Case report: Psychosis and catatonia in an adolescent patient with adipsic hypernatremia and autoantibodies against the subfornical organ.

This is the first description of a patient in which adipsic hypernatremia, a rare autoimmune encephalitis, presented in combination with complex psychiatric symptomatology, including psychosis and catatonia. Adipsic hypernatremia is characterized by autoantibodies against the thirst center of the brain. These autoantibodies cause inflammation and apoptosis in key regions of water homeostasis, leading to lack of thirst and highly increased serum sodium. To date, the symptoms of weakness, fatigue and drowsiness have been associated with adipsic hypernatremia, but no psychiatric symptomatology. Here, we showcase the first description of an adolescent patient, in which severe and complex psychiatric symptoms presented along with adipsic hypernatremia. The patient experienced delusion, hallucinations, restlessness and pronounced depression. Further, he showed ritualized, aggressive, disinhibited and sexualized behavior, as well as self-harm and psychomotor symptoms. Due to his severe condition, he was hospitalized on the emergency unit of the child and adolescent psychiatry for 8 months. Key symptoms of the presented clinical picture are: childhood-onset complex and treatment-resistant psychosis/catatonia, pronounced behavioral problems, fatigue, absent thirst perception, hypernatremia and elevated prolactin levels. This case report renders first evidence speaking for a causal link between the autoimmune adipsic hypernatremia and the psychotic disorder. Moreover, it sheds light on a new form of autoimmune psychosis.

Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system's response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

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.

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.

Nasal Opioid Agonist Treatment in Patients with Severe Opioid Dependence: A Case Series.

INTRODUCTION: Opioid agonist treatment (OAT) is the first-line treatment for opioid dependence. Currently available OAT options comprise oral (methadone and morphine) and sublingual (buprenorphine) routes of administration. In Switzerland and some other countries, severely opioid-dependent individuals with insufficient response to oral or sublingual OAT are offered heroin-assisted treatment (HAT), which involves the provision of injected or oral medical heroin (diacetylmorphine [DAM]). However, many patients on treatment with injectable DAM (i-HAT) suffer from injection-related problems such as deteriorated vein status, ulcerations, endocarditis, and abscesses. Other patients who do not respond to oral OAT do not inject but snort opioids, and are not eligible for i-HAT. For this population, there is no other short-acting OAT with rapid onset of action available unless they switch to injecting, which is associated with higher risks. Nasal DAM (n-HAT) could be an alternative treatment option suitable for both populations of patients. METHODS: We present a case series of 3 patients on i-HAT who successfully switched to n-HAT. RESULTS/CONCLUSIONS: This is the first description of the clinical use of the nasal route of administration for HAT. n-HAT may constitute an important risk-reduced rapid-onset alternative to i-HAT. In particular, it may be suited for patients with injection-related complications, or noninjecting opioid-dependent patients failing to respond to oral OAT.

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.

Cannabidiol Cigarettes as Adjunctive Treatment for Psychotic Disorders - A Randomized, Open-Label Pilot-Study.

Background: Psychotic disorders are associated with high rates of comorbid substance use disorders. Use of cannabis rich in tetrahydrocannabinol (THC) is linked to an increased risk of psychosis, worsening of psychotic symptoms, and an adverse course of psychotic disorders. Previous studies suggest oral cannabidiol (CBD) as possible novel antipsychotic agent; however, no studies evaluated the effects of smoked CBD. Objective: The main aim of the study was to clarify the antipsychotic potential of CBD used as adjunctive therapy simulating a naturalistic setting. Our trial is the first study evaluating the effects of smoked CBD-cigarettes as adjunctive therapy for psychotic symptoms. Methods: A randomized, placebo-controlled open-label trial of cigarettes containing CBD-rich cannabis (THC < 1%) as adjunctive therapy to standard psychiatric treatment was conducted (ClinicalTrials.gov identifier NCT04700930). Primary outcomes were mean scores of Positive and Negative Syndrome Scale (PANSS), Brøset Violence Checklist, the Beck's Depression Inventory (BDI), the Subjective Well-Being Under Neuroleptics Scale short form (SWN-K), and antipsychotic medication equivalent doses. Outcomes were assessed after 4 weeks of acute treatment and long-term follow-up after discontinuation of CBD-cigarettes after 25 weeks. Participants were 31 acutely psychotic patients with tobacco use disorder and a mean age of 35.1 ± 10.58 years (71% male). Comorbid cannabis use was diagnosed in 51.6%. Results: A discontinuous multilevel model revealed no significant group differences for primary outcomes. After 4 weeks of acute treatment, mean PANSS and BDI decreased in both groups, while an increase of antipsychotic medication equivalent was observed in the placebo group. Conclusions: The presented findings might suggest an antipsychotic medication sparing effect of CBD-cigarettes as adjunctive treatment of acute psychosis. However, the low number of participants did not allow for further statistical analysis. Hence, a larger study sample and a more rigorous study design (blinding of the interventional product, fixed dosing regimen) may reveal different results. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04700930.

Case Report: CBD Cigarettes for Harm Reduction and Adjunctive Therapy in a Patient With Schizophrenia and Substance Use Disorder.

The treatment of patients with schizophrenia and substance use disorder poses a challenge for clinicians. Continued use of cannabis and cocaine can exacerbate psychotic symptoms and worsen the course of disease. To date, no pharmacotherapy is available for patients with cannabis use disorder (CUD). Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the main active constituents in Cannabis sativa, with the latter being linked to an increased risk of psychosis. We describe a clinical case of a male patient diagnosed with schizophrenia, combined personality disorder, CUD and cocaine use disorder. Over the course of 8 years, he was hospitalized 30 times due to psychotic relapses and continued substance use. Consequently, CBD cigarettes with a low THC content (<1%) were used as adjunctive therapy. Additionally, we established off-label treatment with methylphenidate to support abstinence. The patient reported to feel significantly less need to consume illegal cannabis with a high THC content. He stopped to use cocaine, for the time being, and has not been hospitalized since. This case report demonstrates the potential of smoked CBD as a substitute for severe and chronic CUD.

[Opioid Agonist Therapy (OAT) for opioid dependency]. / Opioid-Agonisten-Therapie bei Opioidabhängigkeit.

Opioid Agonist Therapy (OAT) for opioid dependency Abstract. The process of evaluating the necessity of an Opioid Agonist Therapy (OAT) is relatively simple. Once the criteria for an opioid dependency according to the ICD-10 (or DSM V) are met, treatment should be offered. Adequate individual dosing of the opioid agonist is crucial to treatment success. Several equally effective opioids are available. Comorbidities are common and should be taken into account when planning and conducting an OAT. In this article the State-Of-The-Art of the OAT will be presented, focusing upon the German-speaking European countries. The article provides an overview of diagnosis, treatment modalities, drug therapy and some specific challenges of the OAT. Treatment recommendations are in accordance with the Swiss model, hence adaptations to treatment due to local state laws may be necessary in other countries.

Chronic High-Dose Buprenorphine Does Not Block Subjective High from Diacetylmorphine in a Patient in Heroin-Assisted Treatment.

We present the case of a 35-year-old woman in heroin-assisted treatment (HAT) expressing the wish for the transition to oral opioid agonist treatment. After failed attempts to change to oral diacetylmorphine and slow-release oral morphine, respectively, she was induced on overlapping buprenorphine (BUP) treatment with the Bernese method. Gradual dose increases to BUP 48 mg per day did not result in attenuation of subjective effects of IV diacetylmorphine (DAM) 190 mg. Instead, the patient showed increased sedation. BUP was then reduced to 32 mg per day. After the gradual reduction of IV DAM, she reinitiated illicit substance use. IV DAM was again raised to an effective dose leading to stabilization and reduction of illicit substance use. BUP was subsequently reduced to 8 mg per day. This combination was continued as the patient felt comfortable and reported less early morning withdrawal than with exclusive DAM treatment. We discuss possible underlying mechanisms and explanations as well as clinical implications.