New insights into the mechanism of drug-induced dyskinesia

CNS Spectrums ◽  
2012 ◽  
Vol 18 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Anton J. M. Loonen ◽  
Svetlana A. Ivanova
Keyword(s):  
Antipsychotic Drugs ◽  
Term Treatment ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Drug Induced ◽  
Disease Research ◽  
Spiny Neurons ◽  
Long Term Treatment ◽  
Cortical Circuit

Dyskinesia is an extrapyramidal movement disorder characterized by involuntary, repetitive, irregular motions that affect the mouth and face and/or the limbs and trunk. Tardive dyskinesia (TD) is a well-known complication of long-term treatment with antipsychotic drugs. Dyskinesia is also induced with levodopa, a treatment for Parkinson's disease, and it occurs spontaneously as a symptom of Huntington's disease. Research on the pathogenesis of TD has focused on a dysfunction of either the dopaminergic or serotonergic system. However, recent evidence has suggested that we should focus on the possible damage of GABAergic medium spiny neurons (MSNs). MSNs are the first station in the cortico-striato-thalamo-cortical circuit that regulates the amplitude and velocity of movements. Two pathways can be distinguished in this circuit: a direct pathway, which increases movements (hyperkinesia), and an indirect pathway, which decreases movements (hypokinesia). Both pathways are activated by glutamatergic corticostriatal neurons. Here, we discuss some evidence that supports the hypothesis that indirect pathway MSNs are damaged in dyskinesia.

scholarly journals Accumbens D2-MSN hyperactivity drives behavioral supersensitivity

2020 ◽  
Author(s):  
Anna Kruyer ◽  
Jeffrey Parilla-Carerro ◽  
Courtney Powell ◽  
Lasse Brandt ◽  
Stefan Gutwinski ◽  
...  
Keyword(s):  
D2 Receptor ◽  
Treatment Resistance ◽  
Term Treatment ◽  
Antipsychotic Treatment ◽  
Medium Spiny Neurons ◽  
Therapeutic Approaches ◽  
Spiny Neurons ◽  
Long Term Treatment ◽  
Underlying Mechanisms

ABSTRACTAntipsychotic-induced behavioral supersensitivity is a problematic consequence of long-term treatment with antipsychotic drugs and is characterized by emergence of refractory symptoms and dyskinesias. The underlying mechanisms are unknown, and no rational approaches exist to prevent or reverse antipsychotic-induced supersensitivity. Here we describe major adaptations impacting populations of striatal medium spiny neurons (MSNs) during the development of behavioral supersensitivity and reveal a prominent role played by D2 receptor expressing MSNs. We show that enhanced D2-MSN activity underlies several symptoms spanning from psychostimulant sensitization, to antipsychotic treatment resistance and drug addiction. Our data warn against severe adverse events following antipsychotic treatment discontinuation and offer insight that may inform therapeutic approaches to overcome antipsychotic-induced supersensitivity.

scholarly journals Do antipsychotic drugs lose their efficacy for relapse prevention over time?

2017 ◽  
Vol 211 (3) ◽  
pp. 127-129 ◽  
Author(s):  
Stefan Leucht ◽  
John M. Davis
Keyword(s):  
Relapse Prevention ◽  
Antipsychotic Drugs ◽  
Meta Analysis ◽  
Term Treatment ◽  
First Episode ◽  
Brain Volume Loss ◽  
New Findings ◽  
Long Term Treatment ◽  
Long Term Follow Up

SummaryThere is a debate about long-term treatment of schizophrenia with antipsychotic drugs, with some experts suggesting that these drugs should be discontinued. In this issue, Takeuchi et al demonstrated by a meta-analysis of 11 trials that antipsychotic drugs maintained their efficacy for relapse prevention for 1 year, whereas patients on placebo kept getting worse. We consider these findings in the light of the current discussion about possible dose-related brain volume loss, supersensitivity psychosis, the high variability of results in long-term follow-up studies and recent approaches to discontinue antipsychotics in patients with a first-episode. The new findings speak in favour of continuing antipsychotics at the same dose, at least in patients whose condition is chronic, but the topic is complex.

scholarly journals Putative role of pharmacogenetics to elucidate the mechanism of tardive dyskinesia in schizophrenia

2019 ◽  
Vol 20 (17) ◽  
pp. 1199-1223 ◽  
Author(s):  
Anton JM Loonen ◽  
Bob Wilffert ◽  
Svetlana A Ivanova
Keyword(s):  
Oxidative Stress ◽  
Tardive Dyskinesia ◽  
Genetic Variants ◽  
Long Term Potentiation ◽  
Specific Gene ◽  
Medium Spiny Neurons ◽  
Spiny Neurons ◽  
Long Term Treatment

Identifying biomarkers which can be used as a diagnostic tool is a major objective of pharmacogenetic studies. Most mental and many neurological disorders have a compiled multifaceted nature, which may be the reason why this endeavor has hitherto not been very successful. This is also true for tardive dyskinesia (TD), an involuntary movement complication of long-term treatment with antipsychotic drugs. The observed associations of specific gene variants with the prevalence and severity of a disorder can also be applied to try to elucidate the pathogenesis of the condition. In this paper, this strategy is used by combining pharmacogenetic knowledge with theories on the possible role of a dysfunction of specific cellular elements of neostriatal parts of the (dorsal) extrapyramidal circuits: various glutamatergic terminals, medium spiny neurons, striatal interneurons and ascending monoaminergic fibers. A peculiar finding is that genetic variants which would be expected to increase the neostriatal dopamine concentration are not associated with the prevalence and severity of TD. Moreover, modifying the sensitivity to glutamatergic long-term potentiation (and excitotoxicity) shows a relationship with levodopa-induced dyskinesia, but not with TD. Contrasting this, TD is associated with genetic variants that modify vulnerability to oxidative stress. Reducing the oxidative stress burden of medium spiny neurons may also be the mechanism behind the protective influence of 5-HT2 receptor antagonists. It is probably worthwhile to discriminate between neostriatal matrix and striosomal compartments when studying the mechanism of TD and between orofacial and limb-truncal components in epidemiological studies.

Sumatriptan dose increase-induced acute angle closure glaucoma in chronic migraine sufferer

2021 ◽  
Vol 14 (2) ◽  
pp. e235880
Author(s):  
Sokratis Zormpas ◽  
Artemis Matsou ◽  
Diandra Monique Antunes ◽  
Chris Panos
Keyword(s):  
Term Treatment ◽  
Acute Angle ◽  
Angle Closure ◽  
Dose Increase ◽  
Drug Induced ◽  
Long Term Treatment ◽  
Acute Angle Closure ◽  
Acute Angle Closure Glaucoma

In this case study, we explore a case of bilateral acute angle closure (AAC) attack detected in a 52-year-old female patient with no other ophthalmic background or predisposition to angle closure, following an increase of her regular sumatriptan dose used for migraine relief. Even though the initial presentation was misinterpreted as migraine attack, it nevertheless alerted the treating physicians to immediate cessation of the drug, allowing for the pertinent ocular symptomatology to be unveiled. Drug-induced bilateral AAC is a rare occurrence and can lead to significant ocular morbidity if not detected and treated early. Clinicians of emergency care should be aware of this uncommon association, as prompt ophthalmology input is vital. Interestingly, although it would be anticipated that people prone to angle closure attack after sumatriptan intake would exhibit symptoms after initiation of the drug, our patient suffered an attack while on long-term treatment and following dose increase.

scholarly journals Metabolic side effects of antipsychotic drugs in individuals with schizophrenia during medium- to long-term treatment: protocol for a systematic review and network meta-analysis of randomized controlled trials

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Johannes Schneider-Thoma ◽  
Angelika Kapfhammer ◽  
Dongfang Wang ◽  
Irene Bighelli ◽  
Spyridon Siafis ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Antipsychotic Drugs ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Term Treatment ◽  
Controlled Trials ◽  
Metabolic Side Effects ◽  
Long Term Treatment

Abstract Background Antipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking. Methods We will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group’s Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework. Discussion This systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians. Systematic review registration PROSPERO CRD42020175414

scholarly journals Drug-Induced Psychosis after Long-Term Treatment with Levetiracetam

2004 ◽  
Vol 49 (12) ◽  
pp. 870-870 ◽  
Author(s):  
Kristina Bayerlein ◽  
Helge Frieling ◽  
Barabara Beyer ◽  
Johannes Kornhuber ◽  
Stefan Bleich
Keyword(s):  
Term Treatment ◽  
Drug Induced ◽  
Long Term Treatment ◽  
Drug Induced Psychosis
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