Clozapine and D1/D2 Antagonism in Extrapyramidal Functions

1992 ◽  
Vol 160 (S17) ◽  
pp. 34-37 ◽  
Author(s):  
Jes Gerlach ◽  
Lars Hansen
Keyword(s):  
Side Effects ◽  
Tardive Dyskinesia ◽  
Side Effect ◽  
Receptor Blockade ◽  
Biochemical Profile ◽  
Extrapyramidal Side Effects ◽  
Receptor Function ◽  
Extrapyramidal Side Effect ◽  
Extrapyramidal Syndromes

One of the main advantages of clozapine is that it rarely produces extrapyramidal syndromes and tardive dyskinesia. This advantage is linked to the atypical biochemical profile of clozapine, especially its combined and low blockade of D1 and D2 receptors. The level of D2 receptor blockade is too low to induce extrapyramidal side-effects, and D1 antagonists have a lower extrapyramidal side-effect potential than traditional D2 neuroleptics, especially with respect to dystonia. The combined and balanced D1/D2 receptor blockade may prevent the development of a dysbalance between D1/D2 receptor function (in favour of D1) which otherwise might lead to tardive dyskinesia.

Extrapyramidal Syndromes and New Antipsychotic Drugs: Findings in Patients and Non-human Primate Models

1996 ◽  
Vol 168 (S29) ◽  
pp. 32-39 ◽  
Author(s):  
Daniel E. Casey
Keyword(s):  
Side Effects ◽  
Side Effect ◽  
Antipsychotic Drugs ◽  
Side Effect Profile ◽  
Neuroleptic Drugs ◽  
Extrapyramidal Side Effects ◽  
Primary Mode ◽  
Neuroleptic Therapy ◽  
Extrapyramidal Syndromes ◽  
Human Primate

Since neuroleptic drugs were introduced in the 1950s they have become the primary mode of therapy for managing both acute and chronic psychoses. Although some antipsychotic drugs are free of disturbing extrapyramidal side-effects (EPS), most have a very narrow therapeutic/toxic index. Clozapine is the best example of an antipsychotic with a wide separation between antipsychotic actions and liability to EPS, but its side-effect profile of sedation, salivation, seizures, and agranulocytosis are factors that limit its use, and clearly indicate the need for further advancement in neuroleptic therapy.

Tardive Dyskinesia: A Concern for the Pediatrician

PEDIATRICS ◽  
1986 ◽  
Vol 77 (4) ◽  
pp. 553-556
Author(s):  
HARVEY S. SINGER
Keyword(s):  
Side Effects ◽  
Tardive Dyskinesia ◽  
Children And Adolescents ◽  
Behavior Disorders ◽  
Antipsychotic Drugs ◽  
Extrapyramidal Side Effects ◽  
Body Movements ◽  
Neuroleptic Therapy

Antipsychotic drugs, such as the phenothiazines (chlorpromazine, fluphenazine, thioridazine), butyrophenones (haloperiodol), and diphenylbutylpiperidines (pimozide) are used in children and adolescents to treat a variety of clinical entities including psychoses, tics, behavior disorders, and movement problems. Because virtually all of these drugs have a potential to affect body movements and posture, they have also been termed neuroleptics.1 Most physicians are aware of the more common acute extrapyramidal side effects of these drugs, such as oculogyria, pseudoparkinsonism, dystonia, and restlessness (akathisia). Despite the widespread use of neuroleptics, however, little is known about the long-term neurologic consequences of such treatment. Of particular concern, based originally on data in adults, is the risk of severe and persistent tardive dyskinesia developing in persons receiving neuroleptic therapy.

The Science of Antipsychotics: Mechanistic Insight

CNS Spectrums ◽  
2003 ◽  
Vol 8 (S2) ◽  
pp. 5-9 ◽  
Author(s):  
Carol A. Tamminga
Keyword(s):  
Side Effects ◽  
Tardive Dyskinesia ◽  
Side Effect ◽  
Negative Symptoms ◽  
New Drugs ◽  
Receptor Subtypes ◽  
Side Effect Profile ◽  
Cognitive Symptoms ◽  
Conventional Antipsychotics ◽  
New Antipsychotics

ABSTRACTWith the introduction of conventional antipsychotics in the 1950s, clinicians began to expect effective treatment of positive symptoms of schizophrenia. However, these drugs do not resolve negative and cognitive symptoms of schizophrenia and are also associated with serious side effects, including extrapyramidal side effects (EPS) and tardive dyskinesia. In 1989, clozapine was introduced and labeled the first new antipsychotic owing to its improved efficacy and side-effect profile. Clozapine proved effective in alleviating many of the positive, negative, and cognitive symptoms of schizophrenia, without causing inevitable EPS or tardive dyskinesia. Over the past decade, a number of different new antipsychotics have been developed. These drugs have an affinity for multiple dopamine-receptor subtypes as well as serotonin, norepinephrine, and glutamate receptors, allowing for better treatment outcomes. The antagonism of the 5-HT2A receptor may be responsible for improvement in negative symptoms and decrease in EPS. In addition to providing enhanced efficacy, the affinity of the new drugs for multiple receptors introduces new side effects not seen with the conventional agents, including weight gain. Each new antipsychotic has a unique receptor-binding profile that corresponds to its pharmacologic and side-effect profile. Understanding the differences in mechanisms of action of new antipsychotics will allow physicians to better choose treatment that meets the needs of each individual patient.

Applied monitoring for tardive dyskinesia and other extrapyramidal side effects

2012 ◽  
Vol 1 (7) ◽  
pp. 159-163 ◽  
Author(s):  
John E. Kalachnik
Keyword(s):  
Side Effects ◽  
Early Detection ◽  
Tardive Dyskinesia ◽  
Antipsychotic Drugs ◽  
Standard Of Care ◽  
Magic Bullet ◽  
Assessment Instruments ◽  
Extrapyramidal Side Effects ◽  
Antipsychotic Medications ◽  
Prevention Model

While the rate of tardive dyskinesia (TD) and other extrapyramidal side effects (EPSE) is lower with second generation antipsychotic medications compared to first generation antipsychotic medications, these side effects remain of clinical concern. This paper reviews the basis for the continued concern and the importance of secondary prevention, or early detection, within the primary-secondary-tertiary prevention model. The importance of standardized assessment instruments, education, and training is reviewed. Given the widespread use of antipsychotic drugs, the fact that antipsychotic drugs are the standard of care for several psychiatric conditions (with little indication that the magic bullet is on the immediate horizon to replace current antipsychotic drugs) applied monitoring and the early detection of TD and EPSE takes on added importance.

Prevalence of Extrapyramidal Side Effects in Patients Receiving Depot Antipsychotic Medication

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
B. Luft ◽  
E. Berent
Keyword(s):  
Side Effects ◽  
Tardive Dyskinesia ◽  
Antipsychotic Medication ◽  
Rating Scales ◽  
Involuntary Movement ◽  
Extrapyramidal Side Effects ◽  
Drug Induced ◽  
Adherence To Medication ◽  
Depot Antipsychotic ◽  
Long Acting

Introduction:Long-acting depot antipsychotic medication is associated with extrapyramidal side effects (EPS). This may reduce adherence to medication, and precipitate relapse (1). Clearly, EPS is a major drawback and early detection is essential. However, in an earlier review of patients’ medical notes, we identified only one patient with an examination that recorded the presence of EPS. Despite the fact that a number of rating scales are available. We proposed that the application of these rating scales, would allow us to improve the assessment of EPS.Method:All patients prescribed a depot antipsychotic or long-acting risperidone injection, were identified. the Barnes Akathisia Scale (2) was chosen to rate akathisia, a modified Simpson-Angus scale (3) was chosen to rate parkinsonism and the Abnormal Involuntary Movement Scale (4) was chosen to rate tardive dyskinesia.Results:A total of 43 patients were evaluated. 23 (53%) patients showed drug induced EPS. the total number of positive cases of akathisia was 12 (28%), and 10 (23%) patients were found to have tardive dyskinesia. 13 (30%) patients were found to have drug induced parkinsonism.Conclusions:Our screening programme has identified high rates of previously undiscovered drug induced EPS.

scholarly journals Antipsychotic-induced extrapyramidal side effects: A systematic review and meta-analysis of observational studies

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257129
Author(s):  
Tilahun Ali ◽  
Mekonnen Sisay ◽  
Mandaras Tariku ◽  
Abraham Nigussie Mekuria ◽  
Assefa Desalew
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Tardive Dyskinesia ◽  
Publication Bias ◽  
Psychotic Disorders ◽  
Meta Analysis ◽  
Extrapyramidal Side Effects ◽  
Bias Analysis ◽  
Pharmacological Management ◽  
Early Management

Background Antipsychotic agents are the basis for the pharmacological management of acute and chronic schizophrenia, bipolar disorders, mood disorders with psychotic feature, and other psychotic disorders. Antipsychotic medication use is frequently associated with unfavorable adverse effects such as extrapyramidal side effects (EPSEs). Hence, this systematic review and meta-analysis was aimed to determine the magnitude of antipsychotic-induced EPSEs. Method A literature search was conducted using legitimate databases, indexing services, and directories including PubMed/MEDLINE (Ovid®), EMBASE (Ovid®), google scholar and WorldCat to retrieve studies. Following screening and eligibility, the relevant data were extracted from the included studies using an Excel sheet and exported to STATA 15.0 software for analyses. The Random effects pooling model was used to analyze outcome measures at a 95% confidence interval. Besides, publication bias analysis was conducted. The protocol has been registered on PROSPERO with ID: CRD42020175168. Result In total, 15 original articles were included for the systematic review and meta-analysis. The pooled prevalence of antipsychotic-induced EPSEs among patient taking antipsychotic medications was 37% (95% CI: 18–55%, before sensitivity) and 31% (95% CI: 19–44%, after sensitivity). The prevalence of antipsychotic-induced parkinsonism, akathisia, and tardive dyskinesia was 20% (95% CI: 11–28%), 11% (95% CI: 6–17%), and 7% (95% CI: 4–9%), respectively. To confirm a small-study effect, Egger’s regression test accompanied by funnel plot asymmetry demonstrated that there was a sort of publication bias in studies reporting akathisia and tardive dyskinesia. Conclusion The prevalence of antipsychotic-induced EPSEs was considerably high. One in five and more than one in ten patients experienced parkinsonism and akathisia, respectively. Appropriate prevention and early management of these effects can enhance the net benefits of antipsychotics.

Dopamine Blockers (“Antipsychotics”)

2018 ◽  
pp. 101-126
Author(s):  
S. Nassir Ghaemi
Keyword(s):  
Metabolic Syndrome ◽  
Clinical Pharmacology ◽  
Weight Gain ◽  
Side Effects ◽  
Tardive Dyskinesia ◽  
Drug Class ◽  
Acute Mania ◽  
Psychotic Symptoms ◽  
Extrapyramidal Side Effects ◽  
Bipolar Illness

The drug class of dopamine blockers includes agents called antipsychotics. It consists of dopamine blockers, often with serotonin blockade. Dopamine blockers are agents used to treat psychotic symptoms such as delusions and hallucinations. These medications have been developed mostly for use in schizophrenia, but they always have been found to be effective in acute mania as well. For the latter reason, they have been used in bipolar illness as well. Several of these agents have been proven effective in the depressive phase of bipolar illness, not just the manic phase. Also, some of them have been shown to be effective in the depressive phase of unipolar mood illness. The clinical pharmacology of specific agents within each class of dopamine blockers, including efficacy and side effects, is explored. Specific phenomena surveyed include metabolic syndrome, weight gain, extrapyramidal side effects, Parkinsonism, akathisia, and tardive dyskinesia.

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