The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for Their Use as an Add-on Therapy in Schizophrenia

2020 ◽  
Vol 26 ◽  
Author(s):  
Felix-Martin Werner ◽  
Rafael Coveñas
Keyword(s):  
Clinical Trials ◽  
Maintenance Therapy ◽  
Antipsychotic Drug ◽  
Cognitive Functions ◽  
Antipsychotic Drugs ◽  
Psychotic Disorders ◽  
Therapeutic Effects ◽  
Treatment Resistant ◽  
Long Acting ◽  
Novel Antipsychotic

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders and, in this case, they can be treated with clozapine. In these patients and based on previous reviews on novel antipsychotic drugs, it is important to know whether an add-on therapy with new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objective: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of current available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole and lumateperone are up-dated. Published case reports of patients with treatmentresistant psychoses are also discussed. These patients were treated with clozapine but a high PANSS total score was observed. Only an add-on therapy with cariprazine improved the score and, above all, negative schizophrenic symptoms and cognitive functions. To ensure a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs may be a choice for a maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, are being investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether a combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are a safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by an add-on therapy with cognition enhancing drugs.

The effects of adding long-acting injectable antipsychotic drugs to clozapine on relapse and hospitalization in patients with treatment-resistant schizophrenia: a mirror-image retrospective study

2020 ◽  
Vol 36 (1) ◽  
pp. 30-33
Author(s):  
Ali Metehan Caliskan ◽  
Munir Karaaslan ◽  
Ikbal Inanli ◽  
Sila Caliskan ◽  
Mehmet Arslan ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Antipsychotic Drugs ◽  
Mirror Image ◽  
Treatment Resistant ◽  
Long Acting

scholarly journals Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Miquel Bioque ◽  
Eduard Parellada ◽  
Clemente García-Rizo ◽  
Sílvia Amoretti ◽  
Adriana Fortea ◽  
...  
Keyword(s):  
Side Effects ◽  
Psychotic Disorders ◽  
Rating Scale ◽  
Symptom Control ◽  
Combined Treatment ◽  
Mirror Image ◽  
Paliperidone Palmitate ◽  
Treatment Resistant ◽  
Image Study ◽  
Long Acting

Abstract Background: Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders. Methods: We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed. Results: Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004). Conclusions: This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients. Policy Significance Statement: Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination.

Are Atypical Antipsychotic Drugs also Atypical Antidepressants?

2001 ◽  
Vol 35 (5) ◽  
pp. 631-638 ◽  
Author(s):  
Gordon Parker ◽  
Gordon Parker ◽  
Gin Malhi
Keyword(s):  
Atypical Antipsychotic ◽  
Antipsychotic Drug ◽  
Antipsychotic Drugs ◽  
Case Series ◽  
Antidepressant Activity ◽  
Typical Antipsychotic ◽  
Treatment Resistant ◽  
Melancholic Depression ◽  
Atypical Antipsychotic Drug ◽  
Atypical Antipsychotic Drugs

Objective: To report a case series and review the psychopharmacology of the neuroleptic drugs to suggest that the atypical antipsychotic drugs may have an antidepressant action, at least for those patients with the melancholic subtype. Method: We note the literature suggesting that the older (or typical) antipsychotic drugs were established as having antidepressant activity, describe an open study of some two dozen patients with a treatment-resistant melancholic depression, describe rapid resolution of depression and augmentation benefits associated with commencing an atypical antipsychotic drug in a percentage of subjects, and then review relevant psychopharmacological studies to consider whether there is a rationale for use of antipsychotic drugs to treat depression. Results: Of some two dozen patients treated with an atypical antipsychotic drug, almost immediate improvement was noted in four patients, and evidence of augmentation benefit obtained in another three patients. Conclusions: Impressions from this case series are encouraging. However, as open clinical observational studies are problematic, controlled studies are required to establish whether the atypical antipsychotic drugs have a role in the management of certain expressions of depression, and, in particular, treatment-resistant melancholic depression.

Systematic Review of Gender Bias in the Clinical Trials of New Long-Acting Antipsychotic Drugs

2019 ◽  
Vol 39 (3) ◽  
pp. 264-272
Author(s):  
María Santos-Casado ◽  
Adela García-Avello
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Gender Bias ◽  
Antipsychotic Drugs ◽  
Long Acting

Cohort Analysis of Randomized Clinical Trials on long acting GLP-1 receptor agonists versus DPP4 inhibitors

2016 ◽  
Author(s):  
Thuy Pham ◽  
Mukunda Singh ◽  
Marvin Dao ◽  
Griselda Herrera ◽  
Katherine Asuncion
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Cohort Analysis ◽  
Receptor Agonists ◽  
Dpp4 Inhibitors ◽  
Long Acting

Current RNA-based Therapeutics in Clinical Trials

2019 ◽  
Vol 19 (3) ◽  
pp. 172-196 ◽  
Author(s):  
Ling-Yan Zhou ◽  
Zhou Qin ◽  
Yang-Hui Zhu ◽  
Zhi-Yao He ◽  
Ting Xu
Keyword(s):  
Clinical Trials ◽  
Rapid Development ◽  
Genetic Diseases ◽  
Three Dimensional ◽  
Therapeutic Effects ◽  
Messenger Rnas ◽  
Small Interfering Rnas ◽  
Rna Modifications ◽  
Guide Rna ◽  
Endogenous Genes

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

scholarly journals Applicability of somatic monitoring instructions in clinical practice guidelines on antipsychotic drug use

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jurriaan M. J. L. Brouwer ◽  
Erien Olde Hengel ◽  
Arne J. Risselada ◽  
Eric N. van Roon ◽  
Hans Mulder
Keyword(s):  
Clinical Practice ◽  
Drug Use ◽  
Adverse Effects ◽  
Antipsychotic Drug ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Frail Elderly ◽  
Antipsychotic Drugs ◽  
Electronic Database ◽  
Elderly Populations

Abstract Background Clinical practice guidelines (CPGs) recommend the monitoring of somatic parameters in patients treated with antipsychotic drugs in order to detect adverse effects. The objective of this study was to assess, in adult and (frail) elderly populations, the consistency and applicability of the somatic monitoring instructions recommended by established CPGs prior to and during antipsychotic drug use. Methods A search for national and international CPGs was performed by querying the electronic database PubMed and Google. Somatic monitoring instructions were assessed for adult and (frail) elderly populations separately. The applicability of somatic monitoring instructions was assessed using the Systematic Information for Monitoring (SIM) score. Somatic monitoring instructions were considered applicable when a minimum SIM score of 3 was reached. Results In total, 16 CPGs were included, with a total of 231 somatic monitoring instructions (mean: 14; range: 0–47). Of the somatic monitoring instructions, 87% were considered applicable, although critical values and how to respond to aberrant values were only present in 28 and 52% of the available instructions respectively. Only 1 CPG presented an instruction specifically for (frail) elderly populations. Conclusions We emphasize the need for a guideline with somatic monitoring instructions based on the SIM definition for both adult and (frail) elderly populations using antipsychotic drugs. In addition, CPGs should state that clear agreements should be made regarding who is responsible for interventions and somatic monitoring prior to and during antipsychotic drug use.

scholarly journals Characteristics of voluntary reporting of adverse drug events related to antipsychotics in Australia: 14-year analysis

2021 ◽  
Vol 12 ◽  
pp. 204209862110128
Author(s):  
Hanan Khalil ◽  
Dimi Hoppe ◽  
Nabil Ameen
Keyword(s):  
Adverse Event ◽  
Adverse Effects ◽  
Adverse Events ◽  
Neuroleptic Malignant Syndrome ◽  
Antipsychotic Drug ◽  
Antipsychotic Drugs ◽  
Common Adverse Event ◽  
Drug Misuse ◽  
Large Databases ◽  
Chi Squared

Background: Retrospective analyses of large databases of treated patients can provide useful links to the presence of drug misuse or rare and infrequent adverse effects, such as agranulocytosis, diabetic ketoacidosis or neuroleptic malignant syndrome. The aim of this study is to describe the adverse effects to antipsychotics reported in the Australian Database of Adverse Event Notifications (DAEN). Methods: Data were collected from the DAEN – a spontaneous reporting database. The database, which covered the period from January 2004 to December 2017, was obtained from the Therapeutic Goods Administration (TGA) website ( www.TGA.gov ). The drugs selected for this investigation are the following: aripiprazole, clozapine, olanzapine, paliperidone, risperidone, ziprasidone, quetiapine, haloperidol and pimozide. All data were analysed descriptively. Comparison of reporting and management of adverse events between adults (older than 20 years) and children (5–19 years) was undertaken using chi squared test, where p < 0.05 is significant. Results: A total of 7122 adverse events associated with the antipsychotics aripiprazole, clozapine, haloperidol, olanzapine, paliperidone, pimozide, quetiapine and risperidone were reported to the TGA between January 2004 and December 2017. On average, there were 2.6 adverse events reported for each case. The most common adverse event reported for antipsychotics was neuroleptic malignant syndrome. There were no significant differences in the number of co-medications, formulations, indications, therapeutic dose, hospital admission and overdose among the antipsychotics between paediatric and adult populations. However, there were significant differences between causality, death and the management of adverse events between adult and paediatric populations (5–19 years) ( p < 0.05, chi squared test). Conclusion: The antipsychotic drug associated with the highest adverse events in adults was clozapine, followed by olanzapine. The most common adverse event in adults, and reported with a number of antipsychotic drugs, was neuroleptic malignant syndrome. In children, the highest numbers of adverse events reported in the database were associated with risperidone, clozapine and olanzapine. Plain language summary Adverse events reported of antipsychotics Background: Retrospective analyses of large databases of treated patients can provide useful clues to the presence of drug misuse or rare and infrequent adverse effects associated with antipsychotics. The drugs selected for this investigation are the following: aripiprazole, clozapine, olanzapine, paliperidone, risperidone, ziprasidone, quetiapine, haloperidol and pimozide. Methods: All data were analysed descriptively and investigated for any associations between the variables collected. Comparison of reporting and management of adverse events between adults (older than 20 years) and children (5–19 years) was undertaken using chi squared test, where p < 0.05 is significant. Results: The antipsychotic drug associated with the highest adverse events was clozapine, followed by olanzapine. In children, the highest numbers of adverse events reported in the database were associated with risperidone, clozapine and olanzapine. The most common adverse event in adults, and reported with a number of antipsychotic drugs, was neuroleptic malignant syndrome. Conclusion: There were significant differences between causality, death and the management of adverse events between adult and paediatric populations (5–19 years).Keywords: Antipsychotics, adverse effects, adverse events, safety

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