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CPT: Pharmacometrics & Systems... Sep 2017Schizophrenia is a common disease, characterized by progressive functional decline exacerbated by psychotic relapses that often result from a lack of full adherence to...
Schizophrenia is a common disease, characterized by progressive functional decline exacerbated by psychotic relapses that often result from a lack of full adherence to antipsychotic (APS) medication. Although atypical APS medications do not have clear therapeutic windows, as generally required for therapeutic drug monitoring (TDM), measuring APS plasma levels in the context of a population expected range at the point-of-care (POC) may provide valuable clinical insights for differentiating lack of efficacy from a lack of adherence to medication.
Topics: Antipsychotic Agents; Humans; Models, Biological; Point-of-Care Testing; Schizophrenia
PubMed: 28575540
DOI: 10.1002/psp4.12212 -
Tijdschrift Voor Psychiatrie 2022More than half of the patients suffering from a first psychotic episode withdraw from antipsychotic medication within the first...
More than half of the patients suffering from a first psychotic episode withdraw from antipsychotic medication within the first year of treatment. Shared decision making could enhance the therapeutic relationship and thus adherence. AIM: To describe an online decision aid for the selection of antipsychotic medication: the Personal Antipsychotic Choice Index (www.pakwijzer.nl). METHOD: Per effect and side effect, the 15 most commonly prescribed antipsychotics in the Netherlands have been ranked on the basis of data on the magnitude of a desired effect and the chance of a side effect, based on a systematic literature study. We assigned scores to antipsychotics for each desired and undesired effect and processed these scores in an algorithm. A personal ranking of antipsychotics is calculated based on the value that patients attach to these effects. RESULTS: These desired and undesired criteria used are rated in the PACindex: effectiveness concerning psychotic, depressive and cognitive symptoms, weight gain, sexual dysfunction, drowsiness, hypersomnia, extrapyramidal symptoms, anticholinergic adverse effects, hypersalivation, nausea, dizziness, energy loss, blunted affect/less need for companionship. High level evidence was available for ranking weight gain, sexual dysfunction, menstrual disorders, extrapyramidal symptoms and effectiveness on psychotic symptoms. We used lower level evidence ranking the remaining criteria. CONCLUSION: A ready applicable online choixe index for the use of an antipsychotic agent has been developed and put into use. The PACindex could be updated when new evidence of new antipsychotics became available..
Topics: Humans; Antipsychotic Agents; Psychotic Disorders; Mood Disorders; Problem Behavior; Disorders of Excessive Somnolence
PubMed: 36583278
DOI: No ID Found -
Journal of the American Academy of... May 1999To present a critical overview of the available evidence for the efficacy and safety of antipsychotic agents in children and adolescents and to identify knowledge gaps... (Review)
Review
OBJECTIVES
To present a critical overview of the available evidence for the efficacy and safety of antipsychotic agents in children and adolescents and to identify knowledge gaps and needs for further research. Data from adults that are relevant to children are discussed.
METHOD
Mainly reports of double-blind, placebo-controlled studies were reviewed.
RESULTS
In children and adolescents, antipsychotics are used to treat psychotic and a variety of nonpsychotic conditions. The amount of data based on well-designed, double-blind, placebo-controlled studies with satisfactory sample sizes in diagnostically homogeneous subjects is modest.
CONCLUSIONS
Currently available standard antipsychotics have a definite role in the treatment of children and adolescents. The use of these agents is limited mainly by tardive and withdrawal dyskinesias and, in some patients, by excessive sedation. The atypical antipsychotics should be critically assessed and compared with psychosocial interventions; if effective, the combination of both types of treatments should be evaluated.
Topics: Adolescent; Adolescent Psychiatry; Antipsychotic Agents; Child; Child Psychiatry; Clinical Trials as Topic; Humans; Psychotic Disorders; Research Design; Treatment Outcome
PubMed: 10230185
DOI: 10.1097/00004583-199905000-00015 -
Acta Pharmacologica Sinica Oct 2011Aripiprazole is an antipsychotic agent to treat schizophrenia, which acts through dopamine D(2) partial agonism, serotonin 5-HT(1A) partial agonism and 5-HT(2A)...
AIM
Aripiprazole is an antipsychotic agent to treat schizophrenia, which acts through dopamine D(2) partial agonism, serotonin 5-HT(1A) partial agonism and 5-HT(2A) antagonism. This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent, as well as its effects on lipoperoxidation.
METHODS
Open field and inhibitory avoidance tasks were used. Thirty min before performing the behavioral tasks, adult male CF-1 mice were administered aripiprazole (1, 3 or 10 mg/kg, ip) once for the acute treatment, or the same doses for 5 d for the subchronic treatment. Genotoxic effects were assessed using comet assay in the blood and brain tissues. Mutagenic effects were evaluated using bone marrow micronucleus test. Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS).
RESULTS
Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task. Acute treatment significantly increased the step-down latency for both the short- and long-term memory in the inhibitory avoidance task. Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain. Mutagenic effect was not detected in the acute and subchronic treatments. Nor TBARS levels in the liver were affected.
CONCLUSION
Aripiprazole improved memory, but could impair motor activities in mice. The drug increased DNA damage in blood, but did not show mutagenic effects, suggesting that it might affect long-term genomic stability.
Topics: Animals; Antipsychotic Agents; Aripiprazole; Avoidance Learning; Behavior, Animal; Brain; Comet Assay; Humans; Lipid Peroxidation; Male; Mice; Micronucleus Tests; Mutagens; Piperazines; Quinolones; Schizophrenia
PubMed: 21841809
DOI: 10.1038/aps.2011.77 -
International Journal of Molecular... Oct 2018Polypharmacology is nowadays considered an increasingly crucial aspect in discovering new drugs as a number of original single-target drugs have been performing far... (Review)
Review
Polypharmacology is nowadays considered an increasingly crucial aspect in discovering new drugs as a number of original single-target drugs have been performing far behind expectations during the last ten years. In this scenario, multi-target drugs are a promising approach against polygenic diseases with complex pathomechanisms such as schizophrenia. Indeed, second generation or atypical antipsychotics target a number of aminergic G protein-coupled receptors (GPCRs) simultaneously. Novel strategies in drug design and discovery against schizophrenia focus on targets beyond the dopaminergic hypothesis of the disease and even beyond the monoamine GPCRs. In particular these approaches concern proteins involved in glutamatergic and cholinergic neurotransmission, challenging the concept of antipsychotic activity without dopamine D₂ receptor involvement. Potentially interesting compounds include ligands interacting with glycine modulatory binding pocket on -methyl-d-aspartate (NMDA) receptors, positive allosteric modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, positive allosteric modulators of metabotropic glutamatergic receptors, agonists and positive allosteric modulators of α7 nicotinic receptors, as well as muscarinic receptor agonists. In this review we discuss classical and novel drug targets for schizophrenia, cover benefits and limitations of current strategies to design multi-target drugs and show examples of multi-target ligands as antipsychotics, including marketed drugs, substances in clinical trials, and other investigational compounds.
Topics: Animals; Antipsychotic Agents; Biomarkers; Drug Design; Drug Discovery; Humans; Ligands; Molecular Targeted Therapy; Schizophrenia
PubMed: 30309037
DOI: 10.3390/ijms19103105 -
The International Journal of... May 2023Schizophrenia is a disabling disorder that profoundly affects functioning and quality of life. While available antipsychotics have improved outcomes for patients with...
BACKGROUND
Schizophrenia is a disabling disorder that profoundly affects functioning and quality of life. While available antipsychotics have improved outcomes for patients with schizophrenia, they are relatively ineffective for negative and cognitive symptoms and are associated with a range of troublesome side effects. A significant unmet medical need for more effective and better-tolerated therapies remains.
METHODS
A roundtable consisting of 4 experts in the treatment of patients with schizophrenia convened to discuss the current treatment landscape, unmet needs from patient and societal perspectives, and the potential of emerging therapies with novel mechanisms of action (MOAs).
RESULTS
Key areas of unmet need include optimal implementation of available treatments, effective treatment of negative and cognitive symptoms, improvements in medication adherence, novel MOAs, avoidance of postsynaptic dopamine blockade-related adverse effects, and individualized approaches to treatment. With the possible exception of clozapine, all currently available antipsychotics primarily act by blocking dopamine D2 receptors. Agents with novel MOAs are urgently needed to effectively target the full range of symptoms in schizophrenia and facilitate an individualized treatment approach. Discussion focused on promising novel MOAs that have demonstrated potential in phase 2 and 3 trials include muscarinic receptor agonism, trace amine-associated receptor 1 agonism, serotonin receptor antagonism/inverse agonism, and glutamatergic modulation.
CONCLUSIONS
Results from early clinical trials of agents with novel MOAs are encouraging, particularly for muscarinic and trace amine-associated receptor 1 agonists. These agents offer renewed hope for meaningful improvement in the management of patients with schizophrenia.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Drug Inverse Agonism; Quality of Life; Clozapine
PubMed: 36932673
DOI: 10.1093/ijnp/pyad011 -
Neuropsychopharmacologia Hungarica : a... Jun 2021Dopamine D3 receptors belong to the dopamine D2-like receptor family, which also includes D2 and D4 receptors. These receptors have limited anatomical distribution and...
Dopamine D3 receptors belong to the dopamine D2-like receptor family, which also includes D2 and D4 receptors. These receptors have limited anatomical distribution and are mainly expressed in brain regions and pathways that typically mediate the actions of antipsychotic drugs and medication used against Parkinson's disease (PD). The development of cariprazine, the fi rst D2/D3 partial agonist with prominent affi nity and preferential activity at D3 receptors over other dopamine receptor subtypes was a landmark that provided new insights into the neurochemical and physiological functions of D3 receptors. Preclinical studies and clinical trials provided evidence for the clinical advantages of cariprazine in the treatment of schizophrenia and bipolar disorder. Cariprazine became the fi rst antipsychotic drug approved for the treatment of manic, mixed and depressive episodes in bipolar I disorder. Antagonism of D3 receptors may play a role in ameliorating symptoms of levodopa-induced dyskinesia and psychosis in PD patients treated with levodopa/carbidopa. Accordingly, D3 receptors constitute attractive targets for developing novel drugs for the improved treatment of different psychiatric and neurological disorders. (Neuropsychopharmacol Hung 2021; 23(2): 272-280).
Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Receptors, Dopamine D2; Receptors, Dopamine D3; Schizophrenia
PubMed: 34342419
DOI: No ID Found -
Revista Brasileira de Psiquiatria (Sao... Oct 2007Mood disorders are the most prevalent psychiatric disorders. Despite new insights and advances on the neurobiological basis and therapeutic approaches for bipolar... (Review)
Review
OBJECTIVE AND METHOD
Mood disorders are the most prevalent psychiatric disorders. Despite new insights and advances on the neurobiological basis and therapeutic approaches for bipolar disorders and recurrent depression, elevated prevalence of recurrence, persistent sub-syndromal symptoms and treatment resistance are challenging aspects and need to be urgently addressed. The objective of this literature review is to evaluate the current concepts of treatment resistance and refractoriness in mood disorders.
RESULTS
Genetic factors, misdiagnosis, use of inappropriate pharmacological approaches, non-compliance and biological/psychosocial stressors account for dysfunctions in mood regulation, thus increasing the prevalence of refractory mood disorders. Regarding available treatments, the use of effective doses during an adequate period followed by augmentation with a second and/or third agent, and finally switching to other agent are steps frequently necessary to optimize efficacy. However, in the treatment-resistant paradigm, drugs mimicking standard strategies, which target preferentially the monoaminergic system, can present reduced therapeutic effects. Thus, the search for new effective treatments for mood disorders is critical to decreasing the overall morbidity secondary to treatment resistance.
CONCLUSION
Emerging strategies targeting brain plasticity pathways or 'plasticity enhancers', including antiglutamatergic drugs, glucocorticoid receptor antagonists and neuropeptides, have been considered promising therapeutic options for difficult-to-treat mood disorders.
Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Drug Resistance; Drug Therapy, Combination; Humans; Mood Disorders; Neuronal Plasticity; Refractory Period, Psychological; Stress, Psychological
PubMed: 17713691
DOI: 10.1590/s1516-44462006005000058 -
Neuropsychopharmacologia Hungarica : a... Dec 2011Schizophrenia is a disorder of the brain with multicausality, chronicity, and various symptom manifestations within its course. The therapeutic interventions are... (Review)
Review
Schizophrenia is a disorder of the brain with multicausality, chronicity, and various symptom manifestations within its course. The therapeutic interventions are determined by the actual psychiatric condition characterized by the three main syndromes (positive, negative and cognitive symptoms). Antipsychotics are essential drugs in the therapy of schizophrenia and anxiolytics, antidepressants, antiepileptics are only adjuvants with temporary use. The previous studies show no results in the therapy of the cognitive symptoms, and the new antipsychotics improve the negative symptoms moderately. The reduction and prevention of positive symptoms is practicable with the established selection of antipsychotics. The antipsychotics are the basis therapy of schizophrenia so the knowledge of their pharmacology and clinical effects are essential for the clinicians. The typical-atypical classification is an outworn concept because there are pharmacological differences not only between the two groups but within the groups too. There are no significant differences among the antipsychotics with respect to efficiency but their side effect profiles are very different. The choice of a drug is influenced by the actual psychic and somatic conditions, comorbidity on one hand, and on the other hand by the pharmacodynamic and pharmacokinetic characteristics of the drugs. For example an antipsychotic with high affinity to dopamine receptors would be the good choice to eliminate the psychotic syndrome, but another one with low risk to cause extrapyramidal side effects would be the right choice for long term therapy. The next important question is the adjustment of the dose which is determined by the patient's somatic conditions and pharmacological factors, such as absorption, activity of metabolizing enzymes, function of the blood-brain barrier. In the lack of this property the clinicians can optimalize the dose only with the evaluation of the clinical response. The switch of a drug is required if it is ineffective or causes side effects. In these cases the clinicians have to be familiar with the pharmacological features of the two drugs and the condition of the patient. In the course of schizophrenia you can experience depressive, anxious, aggressive states that can be treated with adjuvants, but the risk/benefit ratio of these therapies should be considered. In addition to the drug administration the patients need psychological intervention and/or social therapy, however that cannot work without effectively tailored pharmacotherapy. Important viewpoints are the patient's well-being and the level of his functionality, that also depends on the right drug therapy. The aim of the author was to help clinicians in their decision making.
Topics: Acute Disease; Antipsychotic Agents; Drug Therapy, Combination; Humans; Schizophrenia
PubMed: 22184193
DOI: No ID Found -
Psychiatria Danubina Jun 2019Schizophrenia and bipolar disorders are serious psychiatric disorders with substantial health risks. Asenapine is a new second-generation antipsychotic, available as a... (Review)
Review
Schizophrenia and bipolar disorders are serious psychiatric disorders with substantial health risks. Asenapine is a new second-generation antipsychotic, available as a sublingual tablet, approved in Europe for the treatment of moderate-to-severe manic episodes in adults, and in US for manic or mixed episodes of bipolar I disorder in adults and adolescents. In this review, we searched the available literature to appreciate the role of asenapine in the management of psychiatric conditions such as bipolar disorders and schizophrenia and describe its mechanism of action, efficacy and tolerability. Asenapine has demonstrated efficacy in the management of bipolar disorders and schizophrenia, while a possible role in the management of borderline personality disorder and agitation needs further research. Asenapine has favourable side effects profile and combining with other pharmacological treatment in post-traumatic stress disorder has shown promising results. Asenapine fulfils important requirements of efficacy and tolerability as an anti-psychotic. These findings should support psychiatrists and pharmacists in the care of their patients while on asenapine.
Topics: Antipsychotic Agents; Bipolar Disorder; Borderline Personality Disorder; Dibenzocycloheptenes; Europe; Heterocyclic Compounds, 4 or More Rings; Humans; Schizophrenia; United States
PubMed: 31291219
DOI: 10.24869/psyd.2019.157