This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
REM sleep behavior disorder (RBD) is a parasomnia associated with dream enactment often involving violent or potentially injurious behaviors during REM sleep that is strongly associated with synucleinopathy neurodegeneration. Clonazepam has long been suggested as the first-line treatment option for RBD. However, evidence supporting melatonin therapy is expanding. Melatonin appears to be beneficial for the management of RBD with reductions in clinical behavioral outcomes and decrease in muscle tonicity during REM sleep. Melatonin also has a favorable safety and tolerability profile over clonazepam with limited potential for drug-drug interactions, an important consideration especially in elderly individuals with RBD receiving polypharmacy. Prospective clinical trials are necessary to establish evidence-basis for melatonin and clonazepam as RBD therapies.
Background Lithium is a first-line pharmacotherapy for the treatment of bipolar disorder, but long-term use is associated with nephrotoxicity. However, as dialysis effectively eliminates lithium, it remains a pharmacotherapeutic option for patients on dialysis. This systematic review seeks to evaluate the dosing, safety, efficacy, and monitoring of lithium in patients receiving dialysis. Method A PubMed database search performed May 5th, 2020, identified 535 article titles. After exclusion criteria were applied, a total of 15 articles were included in this systematic review. Results In 18 patients receiving dialysis, lithium was primarily used for the treatment of mood disorders. The majority of patients received 300–900 mg lithium carbonate thrice-weekly following dialysis, but several alternative lithium salts and dosing strategies were utilized. The pharmacokinetic properties of lithium in dialysis are not well understood and can be complicated by a serum lithium “rebound effect” following dialysis, due to a two-compartment volume of distribution. Additionally, presence of residual diuresis in some patients may be reason to administer lithium more frequently than thrice-weekly following dialysis. Lithium was shown to be an effective pharmacotherapy in all patients, with many demonstrating rapid improvement after drug initiation. Five patients experienced an adverse event on lithium, but only one patient required lithium discontinuation. Conclusion Lithium may be used in patients on dialysis, with close monitoring of pre-dialysis serum lithium concentrations for at least two weeks after treatment initiation, followed by a lower frequency after stabilization to ensure therapeutic concentrations and reduce toxicity risk.
Garcinia cambogia is a Southeast Asian fruit becoming increasingly popular as a weight management supplement. Hydroxycitric acid (HCA) is the primary active ingredient which demonstrates serotonergic- and muscarinic-enhancing properties via inhibition of selective serotonin reuptake and acetylcholinesterase. We report a young adult female with no history of bipolar disorder who developed mania and psychosis approximately 1 week following initiation of G cambogia and the Cleanse and Detox™ dietary supplement manufactured by Apex Vitality Health. She presented with a predominantly expansive mood, psychomotor agitation, disorganized and pressured speech, flight of ideas, grandiosity, delusions, and auditory hallucinations. Following discontinuation of G cambogia and the initiation of lithium and quetiapine, the patient experienced rapid and progressive mood stabilization and was discharged after 8 days. Seven previous case reports associating (hypo)mania and/or psychosis with G cambogia consumption have been published. The chronology of mania and/or psychosis onset may appear between 1 and 8 weeks following initiation of G cambogia. Psychiatric symptoms have resolved with G cambogia discontinuation in some instances and may not require chronic pharmacotherapy. Our report should encourage further research and case reports regarding this adverse event and the reconciliation of complete herbal supplement use at clinic visits and hospital admissions.
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