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CNS & Neurological Disorders Drug... 2023Cariprazine is a piperazine derivative approved by the USFDA in 2015 as a novel atypical antipsychotic drug (APD) to treat adults with schizophrenia and bipolar manic or... (Review)
Review
Cariprazine is a piperazine derivative approved by the USFDA in 2015 as a novel atypical antipsychotic drug (APD) to treat adults with schizophrenia and bipolar manic or mixed episodes in adults. However, due to the partial agonist action on dopamine D, D receptors, and serotonin 5-HT receptors as well as the antagonist effect on 5-HT, 5-HT, and H receptors, cariprazine differs pharmacologically from other APDs, both typical and atypical. Moreover, cariprazine also has a unique pharmacokinetic profile due to the formation of two clinically significant metabolites: desmethyl-cariprazine (DCAR) and desmethyl-cariprazine (DDCAR). They are eliminated by CYP3A4 and also, to a lesser extent, by CYP2D6. Here, we also review the effectiveness, safety, as well as current clinical update of cariprazine in bipolar I disorder associated with/without mania and schizophrenia through randomized and post-hoc analysis. The potential benefits of cariprazine as a promising therapeutic alternative in addressing major clinical requirements for better therapy of such severe neuropsychiatric conditions were demonstrated in this summarized review study.
Topics: Antipsychotic Agents; Serotonin
PubMed: 35331126
DOI: 10.2174/1871527321666220324121935 -
Clinical Pharmacokinetics Sep 1999Multicentre trials in patients with schizophrenia confirm that olanzapine is a novel antipsychotic agent with broad efficacy, eliciting a response in both the positive... (Review)
Review
Multicentre trials in patients with schizophrenia confirm that olanzapine is a novel antipsychotic agent with broad efficacy, eliciting a response in both the positive and negative symptoms of schizophrenia. Compared with traditional antipsychotic agents, olanzapine causes a lower incidence of extrapyramidal symptoms and minimal perturbation of prolactin levels. Generally, olanzapine is well tolerated. The pharmacokinetics of olanzapine are linear and dose-proportional within the approved dosage range. Its mean half-life in healthy individuals was 33 hours, ranging from 21 to 54 hours. The mean apparent plasma clearance was 26 L/h, ranging from 12 to 47 L/h. Smokers and men have a higher clearance of olanzapine than women and nonsmokers. After administering [14C]olanzapine, approximately 60% of the radioactivity was excreted in urine and 30% in faeces. Olanzapine is predominantly bound to albumin (90%) and alpha 1-acid glycoprotein (77%). Olanzapine is metabolised to its 10- and 4'-N-glucuronides, 4'-N-desmethylolanzapine [cytochrome P450 (CYP) 1A2] and olanzapine N-oxide (flavin mono-oxygenase 3). Metabolism to 2-hydroxymethylolanzapine via CYP2D6 is a minor pathway. The 10-N-glucuronide is the most abundant metabolite, but formation of 4'-N-desmethylolanzapine is correlated with the clearance of olanzapine. Olanzapine does not inhibit CYP isozymes. No clinically significant metabolic interactions were found between olanzapine and diazepam, alcohol (ethanol), imipramine, R/S-warfarin, aminophylline, biperiden, lithium or fluoxetine. Fluvoxamine, an inhibitor of CYP1A2, increases plasma concentrations of olanzapine; inducers of CYP1A2, including tobacco smoke and carbamazepine, decrease olanzapine concentrations. Orthostatic changes were observed when olanzapine and diazepam or alcohol were coadministered. Pharmacodynamic interactions occurred between olanzapine and alcohol, and olanzapine and imipramine, implying that patients should avoid operating hazardous equipment or driving an automobile while experiencing the short term effects of the combinations. Individual factors with the largest impact on olanzapine pharmacokinetics are gender and smoking status. The plasma clearance of olanzapine generally varies over a 4-fold range, but the variability in the clearance and concentration of olanzapine does not appear to be associated with the severity or duration of adverse effects or the degree of efficacy. Thus, dosage adjustments appear unnecessary for these individual factors. However, dosage modification should be considered for patients characterised by a combination of factors associated with decreased oxidative metabolism, for example, debilitated or elderly women who are nonsmokers.
Topics: Antipsychotic Agents; Benzodiazepines; Comorbidity; Drug Interactions; Female; Humans; Male; Multicenter Studies as Topic; Olanzapine; Pirenzepine; Racial Groups; Time Factors
PubMed: 10511917
DOI: 10.2165/00003088-199937030-00001 -
The New England Journal of Medicine Mar 1991
Review
Topics: Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Double-Blind Method; Humans; Schizophrenia
PubMed: 1671793
DOI: 10.1056/NEJM199103143241107 -
Expert Opinion on Drug Safety Feb 2021: Management of patients with acute agitation or aggressive behavior can pose a significant challenge to health-care providers in emergency departments. : This article... (Review)
Review
: Management of patients with acute agitation or aggressive behavior can pose a significant challenge to health-care providers in emergency departments. : This article provides a comprehensive review of the pharmacologic properties, efficacy, and safety profiles of select intramuscular (IM) sedative agents (i.e., antipsychotics, benzodiazepines, and ketamine) for rapid tranquilization. : Using antipsychotics and benzodiazepines - whether a single agent or combined - will have similar efficacy in producing sedation. But there are differences in the time to sedation depending on which agent is used. Based upon the available studies, droperidol (5-10 mg IM) and midazolam (5-10 mg IM) have the fastest onset of sedation when either is used as a single agent. When combination therapy is used, using midazolam with an antipsychotic agent, instead of lorazepam, may result in faster sedative effect. QT prolongation and torsades de pointes are uncommon adverse drug effects of antipsychotic administration. Ketamine is often reserved as a second-line agent when antipsychotics and benzodiazepines fail to produce the desired tranquilization. However, ketamine (5 mg/kg IM) is more frequently associated with airway compromise requiring endotracheal intubation. A low-dose of ketamine (2 mg/kg IM) may reduce the risk of airway compromise while providing adequate sedation.
Topics: Acute Disease; Aggression; Antipsychotic Agents; Benzodiazepines; Delirium; Emergency Service, Hospital; Excitatory Amino Acid Antagonists; Humans; Ketamine; Psychomotor Agitation
PubMed: 33327811
DOI: 10.1080/14740338.2021.1865911 -
The American Journal of Hospice &... Mar 2017Delirium is a palliative care emergency where patients experience changes in perception, awareness, and behavior. Common features include changes in the sleep-wake... (Review)
Review
Delirium is a palliative care emergency where patients experience changes in perception, awareness, and behavior. Common features include changes in the sleep-wake cycle, emotional lability, delusional thinking, and language and thought disorders. Delirium results from neurotransmitter imbalances involving several neurotransmitters such as dopamine, glutamate, norepinephrine, acetylcholine, gamma-aminobutyric acid, and serotonin. Untreated delirium causes significant morbidity and mortality. Nonpharmacologic and pharmacologic approaches treat delirium. Current pharmacologic management of delirium involves using agents such as haloperidol or second-generation antipsychotics. Third-generation atypical antipsychotic drugs have emerged as a potential choice for delirium management. Aripiprazole is a third-generation antipsychotic with a dopamine receptor-binding profile distinct from other second-generation antipsychotics. Aripiprazole acts as partial agonist at dopamine D and 5-hydroxytryptamine (5-HT) receptors, stabilizing the dopamine receptor leading to improvement in symptoms. The article reviews the pharmacology, pharmacodynamics, metabolism, and evidence of clinical efficacy for this new antipsychotic agent. This article explores possible roles in palliative care.
Topics: Alzheimer Disease; Antipsychotic Agents; Aripiprazole; Delirium; Humans; Psychotic Disorders
PubMed: 26589880
DOI: 10.1177/1049909115612800 -
The Journal of Medical Investigation :... Nov 2005It is obvious that DA is an important neurotransmitter in vivo. It is involved in a variety of physiological processes such as mental processes, motor function and... (Review)
Review
It is obvious that DA is an important neurotransmitter in vivo. It is involved in a variety of physiological processes such as mental processes, motor function and hormone regulation. In this context, it is quite understandable that a DA D2 receptor antagonist that inhibits the DA D2 receptor regardless of the state of activity of dopaminergic neurotransmission and inhibit the physiological function of DA can have a variety of adverse effects. In contrast to DA D2 antagonists, aripiprazole acts as an antagonist at the DA D2 receptor in the state of excessive dopaminergic neurotransmission, while it acts as an agonist at the DA D2 receptor in the state of low dopaminergic neurotransmission, and thus attempts to bring the state of dopaminergic neurotransmission to normal. This activity of aripiprazole to regulate dopaminergic neurotransmission is physiologically reasonable, and can be regarded as a stabilizing effect, for which aripiprazole is called a dopamine system stabilizer.
Topics: Animals; Antipsychotic Agents; Aripiprazole; Dopamine Agonists; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Humans; Molecular Structure; Piperazines; Quinolones; Receptors, Dopamine D2; Schizophrenia
PubMed: 16366516
DOI: 10.2152/jmi.52.284 -
Journal of the American Pharmacists... 2006To model the risk of long-term, adverse cardiovascular events after switching from one second-generation antipsychotic medication (SGA) to another in patients with... (Review)
Review
OBJECTIVE
To model the risk of long-term, adverse cardiovascular events after switching from one second-generation antipsychotic medication (SGA) to another in patients with schizophrenia or schizoaffective disorder.
DATA SOURCES
PubMed from 1985 to 2004 using the search terms atypical antipsychotics, obesity, weight, diabetes mellitus, dyslipidemia, hypercholesterolemia, lipids, second generation antipsychotics, antipsychotic agents, schizophrenia, metabolic syndrome, cardiovascular disease, and cardiovascular risk factors.
STUDY SELECTION
By the authors.
DATA EXTRACTION
By the authors.
DATA SYNTHESIS
The selection of an SGA for an individual patient should be primarily based upon its therapeutic effectiveness. However, when two medications are clinically equivalent with respect to treatment outcomes, other important consequences of the medication choice should be considered. Depending upon the type of SGA switch, the risk of an adverse cardiovascular event may be lower, as when olanzapine is switched to risperidone, or may increase by as much as 33%, as when risperidone is switched to olanzapine or clozapine.
CONCLUSION
Cardiovascular risk likely differs depending upon SGA choice, but limited data make it difficult to predict the metabolic changes associated with switching. Prospective controlled studies are needed to describe the cardiovascular consequences of switching among the antipsychotic agents so that evidence-based strategies can be developed for selection of the optimal SGA.
Topics: Antipsychotic Agents; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus; Humans; Lipids; Risk; Schizophrenia; Weight Gain
PubMed: 16913393
DOI: 10.1331/154434506778073574 -
American Journal of Health-system... Nov 2012Research supporting the "early-onset" theory of antipsychotic activity is reviewed, with an emphasis on psychometric assessment of early response to antipsychotic agents... (Review)
Review
PURPOSE
Research supporting the "early-onset" theory of antipsychotic activity is reviewed, with an emphasis on psychometric assessment of early response to antipsychotic agents as a tool for optimizing schizophrenia treatment outcomes.
SUMMARY
A growing body of evidence indicates that a poor response to antipsychotic therapy in the first weeks of schizophrenia treatment may justify a prompt switch to alternative medication in some cases. In placebo-controlled trials of both first- and second-generation antipsychotics, nonresponse at week 1 or 2, as determined with assessment instruments such as the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS), was found highly predictive of nonresponse at week 4 or later; however, an early favorable response to a particular antipsychotic agent does not appear to be a similarly strong predictor of continued responsiveness. While the available evidence indicates that the BPRS, PANSS, and other scoring tools can be useful in guiding schizophrenia treatment decisions, it also emphasizes the importance of patient-specific factors (e.g., severity of illness at diagnosis, age at symptom onset, premorbid adolescent functioning) as determinants of both initial and longer-term antipsychotic response.
CONCLUSION
The current evidence suggests that early nonresponse to antipsychotic treatment may predict subsequent non-response, though early response is not necessarily indicative of future response. If patients do not respond to treatment within the first two weeks of an acute exacerbation, clinicians (being cognizant of patient-specific factors) should consider switching antipsychotic agents, except in patients with first-episode psychosis, for whom a longer trial of the initially prescribed therapy appears to be appropriate.
Topics: Antipsychotic Agents; Decision Making; Disease Progression; Forecasting; Humans; Psychiatric Status Rating Scales; Schizophrenia; Time Factors; Treatment Outcome
PubMed: 23111671
DOI: 10.2146/ajhp110559 -
The Annals of Pharmacotherapy Nov 1997To review the pharmacology, pharmacokinetics, efficacy data, and adverse effects of olanzapine as a treatment for schizophrenia and to determine the advantages and... (Comparative Study)
Comparative Study Review
OBJECTIVE
To review the pharmacology, pharmacokinetics, efficacy data, and adverse effects of olanzapine as a treatment for schizophrenia and to determine the advantages and disadvantages of this atypical antipsychotic agent compared with currently marketed agents.
DATA SOURCES
A MEDLINE computer literature search was conducted to retrieve all English-language studies and review articles involving olanzapine published as of October 1, 1996. The manufacturer of the drug, Eli Lilly and Company, provided the clinical investigator's brochure and abstracts of unpublished Phase III clinical trials.
STUDY SELECTION
Animal studies evaluating the pharmacology of olanzapine were evaluated, as were all open-label and double-blind studies involving the evaluation of olanzapine for the treatment of patients with schizophrenia.
DATA EXTRACTION
All available clinical studies were reviewed and the interpretation of data for each study was influenced by the size of the study sample, the nature of the inclusion and exclusion criteria, and the data analysis techniques used.
DATA SYNTHESIS
Olanzapine is a thienobenzodiazepine analog with an in vitro receptor affinity profile similar to that of clozapine. Olanzapine exhibits linear kinetics over the dosage range studied and is extensively metabolized in humans. Clinical evaluations to date have shown olanzapine to be at least as efficacious as typical antipsychotic agents in the treatment of the acute phase of schizophrenia. The drug was well tolerated, with significantly fewer extrapyramidal adverse effects than haloperidol. Current data suggest that olanzapine may be more effective than haloperidol for the treatment of negative symptoms; moreover, preliminary data suggest that fewer relapses occur over the course of treatment in patients treated with olanzapine compared with those taking haloperidol.
CONCLUSIONS
The exact place of olanzapine in the therapy of psychotic patients remains unclear, as more data are needed to evaluate the long-term efficacy of this agent, its impact on negative symptoms, and its potential use in patients resistant to the standard agents. Despite limitations in the current database, olanzapine is a promising treatment option for patients with schizophrenia.
Topics: Aged; Animals; Antipsychotic Agents; Benzodiazepines; Child; Clinical Trials as Topic; Humans; Olanzapine; Pirenzepine; Schizophrenia
PubMed: 9391688
DOI: 10.1177/106002809703101110 -
Pharmacotherapy 1994Risperidone, a benzisoxazole derivative, is a novel antipsychotic agent that has an extremely strong binding affinity for serotonin 5-HT2 receptors, a strong binding... (Comparative Study)
Comparative Study Review
Risperidone, a benzisoxazole derivative, is a novel antipsychotic agent that has an extremely strong binding affinity for serotonin 5-HT2 receptors, a strong binding affinity for dopamine D2 receptors, and a high affinity for alpha 1- and alpha 2-adrenergic receptors and histamine H1 receptors. Its affinity for serotonin receptors is approximately 200 times greater than that of haloperidol, and its dopamine antagonistic potency is comparable to that of haloperidol. Its major metabolite, 9-hydroxyrisperidone, has similar pharmacologic activity, and thus the parent compound and metabolite form the active antipsychotic moiety. Clinical trials demonstrate that risperidone is an effective antipsychotic agent that improves negative as well as positive symptoms of schizophrenia. At recommended dosages, the frequency of extrapyramidal side effects is no greater than that seen with placebo. The drug appears to be an advance in the treatment of psychoses.
Topics: Antipsychotic Agents; Clinical Trials as Topic; Dopamine Antagonists; Double-Blind Method; Humans; Isoxazoles; Piperidines; Risperidone; Schizophrenia; Serotonin Antagonists; Time Factors
PubMed: 7524043
DOI: No ID Found