The sociodemographic profile and the challenges associated with treatment and rehabilitation in female heroin users: A case series from Northeast India.

Females with opioid use disorder (OUD) rarely seek help for addiction. We present a series of seven females with OUD attending a tertiary care addiction treatment setting in Assam between December 2022 to August 2023. Most of the patients were primary-educated, young adults, housewives, from lower to middle socioeconomic strata, and were residents of rural or semi-urban areas. All were married, and around half of them were separated. All the patients were dependent on heroin and tobacco. Five of them initiated heroin use while modeling their spouse. Three patients were injecting heroin, and one was seropositive with both HCV and HIV. Five patients received sublingual buprenorphine-naloxone, and three of them followed up subsequently. Financial difficulty, poor family support, and intimate partner violence were major challenges for treatment-seeking and regular follow-up. This case series highlights the need for systematic study and gender-responsive care of females with OUD in Assam.

Service users' perception and attitude toward telemedicine-based treatment for substance use disorders: A qualitative study from India.

Aim: We aimed to assess the service user's acceptability, feasibility, and attitude toward telemedicine practice and compare it with in-person consultation in substance use disorder (SUD). Materials and Methods: We recruited 15 adult patients with SUD who accessed both telemedicine and in-person care. We conducted in-depth interviews on awareness and access, facilitators and barriers, treatment satisfaction, and therapeutic relationship in the telemedicine context. We performed a conventional content analysis of the interview excerpts and used inductive and deductive coding. We assumed that social, personal, and logistic contexts influence patients' perceptions and experiences with telemedicine-based addiction care (TAC). Results: Most participants were middle-aged men (40.5 years, 86.7%), dependent on two or more substances (86.7%), and had a history of chronic, heavy substance use (use ~16 years, dependence ~11.5 years). Patients' perspectives on TAC could broadly be divided into three phases: pre-consultation, consultation, and post-consultation. Patients felt that TAC improved treatment access with adequate autonomy and control; however, there were technical challenges. Patients expressed privacy concerns and feared experiencing stigma during teleconsultation. They reported missing the elaborate inquiry, physical examination, and ritual of visiting their doctors in person. Additionally, personal comfort and technical difficulties determine the satisfaction level with TAC. Overall perception and suitability of TAC and the decision to continue it developed in the post-consultation phase. Conclusion: Our study provides an in-depth insight into the barriers and facilitators of telemedicine-based SUD treatment access, use, and retention; it also helps to understand better the choices and preferences for telehealth care vis-à-vis standard in-person care for SUDs.

The toll of opioid dependence: A research report on the possible role of Toll-like receptor-4 and related immune markers in opioid dependence.

Background: The opioid receptors in the central nervous system and immune system contribute to its reinforcing effect. Xenobiotics-associated molecular pattern of opioids interacts with Toll-like receptor-4 (TLR-4) on the glial cell surface and increases dopaminergic activity in the nucleus accumbens in preclinical studies. We wanted to examine whether treatment with buprenorphine-naloxone (BNX) might be associated with changes in immunological markers in individuals with opioid dependence (OD). Methods: We recruited 30 individuals with OD on buprenorphine and 30 age- and sex-matched healthy controls (HCs). We measured the neutrophil (N), lymphocyte (L), CD-4, and CD-8 T-cell count and estimated plasma TLR-4 level in the HC group once. We measured the immunological markers, craving, pain, and perceived stress in the OD group at the treatment initiation (baseline) and after 4 weeks (±2 weeks) of treatment with BNX. Results: The mean severity score on the OD questionnaire was 72.8 (SD 5.4). At baseline, OD had a higher N: L ratio and lower lymphocyte percentage than HC. Plasma TLR-4 concentration increased significantly after 1 month of treatment (t = -3.09, P = 0.004). Craving, pain, and perceived stress correlated with absolute neutrophil count, N: L ratio, and CD-8 T-cell count, although lost significance after corrections for multiple comparisons. Conclusion: The increase in TLR-4 after treatment with BNX may indicate the rescue from nonprescription opioid-induced immunosuppression or the introduction of a novel xenobiotics-associated molecular pattern of BNX.

Does Prescription Length of Buprenorphine Influence Treatment Outcomes in Opioid Use Disorder? A Retrospective Cohort Study from North India.

OBJECTIVE: Buprenorphine (BUP) effectively suppresses non-prescription opioid use and increases treatment retention in opioid use disorder (OUD). However, short prescription length may interfere with treatment retention and recovery. We wanted to examine whether the outcomes of BUP treatment differ in high (HPL up to 4 wk) and low-prescription (LPL 1-2 wk) length groups. METHODS: We compared time to treatment discontinuation (TD), non-prescription opioid-positive urine screen, buprenorphine-negative urine screen, and self-reported non-prescription opioid use between two different cohorts of LPL (case record: June 2018 to August 2019; n = 105; observation endpoint: 31 October 2019) and HPL groups (case record: June 2020 to Aug 2021; n = 133; observation endpoint: 31 October 2021). We used Kaplan-Meier survival analysis and log-rank tests for between-group comparisons. We used Cox regression analysis to adjust for age, opioid potency, comorbidities, family income, and marital status. RESULTS: Subjects' age and buprenorphine dose were significantly lower, and the percentage of high-potency opioid users was significantly higher in the LPL group. In the unadjusted survival analysis, the median time to BUP discontinuation in the HPL was longer than that of the LPL [LPL= 22.4 ± 4.3 wk; HPL = 33.1 ± 8.5 wk; χ2(1)= 5.7; p=.02]. The survival distributions of other outcomes did not differ between groups. When adjusted for covariates, neither the prescription length nor other covariates independently predicted any treatment outcome. CONCLUSION: Higher prescription length might be associated with longer treatment retention. We provide preliminary evidence to support greater flexibility in BUP treatment, enhancing its scalability and attractiveness.

Neurocognitive Functions in Patients with Comorbid Hepatitis C and Opioid Dependence: A Comparative Study.

Background: Hepatitis C virus (HCV) infection is commonly comorbid with opioid dependence (OD). We wanted to compare the neurocognitive functions of OD subjects with or without HCV [HCV (+), HCV (-)] and healthy controls (HC). Methods: We recruited 40 adult subjects (age 18-55 years) in each group. HCV(+) group had a detectable viral load. Subjects with HIV or hepatitis B infection, head injury, epilepsy, or comorbid mental illness were excluded. We administered Standard Progressive Matrices (SPM), Wisconsin Card Sorting Test, Iowa Gambling Task (IGT), trail-making tests A and B, and verbal and visual N-back tests (NBT) one week after opioid abstinence. The group differences in cognitive performance were adjusted for age and years of education. Effect size (ES) is expressed as Cohen's D. Results: The HCV(+) and HCV(-) groups did not differ in potential effect modifiers (age and years of education) or confounders (age of opioid initiation, duration of use, dependence severity, tobacco use, and cannabis use) of neuropsychological functioning. HCV(+) showed significantly poorer performance than HCV(-) in SPM (P = 0.006; ES = 0.72). Both HCV(+) and HCV(-) performed worse than controls in IGT(P < 0.001; ES = 0.8) and visual NBT[P < 0.01 and ES > 1 for total errors]; HCV(+) had a larger ES of group difference than HCV(-). HCV(+) had higher error scores in verbal NBT than control. Conclusion: HCV(+) has poorer general intellectual ability and reasoning than HCV(-) persons and controls. Chronic HCV infection causes a higher magnitude of dysfunction in decision-making and visual working memory in opioid-dependent individuals.

The therapeutic relationships, empathy, and satisfaction in teleconsultation for substance use disorders: Better or worse than in-person consultation?

Context: Telemedicine has become one of the essential modes of healthcare delivery. Different aspects of the physician-patient relationship during tele and in-person consultation need to be studied. Aims: This study aimed to compare perceived empathy and therapeutic relationship between tele and in-person consultation and assess the patient's satisfaction during teleconsultation for substance use disorder (SUD). Methodology: We consecutively recruited 100 adult patients with SUD, registered to the tele-addiction service between June and September 2020, and experienced both video and in-person consultations. We assessed therapeutic relationships, perceived empathy (for teleconsultation and in-person consultation), and patients' satisfaction (with teleconsultation) with specific scales. We compared the scores of the therapeutic relationship and physician empathy scales for tele and in-person consultation. Results: The mean age of the patients was 35.5 (±10.4) years. Sixty percent had alcohol, followed by opioids (42%) and cannabis dependence (24%). Sixty percent of patients had comorbid tobacco dependence. Telehealth satisfaction (TSS) rating shows around 40% of patients had difficulty accessing the telehealth service and 7% felt their privacy was poorly respected. The mean total therapeutic relation (STAR) (t = -14.4; P <.001), positive collaboration (t = -12.8; P <.001), positive clinical input (t = -11.9; P <.001), and total Patient's Perceptions of Physician Empathy (PPPE) score (t = -8.4; P < .001) were lower in the teleconsultation than in-person consultation group. TSS was positively correlated with positive collaboration, positive clinician input, and STAR total score. Conclusions: Our study suggests a stronger therapeutic relationship and higher physician empathy during in-person consultations. Poor accessibility and privacy concerns were critical challenges in telehealth service. TSS and therapeutic relationships positively influence each other.

Course and Correlates of Stigma in Patients on Opioid Agonist Treatment: A Prospective Study from an Outpatient Treatment Program in India.

Background: Individuals with opioid dependence experience stigma and discrimination. Stigma can potentially reduce treatment-seeking and negatively affect treatment outcomes. We aimed to study the course of stigma and its correlates among patients receiving opioid agonist treatment (OAT). Methods: We recruited 51 subjects (aged between 18 and 45 years) registered in the OAT clinic from February to September 2019. We excluded subjects dependent on alcohol and other drugs (except for cannabis and tobacco), with severe mental illness, intellectual disability, and organic brain disease. We assessed the internalized and enacted stigma and quality of life at the treatment entry and after 3 months. Relationship of stigma with quality of life, socio-demographic, and other clinical variables were examined at the treatment entry. Results: Mean age of the subjects was 26.7 (± 5) years. At the end of three months, 33 (64.7%) patients were retained in the treatment. Internalized stigma correlated negatively with the social and environmental domains of quality of life. The strength of the correlations was modest. No significant correlation was found between demographic and clinical variables and internalized stigma and enacted stigma scores. Both internalized and enacted stigma scores reduced significantly at 3 months follow-up. The significance levels were retained even after controlling for the baseline quality of life scores. Stigma at the treatment entry did not predict early dropout. Conclusion: Despite higher severity at the treatment entry, the level of internalized and enacted stigma reduced significantly within three months of an outpatient-based OAT program.

Six-month buprenorphine-naloxone treatment is associated with neurocognitive function improvement in opioid dependence.

Background and Aim: The number of longitudinal studies on cognitive functions in patients on buprenorphine-based agonist treatment is limited. Our objective was to assess the change in neurocognitive functions over the first 6 months of buprenorphine-naloxone (BNX) treatment for opioid dependence (OD) and compare cognitive functions on BNX and controls. Methods: We selected 60 patients with OD aged 18 to 55 years and 20 sex-matched controls; and excluded patients with other substance dependence, human immunodeficiency virus (HIV), head injury, epilepsy, and severe mental illness. We assessed patients thrice: at baseline, 3, and 6 months and Controls once. Cognitive tests included Wisconsin card sorting test (WCST), Iowa gambling task (IGT), trail making tests A and B (TMT-A and B), verbal and visual N-back test (NBT), and standard progressive matrices (SPM). We measured with-in group effect size with Cohen's D (d). Results: A total of 24 participants completed at least one follow-up; 17 completed both follow-up assessments. All participants were men. At baseline, the patients performed worse than healthy controls in IGT, TMT-A, and B, and visual and verbal NBT. At 3 months, the performance of visual NBT improved significantly (d = 1.2 for NBT1; 1.3 for NBT2). At 6 months, additional performance improvements were seen in WCST ("perseverative error" d = 1.2), IGT ("net total score" d = 1.2), TMT-A (d = 1.1), and verbal NBT ("omission error" d = 1.7). Except for visual-NBT, results did not differ between patients and controls at both follow-ups. Conclusion: Cognitive flexibility, decision making, attention, working memory, and psychomotor speed showed improvements over 6 months of a stable dose of BNX.

Google Trends Data: A Potential New Tool for Monitoring the Opioid Crisis.

INTRODUCTION: There is a need to strengthen the standard surveillance of the opioid overdose crisis in the USA. The role of Google Trends (GT) was explored in this context. METHODS: In this study, a systemic GT search was done for a period from January 2004 to December 2018. "Naloxone" and "drug overdose" were chosen as search inputs. By using locally weighted scatterplot smoothing, we locally regressed and smoothed the relative search data generated by the GT search. We conducted a changepoint analysis (CPA) to detect significant statistical changes in the "naloxone" trend from 2004 to 2018. Cross-correlation function analyses were done to examine the correlation between 2 time series: year-wise relative search volume (RSV) for "naloxone" and "drug overdose" with the age-adjusted drug overdose mortality rate. Pearson's correlation was performed for the state-wise age-adjusted mortality rate due to drug overdose and RSV for "naloxone" and "drug overdose." RESULTS: Smoothed and regressed GT of "naloxone" were similar to the "opioid overdose" trend published by the National Center for Health Statistics. The CPA showed 2 statistically significant points in 2011 and 2015. CPA of year-wise RSV for "naloxone" and "drug overdose" showed significantly positive correlation with the age-adjusted drug overdose mortality at lag zero. State-wise RSV for "naloxone" and "drug overdose" too showed a strong and significant positive correlation with the state-wise mortality data. DISCUSSION/CONCLUSION: Inexpensive, publicly accessible, real-time GT data could supplement and strengthen the monitoring of opioid overdose epidemic if used in conjunction with the existing official data sources.

Depressive symptoms in early alcohol or opioid abstinence: course & correlates.

BACKGROUND: Depressive symptoms are common during abstinence from psychoactive substances. Research caveats limit the study of persistence of significant depressive symptoms beyond four weeks of abstinence. This prospective study examined the course and correlates of depressive symptoms in patients with alcohol or opioid use disorder over 5-8 weeks. METHODS: Sample consisted of 100 men randomly selected out of 307 inpatient men with either alcohol or opioid use disorder. Weekly assessments focused on depressive symptoms (HDRS, BDI), and their correlates (HAM-A for anxiety symptoms, CIWA-Ar and COWS for withdrawal symptoms, OCDS and OCDUS for craving for alcohol and opioids respectively). Other correlates assessed were severity of dependence and family support. PRISM (Psychiatric Research Interview for Substance and Mental disorders) was used for diagnosis of substance-induced depression and major depressive episode. Repeated measures ANOVA was used for weekly comparison of depressive symptoms. RESULTS: Participants were dependent on opioids (56%), or alcohol (41%), or both (3%). Mean age was 33.5 years. Eighty-eight participants completed the study. Substance-induced depressive episode was diagnosed by PRISM in 59% participants. Weekly assessments of depressive symptoms recorded significant reductions (p < 0.0001; Wilk's Lambda for HDRS and BDI 137.01 and 105.4 respectively). Baseline depressive symptoms correlated significantly with anxiety, withdrawal symptoms, and negatively with social support. No participant was diagnosed with a major depressive episode at 6-8 weeks. CONCLUSION: Depressive symptoms in early alcohol or opioid abstinence resolve significantly over a month; therefore, clinicians should exercise watchful waiting before starting antidepressant therapy.

Serious health threats of novel adulterants of the street heroin: a report from India during the COVID-19 pandemic.

The COVID-19 pandemic and a consequent nationwide lockdown in India for several weeks had restricted the access to street heroin and treatment for substance abuse. Use of cutting agents to increase the volume or psychoactive effect has been widely practised under such circumstances. Our patient with opioid use disorder chased heroin with an unknown cutting agent to enhance psychoactive effect from the limited quantities of heroin. He suffered from an abrupt onset sedation, weakness, postural imbalance, slurred speech, cognitive dysfunctions and disinhibited behaviour. Symptoms rapidly reversed following abstinence and initiation of buprenorphine-naloxone. Gas chromatography-mass spectrometric analysis of the adulterant revealed high concentrations of benzodiazepines and barbiturates, alongside the usual cutting agents-caffeine and acetaminophen. Abrupt reduction in availability of 'street drugs' in conjunction with poor healthcare access can lead to the use of novel adulterants with potentially serious clinical and public health implications.

Telemedicine-assisted stepwise approach of service delivery for substance use disorders in India.

Restricted access to healthcare during COVID-19 pandemic warranted an urgent adaptation of telemedicine practice. We describe a synchronous, stepwise (telephonic, video, and in-person consultation) direct-care model. From 18th May to 31st August 2020, 128 new and 198 follow-up patients received consultation. Eighty-nine percent of new patients required video-consultation. Sixty-eight percent of follow-up cases were managed by telephonic consultation. A third of new and a fifth of the follow-up patients had to be called for physical consultation. Limited access to and understanding of the technologies, potential breach in privacy, and restrictions imposed on online prescription of medications posed significant challenges.

The Effectiveness of Non-Benzodiazepine, Non-Barbiturate Medications for Alcohol Withdrawal Syndrome: A Rapid Systematic Review.

AIM: There are potential clinical, ethical and legal concerns with overdosing benzodiazepines (or barbiturates) for the treatment of moderate to severe alcohol withdrawal symptoms (AWS) through telemedicine or ambulatory outpatients. A rapid systematic review to (a) qualitatively summarize the non-benzodiazepine treatment alternatives, (b) evaluate the quality of evidence for the same to effectively manage moderate to severe AWS. METHODS: We conducted searches on PubMed (January 1990 to 31 March 2020), Cochrane Central Register of Controlled Trials, and Google Scholar. We selected the English language randomized controlled trials (RCTs) assessing the efficacy and adverse effects of non-benzodiazepine and non-barbiturate medications among adults with a diagnosis of AWS. Data extraction was done in a predefined format. Risk of bias (RoB) assessment and qualitative synthesis of evidence was done with the RoB2 tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) proGDT. RESULTS: Thirty-four RCTs were included. Gabapentin (n = 6), carbamazepine (n = 5), baclofen (n = 5), valproate (n = 3), clonidine/lofexidine (n = 3) and acamprosate (n = 2) had more than one trial with a particular comparison group. Four studies were found to have a low ROB. The GRADE evidence summary showed gabapentin had a 'moderate' level of evidence against standard benzodiazepine treatments for reducing the severity of AWS. The level of certainty was 'low' for carbamazepine, baclofen and valproate and 'very low' for acamprosate and clonidine/lofexidine. Reported adverse events between these alternative medications and benzodiazepines or placebo were generally unremarkable. CONCLUSIONS: Although benzodiazepines remain the treatment of choice for AWS, during particular circumstances, gabapentin could be an alternative although like benzodiazepines is not without risk when used in the community. Future RCTs must aim to improve upon the quality of evidence.

Disulfiram Ethanol Reaction with Alcohol-Based Hand Sanitizer: An Exploratory Study.

AIMS: We conducted a cross-sectional survey to estimate the prevalence and clinical manifestation of disulfiram ethanol reaction (DER) and isopropanol toxicity (IT) in patients with alcohol use disorders, on disulfiram. Alcohol-based hand rub contains either ethanol or isopropanol or both. COVID-19 pandemic has led to wide scale usage of sanitizers. Patients with alcohol use disorders, on disulfiram, might experience disulfiram ethanol like reactions with alcohol-based sanitizers. METHODS: We telephonically contacted 339 patients, prescribed disulfiram between January 2014 and March 2020. The assessment pertained to the last 3 months (i.e. third week of March to third week of June 2020). RESULT: The sample consisted of middle-aged men with a mean 16 years of alcohol dependence. Among the 82 (24%) patients adherent to disulfiram, 42 (12.3%) were using alcohol-based hand rubs. Out of these, a total of eight patients (19%; 95% CI 9-33) had features suggestive of DER; four of whom also had features indicative of IT. Five patients (62.5%) had mild and self-limiting symptoms. Severe systemic reactions were experienced by three (37.5%). Severe reactions were observed with exposure to sanitizers in greater amounts, on moist skin or through inhalation. CONCLUSION: Patients on disulfiram should be advised to use alternate methods of hand hygiene.

Extended lockdown and India's alcohol policy: a qualitative analysis of newspaper articles.

OBJECTIVES: Since 25th March 2020 India went into a complete and extended lockdown. Alcohol production, sales, and purchase were barred with this overnight prohibition order. We conducted a qualitative analysis of the media reports published within the first month of the nationwide lockdown with the objectives (a) using the media reports as indications of possible public health impact and population response of a sudden alcohol prohibition in India, (b) suggesting areas for future research. METHODS: We performed thematic and content analysis of 350 articles published online in national newspapers between the 26th March, 2020 and 25th April, 2020. Initial inductive, followed by deductive coding was done in this exploratory thematic analysis. RESULTS: The thematic analysis revealed four main themes: the beneficial aspects of the policy, the harmful aspects of the policy, non-compliance and attempts to change and / or subvert the policy, popularity and level of public buy-in of the policy. We generated relevant sub-themes under main themes. Two additional themes, not directly related to the sudden prohibition, were use of stigmatizing language and ethical concerns. The content analysis showed the frequency of the appearance of the main themes and proportions of sub-themes and codes under those main themes. CONCLUSION: The harms, perceived from the media reports, should be balanced against the potential benefits. Absence of a national-level alcohol policy was made apparent by the reflexive, disconnected, and conflictual measures. Future research could systematically examine the potential ramifications of alcohol prohibition on public health, social, and economic aspects.

Neurocognitive functions in patients on buprenorphine maintenance for opioid dependence: A comparative study with three matched control groups.

BACKGROUND: Neurocognitive dysfunction with buprenorphine has mixed evidence, with many confounding factors. We compared the neurocognitive functions in patients with opioid dependence on buprenorphine maintenance (Index Group; IG) with those on naltrexone (NG), opioid-dependent in early detoxification (OD), and healthy control (CG). MATERIALS & METHODS: The four groups were matched for age, sex, and years of education. Except for the healthy control group (CG; n = 30), the two other comparison groups had twenty participants each. Subjects with other substance use disorders, HIV infection, head injury, epilepsy, and severe mental illness were excluded. Cognitive tests consisted of Trail Making Tests (TMT-A & B), Digit Vigilance test (DVT), verbal and visual N-Back Test (NBT), Rey's Auditory Verbal Learning Test (RAVLT), Wisconsin Card Sorting Test (WCST), Controlled Oral Word Association Test (COWA), and Wechsler Adult Intelligence Scale (WAIS). RESULTS: IG performed significantly worse in TMT-B, DVT, verbal NBT, and WCST (non-perseverative error) than CG. When IQ was controlled for, significance persisted in TMT-B, a marker of poor cognitive flexibility. The OD showed significantly poorer performance than NG and CG in the TMT-A & B, visual and verbal NBT, DVT, and RAVLT. When compared to the IG, the performance of the OD was significantly poor in the TMT-A & B. IG performed worse than NG in TMT-B, and NG performed poorer (than CG) in RAVLT. CONCLUSION: Patients on medication-assisted treatment had significant cognitive impairment limited to fewer cognitive domains, however, the extent and severity were highest in the group with active opioid dependence.