Therapeutic effect of psilocybin in addiction: A systematic review.

Background: Psychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous systematic reviews assessing the efficacy of psilocybin in SUDs only included clinical trials conducted in the last 25 years, but they may have missed clinical trials assessing the efficacy of psilocybin that were conducted before the 1980s, given much research has been done with psychedelics in the mid-20th century. In this systematic review, we specifically assessed the efficacy of psilocybin in patients with a SUD or non-substance-related disorder with no publication date restrictions in our search strategy. Methods: A systematic literature search was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from the earliest published manuscript up to September 2, 2022, in seven electronic databases, including clinical trials in patients with a SUD or non-substance-related disorder evaluating the efficacy of psilocybin. Results: A total of four studies (six articles, of which two articles were long-term follow-up results from the same trial) were included in this systematic review. Psilocybin-assisted therapy was administered to n = 151 patients in a dose ranging from 6 to 40 mg. Three studies focused on alcohol use disorder, and one study on tobacco use disorder. In a pilot study (n = 10), the percentage of heavy drinking days decreased significantly between baseline and weeks 5-12 (mean difference of 26.0, 95% CI = 8.7-43.2, p = 0.008). In another single-arm study (n = 31), 32% (10/31) became completely abstinent from alcohol (mean duration of follow-up 6 years). In a double-blind, placebo-controlled randomized controlled trial (RCT, n = 95), the percentage of heavy drinking days during the 32-week double-blind period was significantly lower for psilocybin compared to placebo (mean difference of 13.9, 95% CI = 3.0-24.7, p = 0.01). In a pilot study (n = 15), the 7-day point prevalence of smoking abstinence at 26 weeks was 80% (12/15), and at 52 weeks 67% (10/15). Conclusion: Only one RCT and three small clinical trials were identified assessing the efficacy of psilocybin combined with some form of psychotherapy in patients with alcohol and tobacco use disorder. All four clinical trials indicated a beneficial effect of psilocybin-assisted therapy on SUD symptoms. Larger RCTs in patients with SUDs need to evaluate whether psilocybin-assisted therapy is effective in patients with SUD.

Antithrombotic Therapy for Symptomatic Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND: High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD. METHODS: A systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group. RESULTS: Twenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking. CONCLUSION: Clopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.

Meropenem to Treat Valproic Acid Intoxication.

ABSTRACT: This therapeutic drug monitoring (TDM) grand round describes a patient with serious valproic acid intoxication. A total valproic acid level of 844 mg/L and an unbound valproic acid level of 604 mg/L were observed. Meropenem was administered to enhance the clearance of valproic acid. This off-label usage of meropenem is based on the drug-drug interaction between carbapenems and valproic acid, which reduced the level of valproic acid within 24 hours after administration.

Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study.

BACKGROUND AND AIMS: Ibogaine is an indole alkaloid used in rituals of the African Bwiti tribe. It is also used in non-medical settings to treat addiction. However, ibogaine has been linked to several deaths, mainly due to cardiac events called torsades des pointes preceded by QTc prolongation as well as other safety concerns. This study aimed to evaluate the cardiac, cerebellar and psychomimetic safety of ibogaine in patients with opioid use disorder. DESIGN: A descriptive open-label observational study. SETTING: Department of psychiatry in a university medical center, the Netherlands. PARTICIPANTS: Patients with opioid use disorder (n = 14) on opioid maintenance treatment with a lasting wish for abstinence, who failed to reach abstinence with standard care. INTERVENTION AND MEASUREMENTS: After conversion to morphine-sulphate, a single dose of ibogaine-HCl 10 mg/kg was administered and patients were monitored at regular intervals for at least 24 hours assessing QTc, blood pressure and heart rate, scale for the assessment and rating of ataxia (SARA) to assess cerebellar side effects and the delirium observation scale (DOS) to assess psychomimetic effects. FINDINGS: The maximum QTc (Fridericia) prolongation was on average 95ms (range 29-146ms). Fifty percent of subjects reached a QTc of over 500ms during the observation period. In six out 14 subjects prolongation above 450ms lasted beyond 24 hours after ingestion of ibogaine. No torsades des pointes were observed. Severe transient ataxia with inability to walk without support was seen in all patients. Withdrawal and psychomimetic effects were mostly well-tolerated and manageable (11/14 did not return to morphine within 24 hours, DOS scores remained below threshold). CONCLUSIONS: This open-label observational study found that ibogaine treatment of patients with opioid use disorder can induce a clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia.

RYR1-Related Rhabdomyolysis: A Spectrum of Hypermetabolic States Due to Ryanodine Receptor Dysfunction.

Variants in the ryanodine receptor-1 gene (RYR1) have been associated with a wide range of neuromuscular conditions, including various congenital myopathies and malignant hyperthermia (MH). More recently, a number of RYR1 variants, mostly MH-associated, have been demonstrated to contribute to rhabdomyolysis events not directly related to anesthesia in otherwise healthy individuals. This review focuses on RYR1-related rhabdomyolysis in the context of several clinical presentations (i.e., exertional rhabdomyolysis, exertional heat illnesses and MH), and conditions involving a similar hypermetabolic state, in which RYR1 variants may be present (i.e., neuroleptic malignant syndrome and serotonin syndrome). The variety of triggers that can evoke rhabdomyolysis, on their own or in combination, as well as the number of potentially associated complications, illustrates that this is a condition relevant to several medical disciplines. External triggers include but are not limited to strenuous physical exercise, especially if unaccustomed or performed under challenging environmental conditions (e.g., high ambient temperature or humidity), alcohol/illicit drugs, prescription medication (in particular statins, other anti-lipid agents, antipsychotics and antidepressants) infection, or heat. Amongst all patients presenting with rhabdomyolysis, genetic susceptibility is present in a proportion, with RYR1 being one of the most common genetic causes. Clinical clues for a genetic susceptibility include recurrent rhabdomyolysis, creatine kinase (CK) levels above 50 times the upper limit of normal, hyperCKemia lasting for 8 weeks or longer, drug/medication doses insufficient to explain the rhabdomyolysis event, and positive family history. For the treatment or prevention of RYR1-related rhabdomyolysis, the RYR1 antagonist dantrolene can be administered, both in the acute phase or prophylactically in patients with a history of muscle cramps and/or recurrent rhabdomyolysis events. Aside from dantrolene, several other drugs are being investigated for their potential therapeutic use in RYR1-related disorders. These findings offer further therapeutic perspectives for humans, suggesting an important area for future research.

[Medicines: what has the last decade given us and what can we expect in the coming 10 years?] / Geneesmiddelen: 10 jaar terug en vooruitkijken.

Recent years have seen important changes in pharmacology. New techniques have been developed which are increasingly aimed at smaller groups of patients or even individual patients. In the past, thousands of chemical molecules were tested on a potential molecular target and the most effective molecules were selected. Nowadays a growing number of drugs are designed to aim at a specific molecular target, an example being monoclonal antibodies. There are developments that go fundamentally further and enable patients to be treated in an increasingly targeted and individual manner. These new therapies (i.e., Advanced Therapy Medicinal Products) are based on different principles than those of classical pharmacotherapy, and require different risk assessments as well as a different regulatory system. In this paper we discuss a selection of the developments in pharmacotherapy that have taken place during the past decade. In addition, we look into what sort of developments can be expected in the future.

[Iron supplementation in iron deficiency anaemia]. / Suppletie van ijzer bij ijzergebreksanemie.

Iron deficiency anaemia is a common problem. The majority of patients are treated with oral iron supplements. The current recommended dosage for oral supplementation of 200 mg ferrous fumarate 3x per day however, is based on a single small study of poor quality. There is no consensus concerning parenteral dosing. In recent years, new insights have been gained regarding both the dosage of oral supplementation and the indication for parenteral supplementation. Oral therapy is preferred. In principle, 100 mg ferrous fumarate once a day is sufficient for the treatment of symptom-free patients with anaemia. In cases of severe anaemia, or in patients with symptoms, 200 mg/day should be prescribed. If side effects appear, it can be dosed every other day. Where oral therapy does not show effectiveness, the anaemia is severe, or rapid increase of haemoglobin is indicated, parenteral supplementation should be chosen. Parenteral supplementation is more effective than oral supplementation in specific conditions, such as dialysis-dependent renal insufficiency, heart failure or active IBD.

[Insufficient medication compliance in Parkinson's disease]. / Onvoldoende therapietrouw bij ziekte van Parkinson.

Medication compliance is generally suboptimal, particularly in patients with complex polypharmacy. This generic treatment problem is described here for Parkinson's disease (PD). We would expect patients with PD to have good medication compliance, since missed doses immediately result in worsening of symptoms. However, recent research has revealed that PD patients demonstrate poor medication compliance. Poor medication compliance is particularly undesirable for patients with PD because regular intake of medication is required for optimal treatment effect. Possible ways of improving medication compliance are pharmacotherapeutic measures and behavioural interventions. Modern methods of communication (text message reminders) and 'smart' pill dispensers may be beneficial, but the advantages of such interventions have not yet been scientifically studied.

A man who wanted to commit suicide by hanging himself: an adverse effect of ciprofloxacin.

In this case report, we describe a man who developed recurrent depression and suicidal ideation with a serious plan to commit suicide as definite adverse effect of ciprofloxacin, which had been prescribed for recurrent prostatitis.