Antipsychotic-induced tardive dyskinesia: The role of glutamatergic system

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.

scholarly journals Genetic Polymorphisms of 5-HT Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia

2021 ◽  
Vol 11 (3) ◽  
pp. 181
Author(s):  
Diana Z. Paderina ◽  
Anastasiia S. Boiko ◽  
Ivan V. Pozhidaev ◽  
Anna V. Bocharova ◽  
Irina A. Mednova ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Metabolic Dysfunction ◽  
Nucleotide Polymorphisms ◽  
Antipsychotic Therapy ◽  
Drug Induced ◽  
Gene Encoding ◽  
Chi Square ◽  
Single Nucleotide ◽  
Hardy Weinberg Equilibrium

Background: Antipsychotic-induced metabolic syndrome (MetS) is a multifactorial disease with a genetic predisposition. Serotonin and its receptors are involved in antipsychotic-drug-induced metabolic disorders. The present study investigated the association of nine polymorphisms in the four 5-hydroxytryptamine receptor (HTR) genes HTR1A, HTR2A, HTR3A, and HTR2C and the gene encoding for the serotonin transporter SLC6A4 with MetS in patients with schizophrenia. Methods: A set of nine single-nucleotide polymorphisms of genes of the serotonergic system was investigated in a population of 475 patients from several Siberian regions (Russia) with a clinical diagnosis of schizophrenia. Genotyping was performed and the results were analyzed using chi-square tests. Results: Polymorphic variant rs521018 (HTR2C) was associated with higher body mass index in patients receiving long-term antipsychotic therapy, but not with drug-induced metabolic syndrome. Rs1150226 (HTR3A) was also associated but did not meet Hardy–Weinberg equilibrium. Conclusions: Our results indicate that allelic variants of HTR2C genes may have consequences on metabolic parameters. MetS may have too complex a mechanistic background to be studied without dissecting the syndrome into its individual (causal) components.

scholarly journals Tardive Dyskinesia in the Era of Typical and Atypical Antipsychotics. Part 2: Incidence and Management Strategies in Patients with Schizophrenia

2005 ◽  
Vol 50 (11) ◽  
pp. 703-714 ◽  
Author(s):  
Howard C Margolese ◽  
Guy Chouinard ◽  
Theodore T Kolivakis ◽  
Linda Beauclair ◽  
Robert Miller ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Tardive Dyskinesia ◽  
Atypical Antipsychotics ◽  
De Novo ◽  
Management Strategies ◽  
Antipsychotic Agents ◽  
Antipsychotic Treatment ◽  
Antipsychotic Therapy ◽  
Conventional Antipsychotic

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.

Antipsychotic-induced supersensitivity – A reappraisal

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.

Treatment of tardive dyskinesia

1978 ◽  
Vol 16 (14) ◽  
pp. 55-56
Keyword(s):  
Tardive Dyskinesia ◽  
Late Onset ◽  
Psychiatric Patients ◽  
Term Treatment ◽  
Neuroleptic Drugs ◽  
Abnormal Movements ◽  
Long Term Treatment ◽  
The Face ◽  
Schizophrenic Patients

Neuroleptic drugs cause many forms of extra-pyramidal syndromes. One of these, tardive dyskinesia,1 occurs only after the patient has been taking the drug for some time (‘tardive’ refers to the late onset). The movements are involuntary and repetitive usually involving the face and tongue, but they may also affect the limbs and trunk. Tongue protrusion, licking and smacking of the lips, sucking and chewing movements, grimacing, grunting, blinking and furrowing of the forehead have all been described and attributed to long-continued medication with neuroleptic drugs of the phenothiazine, butyrophenone and thioxanthene groups. The patient can inhibit the movements, but anxiety makes them worse. Many of these symptoms were noticed in schizophrenic patients before neuroleptic drugs were introduced2 and they can occur in otherwise normal untreated elderly people. Nevertheless it is generally accepted that in most cases tardive dyskinesia is an unwanted effect of neuroleptic medication. Despite suggestions to the contrary, the abnormal movements are not necessarily associated with high dosage of neuroleptic drugs or with pre-existing brain damage.3 4 Tardive dyskinesia has been reported in 3–6% of a mixed population of psychiatric patients5 and over half of a group of chronic schizophrenics on long-term treatment.4 The more careful the neurological examination, the greater the apparent incidence.

The management of tardive dyskinesia

1986 ◽  
Vol 24 (7) ◽  
pp. 27-28
Keyword(s):  
Tardive Dyskinesia ◽  
Antipsychotic Drugs ◽  
Disease Process ◽  
Neuroleptic Drug ◽  
Blocking Drug ◽  
Unwanted Effect ◽  
Difficult Condition ◽  
The Face ◽  
Schizophrenic Patients

Dyskinesias are involuntary movements usually of the face and tongue and sometimes of the limbs and trunk. Tardive (delayed) dyskinesia occurs in patients who have been taking an antipsychotic (neuroleptic) drug or, rarely, another central dopamine-receptor-blocking drug such as metoclopramide. It generally occurs only in those treated for longer than a year, although much shorter exposures have been implicated with the antipsychotics. A similar dyskinesia occurred in schizophrenic patients before antipsychotic drugs were introduced, and can occur in healthy untreated elderly people; risk factors include old age, brain damage1 and the schizophrenic disease process.2 Nevertheless, in most patients on an antipsychotic drug (whether psychotic or not), tardive dyskinesia is an unwanted effect of the drug. It occurs in 5–40% of patients on long-term antipsychotic medication.3–5 we discuss here advances in the management of this difficult condition since our last review.6

scholarly journals Serum Cortisol and DHEA-S Levels in Schizophrenic Patients with Different Response to Antipsychotic Therapy: Association with Psychopathology / Серумски Концентрации На Кортизол И DHEA-S Кал Пациенти Со Шизофренша Со Различен Одговор На Антипсихотичната Терапша Асоци.1Аци.1А Со Психопатологшата

PRILOZI ◽  
2015 ◽  
Vol 36 (1) ◽  
pp. 175-182 ◽  
Author(s):  
Zoja Babinkostova ◽  
Branislav Stefanovski ◽  
Danijela Janicevic-Ivanovska ◽  
Valentina Samardziska ◽  
Lila Stojanovska
Keyword(s):  
Elevated Serum ◽  
Serum Cortisol ◽  
Control Group ◽  
Antipsychotic Treatment ◽  
Healthy Controls ◽  
Symptom Scale ◽  
Antipsychotic Therapy ◽  
Schizophrenic Patients ◽  
Different Response ◽  
Age And Sex

Abstract Background: Previous studies suggested that alterations in serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia. Imbalance in serum cortisol and DHEA-S levels may be related to responsivity to antipsychotic treatment. Aim: To compare serum cortisol and DHEA-S levels between patients with schizophrenia and healthy controls and to evaluate their association with psychopathology in schizophrenic patients with different response to antipsychotic treatment. Material and Methods: This clinical prospective study included 60 patients with schizophrenia and 40 healthy age and sex matched controls. All patients experienced an acute exacerbation of the illness (PANSS: P1 and P3 ≥ 4). Clinical evaluation of patients was performed using the Positive and Negative Symptom Scale. A questionnaire for socio-demographic and clinical data collection was used. For the purposes of the study, the examined group was divided in two subgroups: responders and nonresponders. Serum cortisol and DHEA-S levels were measuredat baseline in all participants and after 3 and 6 weeks of the antipsychotic treatment in patients with schizophrenia. Results: Patients with schizophrenia had significantly higher serum cortisol and DHEA-S levels comparedwith control group. Responders had significantly higher serum cortisol and DHEA-S levels compared with nonresponders. Responders group had significant correlation between serum cortisol and PANSS positive scale score as well as between hostility and serum DHEA-S. Conclusion: Elevated serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia. Serum cortisol and DHEA-S are associated with psychopathology in schizophrenic patients with different response to antipsychotic therapy.

Pseudoakathisia in a patient with clotiapine abuse: Report of a case

2016 ◽  
Vol 33 (S1) ◽  
pp. S550-S550 ◽  
Author(s):  
P. Quandt ◽  
M.D.R. Cejas Méndez
Keyword(s):  
Rating Scale ◽  
Beta Blockers ◽  
Lower Limbs ◽  
Antipsychotic Treatment ◽  
Clinical Progression ◽  
Drug History ◽  
Competing Interest ◽  
Confusional States ◽  
Subjective Discomfort

IntroductionObjective symptoms of akathisia in the absence of subjective symptoms is known as pseudoakathisia, more often diagnosed in older patients with long-term antipsychotic treatment.ObjectiveTo describe a case of pseudoakathisia in a patient with clotiapine abuse.AimsPseudoakathisia management.MethodsX is a 47-year-old male with chronic insomnia treated with clotiapine 40 mg/day for four years. He admits abusive neuroleptic consumption in the past eight months (160 mg/day), without any psychiatric control for years. In recent months he has experienced different organic complications, requiring multiple hospitalizations. During psychiatric examinations due to confusional states, repeated lower limbs movements were objectified. X reported he presented these movements for at least six months, without complaints of inner restlessness feeling. Neurological examination showed normal DAT-SCAN result. Clinical progression was evaluated using BARS scale (Barnes Akathisia Rating Scale).ResultsFollowing the results of tests and statements of drug history, X was diagnosed with clotiapine-induced pseudoakathisia. Neuroleptic treatment was suspended, and clonazepam 6 mg/day and propranolol in ascending doses up to 80 mg/day were initiated. In subsequent evaluations, progressive decrease in movement intensity was observed. However, complete remission after four months from clotiapine suspension was not achieved.ConclusionsPseudoakathisia is a concept not well defined at this moment and different hypotheses about its nature are considered. It has been suggested that it is a form of delayed dyskinesia, or a clinical progression from akathisia, with acquired subjective discomfort tolerance. The most widely used treatment includes benzodiazepines, beta-blockers and anticholinergics, although their effectiveness is limited.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Increased Homotopic Connectivity in the Prefrontal Cortex Modulated by Olanzapine Predicts Therapeutic Efficacy in Patients with Schizophrenia

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Xiaoxiao Shan ◽  
Rongyuan Liao ◽  
Yangpan Ou ◽  
Yudan Ding ◽  
Feng Liu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Support Vector ◽  
Individual Treatment ◽  
Antipsychotic Treatment ◽  
Individual Response ◽  
Healthy Controls ◽  
Imaging Data ◽  
Antipsychotic Therapy ◽  
Olanzapine Treatment ◽  
Schizophrenic Patients

Background. Previous studies have revealed the abnormalities in homotopic connectivity in schizophrenia. However, the relationship of these deficits to antipsychotic treatment in schizophrenia remains unclear. This study explored the effects of antipsychotic therapy on brain homotopic connectivity and whether the homotopic connectivity of these regions might predict individual treatment response in schizophrenic patients. Methods. A total of 21 schizophrenic patients and 20 healthy controls were scanned by the resting-state functional magnetic resonance imaging. The patients received olanzapine treatment and were scanned at two time points. Voxel-mirrored homotopic connectivity (VMHC) and pattern classification techniques were applied to analyze the imaging data. Results. Schizophrenic patients presented significantly decreased VMHC in the temporal and inferior frontal gyri, medial prefrontal cortex (MPFC), and motor and low-level sensory processing regions (including the fusiform gyrus and cerebellum lobule VI) relative to healthy controls. The VMHC in the superior/middle MPFC was significantly increased in the patients after eight weeks of treatment. Support vector regression (SVR) analyses revealed that VMHC in the superior/middle MPFC at baseline can predict the symptomatic improvement of the positive and negative syndrome scale after eight weeks of treatment. Conclusions. This study demonstrated that olanzapine treatment may normalize decreased homotopic connectivity in the superior/middle MPFC in schizophrenic patients. The VMHC in the superior/middle MPFC may predict individual response for antipsychotic therapy. The findings of this study conduce to the comprehension of the therapy effects of antipsychotic medications on homotopic connectivity in schizophrenia.

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