and trauma can be simultaneously addressed. Future clinical trials should investigate trauma-focused treatment for veterans with comorbid PTSD who are seeking buprenorphine for OUD.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Psychotherapy; Retrospective Studies; Stress Disorders, Post-Traumatic; Veterans

Purpose To evaluate the efficacy of a brief education session affecting patient perspectives on follow up care of substance use and trauma treatment in pregnant women admitted to a medical hospital. Description Participants (N = 31) were recruited from the antepartum unit at Magee-Women's Hospital at the University of Pittsburgh who had current substance use and history of trauma. A voluntary individual educational session was offered that discussed the diagnosis and treatment of substance use and trauma, fundamental coping skills, and local resources. Utility of the session, knowledge of PTSD, and barriers of care were evaluated through a pre- and post- session questionnaire. Assessment All participants found the session improved their knowledge of PTSD, substance use, safe coping skills, and increased their likelihood of pursuing further follow up treatment. Conclusion Brief educational interventions that are integrated in the medical hospital are found to be useful by patients and reported to influence their decision to seek further treatment. Further studies are needed to analyze the long-term outcomes of brief interventions.

Topics: Adaptation, Psychological; Adult; Alcoholism; Benzodiazepines; Buprenorphine; Female; Humans; Maternal Health Services; Methadone; Opiate Substitution Treatment; Pregnancy; Psychometrics; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Surveys and Questionnaires

The core pharmacological treatment of Post-Traumatic Stress Disorder (PTSD) is selective serotonin reuptake inhibitors (SSRIs), although remission is only around 30% with them. Many patients will self-treat with opioids and due to the opiate system involvement in dysphoric mood and anxiety/stress responses, it is likely that antagonism of the kappa opioid receptor (KOR) system represents a potential target for treatment of PTSD. The aim of this study is to compare response of PTSD symptoms when antagonizing KOR via buprenorphine/naloxone compared to SSRIs or opioid therapy.. A retrospective chart review of patients in the MEDVAMC between June 1, 2010 and June 30, 2016 was conducted. Inclusion criteria included patients with a documented diagnosis of PTSD with at least two documented PTSD scores (either PCLC or PC-PTSD). Exclusion criteria included patients not prescribed one of the study medications (ie, buprenorphine, SSRI, or opiate for chronic pain), and patients not on the study medication for at least 30 days.. Buprenorphine patients exhibited the lowest final average PTSD score (2.47) and the largest change from baseline (-24.0%) compared to opioids (-16.1%) or SSRIs (1.16%). The average buprenorphine dose was 23.3 mg/day, and the average length of therapy was 860 days.. Buprenorphine may help decrease PTSD symptoms more than SSRIs or opioids alone. Prospective studies are needed to determine whether these effects are reproducible.. Pharmacotherapy advancements in PTSD treatment have been limited and the kappa opioid receptor system presents a new target that warrants further research. (Am J Addict 2019;XX:1-6).

Topics: Adult; Analgesics, Opioid; Buprenorphine; Comparative Effectiveness Research; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Receptors, Opioid, kappa; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic; Treatment Outcome; United States

Patients with post-traumatic stress disorder frequently report persistent problems with social interactions, emerging after a traumatic experience. Chronic social defeat stress is a widely used rodent model of stress that produces robust and sustained social avoidance behavior. The avoidance of other rodents can be reversed by 28 days of treatment with selective serotonin reuptake inhibitors, the only pharmaceutical class approved by the U.S. Food and Drug Administration for treating post-traumatic stress disorder. In this study, the sensitivity of social interaction deficits evoked by 10 days of chronic social defeat stress to prospective treatments for post-traumatic stress disorder was examined.. The effects of acute and repeated treatment with a low dose of buprenorphine (0.25 mg/kg/d) on social interaction deficits in male C57BL/6 mice by chronic social defeat stress were studied. Another cohort of mice was used to determine the effects of the selective serotonin reuptake inhibitor fluoxetine (10 mg/kg/d), the NMDA antagonist ketamine (10 mg/kg/d), and the selective kappa opioid receptor antagonist CERC-501 (1 mg/kg/d). Changes in mRNA expression of Oprm1 and Oprk1 were assessed in a separate cohort.. Buprenorphine significantly reversed social interaction deficits produced by chronic social defeat stress following 7 days of administration, but not after acute injection. Treatment with fluoxetine for 7 days, but not 24 hours, also reinstated social interaction behavior in mice that were susceptible to chronic social defeat. In contrast, CERC-501 and ketamine failed to reverse social avoidance. Gene expression analysis found: (1) Oprm1 mRNA expression was reduced in the hippocampus and increased in the frontal cortex of susceptible mice and (2) Oprk1 mRNA expression was reduced in the amygdala and increased in the frontal cortex of susceptible mice compared to non-stressed controls and stress-resilient mice.. Short-term treatment with buprenorphine and fluoxetine normalized social interaction after chronic social defeat stress. In concert with the changes in opioid receptor expression produced by chronic social defeat stress, we speculate that buprenorphine's efficacy in this model of post-traumatic stress disorder may be associated with the ability of this compound to engage multiple opioid receptors.

Topics: Animals; Behavior, Animal; Brain; Buprenorphine; Disease Models, Animal; Excitatory Amino Acid Antagonists; Fluoxetine; Ketamine; Male; Mice; Mice, Inbred C57BL; Narcotic Antagonists; Receptors, Opioid, kappa; Receptors, Opioid, mu; Selective Serotonin Reuptake Inhibitors; Social Behavior; Stress Disorders, Post-Traumatic; Stress, Psychological

Posttraumatic stress disorder (PTSD), chronic pain, and substance use disorders are prevalent co-occurring conditions that are challenging to treat individually, and there is no evidence-based treatment for all 3. Buprenorphine, used to treat opioid use disorder and chronic pain, is a partial nociceptin opioid receptor agonist. In preclinical studies, a nociceptin opioid receptor agonist was shown to mitigate PTSD symptoms in acute trauma. We compared buprenorphine to other opioid medications in its impact on PTSD symptoms in patients with chronic pain and opioid and/or other substance use disorders.. We assembled a retrospective cohort of 382 Iraq and Afghanistan veterans in US Department of Veterans Affairs health care from October 1, 2007, to July 29, 2013, with ICD-9-CM diagnoses of PTSD, chronic pain, and substance use disorders. We used time-varying general estimating equation models to assess the primary outcome, which was change in PTSD symptoms (measured using the PTSD Checklist and the Primary Care PTSD Screen) among veterans initiated on sublingual buprenorphine versus those maintained on moderately high-dose opioid therapy.. Twice as many veterans in the buprenorphine group (23.7%) compared to those in the opioid therapy group (11.7%) experienced improvement in PTSD symptoms (P = .001). Compared to veterans in the opioid therapy group, veterans receiving buprenorphine showed significant improvement in PTSD symptoms after 8 months, with increasing improvement up to 24 months (incidence rate ratio = 1.79; 95% CI, 1.16-2.77; P = .009). There were no differences in the longitudinal course of pain ratings between groups.. This observational study is the first to report an incidental effect of buprenorphine compared to opioid therapy in improving PTSD symptoms in veterans.

Topics: Adult; Afghan Campaign 2001-; Buprenorphine; Chronic Pain; Comorbidity; Female; Humans; Iraq War, 2003-2011; Male; Narcotic Antagonists; Nociceptin; Opiate Substitution Treatment; Opioid Peptides; Opioid-Related Disorders; Outcome Assessment, Health Care; Receptors, Opioid; Retrospective Studies; Stress Disorders, Post-Traumatic; United States; Veterans

Perinatal opioid use disorders negatively impact maternal and neonatal outcomes and are a public health problem of increasing severity. More than half of women with a substance use disorder have a history of posttraumatic stress disorder that, if not adequately addressed, can impede substance use disorder treatment. This case report describes complexities in the treatment of a pregnant woman with opioid use disorder and posttraumatic stress disorder and reviews the psychotherapeutic and pharmacologic approaches available to treat these co-occurring disorders in pregnancy. This case demonstrates the importance of early screening and intervention for co-occurring posttraumatic stress disorder in pregnant women who use substances in a closely coordinated, multidisciplinary approach to improve outcomes for women and their infants.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Female; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Smoking; Smoking Cessation; Stress Disorders, Post-Traumatic; Treatment Outcome; Young Adult

On October 2012, Hurricane Sandy struck New York City, resulting in unprecedented damages, including the temporary closure of Bellevue Hospital Center and its primary care office-based buprenorphine program.. At 6 months, we assessed factors associated with higher rates of substance use in buprenorphine program participants that completed a baseline survey one month post-Sandy (i.e. shorter length of time in treatment, exposure to storm losses, a pre-storm history of positive opiate urine drug screens, and post-disaster psychiatric symptoms).. Risk factors of interest extracted from the electronic medical records included pre-disaster diagnosis of Axis I and/or II disorders and length of treatment up to the disaster. Factors collected from the baseline survey conducted approximately one month post-Sandy included self-reported buprenorphine supply disruption, health insurance status, disaster exposure, and post-Sandy screenings for PTSD and depression. Outcome variables reviewed 6 months post-Sandy included missed appointments, urine drug results for opioids, cocaine, and benzodiazepines.. 129 (98%) patients remained in treatment at 6 months, and had no sustained increases in opioid-, cocaine-, and benzodiazepine-positive urine drug tests in any sub-groups with elevated substance use in the baseline survey. Contrary to our initial hypothesis, diagnosis of Axis I and/or II disorders pre-Sandy were associated with significantly less opioid-positive urine drug findings in the 6 months following Sandy compared to the rest of the clinic population.. These findings demonstrate the adaptability of a safety net buprenorphine program to ensure positive treatment outcomes despite disaster-related factors.

Topics: Analgesics, Opioid; Appointments and Schedules; Benzodiazepines; Bipolar Disorder; Buprenorphine; Cocaine; Cocaine-Related Disorders; Cohort Studies; Comorbidity; Cyclonic Storms; Depressive Disorder; Disaster Planning; Disasters; Female; Health Services Accessibility; Humans; Male; Narcotic Antagonists; New York City; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatient Clinics, Hospital; Prospective Studies; Psychotic Disorders; Risk Factors; Stress Disorders, Post-Traumatic; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

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