The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis.

The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients. Through an in-depth systematic search in 2010-2022, we identified 501 records.

Clozapine Optimization: A Delphi Consensus Guideline From the Treatment Response and Resistance in Psychosis Working Group.

Background And Hypothesis: There is limited evidence to guide the approaches to clozapine treatment. Accordingly, an international initiative was undertaken with the aim of developing consensus recommendations for the optimization of clozapine monotherapy.

Study Design: We conducted an online Delphi survey among members of the Treatment Response and Resistance in Psychosis (TRRIP) working group comprising experts from twenty-nine countries.

Review article: An analysis of the pharmacological rationale for selecting drugs to inhibit vomiting or increase gastric emptying during treatment of gastroparesis.

Background: Drugs which can inhibit nausea/vomiting and/or increase gastric emptying are used to treat gastroparesis, mostly 'off-label'. Within each category, they act at different targets and modulate different physiological mechanisms.

Aims: Address the questions: In gastroparesis, why should blocking one pathway causing vomiting, be more appropriate than another? Why might increasing gastric emptying via one mechanism be more appropriate than another?

Methods: Drugs used clinically were identified via consensus opinions and reviews, excluding the poorly characterised.

Deep Brain Stimulation in the Treatment of Tardive Dyskinesia.

Tardive dyskinesia (TD) is a phenomenon observed following the predominantly long-term use of dopamine receptor blockers (antipsychotics) widely used in psychiatry. TD is a group of involuntary, irregular hyperkinetic movements, mainly in the muscles of the face, eyelid, lips, tongue, and cheeks, and less frequently in the limbs, neck, pelvis, and trunk. In some patients, TD takes on an extremely severe form, massively disrupting functioning and, moreover, causing stigmatization and suffering.

Tardive Syndrome Is a Mysterious Phenomenon with Different Clinical Manifestations-Review.

Tardive syndrome (TS) refers to persistent hyperkinetic, hypokinetic, and sensory complaints appearing after chronic neuroleptics and other dopamine receptor-blocking agents (DRBAs). It is defined as involuntary movements, often rhythmic, choreiform, or athetoid, involving the tongue, face, extremities, and sensory urges such as akathisia and lasts for a few weeks. TS develops in association with neuroleptic medication usage for a few months at least.

Enhancement of adenosine A signaling improves dopamine D receptor antagonist-induced dyskinesia β-arrestin signaling.

Repeated administration of dopamine D receptor (D2R) antagonists, which is the treatment for psychosis, often causes tardive dyskinesia (TD). Despite notable clinical demand, effective treatment for TD has not been established yet. The neural mechanism involving the hyperinhibition of indirect pathway medium spiny neurons (iMSNs) in the striatum is considered one of the main causes of TD.

Oromandibular tics associated with Tourette syndrome.

Background: Tourette syndrome (TS) is the most common cause of chronic tics. Patients with TS frequently manifest motor tics involving the eyes and face but oromandibular (OM) tics have been rarely studied.

Materials And Methods: We reviewed the medical records and video-recordings of 155 consecutive patients with TS in our movement disorders clinic.

Case report: Pallidal deep brain stimulation for treatment of tardive dystonia/dyskinesia secondary to chronic metoclopramide medication.

Objectives: Tardive dystonia/dyskinesia (TDD) occurs as a side effect of anti-dopaminergic drugs, including metoclopramide, and is often refractory to medication. While pallidal deep brain stimulation (DBS) has become an accepted treatment for TDD secondary to neuroleptic medication, there is much less knowledge about its effects on metoclopramide-induced TDD.

Methods: We present the case of a woman with metoclopramide-induced TDD, whose symptoms were initially misjudged as "functional.

Tardive Dyskinesia Following Low-Dose Risperidone.

Tardive dyskinesia is an involuntary athetoid or choreiform movement lasting a minimum of a few weeks. It is associated with the use of neuroleptic medication for at least three months and persists beyond four to eight weeks. Tardive dyskinesia usually occurs as a result of the long-term use of dopamine receptor-blocking agents, mainly first-generation antipsychotics or a high-dose, second-generation antipsychotic.

Current perspectives on the epidemiology and burden of tardive dyskinesia: a focused review of the clinical situation in Japan.

Unlabelled: Tardive dyskinesia (TD) is a movement disorder that can develop with the use of dopamine receptor-blocking agents and is most commonly caused by antipsychotics. The use of antipsychotics is expanding, which may lead to an increased number of patients experiencing TD. To summarise the current knowledge of the epidemiology and risk factors for TD in Japan, we reviewed articles related to the current state of knowledge around TD identified through a PubMed search, and held a roundtable discussion of experts in Japan on 9 September 2021 to form the basis of the opinion presented within this review.

Why Does Tardive Dyskinesia Have Oro-facial Predominance? A Network Analysis.

Tardive dyskinesia is a involuntary hyperkinetic disorder which usually occurs in older patients after long-term treatment with antipsychotic drugs. These dyskinesias are mostly irreversible and are frequently expressed in the tongue, cheeks, mandible, perioral area and other regions of the face. In this theoretical study we asked the question, why does tardive dyskinesia often have orofacial predominance? What might be the underlying neural network structure which contributes to this propensity? Graph analysis of high-level cortico-striato-thalamo-cortical network structure suggests a connectivity bottleneck.

[Idiopathic (Oral) and Tardive Dyskinesia: Pathogenesis, Epidemiology, and Treatment].

Etymologically, dyskinesia is a combination of the prefix "dys-," which means 'abnormality' and the suffix "-kinesia," which means 'movement.' In a broad sense, dyskinesia indicates hyperkinetic involuntary movements. In a narrow sense, as a general term, dyskinesia refers to combinations of one or more of the following movements: chorea, dystonia, tremor, ballism, athetosis, tics, and myoclonus.

Clinician Perceptions of the Negative Impact of Telehealth Services in the Management of Drug-Induced Movement Disorders and Opportunities for Quality Improvement: A 2021 Internet-Based Survey.

Purpose: Tardive dyskinesia (TD) is a drug-induced movement disorder (DIMD) seen in patients taking dopamine-receptor blocking agents (DRBAs). Clinicians should regularly monitor patients with or at risk of developing DIMDs; however, telehealth visits during the COVID-19 pandemic presented several significant challenges related to screening and care of these patients. In this observational survey study, respondents compared in-person with video/telephone visits to determine the impact on the evaluation, diagnosis, and monitoring of patients with DIMDs.

Pharmacokinetic and Pharmacologic Characterization of the Dihydrotetrabenazine Isomers of Deutetrabenazine and Valbenazine.

Valbenazine and deutetrabenazine are vesicular monoamine transporter 2 (VMAT2) inhibitors approved for tardive dyskinesia. The clinical activity of valbenazine is primarily attributed to its only dihydrotetrabenazine (HTBZ) metabolite, [+]-α-HTBZ. Deutetrabenazine is a deuterated form of tetrabenazine and is metabolized to four deuterated HTBZ metabolites: [+]-α-deuHTBZ, [+]-β-deuHTBZ, [-]-α-deuHTBZ, and [-]-β-deuHTBZ.

Phenomenology, quality of life, and predictors of reversibility in patients with drug-induced movement disorders: a prospective study.

Background: Drug-induced movement disorders (DIMDs) form an important subgroup of secondary movement disorders, which despite conferring a significant iatrogenic burden, tend to be under-recognized and inappropriately managed.

Objective: We aimed to look into phenomenology, predictors of reversibility, and its impact on the quality of life of DIMD patients.

Methods: We conducted the study in the Department of Neurology at a tertiary-care centre in India.

Pharmacokinetics, safety and tolerability of valbenazine in Korean CYP2D6 normal and intermediate metabolizers.

Valbenazine is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for tardive dyskinesia treatment by the US Food and Drug Administration; its major active metabolite (NBI-98782) is a 45-fold more potent inhibitor of VMAT2 than the parent drug. This study aimed to evaluate the pharmacokinetics (PKs), safety, and tolerability and the effect of cytochrome P450 2D6 (CYP2D6) genotypes to the PKs after the administration of valbenazine in Korean participants. A randomized, double-blind, placebo-controlled, single- and multiple-dose study was conducted in healthy Korean male participants.

Dopamine partial agonists: a discrete class of antipsychotics.

Worldwide, there are now three marketed dopamine D2 partial agonists: aripiprazole, brexpiprazole and cariprazine. These three drugs share a number of properties other than their action at D2 receptors. Pharmacologically, they are 5HT2 antagonists and D3 and 5HT1A partial agonists but with little or no alpha-adrenergic, anticholinergic or antihistaminic activity.

Altered DNA methylation of CYP2E1 gene in schizophrenia patients with tardive dyskinesia.

Background: About 20-30% of patients with schizophrenia develop tardive dyskinesia (TD). Oxidative stress is one potential causes of TD. CYP2E1 is considered as an oxidative stress-related gene, however, no study has been reported on the DNA methylation levels of the CYP2E1 in schizophrenia or TD.