Incidence of Tardive Dyskinesia and Tardive Dystonia in African Caribbean Patients on Long-Term Antipsychotic Treatment

Objective: Tardive dyskinesia (TD), the principal adverse effect of long-term conventional antipsychotic treatment, can be debilitating and, in many cases, persistent. We sought to explore the incidence and management of TD in the era of atypical antipsychotics because it remains an important iatrogenic adverse effect. Methods: We conducted a review of TD incidence and management literature from January 1, 1965, to January 31, 2004, using the terms tardive dyskinesia, management, therapy, neuroleptics, antipsychotics, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. Additional articles were obtained by searching the bibliographies of relevant references. We considered articles that contributed to the current understanding of both the incidence of TD with atypical antipsychotics and management strategies for TD. Results: The incidence of TD is significantly lower with atypical, compared with typical, antipsychotics, but cases of de novo TD have been identified. Evidence suggests that atypical antipsychotic therapy ameliorates long-standing TD. This paper outlines management strategies for TD in patients with schizophrenia. Conclusion: The literature supports the recommendation that atypical antipsychotics should be the first antipsychotics used in patients who have experienced TD as a result of treatment with conventional antipsychotic agents. The other management strategies discussed may prove useful in certain patients.

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Antipsychotic-induced tardive dyskinesia: The role of glutamatergic system

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.069 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S97-S97

Author(s):

A. Boiko ◽

S. Ivanova ◽

A. Semke

Keyword(s):

Tardive Dyskinesia ◽

Glutamate Transporter ◽

Antipsychotic Treatment ◽

Nucleotide Polymorphisms ◽

Antipsychotic Therapy ◽

Drug Induced ◽

Schizophrenic Patients ◽

Competing Interest

Tardive dyskinesia (TD) occurs in 20–25% of patients with long-term antipsychotic therapy. Abnormalities in glutamatergic transmission are considered one of the key components of the pathogenesis of drug-induced side effects. Glutamate acts as excitotoxin under certain conditions and in excessive concentrations.Aim is to study the concentration of glutamate and analysis of single nucleotide polymorphisms (SNP) in genes coding the glutamate transporter and NMDA-receptors in schizophrenic patients with TD and without it.The study group included 156 patients with schizophrenia receiving long-term antipsychotic treatment. Patients were divided into two groups: 63 patients with TD and 93 patients without it. Glutamate was determined in serum by spectrophotometric method. Determination of allelic variants of gene SLC1A2 (rs4354668) and GRIN2A (rs2650427, rs1969060) was performed by polymerase chain reaction in real-time.We found a significant (P < 0.05) increase of the concentration of glutamate in patients with TD. Significant (P < 0.05) reduction in frequency of genotype GG of GRIN2A (rs1969060) and TT of SLC1A2 (rs4354668) were found in patients with TD in comparison to group without TD. In the study of glutamate concentration depending on the genotype GRIN2A (rs1969060) and genotype SLC1A2 (rs4354668) we observed a statistically significant change: elevated levels of glutamic acid identified with the heterozygous genotype in patients.It is possible to suggest that reduction in frequency of these genotypes increases the risk of movement disorders due to the protective effect of these genotypes.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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P.3.050 Association analysis of dopamine D2 receptor genetic variants and tardive dyskinesia in schizophrenia following long-term antipsychotic treatment

European Neuropsychopharmacology ◽

10.1016/s0924-977x(05)80986-1 ◽

2005 ◽

Vol 15 ◽

pp. S476-S477

Keyword(s):

Tardive Dyskinesia ◽

Association Analysis ◽

Genetic Variants ◽

Dopamine D2 Receptor ◽

D2 Receptor ◽

Antipsychotic Treatment ◽

Dopamine D2

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Antipsychotic-induced supersensitivity – A reappraisal

Australian & New Zealand Journal of Psychiatry ◽

10.1177/00048674211025694 ◽

2021 ◽

pp. 000486742110256

Author(s):

William Lugg

Keyword(s):

Tardive Dyskinesia ◽

Significant Proportion ◽

Underlying Mechanism ◽

Antipsychotic Treatment ◽

Physiological Changes ◽

Antipsychotic Therapy ◽

Neurotransmitter Systems ◽

Potential Benefits ◽

Treatment Refractory ◽

Brain Pathways

Objectives: Tardive dyskinesia, psychotic relapse and treatment-refractory psychosis have long been associated. A common underlying mechanism involving antipsychotic-induced ‘supersensitivity’, albeit in different brain pathways, was proposed as early as 1978. This piece seeks to reappraise the concept and potential implications of antipsychotic-induced supersensitivity. Conclusions: Evidence increasingly suggests that chronic antipsychotic exposure induces neuroadaptive physiological changes in dopaminergic, and other, neurotransmitter systems that may render some individuals more vulnerable to psychotic relapse - including those receiving continuous antipsychotic treatment. It is possible that in treating every episode of psychosis with prolonged or indefinite antipsychotic therapy, we paradoxically increase the risk of psychotic relapse in a significant proportion of people. A greater appreciation of supersensitivity may allow us to optimise any potential benefits of antipsychotics while minimising the risk of inadvertent iatrogenic harms. More research is needed to improve our understanding of the underlying neurophysiology of supersensitivity and to better identify which individuals are most vulnerable to its development. It is time we paid more attention to the concept, emerging evidence and potential implications of antipsychotic-induced supersensitivity and, where appropriate, adjusted our practice accordingly.

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Onset and Resolution of Key Adverse Events in Valbenazine-Treated Patients with Tardive Dyskinesia: Pooled Analyses from Two Long-Term Clinical Trials

CNS Spectrums ◽

10.1017/s1092852920002394 ◽

2021 ◽

Vol 26 (2) ◽

pp. 151-151

Author(s):

Stephen R. Marder ◽

Jean-Pierre Lindenmayer ◽

Chirag Shah ◽

Tara Carmack ◽

Angel S. Angelov ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Tardive Dyskinesia ◽

Suicidal Behavior ◽

Prolonged Exposure ◽

First Occurrence ◽

Balance Disorder ◽

Clinical Interest ◽

Post Hoc

AbstractObjectiveTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).MethodsParticipants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.ResultsIn the pooled population (N=314), all AEs of potential clinical interest occurred in <10% of participants, with somnolence (9.6%), suicidal behavior/ideation (6.4%), and dizziness (5.7%) being the most common AEs. Mean time to first occurrence ranged from 36 days (akathisia [n=9]) to 224 days (parkinsonism [n=2]). By end of study (or last study visit), resolution of AEs was as follows: 100% (suicidal ideation/behavior, parkinsonism); >85% (somnolence/sedation, dizziness); >70% (akathisia, balance disorder, tremor).ConclusionsIn long-term clinical trials, the incidence of AEs of potential clinical interest was low (<10%) and most were resolved by end of treatment (>70–100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.FundingNeurocrine Biosciences, Inc.

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Real-world evaluation of patient characteristics and disease management in long-term valbenazine treatment in adults with Tardive dyskinesia

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2020.06.426 ◽

2020 ◽

Vol 79 ◽

pp. e117-e118

Author(s):

S. Siegert ◽

C. Yonan ◽

N. Longo ◽

H. Cratty ◽

M. Nicosia ◽

...

Keyword(s):

Disease Management ◽

Tardive Dyskinesia ◽

Real World ◽

Patient Characteristics

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Treatment-resistant schizophrenia characterised by dopamine supersensitivity psychosis and efficacy of asenapine

BMJ Case Reports ◽

10.1136/bcr-2021-242495 ◽

2021 ◽

Vol 14 (4) ◽

pp. e242495

Author(s):

Nagara Takao ◽

Toshiya Murai ◽

Hironobu Fujiwara

Keyword(s):

Animal Studies ◽

Significant Proportion ◽

Antipsychotic Treatment ◽

High Dose ◽

Receptor Density ◽

Treatment Resistant ◽

Psychomotor Activity ◽

Receptor Blockers ◽

Dopamine Supersensitivity

Dopamine supersensitivity psychosis (DSP) frequently arises with long-term antipsychotic treatment and accounts for a significant proportion of treatment-resistant schizophrenia. The mechanism underlying DSP is thought to be a compensatory increase in dopamine receptor density in the striatum caused by long-term antipsychotic treatment. Previous animal studies have reported that antipsychotics increase serotonin 5-HT2A receptor density in the striatum and that 5-HT2A receptor blockers suppress dopamine-sensitive psychomotor activity, which may be linked to the pathophysiology of DSP. In this paper, we describe a patient who was hospitalised with treatment-resistant schizophrenia. Following treatment with high-dose antipsychotic polypharmacy for 10 weeks, the patient experienced worsening of psychotic and extrapyramidal symptoms. The patient was then started on second-generation antipsychotic asenapine while other antipsychotics were tapered off, resulting in improvement of these symptoms. Retrospectively, we presumed that the high-dose antipsychotic polypharmacy caused DSP, which was effectively treated by the potent 5-HT2A receptor antagonism of asenapine.

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