The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients.

OBJECTIVE: Ibogaine is a hallucinogenic drug that may be used to treat opioid use disorder (OUD). The relationships between pharmacokinetics (PKs) of ibogaine and its metabolites and their clinical effects on side effects and opioid withdrawal severity are unknown. We aimed to study these relationships in patients with OUD undergoing detoxification supported by ibogaine. METHODS: The study was performed in 14 subjects with OUD. They received a single dose of 10mg/kg ibogaine hydrochloride. Plasma PKs of ibogaine, noribogaine, and noribogaine glucuronide were obtained during 24 h. Cytochrome P450 isoenzyme 2D6 (CYP2D6) genotyping was performed. The PKs were analyzed by means of nonlinear mixed effects modeling and related with corrected QT interval (QTc) prolongation, cerebellar ataxia, and opioid withdrawal severity. RESULTS: The PK of ibogaine were highly variable and significantly correlated to CYP2D6 genotype (p < 0.001). The basic clearance of ibogaine (at a CYP2D6 activity score (AS) of 0) was 0.82 L/h. This increased with 30.7 L/h for every point of AS. The relation between ibogaine plasma concentrations and QTc was best described by a sigmoid Emax model. Spearman correlations were significant (p < 0.03) for ibogaine but not noribogaine with QTc (p = 0.109) and cerebellar effects (p = 0.668); neither correlated with the severity of opioid withdrawal symptoms. CONCLUSIONS: The clearance of ibogaine is strongly related to CYPD2D6 genotype. Ibogaine cardiac side effects (QTc time) and cerebellar effects are most likely more driven by ibogaine rather than noribogaine. Future studies should aim at exploring lower doses and/or applying individualized dosing based on CYP2D6 genotype.

Discontinuation of psychotropic medication: a synthesis of evidence across medication classes.

Pharmacotherapy is an effective treatment modality across psychiatric disorders. Nevertheless, many patients discontinue their medication at some point. Evidence-based guidance for patients, clinicians, and policymakers on rational discontinuation strategies is vital to enable the best, personalized treatment for any given patient. Nonetheless, there is a scarcity of guidelines on discontinuation strategies. In this perspective, we therefore summarize and critically appraise the evidence on discontinuation of six major psychotropic medication classes: antidepressants, antipsychotics, benzodiazepines, mood stabilizers, opioids, and stimulants. For each medication class, a wide range of topics pertaining to each of the following questions are discussed: (1) Who can discontinue (e.g., what are risk factors for relapse?); (2) When to discontinue (e.g., after 1 year or several years of antidepressant use?); and (3) How to discontinue (e.g., what's the efficacy of dose reduction compared to full cessation and interventions to mitigate relapse risk?). We thus highlight how comparing the evidence across medication classes can identify knowledge gaps, which may pave the way for more integrated research on discontinuation.

Not Two Sides of the Same Coin: A Qualitative Comparative Analysis of Post-Treatment Abstinence and Relapse.

Purpose: Substance use disorder (SUD) can be a chronic relapsing condition with poor treatment outcomes. Studies exploring factors associated with abstinence or relapse after treatment are often quantitative in nature, applying linear statistical approaches, while abstinence and relapse result from non-linear, complex, dynamic and synergistic processes. This study aims to explore these underlying dynamics using qualitative comparative analysis (QCA) as a mixed methods approach to further our understanding of factors contributing to post-treatment abstinence and relapse. Patients and Methods: In a prospective study, we gathered both qualitative and quantitative data pertaining to post-treatment substance use and the factors linked to substance use outcomes. These factors encompassed psychiatric comorbidity, intellectual disability, social disintegration, post-treatment support, and engagement in activities among patients who had undergone inpatient treatment for severe SUD (n = 58). QCA, a set-theoretic approach that considers the complex interplay of multiple conditions, was applied to discern which factors were necessary or sufficient for the occurrence of either abstinence or relapse. Results: We found two solutions predicting abstinence, and five for relapse. Post-treatment conditions (support and engagement in activities) were important for retaining abstinence. For relapse, individual baseline characteristics (intellectual disability, social disintegration, psychiatric comorbidity) combined with (post-)treatment factors (post-treatment support, activities) were important. Conclusion: Although abstinence and relapse represent opposing outcomes, they each exhibit distinct dynamics. To gain a comprehensive understanding of these dynamics, it is advisable to examine them as separate outcomes. For clinical practice, it can be worthwhile to recognize that fostering the conditions conducive to abstinence may differ from preventing the factors that trigger relapse.

This study explores why some people who struggle with addiction stay clean after treatment, while others relapse. Previous studies often used traditional statistical methods, with inconclusive results due to their inability to capture the complexity of this process. To address this, we used a different approach called qualitative comparative analysis (QCA). We collected information from 58 individuals who received inpatient treatment for their addiction. We looked at different factors like mental health problems, intellectual disability, the support they got from professionals and their social network, and whether they kept themselves busy with activities. We investigated how these factors are related to staying clean or relapse. With the help of QCA, we analyzed how these factors work together to cause either drug-free living or relapse. We found that staying clean was strongly linked to getting support after treatment and being involved in activities like hobbies or work. On the other hand, relapse was more likely in people with personal problems, like intellectual disabilities and mental health problems, when support and activities were lacking after treatment. In summary, our study indicates that staying clean and relapse are different processes with different factors at play. Helping someone stay clean may therefore require different strategies than preventing relapse. This insight can guide development of more personalized healthcare for individuals dealing with addiction.

A genetic risk score to predict treatment nonresponse in psychotic depression.

Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies have been performed aiming to predict treatment-resistant depression or treatment nonresponse. However, most of these studies excluded patients with psychotic depression. We created a genetic risk score (GRS) based on a large treatment-resistant depression genome-wide association study. We tested whether this GRS was associated with nonresponse, nonremission and the number of prior adequate antidepressant trials in patients with a psychotic depression. Using data from a randomized clinical trial with patients with a psychotic depression (n = 122), we created GRS deciles and calculated positive prediction values (PPV), negative predictive values (NPV) and odds ratios (OR). Nonresponse and nonremission were assessed after 7 weeks of treatment with venlafaxine, imipramine or venlafaxine plus quetiapine. The GRS was negatively correlated with treatment response (r = -0.32, p = 0.0023, n = 88) and remission (r = -0.31, p = 0.0037, n = 88), but was not correlated with the number of prior adequate antidepressant trials. For patients with a GRS in the top 10%, we observed a PPV of 100%, a NPV of 73.7% and an OR of 52.4 (p = 0.00072, n = 88) for nonresponse. For nonremission, a PPV of 100%, a NPV of 51.9% and an OR of 21.3 (p = 0.036, n = 88) was observed for patients with a GRS in the top 10%. Overall, an increased risk for nonresponse and nonremission was seen in patients with GRSs in the top 40%. Our results suggest that a treatment-resistant depression GRS is predictive of treatment nonresponse and nonremission in psychotic depression.

Evaluating the Effectiveness of Take it Personal!+ in People With Mild Intellectual Disability or Borderline Intellectual Functioning and Substance Use Disorder: A Multiple Baseline Single-Case Experimental Study.

Individuals with mild intellectual disabilities or borderline intellectual functioning are at increased risk to develop a substance use disorder-however, effective treatment programs adapted to this target group are scarce. This study evaluated the effectiveness of Take it Personal!+ in individuals with mild intellectual disabilities or borderline intellectual functioning and substance use disorder. Take it Personal!+ is a personalized treatment based on motivational interviewing and cognitive-behavioral therapy supported by an mHealth application. Data were collected in a nonconcurrent multiple baseline single-case experimental design across individuals with four phases (i.e., baseline, treatment, posttreatment, and follow-up). Twelve participants were randomly allocated to baseline lengths varying between 7 and 11 days. Substance use quantity was assessed during baseline, treatment, and posttreatment with a daily survey using a mobile application. Visual analysis was supported with statistical analysis of the daily surveys by calculating three effect size measures in 10 participants (two participants were excluded from this analysis due to a compliance rate below 50%). Secondary, substance use severity was assessed with standardized questionnaires at baseline, posttreatment, and follow-up and analyzed by calculating the Reliable Change Index. Based on visual analysis of the daily surveys, 10 out of 12 participants showed a decrease in mean substance use quantity from baseline to treatment and, if posttreatment data were available, to posttreatment. Statistical analysis showed an effect of Take it Personal!+ in terms of a decrease in daily substance use in 8 of 10 participants from baseline to treatment and if posttreatment data were available, also to posttreatment. In addition, data of the standardized questionnaires showed a decrease in substance use severity in 8 of 12 participants. These results support the effectiveness of Take it Personal!+ in decreasing substance use in individuals with mild intellectual disabilities or borderline intellectual functioning.

Individual differences in GHB consumption in a new voluntary GHB self-administration model in outbred rats.

BACKGROUND AND PURPOSE: The use of the recreational drug gamma-hydroxybutyric acid (GHB) has increased over the past decade, concomitantly leading to a higher incidence of GHB use disorder. Evidence-based treatment interventions are hardly available and cognitive effects of long-term GHB use remain elusive. In order to study the development of GUD and the causal effects of chronic GHB consumption, a GHB self-administration model is required. EXPERIMENTAL APPROACH: Long Evans rats had access to GHB in their home cage according to a two-bottle choice procedure for 3 months. Intoxication and withdrawal symptoms were assessed using an automated sensor-based setup for longitudinal behavioral monitoring. Rats were trained in an operant environment according to a fixed ratio (FR) 1, 2, and 4 schedule of reinforcement. Addiction-like behaviors were assessed through progressive ratio-, non-reinforced-, and quinine-adulterated operant tests. In addition, the novel object recognition test and elevated plus maze test were performed before and after GHB self-administration to assess memory performance and anxiety-like behavior, respectively. KEY RESULTS: All rats consumed pharmacologically relevant levels of GHB in their home cage, and their intake remained stable over a period of 3 months. No clear withdrawal symptoms were observed following abstinence. Responding under operant conditions was characterized by strong inter-individual differences, where only a subset of rats showed high motivation for GHB, habitual GHB-seeking, and/or continued responding for GHB despite an aversive taste. Male rats showed a reduction in long-term memory performance 3 months after home-cage GHB self-administration. Anxiety-like behavior was not affected by GHB self-administration. CONCLUSION AND IMPLICATIONS: The GHB self-administration model was able to reflect individual susceptibility for addiction-like behavior. The reduction in long-term memory performance upon GHB self-administration calls for further research into the cognitive effects of chronic GHB use in humans.

The prevalence of prescription opioid use and misuse among emergency department patients in The Netherlands.

RATIONALE: Prescription opioid use and misuse have increased rapidly in many Western countries in the past decade. Patients (mis)using opioids are at risk of presenting to the emergency department (ED) with opioid-related problems. European data concerning prescription opioid (mis)use among the ED population is lacking. AIMS AND OBJECTIVES: This study aims to determine prevalence of prescription opioid use, misuse, and opioid use disorder (OUD) among Dutch ED patients. Secondary objectives were to explore factors associated with prescription opioid misuse and the number of patients discharged with a new opioid prescription. METHODS: In a cross-sectional multicenter study at three hospitals in the Netherlands, adult ED patients were screened for current prescription opioid use. Opioid users filled out questionnaires regarding opioid (mis)use, and underwent a structured interview to assess OUD criteria. The primary outcomes were prevalence rates of (1) current prescription opioid use, (2) prescription opioid misuse (based on a Current Opioid Misuse Measure [COMM] score > 8), (3) OUD, based on DSM-5 criteria. Independent T-tests, Pearson χ2 and Fisher's Exact tests were used to analyse differences in characteristics between groups. RESULTS: A total of 997 patients were screened, of which 15% (n = 150) used prescription opioids. Out of 93 patients assessed, 22.6% (n = 21) showed signs of prescription opioid misuse, and 9.8% (n = 9, 95% CI: 4.5-17.8) fulfilled criteria for OUD. A medical history of psychiatric disorder was significantly more common in patients with prescription opioid misuse and OUD. CONCLUSION: This study shows that prescription opioid use is relatively common in ED patients in the Netherlands, compared to the overall population. Over one fifth of these patients shows signs of opioid misuse or OUD. Awareness among ED personnel about the high prevalence of prescription opioid (mis)use in their population is critical for signalling opioid-related problems.

The Relationship of Early Sleep Improvement With Response to Pharmacotherapy in Unipolar Psychotic Depression.

BACKGROUND: Since insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether early insomnia improvement (EII) predicted treatment outcome in psychotic depression (PD) and examined if there was an interaction effect between EII and treatment type to assess if findings were treatment-specific. METHODS: This study is a secondary analysis of a randomized trial comparing 7 weeks treatment with the antidepressants venlafaxine, imipramine and venlafaxine plus the antipsychotic quetiapine in PD ( n = 114). Early insomnia improvement, defined as ≥20% reduced insomnia after 2 weeks, was assessed by the Hamilton Rating Scale for Depression (HAM-D-17). Associations between EII and treatment outcome were examined using logistic regressions. Subsequently, we added interaction terms between EII and treatment type to assess interaction effects. The predictive value of EII was compared with early response on overall depression (≥20% reduced HAM-D-17 score after 2 weeks). RESULTS: EII was associated with response (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.7-23.4; P = <0.001), remission of depression (OR, 6.1; 95% CI, 1.6-22.3; P = 0.009), and remission of psychosis (OR, 4.1; 95% CI, 1.6-10.9; P = 0.004). We found no interaction effects between EII and treatment type on depression outcome. Early insomnia improvement and early response on overall depression had a comparable predictive ability for treatment outcome. CONCLUSIONS: Early insomnia improvement was associated with a positive outcome in pharmacotherapy of PD, regardless of the medication type. Future studies are needed to confirm our findings and to examine the generalizability of EII as predictor in treatment of depression.

Using the Recovery Capital Model to Explore Barriers to and Facilitators of Recovery in Individuals with Substance Use Disorder, Psychiatric Comorbidity and Mild-to-Borderline Intellectual Disability: A Case Series.

Recovery capital (RC) encompasses the wide range of resources individuals can employ to recover from Substance Use Disorder (SUD). It consists of five subdomains: human, social, cultural, financial, and community RC. Negative recovery capital (NRC) represents the obstacles to recovery. Research on (N)RC in complex multimorbid populations is scarce. This study offers an initial exploration of the viability of (N)RC in three individuals with SUD, psychiatric comorbidities, and an intellectual disability (a triple diagnosis) in inpatient addiction treatment. We collected case file data, ranked recovery goals, and conducted follow-up interviews. The data were subjected to template analysis, using (N)RC domains as codes. All domains were prevalent and relevant, showing dynamic and reciprocal effects, influenced by critical life events acting as catalysts. Notably, during treatment, patients prioritized individual skill development despite challenges in other domains. RC emerges as a valuable concept for mapping recovery barriers and facilitators in individuals with a triple diagnosis, serving as an alternative to the medical model and complementing the biopsychosocial model. It provides a systematic framework to assess critical factors for recovery in complex cases and accordingly align interventions. Future studies should explore the intersections of NRC domains and the dynamic nature of (N)RC to enhance the understanding of the challenges faced by individuals with a triple diagnosis.

Opioid Analgesics after Bariatric Surgery: A Scoping Review to Evaluate Physiological Risk Factors for Opioid-Related Harm.

The persisting use of opioids following bariatric surgery has emerged as a prevalent complication, heightening the probability of opioid-related harm (ORM), such as opioid-related fatalities and prescription opioid use disorder (OUD). A comprehensive review of PubMed literature from 1990 to 2023 was conducted to pinpoint physiological influences on postoperative ORM. As a result, we found that patients undertaking bariatric operations often exhibit an inherently higher risk for substance use disorders, likely attributable to genetic predisposition and related neurobiological changes that engender obesity and addiction-like tendencies. Furthermore, chronic pain is a common post-bariatric surgery complaint, and the surgical type impacts opioid needs, with increased long-term opioid use after surgeries. Additionally, the subjective nature of pain perception in patients with obesity can distort pain reporting and the corresponding opioid prescription both before and after surgery. Furthermore, the postoperative alterations to the gastrointestinal structure can affect the microbiome and opioid absorption rates, resulting in fluctuating systemic exposure to orally ingested opioids. The prospect of ORM development post-bariatric surgery appears amplified due to a preexisting susceptibility to addictive habits, surgically induced pain, modified gut-brain interaction and pain management and the changed pharmacokinetics post-surgery. Further research is warranted to clarify these potential risk variables for ORM, specifically OUD, in the bariatric population.

Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Evidence of the clinical benefit of pharmacogenetics-informed treatment (PIT) with antidepressants is still limited. Especially for tricyclic antidepressants (TCAs), pharmacogenetics may be of interest because therapeutic plasma concentrations are well defined, identification of optimal dosing can be time consuming, and treatment is frequently accompanied by adverse effects. Objective: To determine whether PIT results in faster attainment of therapeutic TCA plasma concentrations compared with usual treatment in patients with unipolar major depressive disorder (MDD). Design, Setting, and Participants: This randomized clinical trial compared PIT with usual treatment among 111 patients at 4 centers in the Netherlands. Patients were treated with the TCAs nortriptyline, clomipramine, or imipramine, with clinical follow-up of 7 weeks. Patients were enrolled from June 1, 2018, to January 1, 2022. At inclusion, patients had unipolar nonpsychotic MDD (with a score of ≥19 on the 17-item Hamilton Rating Scale for Depression [HAMD-17]), were aged 18 to 65 years, and were eligible for TCA treatment. Main exclusion criteria were a bipolar or psychotic disorder, substance use disorder, pregnancy, interacting comedications, and concurrent use of psychotropic medications. Intervention: In the PIT group, the initial TCA dosage was based on CYP2D6 and CYP2C19 genotypes. The control group received usual treatment, which comprised the standard initial TCA dosage. Main Outcomes and Measures: The primary outcome was days until attainment of a therapeutic TCA plasma concentration. Secondary outcomes were severity of depressive symptoms (measured by HAMD-17 scores) and frequency and severity of adverse effects (measured by Frequency, Intensity, and Burden of Side Effects Rating scores). Results: Of 125 patients randomized, 111 (mean [SD] age, 41.7 [13.3] years; 69 [62.2%] female) were included in the analysis; of those, 56 were in the PIT group and 55 were in the control group. The PIT group reached therapeutic concentrations faster than the control group (mean [SD], 17.3 [11.2] vs 22.0 [10.2] days; Kaplan-Meier χ21 = 4.30; P = .04). No significant difference in reduction of depressive symptoms was observed. Linear mixed-model analyses showed that the interaction between group and time differed for the frequency (F6,125 = 4.03; P = .001), severity (F6,114 = 3.10; P = .008), and burden (F6,112 = 2.56; P = .02) of adverse effects, suggesting that adverse effects decreased relatively more for those receiving PIT. Conclusions and Relevance: In this randomized clinical trial, PIT resulted in faster attainment of therapeutic TCA concentrations, with potentially fewer and less severe adverse effects. No effect on depressive symptoms was observed. These findings indicate that pharmacogenetics-informed dosing of TCAs can be safely applied and may be useful in personalizing treatment for patients with MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03548675.

Mindfulness-based cognitive therapy for chronic noncancer pain and prescription opioid use disorder: A qualitative pilot study of its feasibility and the perceived process of change.

BACKGROUND: Mindfulness-based interventions have a positive impact on pain, craving, and well-being in both patients with chronic pain and those with opioid use disorder (OUD). Although data are limited, mindfulness-based cognitive therapy (MBCT) might be a promising treatment for patients with chronic noncancer pain combined with OUD. The aim of this qualitative study was to explore the feasibility and process of change during MBCT in this particular population. METHODS: In this qualitative pilot study, 21 patients who were hospitalized for rotation to buprenorphine/naloxone as agonist treatment for chronic pain and OUD were offered MBCT. Semistructured interviews were conducted to explore experienced barriers and facilitators to MBCT. Patients who participated in MBCT were also interviewed on their perceived process of change. RESULTS: Of 21 patients invited to participate in MBCT, 12 initially expressed interest but only four eventually participated in MBCT. The timing of the intervention, group format, somatic complaints, and practical difficulties were identified as the main barriers to participation. Facilitating factors included having a positive attribution toward MBCT, an intrinsic motivation to change, and practical support. The four MBCT participants mentioned several important mechanisms of change, including reduction of opioid craving and improved coping with pain. CONCLUSIONS: MBCT offered in the current study was not feasible for the majority of patients with pain and OUD. Changing the timing of MBCT by providing it at an earlier stage of the treatment and offering MBCT in an online format may facilitate participation.

Patients' Perspectives on the Development of Prescription Opioid Use Disorder in Patients with Chronic Non-Cancer Pain.

INTRODUCTION: In the past decade, prescription opioid use increased exponentially and concomitantly opioid use disorders (OUD) are becoming more common. Several risk factors for developing OUD have been identified, but little is known regarding the patients' perspective on developing a prescription OUD. METHODS: We recruited 25 adults undergoing treatment for prescription OUD. In-depth, semi-structured interviews focussed on experiences with long-term opioid use, knowledge and attitudes regarding opioids, and access to opioids. A directed content analysis was conducted on the transcribed interviews using NVivo. RESULTS: Participants showed that the development of an OUD is affected by various factors which could be grouped into three themes: (1) experiences driving initiation, (2) experiences driving continuation, and (3) experiences with prescription OUD. Besides the need for pain management, the dynamics of patient-provider communication, care coordination, provider vigilance, and environmental support all contributed to the way patients used their opioids. CONCLUSION: Patients' experiences illustrate that the first stage of the development of prescription OUD differs from the development of other substance addictions. Negative reinforcement might play a more prominent role in the early phase of prescription opioid use. Patients expressed a lack of guidance, both at the start of use and long-term use, easy access to new prescriptions and a lack of monitoring as main drivers of the development. Poorly controlled pain and subjective stress fuelled continuous opioid use.

An Overview of the Putative Structural and Functional Properties of the GHBh1 Receptor through a Bioinformatics Approach.

The neurotransmitter γ-hydroxybutyric acid (GHB) is suggested to be involved in neuronal energy homeostasis processes, but the substance is also used as a recreational drug and as a prescription medication for narcolepsy. GHB has several high-affinity targets in the brain, commonly generalized as the GHB receptor. However, little is known about the structural and functional properties of GHB receptor subtypes. This opinion article discusses the literature on the putative structural and functional properties of the GHBh1 receptor subtype. GHBh1 contains 11 transmembrane helices and at least one intracellular intrinsically disordered region (IDR). Additionally, GHBh1 shows a 100% overlap in amino acid sequence with the Riboflavin (vitamin B2) transporter, which opens the possibility of a possible dual-function (transceptor) structure. Riboflavin and GHB also share specific neuroprotective properties. Further research into the GHBh1 receptor subtype may pave the way for future therapeutic possibilities for GHB.

Effect of Past Pharmacotherapy for Attention-Deficit/Hyperactivity Disorder on Substance Use Disorder.

BACKGROUND: Substance use disorders (SUDs) are a considerable public health problem. Attention-deficit/hyperactivity disorder (ADHD) frequently occurs in patients with SUD. Several studies demonstrated that ADHD constitutes a significant risk factor for the development of SUDs and suggest that childhood ADHD pharmacotherapy might help prevent development of SUD. OBJECTIVES: The study aimed to explore the effect of childhood ADHD pharmacotherapy on later life's functional impairment and substance use patterns. METHODS: Treatment-seeking SUD patients with ADHD (n = 52) were recruited from various rehabilitation facilities in South Africa. Adult ADHD individuals without SUD (n = 48) were recruited from clinicians, retail pharmacies, and the general public. SUD participants in rehabilitation facilities were screened for and diagnosed with ADHD. Lifetime substance use was assessed using self-report. ADHD-related functional impairment was assessed by the Weiss Functional Impairment Rating Scale (WFIRS). Information on present and lifetime use of ADHD medication was obtained. Clinical outcomes between those with and without a history of ADHD pharmacotherapy were compared. RESULTS: Medicated participants (n = 59) showed lower levels of ADHD-related impairment across all functional domains (p < 0.001), compared to non-medicated participants (n = 41). They also consumed less alcohol (p = 0.04), cannabis (p < 0.001), and illicit drugs (p = 0.006) compared to the non-medicated group. Furthermore, medicated participants had a lower frequency of tobacco use compared to non-medicated participants (p = 0.04). ADHD patients without SUD also more often received medication (100% vs. 18.6%; p < 0.001) and for a longer time (121.10 vs. 9.52 months; p < 0.001). CONCLUSION: Childhood ADHD pharmacotherapy might be associated with a decreased risk for substance use in adulthood and lower ADHD-related impairment. Despite study limitations, these findings underline the importance of early ADHD detection and treatment, which might prevent SUD.

[Dealing with opioid dependence and withdrawal in hospitals]. / Omgaan met opioïdafhankelijkheid en -onthouding in het ziekenhuis.

BACKGROUND: In opioid addiction tolerance occurs requiring substitution with unusually high doses. A balance must be struck between the risk of overdose with respiratory depression and QTc interval prolongation on one hand and underdosing with withdrawal syndrome on the other hand. An unreliable anamnesis can complicate adequate dosing. CASE DESCRIPTION: A 30-year-old polydrug user with a severe dependence on methadone and heroin was admitted to the Intensive Care Unit after surgery for thoracic surgery. Upon cautious initiation with methadone, severe withdrawal and pain symptoms occurred. Doubling the dose made the withdrawal symptoms disappear without signs of overdose. CONCLUSION: During hospital admission of patients with high opioid tolerance the anamnestic equivalent high opioid dose can be started immediately, provided there is a possibility of monitoring the respiration and heart rhythm. The risk of withdrawal and insufficient pain relief in a hospital is generally greater than the risk of an overdose.

Implementation of a decentralized hepatitis C care pathway for people who use drugs in Dutch addiction care. Study protocol for the Hepatitis C: chain of addiction care (CAC) project.

BACKGROUND: People who use drugs (PWUD) are at high risk for hepatitis C virus (HCV) infection and its complications. Given the high prevalence rate of HCV in PWUD, the World Health Organization (WHO) emphasizes PWUD as a target population for HCV elimination. The introduction of pangenotypic direct acting antivirals (DAAs) greatly simplifies HCV treatment, which encourages integration of HCV treatment in primary care. Facilitating low threshold HCV care for PWUD by implementing decentralized models is crucial for HCV elimination. AIMS: With this study we aim to (1) eliminate 90% of identified HCV infections in Dutch addiction care, using a decentralized PWUD-HCV care model, and (2) identify facilitators and barriers for successful implementation of the model using interviews. METHODS: We will perform a multicenter mixed-method study on HCV treatment in addiction care. In a prospective observational study we will examine HCV-related outcomes in PWUD receiving HCV treatment as part of addiction care. The primary outcome is viral elimination, defined as percentage of identified HCV positive patients cured with DAAs. In parallel, we will perform a qualitative study to explore facilitators and barriers for implementation of fully decentralized HCV-PWUD care. We will interview addiction care professionals and board members about their experience with HCV-care as part of addiction care. DISCUSSION: This study will show effectiveness of integration of HCV care within addiction care, and provide insight in facilitators and barriers to implement integrated HCV-addiction care. The results will provide recommendations for implementation and maintenance of the decentralized HCV pathway, which can facilitate scaling-up to contribute to reaching WHO HCV elimination goals. Trial registration NCT05401136.

Buprenorphine/naloxone versus methadone opioid rotation in patients with prescription opioid use disorder and chronic pain: study protocol for a randomized controlled trial.

BACKGROUND: Opioids are effective in pain-management, but long-term opioid users can develop prescription opioid use disorder (OUD). One treatment strategy in patients with OUD is rotating from a short-acting opioid to a long-acting opioid (buprenorphine/naloxone (BuNa) or methadone). Both BuNa and methadone have been shown to be effective strategies in patients with OUD reducing opioid misuse, however data on head-to-head comparison in patients with chronic non-malignant pain and prescription OUD are limited. METHODS: This two-armed open-label, randomized controlled trial aims to compare effectiveness between BuNa and methadone in patients with chronic non-malignant with prescription OUD (n = 100). Participants receive inpatient rotation to either BuNa or methadone with a flexible dosing regimen. The primary outcome is opioid misuse 2 months after rotation. Secondary outcomes include treatment compliance, side effects, analgesia, opioid craving, quality of life, mood symptoms, cognitive and physical functioning over 2- and 6 months follow-up. Linear mixed model analysis will be used to evaluate change in outcome parameters over time between the treatment arms. DISCUSSION: This is one of the first studies comparing buprenorphine/naloxone and methadone for treating prescription OUD in a broad patient group with chronic non-malignant pain. Results may guide future treatment for patients with chronic pain and prescription OUD. Trial registration https://www.trialregister.nl/ , NL9781.