UNASSIGNED: We aimed to examine the common adverse drug reactions (ADRs) of metoclopramide, FDA-approved for treating many gastrointestinal conditions including gastroparesis, and prucalopride, FDA-approved for treating chronic idiopathic constipation but used off-label for other gastrointestinal conditions including gastroparesis.
UNASSIGNED: The FDA Adverse Event Reporting System (FAERS) was analyzed from January 2013 to December 2023. ADR reports regarding use of only metoclopramide or prucalopride were analyzed following exclusion of reports indicating use for treatment of non-gastrointestinal conditions.
UNASSIGNED: Analysis of 1,085 reports on metoclopramide revealed tardive dyskinesia (n = 393, 36.2%) and dystonia (n = 170, 15.7%) among the most reported ADRs in addition to QTc prolongation (n = 16, 1.5%) with progression to Torsade de pointes (n = 5, 0.5%) and triggering of pheochromocytoma crisis (n = 24, 2.2%). Analysis of 865 reports on prucalopride revealed headache (n = 120, 13.9%), diarrhea (n = 116, 13.4%), and abdominal pain (n = 100, 11.6%) as the most common ADRs with 22 reports (2.5%) of dystonia with the use of prucalopride.
UNASSIGNED: This FAERS database analysis shows post-marketing reports of ADRs from metoclopramide most frequently include tardive dyskinesia, dystonia, and tremor in addition to potentially fatal arrhythmias such as Torsade de pointes. Consumers of prucalopride may also be at risk of dystonia and other ADRs.

UNASSIGNED: Tardive dyskinesia (TD) and Huntington\'s disease (HD)-associated chorea are persistent and disabling hyperkinetic disorders that can be treated with vesicular monoamine transporter type 2 (VMAT2) inhibitors, including the recently approved once-daily (QD) formulation of deutetrabenazine (DTBZ ER). While its efficacy and safety profile have not been directly investigated, currently available data confirms bioequivalence and similar bioavailability to the twice-daily formulation (DTBZ BID).
UNASSIGNED: The authors briefly review the pivotal trials establishing efficacy of DTBZ for TD and HD-associated chorea, the pharmacokinetic data for bioequivalence between QD and BID dosing of DTBZ, as well as dose proportionality evidence, titration recommendations, and safety profile for DTBZ ER.
UNASSIGNED: Long-term data show that DTBZ is efficacious and well tolerated for the treatment of TD and HD-associated chorea. DTBZ ER likely demonstrates therapeutic equivalence with no new safety signals. Due to the lack of comparative clinical trial data, no evidence-based recommendation about choice of VMAT2 inhibitor or switching between VMAT2 inhibitors can be made about best practice. Ultimately, QD dosing may offer the chance of improved medication adherence, an important consideration in patients with complex treatment regimens and/or patients with cognitive decline.

OBJECTIVE: The aim of this study is to indirectly compare and rank the different drugs that have been studied in randomized clinical trials (RCTs) in patients with tardive dyskinesia (TD) in terms of their efficacy in ameliorating the symptoms of TD and safety.
METHODS: A network meta-analysis and a systematic review were registered prospectively on PROSPERO under the ID: CRD42023407823 and were conducted in accordance with the PRISMA-NMA guidelines.
METHODS: PubMed, Scopus, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Sciences, and Clinicaltrials.gov were searched to identify relevant records.
METHODS: Any parallel randomized blinded controlled clinical trials that studied the use of any medications in treating TD and assessed the symptoms using a functional scale that has been previously validated.
METHODS: The standardized mean difference of improvement along with the reported adverse events for each drug was extracted from each trial, and a network meta-analysis was conducted using a random-effects model.
RESULTS: One thousand eight hundred seventeen patients in 33 RCTs were included in the analysis. Twenty-three different drugs were compared to placebo in terms of reduction in TD symptoms. Among these, valbenazine 80 mg (SMD =  - 1.66, 95%CI = [- 2.55; - 0.78]), valbenazine 40 mg (- 1.00, [- 1.89; - 0.11]), and vitamin E (- 0.77, [- 1.45; - 0.1]) significantly reduced TD symptoms in comparison to placebo, while deutetrabenazine 36 mg (- 1.00, [- 2.12; 0.11]) and reserpine (- 0.54, [- 1.09; 0.02]) did not significantly reduce symptoms. Some serious adverse events were reported for valbenazine and deutetrabenazine, which included mainly psychiatric symptoms such as depression, worsening of schizophrenia, and suicidal ideation, while mild adverse events were reported for other drugs, and their incidence in the treatment arms was comparable to those in the placebo arm.
CONCLUSIONS: Valbenazine (80 and 40 mg) and vitamin E demonstrated efficacy in treating tardive dyskinesia. However, the significant side effects of valbenazine should prompt further investigation of alternative treatment modalities.

暂无摘要。

BACKGROUND: Deutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use are limited.
METHODS: Patients with TD who completed parent studies ARM-TD or AIM-TD were eligible for the 3-year, open-label extension study (RIM-TD; NCT02198794). In RIM-TD, deutetrabenazine was titrated based on dyskinesia control and tolerability. In this post hoc analysis of RIM-TD, total motor Abnormal Involuntary Movement Scale (AIMS) score and adverse events (AEs) were analyzed by underlying condition and DRA use at parent study baseline.
RESULTS: Of 343 patients enrolled in RIM-TD, 336 were included in the analysis by underlying condition, and 337 were included in the analysis by DRA use. One hundred eighty-nine of 205 (92%) patients with psychotic disorders (schizophrenia/schizoaffective disorder) and 65 of 131 (50%) with mood and other disorders (depression/bipolar disorder/other) were receiving a DRA. Mean (SE) deutetrabenazine doses at week 145 were 40.4 (1.13), 38.5 (1.21), 39.9 (1.00), and 38.5 (1.48) mg/d for patients with psychotic disorders, those with mood and other disorders, and those receiving DRAs or not, respectively. Mean (SD) changes in total motor AIMS score from this study baseline to week 145 were -6.3 (4.53), -7.1 (4.92), -6.1 (4.42), and -7.5 (5.19). Exposure-adjusted incidence rates (number of AEs/patient-years) of AEs were similar across groups: any (1.02, 1.71, 1.08, 1.97), serious (0.10, 0.12, 0.10, 0.12), and leading to discontinuation (0.07, 0.05, 0.06, 0.05).
CONCLUSIONS: Long-term deutetrabenazine provided clinically meaningful improvements in TD-related movements, with a favorable benefit-risk profile, regardless of underlying condition or DRA use.

This study aimed to assess the association between antipsychotic doses and the risk of tardive dyskinesia (TD) in clinical practice using a Japanese claims database from 2010 to 2020.
The study population included patients 15 years or older with a diagnosis record of schizophrenia, depression, or bipolar disorder who were prescribed antipsychotics. Using a case-control design, we categorized patients newly diagnosed with TD as cases, with corresponding 1:10 matching in the control group. The primary endpoint was the relative risk of TD in the >median dose and ≤median dose groups, as determined using conditional logistic regression analysis adjusted for age.
The analysis population included 58,452 patients, and the median daily antipsychotic dose was 75 mg/d of chlorpromazine equivalent (CPZE). Of these, 80 were identified as TD cases, and doses >75 mg/d were associated with a significantly increased risk of TD at the last prescription and the maximum dose, respectively, before the date of the first diagnosis of TD. Post-hoc analysis further showed a significant association between doses ≥300 mg/d and the risk of TD compared to doses ≤75 mg/d and doses >75 to <300 mg/d. Comparing ≥300 mg/d versus >75 to <300 mg/d, the odd ratios at the last prescription and maximum dose before the first diagnosis of TD were 3.40 and 3.50, respectively.
In the Japanese medical claims database of patients receiving relatively low doses of antipsychotics, doses >75 mg/d were associated with an increased risk of TD in a dose-dependent manner.

Painless legs and moving toe syndrome (PoLMT) is a rare syndrome characterized by involuntary movements of the toe without pain. The exact etiology of the patient\'s PoLMT is unknown. We present a case of PoLMT in 45-year-old woman with a history of haloperidol intake for 10 months. Haloperidol was discontinued, and aripiprazole (15 mg) was initiated. After this switch, a reduction in movement was observed in the third and fourth toes; however, the second toe showed no discernible change.
Painless Legs and Moving Toe Syndrome (PoLMT) is a rare condition in which the toe moves on its own without any pain. No one knows for sure what causes PoLMT in patients. In this case report, we discuss a 45-year-old woman with PoLMT who was taking a drug called haloperidol for 10 months prior to their visit to hospital. Another drug, aripiprazole, was started after haloperidol was stopped. It was noticed that the third and fourth toes moved less after this switch in medication, but no change was noticed in the second toe.

OBJECTIVE: Using data from KINECT® 4, a phase 3, 48-week study of valbenazine, post hoc analyses were conducted to assess long-term outcomes that are relevant to the real-world management of tardive dyskinesia (TD).
METHODS: Post hoc analyses of the participants of the KINECT 4 study who completed 48 weeks of open-label valbenazine (40 or 80 mg) treatment were conducted. Valbenazine effects on TD were evaluated using the Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression of Change-TD (CGI-TD), and Patient Global Impression of Change (PGIC).
RESULTS: Of 103 participants completing 48 weeks of treatment, 55% experienced clinically meaningful improvement (defined as ≥2-point reduction in AIMS total score [sum of items 1 - 7, evaluated by site raters]) by week 4; at week 48, 97% met this threshold. The percentage of completers who achieved AIMS total score response thresholds of ≥10% to ≥90% increased over time, with 86% of completers reaching ≥50% improvement. Of the 40 (39%) completers with AIMS ≥50% response at week 8, 38 (95%) sustained this response at week 48; 81% of those who did not meet this threshold at week 8 had achieved it by week 48. At week 48, more than 85% of completers achieved CGI-TD and PGIC ratings of \"much improved\" or \"very much improved.\"
CONCLUSIONS: The majority of participants who completed 48 weeks of treatment with once-daily valbenazine experienced substantial clinically meaningful and sustained TD improvements. These findings indicate that valbenazine can be a highly effective long-term treatment in patients with TD.

Hyponatremia, a common electrolyte disorder, usually has a benign clinical course. However, patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) can suffer unfavorable outcomes, including mortality. Atypical antipsychotics, which are among the drugs associated with SIADH, also cause tardive dyskinesia, a condition that physicians can now effectively manage with the recently approved agent - valbenazine. We herein report a case of severe hyponatremia due to SIADH in a 58-year-old man who developed hyponatremia-induced generalized seizures six weeks after valbenazine was added to his regimen to mitigate olanzapine-associated tardive dyskinesia. His electrolyte derangement and clinical course improved following prompt recognition and treatment of SIADH. The temporal association between the commencement of valbenazine and the onset of SIADH suggests a possible but previously unreported link between valbenazine and the development of SIADH. Awareness of this uncommon association is relevant to patient safety.

Clonazepam has some evidence in the treatment of tardive dyskinesia. It can be used as an alternative treatment option in situations where vesicular monoamine transporter 2 inhibitors are not available or when it is not feasible to use them.