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In 1949, Cade described “sedative effects” after injecting guinea pigs intraperitoneally with lithium (LTM) carbonate. Based on his experiments, he began treating psychiatric patients with LTM. This literature review aims to evaluate the clinical epidemiological profile, pathological mechanisms, and management of LTM-associated movement disorder (MD). Relevant reports in six databases (Excerpta Medica, Google Scholar, Latin American and Caribbean Health Sciences Literature, Medline, Scientific Electronic Library Online, and ScienceDirect) were identified and assessed by two reviewers without language restriction from 1949 to 2021. A total of 250 reports containing 1100 individuals who developed MD associated with LTM were identified. The MDs encountered 148 parkinsonism (PKN), 114 dyskinesia (DKN), 97 myoclonus, 22 dystonia (DTN), 20 Creutzfeldt–Jakob-like syndrome, 11 akathisia, 10 restless legs syndrome (RLS) symptoms, 6 tics, 5 cerebellar syndromes, and 3 stuttering. In the subgroup of cases not clearly defined, there were 320 individuals with extrapyramidal symptoms, 135 with DTN, 37 with DKN, 24 with PKN, and 7 with RLS. Other 141 individuals were only described as presenting an abnormal involuntary movement without further explanation. The mean age was 53.06 years (standard deviation [SD]: 15.64) and the predominant sex was female, i.e., 56.20% (154/274). The mean LTM dose was 963.03 mg/day (SD: 392.03). The mean serum LTM level was 1.53 mEq/L (SD: 1.08). The median onset time was 3 months (1 day to 40 years). The mean recovery time was 0.94 months (SD: 0.87). 45.94% had a full recovery. LTM-induced MD was extensively reported in the literature. Only general terms were used in the majority of the reports. LTM polytherapy probably affected the identification of the MD cause.

Valproate (VPA) was first synthesized in 1882, but it was only in the early 1960s that its anticonvulsant properties were discovered. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of VPA-associated movement disorder (MD). Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 138 reports containing 362 cases of subjects who developed a MD secondary to VPA were reported. The MD identified were parkinsonism (PKN) (252), myoclonus (MCL) (54), dystonia (DTN) (17), dyskinesia (DKN) (16), stutters (4), tics (3), akathisia (AKT) (1). In the not clearly defined group, 15 extrapyramidal symptoms, 3 AKT, 2 DTN, 1 rigidity, 1 unstable gait were assessed. The mean and median age was 55.8 (SD: 16.58) and 61 years (range: 4–87 years). The most common VPA-indication was epilepsy, and 51.36% were males. The mean and median time from the VPA start to the MD onset was 32.75 (SD: 30.05) and 21.15 months (range: 1 day – 20 years). The mean and median time from the VPA withdrawal until the MD recovery was 2.89 (SD: 2.79) and 3 months (1 day – 12 months). The most common management was drug withdrawal. A complete recovery was obtained in 80.61%. VPA-associated MD was extensively reported in the literature. PKN was the most well-described. Future studies need to clearly report the clinical history of the patient, considering the full investigation of other adverse events during their entire life.

Pimavanserin (PMV) is the first approved drug for treating hallucinations and delusions in Parkinson’s disease (PD) psychosis. Psychosis is one of the leading causes of nursing home placement in people with PD. Furthermore, hallucinations are a more frequent cause of institutionalization than motor disability or dementia related to PD. The management of PD psychosis involves antipsychotic medications. Most of the drugs in this class directly block dopamine D2 receptors, leading to significantly worsening motor symptoms in patients with PD. The most commonly used medications for managing PD psychosis are quetiapine, clozapine, and PMV. This literature review aims to study pimavanserin’s history, mechanism, clinical trials, and post-marketing experience. PMV is a potent 5-HT2A receptor antagonist/inverse agonist. Moreover, this drug can interact with 5-HT2C receptors. We calculated some physicochemical descriptors and pharmacokinetic properties of PMV. Eight clinical trials of PMV and PD psychosis are registered on ClinicalTrials.gov. Only four of them have complete results already published. Meta-analytic results showed that PMV efficacy is inferior to clozapine. However, PMV has a significantly lower number of side-effects for managing psychosis in PD. Medicare database assessment revealed 35% lower mortality with PMV compared to other atypical antipsychotics. Moreover, sensitive statistical analysis demonstrated that PMV is a protective factor for the risk of falls in individuals with PD.

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