Microinduction of Buprenorphine/Naloxone: A Review of the Literature.

BACKGROUND AND OBJECTIVES: Buprenorphine's high-binding affinity as a partial µ-opioid agonist displaces preexisting full agonists causing precipitated withdrawal, which requires most individuals starting buprenorphine to endure moderate withdrawal prior to induction to avoid precipitated withdrawal. A novel approach called microinduction has emerged to remove this prerequisite. Our aim is to review the literature on these alternative approaches. METHODS: Using keywords including buprenorphine, buprenorphine/naloxone, transdermal buprenorphine, suboxone, microinduction, microdosing, rapid induction, buprenorphine-dosing protocol, the authors searched PubMed/Medline, EMBASE, PsycINFO, PsychARTICLES, and Scopus databases from the date of inception through April 30, 2020, which yielded 1726 results, which, in turn, after manual exclusion for irrelevant content and publication in languages other than English, generated a total of 18 papers. RESULTS: On the basis of 18 papers included in this review, 63 patients were successfully transitioned to buprenorphine using different microdosing techniques, primarily in the inpatient setting. From the available data, patients were transitioned from a variety of opioids over a range of dosing without significant withdrawal, and initial doses ranged most frequently from 0.2 to 0.5 mg. While the timeframe for the various schedules ranged from 3 to 112 days, most transitioned over a period of 4 to 8 days, and most participants completed the cross titration at 8 to 16 mg. DISCUSSION AND CONCLUSIONS: The growing literature demonstrates some initial promise for alternative induction models, specifically targeting patients averse to withdrawal, patients prescribed opioids for chronic pain, patients on high-dose methadone, and patients using illicit or pharmaceutical fentanyl. SCIENTIFIC SIGNIFICANCE: This manuscript provides a review of the existing literature to help clinicians better understand the approaches to microdosing of buprenorphine in various clinical settings and populations. (Am J Addict 2020;00:00-00).

The burden of psychiatric illnesses in adult patients with beta-thalassemia: a 5-year nationwide inpatient evaluation in the United States.

Beta-thalassemia (ß-thalassemia) is a frequently inherited monogenic disorder worldwide with severe physical and mental health comorbidities. The aim of this study is to evaluate the burden of psychiatric disorders in adult patients hospitalized with ß-thalassemia in the United States (US). We utilized the discharge data from the National Inpatient Sample (NIS) from 2010 through 2014 to identify hospitalized ß-thalassemia patients who are 18 years and older. We assessed categorical and continuous variables using chi-square test and Student's t test respectively. The burden of psychiatric disorders was assessed using descriptive statistics and represented in terms of frequency (n) and percentage (%). A p value threshold of < 0.05 was considered clinically significant. All statistical analyses were performed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Of the 10,046 ß-thalassemia patients studied, 24.4% (n = 2448) reported psychiatric disorders. Mood disorders (15.2%; inclusive of 10.3% depression), followed by anxiety (9.4%), and substance abuse disorder (6.5%; 4.3% drug abuse, 2.2% alcohol abuse) were most prevalent. Comorbid mental illnesses increased the length of stay by 44.6% and total costs by 23.4%. All-cause mortality rate was reported at 1.9% in overall ß-thalassemia patients. This study highlights higher rates of psychiatric disorders such as depression and anxiety and correlated increases in length of stay and cost in hospitalized ß-thalassemia patients. To improve medical outcomes and curtail unnecessary health-care costs, implementation of an integrated care model can be considered.

Therapeutic Potential of Buprenorphine in Depression: A Meta-Analysis of Current Evidence.

Background: Emerging research indicates buprenorphine, used in management of opioid use disorder, has attracted interest for its potential in treating a variety of psychiatric conditions. This meta-analysis aimed to determine the efficacy of buprenorphine in treating symptoms of depression. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a search was conducted of several databases until April 25, 2022, for English language articles related to buprenorphine and its use in treating various mental health conditions. Standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were reported for the Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Statistical analyses were performed using Cochrane RevMan 5. Results: Of the 1,347 identified studies, six clinical trials were included. MADRS-10 least square mean difference (LSMD) inter-group assessment favored buprenorphine over placebo, but it lacked statistical significance. Similarly, MADRS scores as well as HAM-D inter-group assessment were in favor of buprenorphine, however, were not statistically significant. These findings suggest a potential therapeutic role for buprenorphine in treating depression, albeit with caution due to the observed lack of statistical significance and the potential for confounding factors. Conclusions: Preliminary evidence suggests potential efficacy of buprenorphine at lower doses in improving improving outcomes specifically related to depression. However, due to limitations in statistical significance and possible confounding factors, entail cautious interpretation. Further rigorous research is needed to investigate the long-term effects, optimal dosing, and determine the role of adjuvant drug therapy.

Non-opioid psychiatric medications for chronic pain: systematic review and meta-analysis.

Background: The escalating number of deaths related to opioid usage has intensified the pursuit of non-opioid alternatives for managing chronic pain. It's often observed that psychiatric comorbidities coexist in patients suffering from chronic pain. There are a variety of psychotropic medications that have demonstrated effectiveness in treating both psychiatric symptoms and pain. This systematic review and meta-analysis aim to assess the effectiveness of various psychiatric drugs in managing specific types of chronic pain, including fibromyalgia, neuropathic pain, and chronic low back pain. Methods: A comprehensive search of five major databases was conducted through February 2023 to identify randomized controlled trials (RCTs) that met our inclusion criteria, focusing on outpatients Over 18 years of age with chronic pain. The study assessed the effectiveness of duloxetine, mirogabalin, pregabalin, gabapentin, and tricyclic antidepressants (TCAs), including serotonin-norepinephrine reuptake inhibitors (SNRIs), across various chronic pain conditions such as fibromyalgia, neuropathic pain, and chronic low back pain. The primary outcome measures included pain reduction, improvement in function, and quality of life. Of the 29 RCTs in the systematic review, 20 studies qualified for the meta-analysis. The analysis was stratified by pain type and treatment duration (short-term ≤14 weeks vs. long-term >14 weeks), using Hedge's g standardized mean differences and a random-effects model, along with sensitivity and subgroup analyses. Results: The overall short-term intervention effect across all studies was significant (SMD -1.45, 95% CI -2.15 to -0.75, p < 0.001), with considerable heterogeneity (I2 = 99%). For fibromyalgia, both duloxetine and mirogabalin demonstrated substantial efficacy with SMDs of -2.42 (95% CI -3.67 to -1.18, p < 0.0001) and -2.10 (95% CI -3.28 to -0.92, p = 0.0005), respectively. Conversely, treatments for neuropathic pain and chronic low back pain, including those with amitriptyline and desipramine, did not show significant benefits. The effectiveness of gabapentin could not be conclusively determined due to limited representation in the data. Additionally, no consistent long-term benefits were observed for any of the medications. Conclusions: While the results of this study underscore the importance of exploring non-opioid alternatives for chronic pain management, particularly in light of the opioid crisis, it is crucial to interpret the findings carefully. Our analysis suggests that certain psychiatric medications, such Duloxetine and mirogabalin demonstrated significant short-term efficacy in fibromyalgia patients. However, their effectiveness in treating neuropathic pain and chronic low back pain was not statistically significant. Additionally, the effectiveness of gabapentin and other medications, such as pregabalin for neuropathic pain, could not be conclusively determined due to limited data and high study heterogeneity. No consistent long-term benefits were observed for any of the drugs studied, raising questions about their sustained efficacy in chronic pain management. These findings highlight the need for further research to understand better the role of psychiatric medications in managing specific chronic pain conditions without prematurely concluding that they are ineffective or unsuitable for these purposes.

Low-dose buprenorphine initiation in the era of fentanyl and fentanyl analogs: A case series of outpatient inductions.

Buprenorphine, a partial opioid agonist, is a Food and Drug Administration-approved medication for the treatment of opioid use disorder (OUD). However, due to its high binding affinity, precipitated withdrawal may occur if initiated in the presence of other opioids. The growing literature demonstrates promise for alternative induction model of low-dose initiation of buprenorphine for the treatment of OUD, specifically targeting patients averse to withdrawal or using fentanyl. In this case series, we present four clinical cases of outpatient inductions, in which three out of four successfully transitioned from fentanyl to buprenorphine, and one patient transitioned from methadone to buprenorphine using a low-dose induction method.

Beyond physical health: the role of psychosocial challenges and stigma in tackling the COVID-19 pandemic-A scoping review.

Background: The socio-cultural response to the Coronavirus Disease 2019 (COVID-19) and the level of adherence to evidence-based guidelines played a crucial role in determining the morbidity and mortality outcomes during the pandemic. This review aims to evaluate the impact of stigma and psycho-socio-cultural challenges on efforts to control the COVID-19 pandemic and to identify ways to mitigate such challenges in future pandemics. Methods: Using keywords including COVID-19, coronavirus, stigma, psychosocial challenges, and others, the authors searched seven major databases with a time limitation of July 2021, which yielded 2,038 results. Out of these, 15 papers were included in this review. Results: The findings of the review indicated that several psychosocial, socio-economic, and ethno-cultural factors are linked to the transmission and control of COVID-19. The research revealed that stigma and related psychosocial challenges and others, such as anxiety, fear, and stigma-driven social isolation, have resulted in significant mental health problems. Discussion: The review underscores the negative impact of stigma on COVID-19 patients, survivors, and the general population. Addressing stigma and psychosocial challenges is crucial to effectively manage the current pandemic and to prevent similar challenges during future public health crises.

Effectiveness of Gabapentin in Reducing Cravings and Withdrawal in Alcohol Use Disorder: A Meta-Analytic Review.

OBJECTIVE: The current meta-analysis synthesizes previous findings on the effect of gabapentin on alcohol withdrawal and craving. DATA SOURCES: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, a search for relevant English-language literature published between January 1999 and February 2019 was conducted using PubMed and Google Scholar with the keywords alcohol use disorder, alcohol dependence, alcohol withdrawals, alcohol craving, "gabapentin in alcohol use, consumption," and "gabapentin in alcohol withdrawals." STUDY SELECTION AND DATA EXTRACTION: Studies were included wherein gabapentin was used as an adjunctive or primary treatment of alcohol dependence/withdrawal. Studies included participants diagnosed with alcohol use disorder using DSM-IV, DSM-IV-TR, DSM-5, or the International Classification of Diseases, Tenth Revision (ICD-10). The search, as well as data extraction, was carried out by 3 blinded authors to preserve precision, using a template in Microsoft Excel to extract the needed data. Following the review of the initial 65 returns, 2 authors independently judged each trial by applying the inclusionary and exclusionary criteria, and any remaining disagreements were resolved by involving a third independent author. A total of 10 studies met the inclusion criteria and were selected for analysis. Subjects in these 10 studies were pooled using standard techniques of meta-analysis. DATA SYNTHESIS: Three sets of meta-analyses examined outcomes from (1) single-group pretest-posttest changes, (2) posttest differences between independent groups, and (3) differences in pretest-posttest change scores between independent groups. Statistically significant effect sizes were found for craving (P < .01) and withdrawal (P < .01, P < .001) in the meta-analysis of single-group pretest-posttest outcome changes and were associated with a high level of heterogeneity. In contrast, the meta-analyses of posttest differences between independent groups-that of differences in pretest-posttest change scores between independent groups-did not yield significant effect sizes. CONCLUSIONS: Our analysis of pooled data provides evidence that the use of gabapentin to manage alcohol withdrawal symptomatology and related cravings is at least moderately effective. However, given the limited number of available well-designed studies, these findings require further support through more rigorously designed studies.

Primary Causes of Hospitalizations and Procedures, Predictors of In-hospital Mortality, and Trends in Cardiovascular and Cerebrovascular Events Among Recreational Marijuana Users: A Five-year Nationwide Inpatient Assessment in the United States.

Background Recent trends in the legalization of marijuana in many states are increasing the popularity of recreational marijuana use. Since current data on hospitalizations in marijuana users is sparse, we evaluated the primary reasons for admissions, procedures and associated healthcare burden in hospitalized recreational marijuana users. Methods The National Inpatient Sample (NIS) for the years 2010-2014 was queried for the hospitalizations with a history of recreational marijuana usage using applicable ICD-9 CM codes. Descriptive statistics were used to report frequency (N) and percentage (%). Discharge weights were applied to achieve national estimates. The predictors of in-hospital mortality in recreational marijuana users were assessed using a two-way hierarchical multivariate regression after adjusting for the confounders. Results  We analyzed 465,959 (weighted n=2,317,343) hospitalizations with a history of recreational marijuana use. Among psychiatric disorders, most prominent primary discharge diagnoses were mood disorders (20.6%), schizophrenia/other psychotic disorders (10.6%), and substance/alcohol-related disorders (10.4%). Suicide and intentional self-inflicted injury (3.6%) was the leading cause of emergency admission. The most common non-psychiatric primary discharge diagnoses were diabetes mellitus with chronic complications (2.2%), acute myocardial infarction (AMI) (1.2%), nonspecific chest pain (1.1%), congestive cardiac failure (CHF) (1%), arrhythmia (0.8%), and hypertension (0.8%). Acute cerebrovascular diseases were noted in 1.1% and epilepsy in 1.8% of patients. Alcohol/drug rehabilitation and detoxification (6.9%) and psychiatric evaluation/therapy (3.9%) were the most evident psychiatric procedures whereas most frequent non-psychiatric procedures were diagnostic coronary arteriography (1%), percutaneous transluminal coronary angioplasty (0.7%), and echocardiogram (0.7%). Top independent predictors of in-hospital mortality were coagulopathy (OR 5.94), AMI (OR 4.59), pulmonary circulation disorder (OR 2.95), CHF (OR 2.02), renal failure (OR 1.91), coronary atherosclerosis (OR 1.34) and peripheral vascular disorder (OR 1.31). Major cardiovascular and cerebrovascular events also showed increasing trends among users. Conclusion We established the most frequent psychiatric and non-psychiatric causes of admissions and procedures in recreational marijuana users, which may pose a significant healthcare burden and increase the odds of in-hospital mortality.