A systematic literature review of clinical trials and therapeutic applications of ibogaine

BACKGROUND Iboga and its primary alkaloids, ibogaine and noribogaine, have been of interest to researchers and practitioners, mainly due to their putative efficacy in treating substance use disorders (SUDs). For many SUDs, still no effective pharmacotherapies exist. Distinct psychoactive and somatic effects of the iboga alkaloids set them apart from classic hallucinogens like LSD, mescaline, and psilocybin. AIMS The study team performed this systematic review focusing on clinical data and therapeutic interventions involving ibogaine and noribogaine. METHODS The team conducted a search for all publications up to December 7, 2020, using PubMed and Embase following PRISMA guidelines. RESULTS In total, we identified 743 records. In this review, we consider 24 studies, which included 705 individuals receiving ibogaine or noribogaine. This review includes two randomized, double-blind, controlled clinical trials, one double-blind controlled clinical trial, 17 open-label studies or case series (including observational or retrospective studies), three case reports, and one retrospective survey. The published data suggest that ibogaine is an effective therapeutic intervention within the context of SUDs, reducing withdrawal symptoms and craving. Data also point toward a beneficial impact on depressive and trauma-related psychological symptoms. However, studies have reported severe medical complications and deaths, which seem to be associated with neuro- and cardiotoxic effects of ibogaine. Two of these fatalities were described in the 24 studies included in this review. CONCLUSION Treatment of SUDs and persisting comorbidities requires innovative treatment approaches. Rapid-onset therapies such as the application of ibogaine may offer novel treatment opportunities for specific individuals. Rigorous study designs within medical settings are necessary to warrant safe application, monitoring, and, possibly, medical intervention

«One prick and then it´s done»: a mixed-methods exploratory study on intramuscular injection in heroin-assisted treatment

Background Intramuscular (IM) injection of drugs is associated with high rates of injecting-related injuries and diseases. However, little is known about the role of this route of administration in heroin-assisted treatment. The aim of this study was to determine the prevalence of IM diacetylmorphine administration and associated complications as well as to explore patients’ views and opinions on the topic and the underlying reasons for this practice. Methods The research site was a Swiss outpatient treatment centre specialised in heroin-assisted treatment. We conducted in-depth interviews with two patients who intramuscularly inject diacetylmorphine. Interviews were analysed qualitatively, and emerging themes were used to develop a 38-item questionnaire on IM injections. We then offered this questionnaire to all patients in the treatment centre. Results Five main themes emerged from the in-depth interviews: poor venous access, side effects, subjective effects, procedure for IM injection, and consideration of alternatives to IM. These themes covered the rationale for using this route of administration, complications, subjective effects of IM diacetylmorphine, hygiene and safety measures as well as alternative routes of administration. Fifty-three patients filled in the questionnaire. The lifetime prevalence of IM injections was 60.4% (n = 32) and 34.4% (n = 11) of the patients stated that IM injection was their primary route of administration. No participant reported using the IM route for street drugs. The main reason for IM injections was poor vein access. Other reasons given were time saving and less risk of injuries. Complications included induration of muscle tissue and pain, whereas more severe complications like thrombosis and infections of the injection site were reported much less often. Conclusion As the population of opioid-dependent individuals is aging and the deterioration of access veins is likely to increase, the frequency of IM injecting will equally increase. Even though our data show that the IM injection of diacetylmorphine in a clinical setting is a common practice and appears to be relatively safe, research on alternative routes of administration is needed to provide potentially less harmful alternative routes of administration in heroin-assisted treatment

Experiences with take-home dosing in heroin-assisted treatment in Switzerland during the COVID-19 pandemic–Is an update of legal restrictions warranted?

Heroin-assisted treatment comprises the use of diacetylmorphine (pharmaceutical heroin) for individuals with severe opioid use disorder. In Switzerland, take-home doses in heroin-assisted treatment are more strictly regulated as compared to conventional opioid agonist treatment. In light of the COVID-19 pandemic, the Swiss Federal Council provisionally adapted its policy, allowing for longer prescriptions of take-home diacetylmorphine. Before the beginning of the pandemic, take-home doses only occurred in exceptional circumstances and under strict criteria for patient eligibility. Following the legislative adaptations, we critically revised our internal centre policies as well. We report our experiences with oral take-home diacetylmorphine from a Swiss outpatient university centre specialising in heroin-assisted treatment. An additional 45 patients received take-home doses following the first lockdown. While some patients wished to return to their previous treatment regimen, most patients managed their medication well and showed good adherence. We also noticed an increase of treatment admissions that are likely related to the relaxed regulations. Previously, the strict therapeutic framework of visiting a HAT centre twice a day for supervised dispensing seemed to have discouraged these individuals from seeking medical treatment. From a medical point of view, the politically driven restrictions on take-home doses in heroin-assisted treatment are questionable and do not support the goal of harm reduction

Co-occurring Mental Disorders in Transitional Aged Youth With Substance Use Disorders – A Narrative Review

Adolescence and emerging adulthood are often referred to as youth. Transitional psychiatry addresses this target group, which considers patients between 15 and 25 years of age. Substance use usually begins and peaks at this stage of life. Psychiatric disorders, foremost attention-deficit/hyperactivity disorder, and affective disorders, conduct disorders, and first-episodes psychosis frequently appear in early life stages. This review aims to provide a broad overview of transitional-aged youth's most common psychiatric comorbidities with substance use disorders. A literature search was conducted in Embase and Pubmed, and the main findings are described narratively. We present main findings for the following comorbidities: attention-deficit/hyperactivity disorder, conduct disorder, personality disorders, affective disorders, psychotic disorders, and the phenomena of overdose and suicidality. In conclusion, co-occurring mental health disorders are common and appear to facilitate the development of substance use disorders and exacerbate their overall course. Substance use also affects the severity and course of comorbid psychiatric disorders. Overall, data on transition-age youth with substance use disorders are highly inconsistent. Universal screening and treatment guidelines do not yet exist but should be aimed for in the future

Results of a survey among opioid addiction treatment providers on the importance of physical exercise

Background: Physical exercise has significant benefits for mental and physical health. The Federal Office of Public Health in Switzerland defined exercise as a medium-term treatment goal in the manual of heroin-assisted treatment. Methods: Sixty-four opioid agonist treatment providers and specialized psychosocial treatment centers across the German-speaking part of Switzerland were asked to fill in a brief, self-developed questionnaire to find out whether exercise programs are offered and what they consist of. The questionnaire additionally addressed the caregivers’ assessment of their respec- tive treatment facilities importance to their patients, their attitude towards exercising programs, and the frequency of mentioning exercise in patient encounters. In addition, we asked what kind of sports programs caregivers would like to see introduced in their treatment services. Results: Fifty-one questionnaires were returned. According to the caregivers, 76% of patients considered their treatment facility to be the first point of contact in case of an emergency. Caregivers who deemed the provision of exercise programs more important also mentioned exercise more often in their patient encounters and motivated patients more often. While the importance of exercise programs was rated high by 45% of caregivers, only seven respondents reported that regular exercise has been implemented as part of their treatment services. The most com- mon suggestion of a sports program was (Nordic) walking, followed by yoga and endurance sports. Conclusions: There is a mismatch between what is recommended and known regarding cost effectiveness of physical exercise in general, any form of walking in opioid addiction treatment, and what is actually offered and put into practice. Since this intervention allows the inclusion of most patients regardless of their fitness level or health condition, the reasons for this mismatch remain elusive and should be further explored

Influence of adjuvant clonidine on mania, sleep disturbances and cognitive performance – Results from a double-blind and placebo-controlled randomized study in individuals with bipolar I disorder during their manic phase

Background: While the favorable effect of adjuvant clonidine in the treatment of acute mania has been observed already about 40 years ago, this line of treatment has not been further investigated. Here, we resumed this topic, and we tested the effect of adjuvant clonidine, an antihypertensive stimulating the alpha-2 central adrenergic receptor, on symptoms of mania, cognitive performance, and subjective sleep. To this end, we performed a randomized, double-blind and placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania. Methods: A total of 70 inpatients (mean age: 37.40 years; 15.7% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant clonidine (0.2 mg/d to a maximum of 0.6 mg/d) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants' cognitive performance was assessed at baseline and at day 24 at the end of the study. Results: Over time, mania scores significantly decreased (large effect size), but more so in the clonidine condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the clonidine, compared to the placebo condition (medium effect size). Over time, cognitive performance improved (medium effect size), irrespective from the study condition. Conclusions: Compared to placebo, adjuvant clonidine to lithium improved symptoms of mania, as rated by experts', and subjective sleep quality. Adjuvant clonidine had no further favorable (or detrimental) impact on cognitive performance. Keywords: Bipolar disorder; Clonidine; Cognitive performance; Mania; Subjective sleep quality; alpha(2) central adrenergic receptors

Novel Medication Supply Model Guarantees Adequate Management and High Adherence to Polypharmacy in Older Opioid Users – Preliminary Results with Outpatients

Background: Life expectancy of older drug users has increased, primarily thanks to opioid agonist treatment (OAT). Nursing homes are often not adapted to accommodate patients with substance use disorders. Although care and adherence to polypharmacy in older opioid users need considerable resources e.g., daily visits to an outpatient clinic, outpatient treatment and surveillance are provided as long as possible. We developed a novel medication supply model with an electronic dispenser of pre-packed medications located at patient home, after allowing for law requirements concerning the dispensing of opioids, and present preliminary results from three illustrative outpatients. Methods: The community pharmacy provided unit-of-dose pouches with all solid oral medications directly to patient home. Opioids for substitution were obtained at the addiction clinic in at least weekly intervals, otherwise in the pouches. The pouches were loaded into a lockable, remote-controlled medication management aid that was programmed according to the patient’s medication schedule. The dispenser reminds patients with acoustic alerts to take their medication and records dates and times of medication retrievals. It automatically sends an alert if a patient misses to retrieve a dose. Results: Our three outpatients used the electronic dispenser during 659, 118 and 61 days, with a total of 5, 9, and 18 pills to take daily at 1, 3 and 5 intake times, respectively. The majority of the doses were taken on the preset time (94%, 68.2% and 73.7%) or deliberately in advance (pocket dose). Clinical benefits were initiation and maintenance of a therapy for dementia over 18 months and suppression of HIV viral load over 1.8 years (patient 1), prevention of further dose escalation of pain medication (patient 2) and release of prompts to initiate the existential task of cooking (patient 3). Conclusion: Our novel supply model allows adequate implementation and persistence of complex treatments with outpatients. Clinical outcomes improved, patients and caregivers were satisfied, and resources were saved

Sexual dysfunction prevalence, risk factors, and help-seeking behavior in opioid agonist treatment and general psychiatry: a cross-sectional study

BackgroundMental disorders pose a high risk for the occurrence of sexual dysfunctions (SD). This study aimed to investigate prevalence of risk factors and help-seeking behavior for sexual dysfunctions in patients with opioid use disorder compared to patients seeking psychotherapeutic help.MethodsNinety-seven patients at two opioid agonist treatment (OAT) centers and 65 psychotherapeutic patients from a psychiatric practice (PP) in Switzerland were included in the study. Self-report assessments comprised sexual functioning (IIEF: International Index of Erectile Function; FSFI: Female Sexual Function Index), depressive state, psychological distress, alcohol consumption, nicotine use, and a self-designed questionnaire on help-seeking behavior. We used chi-squared and Mann–Whitney U tests for group comparisons and binary logistic regression models to identify variables predicting the occurrence of sexual dysfunctions.ResultsThere was no statistically significant difference (p = 0.140) in the prevalence of SD between OAT (n = 64, 66.0%) and PP sample (n = 35, 53.8%). OAT patients scored significantly higher in scales assessing nicotine use (p < 0.001) and depressive state (p = 0.005). Male OAT patients scored significantly worse on the Erectile Function scale (p = 0.005) and female PP patients scored significantly worse on the FSFI Pain domain (p = 0.022). Opioid use disorder, higher age, and being female predicted the occurrence of SD in the total sample. In the OAT sample, only higher age remained predictive for the occurrence of SD. A lack of help-seeking behavior was observed in both groups, with only 31% of OAT patients and 35% of PP patients ever having talked about their sexual health with their treating physician.ConclusionSD are common among psychiatric patients receiving OAT and general psychiatric patients seeking psychotherapy. Professionals providing mental healthcare to patients must emphasize prevention and routine assessments of sexual functioning needs

Negative symptoms in alcohol use disorder: A pilot study applying the two-factor model of negative symptoms to patients with alcohol use disorder

Background and aimsAlcohol Use Disorder (AUD) is characterized by a reduction in goal-directed behavior, with alcohol use taking precedence over other areas of life. These features in AUD resemble negative symptoms in schizophrenia, especially the reduction in motivation and pleasure (MAP). Given the clinical similarities of negative symptoms across diagnostic categories, it comes as a surprise that there are few investigations on negative symptoms in alcohol and other substance use disorders. To our knowledge, our study is the first to assess negative symptoms in AUD based on a two-factorial approach, and to investigate the interrelation of these dimensions with the severity of AUD, and alcohol craving.Materials and methodsWe examined a sample of 42 patients with AUD at the Psychiatric University Hospital in Zurich. Participants provided self-report and interview-based measures of the severity of AUD, negative symptoms, and alcohol craving. Finally, we used data from the electronic health records of the patients.ResultsPatients with AUD show negative symptoms to a similar extent as patients with schizophrenia or bipolar disorder. We found a positive correlation between the extent of impairment within the MAP factor and overall severity of AUD. Furthermore, MAP negative symptoms were correlated with alcohol craving. In a linear regression, negative symptoms predicted alcohol craving whereas depression did not.SummaryNegative symptoms as conceptualized for schizophrenia are prevalent in patients with AUD and associated with the severity of AUD. More specifically, severity of AUD correlates with diminished motivation and pleasure, highlighting the importance of disturbances in motivational functions in AUD. This is further supported by the correlation between negative symptoms and craving, a hallmark of AUD. Taken together, our findings suggest that negative symptoms might be a highly relevant but hitherto often neglected therapeutic target in AUD

Exploring why patients in heroin-assisted treatment are getting incarcerated - a qualitative study

Background: Heroin-assisted treatment has proven effective in reducing criminal offenses in opioid dependent individuals. Few studies attempted to explain the observed crime reduction and the reasons why these patients keep offending and getting incarcerated have to date not been explored. Methods: Patients with a history of incarcerations during the time of participating in heroin-assisted treatment (n = 22) were invited to a semi-structured, narrative interview. Findings were evaluated with Mayring's qualitative content analysis framework. Additionally, the Montreal Cognitive Assessment test and the multiple-choice vocabulary intelligence test used to assess cognitive impairment and premorbid intelligence levels. Results: Three main categories emerged in patients' narratives on their incarcerations: cocaine use, impaired functioning, and financial constraints. Lifetime prevalence of cocaine use disorder was 95.5% and their cocaine use often led to patients getting incarcerated. Impaired functioning mainly constituted the inability to receive and open mail. Financial constraints led to incarcerations in lieu of payment in 16 participants (72.7%). Categories overlapped notably and often occurred in close temporal proximity. A fourth category on the likelihood of getting incarcerated again in the future was inhomogeneous and ranged from the strong conviction to complete rejection of the scenario. Average premorbid intelligence levels were found, whereas the cognitive assessment suggested severe cognitive impairment in our sample. Conclusion: Participants mainly reported to have committed minor offenses and not being able to pay for resulting fines. The resulting prison sentences are an unconvincing practice from a medical and economic perspective alike. Public expenditure and the interruptions of the continuum of care could be reduced by legislatively protecting these marginalised patients