-
Systematic Reviews Mar 2023There is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review...
BACKGROUND
There is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, conventional pairwise meta-analyses will not be sufficient to inform this choice. To fill this gap, we will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomized controlled trials (RCTs) to rank antipsychotics according to their effect on cognitive functioning.
METHODS
In our NMA, we will include RCTs in patients with schizophrenia or schizophrenia-like psychoses comparing one antipsychotic agent with another antipsychotic agent or placebo that measures cognitive function. We will include studies on patients of every age group, in any phase of illness (e.g., acute or stable, first episode or chronic schizophrenia, in- or outpatients) with an intervention time of at least 3 weeks. The primary outcome will be the composite score of cognitive functioning, preferentially measured with the test battery developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. The secondary outcomes include the seven cognitive domains that the composite score is composed of, as well as functioning and quality of life. Study selection and data extraction will be conducted by at least two independent reviewers. We will use the Cochrane Risk of Bias tool 2 to determine the risk of bias in studies, and we will evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). We will perform NMA using R (package netmeta). We will conduct subgroup and sensitivity analyses to explore the heterogeneity and assess the robustness of our findings.
DISCUSSION
This systematic review and network meta-analysis aims to inform evidence-based antipsychotic treatment choice for cognitive deficits in schizophrenia patients by analyzing existing RCTs on this subject. The results have the potential to support patients' and physicians' decision-making processes based on the latest available evidence.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022312483.
Topics: Humans; Infant, Newborn; Antipsychotic Agents; Network Meta-Analysis; Schizophrenia; Cognition; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 36959619
DOI: 10.1186/s13643-023-02213-5 -
Revista Espanola de Sanidad... 2020To describe the possible relationship between the use of antipsychotic drugs and the presence of metabolic syndrome. Other objectives are to list the main side effects... (Review)
Review
OBJECTIVES
To describe the possible relationship between the use of antipsychotic drugs and the presence of metabolic syndrome. Other objectives are to list the main side effects of antipsychotic treatment, and to determine if there is any pharmacological treatment that can contribute towards counteracting metabolic syndrome.
MATERIAL AND METHOD
A narrative bibliographic review was carried out of the following databases: PubMed, Cochrane, CINAHL, IBECS, LILACS and HealthCare. Preference in the selection process was given to clinical trials and systematic review articles or review articles and some articles that were considered relevant because of their content. The time period was limited to between January 2014 and November 2019. The languages were English and Spanish. Repeated articles and those that were not related to the objectives were rejected. The search criteria were: "antipsychotic AND metabolic syndrome"; "schizophrenia AND metabolic syndrome"; "bipolar disorder AND metabolic syndrome"; "metabolic syndrome AND suicide NOT disorder"; "metabolic syndrome AND prisons"; "metabolic syndrome AND prolactin".
RESULTS
24 articles were selected out of the 510 that were consulted. The relationship between atypical antipsychotics and metabolic syndrome was evident. Other anticholinergic, antidopaminergic effects, extrapyramidal syndromes, neuroleptic malignant syndrome, hypotension, arrhythmias, sedation, hypovitaminosis D, increased prolactin, sexual dysfunction, sleep disturbances, etc. are also highlighted. Pharmacological associations with other drugs were also found.
DISCUSSION
There is a relationship between the use of atypical antipsychotics and weight gain, lipid disorders, glucose and high blood pressure. There are some associated drugs that decrease some symptoms (ranitidine, topiramate, metformin, melatonin, modafinil). Patients taking this type of medication should be monitored and encouraged to lead healthy lifestyles.
Topics: Antipsychotic Agents; Humans; Mental Disorders; Metabolic Syndrome; Prisoners
PubMed: 32697278
DOI: 10.18176/resp.00014 -
The Cochrane Database of Systematic... Nov 2016Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, and valproate is one of these.
OBJECTIVES
To examine whether:1. valproate alone is an effective treatment for schizophrenia and schizoaffective psychoses; and2. valproate augmentation of antipsychotic medication is an effective treatment for the same illnesses.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (July 2002; February 2007; July 2012; March 04, 2016). We also contacted pharmaceutical companies and authors of relevant studies in order to identify further trials.
SELECTION CRITERIA
We included all randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of people with schizophrenia or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We independently inspected citations and, where possible, abstracts, ordered papers, and re-inspected and quality-assessed these. At least two review authors independently extracted data. We analysed dichotomous data using risk ratio (RR) and its 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their 95% CI. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table.
MAIN RESULTS
The 2012 update search identified 19 further relevant studies, most of which were from China. Thus the review currently includes 26 studies with a total of 2184 participants. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With the exception of two studies, the studies were small, the participants and personnel were not blinded (neither was outcome assessment), and most were short-term and incompletely reported.For this update we prespecified seven main outcomes of interest: clinical response (clinically significant response, aggression/agitation), leaving the study early (acceptability of treatment, overall tolerability), adverse events (sedation, weight gain) and quality of life.Adding valproate to antipsychotic treatment resulted in more clinically significant response than adding placebo to antipsychotic drugs (14 RCTs, n = 1049, RR 1.31, 95% CI 1.16 to 1.47, I = 12%, low-quality evidence). However, this effect was removed after excluding open RCTs in a sensitivity analysis. In terms of acceptability of treatment (measured by the number of participants leaving the study early due to any reason) valproate was just as acceptable as placebo (11 RCTs, n = 951, RR 0.76, 95% CI 0.47 to 1.24, I = 55%). Also overall tolerability (measured by the number of participants leaving the study early for adverse events) between valproate and placebo was similar (6 RCTs, n = 974, RR 1.33, 95% CI 0.90 to 1.97, I = 0).Participants in the valproate group were found to be less aggressive than the control group based on the Modified Overt Aggression Scale (3 RCTs, n = 186, MD -2.55, 95% CI -3.92 to -1.19, I = 82%, very low-quality evidence). Participants receiving valproate more frequently experienced sedation (8 RCTs, n = 770, RR 1.38, 95% CI 1.07 to 1.79, I = 0, low-quality evidence) but were no more likely to gain weight than those receiving placebo (4 RCTs, n = 427, RR 1.17, 95% CI 0.76 to 1.82, I = 0, low-quality evidence). No study reported on the important outcome of quality of life.
AUTHORS' CONCLUSIONS
There is limited evidence, based on a number of trials, that the augmentation of antipsychotics with valproate may be effective for overall clinical response, and also for specific symptoms, especially in terms of excitement and aggression. However, this evidence was entirely based on open RCTs. Moreover, valproate was associated with a number of adverse events among which sedation and dizziness appeared significantly more frequently than in the control groups. Further randomised studies which are blinded are necessary before any clear recommendation can be made. Ideally these would focus on people with schizophrenia and aggression, on those with treatment-resistant forms of the illness and on those with schizoaffective disorders.
Topics: Antimanic Agents; Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Valproic Acid
PubMed: 27884042
DOI: 10.1002/14651858.CD004028.pub4 -
Journal of Nippon Medical School =... Mar 2021The effectiveness and safety of antipsychotics have not been fully established in children and adolescents. Many antipsychotics approved for use in adults are prescribed... (Review)
Review
The effectiveness and safety of antipsychotics have not been fully established in children and adolescents. Many antipsychotics approved for use in adults are prescribed off-label to children and adolescents. We investigated the effectiveness and tolerability of antipsychotics for children and adolescents with schizophrenia and bipolar disorder. A literature review of the empirical evidence regarding the use of antipsychotics, particularly second-generation antipsychotics, in children and adolescents showed that these drugs were safe and effective for this population. Antipsychotics were similarly effective for treatment of schizophrenia and bipolar disorder in children and adolescents. When prescribing antipsychotics to this population, clinicians should consider adverse events and the discontinuation rate in treated patients. However, the current evidence shows a lack of consensus regarding the use of antipsychotics in children and adolescents.
Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Drug Tolerance; Female; Humans; Male; Safety; Schizophrenia, Childhood; Treatment Outcome; Withholding Treatment
PubMed: 32999174
DOI: 10.1272/jnms.JNMS.2021_88-108 -
CNS Drugs Mar 2016Schizophrenia is a heterogeneous, debilitating disorder characterized by three distinct sets of clinical features: positive symptoms, negative symptoms, and cognitive... (Review)
Review
Schizophrenia is a heterogeneous, debilitating disorder characterized by three distinct sets of clinical features: positive symptoms, negative symptoms, and cognitive deficits. Extant antipsychotic drugs have been most successful at treating the positive symptoms of patients with schizophrenia but have minimal therapeutic effects on negative symptoms and cognitive deficits, which are the symptoms that best predict the poor prognosis of these patients. Therefore, there has been a major effort towards identifying compounds that alleviate these symptoms. Oxytocin (OT) is a nonapeptide that regulates peripheral reproductive-relevant functions, and also acts as a neurotransmitter in the brain. Converging evidence from both preclinical and clinical research suggests that OT may have therapeutic efficacy for the positive symptoms, negative symptoms, and cognitive deficits of schizophrenia. In the majority of the small, randomized, placebo-controlled clinical trials conducted to date, OT has shown particular promise in its potential to treat the intractable negative symptoms and social cognitive deficits exhibited by most of the patients with this debilitating disorder. In this leading article, we summarize the clinical evidence relevant to (1) endogenous OT and schizophrenia, and (2) the putative therapeutic effects of OT on each of the three clinical domains.
Topics: Animals; Antipsychotic Agents; Brain; Cognition Disorders; Humans; Oxytocin; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology
PubMed: 26895254
DOI: 10.1007/s40263-016-0315-x -
Journal of the American Academy of... Jul 2024Early-onset psychosis (EOP) refers to the development of psychosis before the age of 18 years. We aimed to summarize, for the first time, the meta-analytical evidence in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Early-onset psychosis (EOP) refers to the development of psychosis before the age of 18 years. We aimed to summarize, for the first time, the meta-analytical evidence in the field of this vulnerable population and to provide evidence-based recommendations.
METHOD
We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant, pre-registered (PROSPERO: CRD42022350868) systematic review of several databases and registers to identify meta-analyses of studies conducted in EOP individuals to conduct an umbrella review. Literature search, screening, data extraction, and quality assessment were carried out independently. Results were narratively reported, clustered across core domains. Quality assessment was performed with the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool.
RESULTS
A total of 30 meta-analyses were included (373 individual studies, 25,983 participants, mean age 15.1 years, 38.3% female). Individuals with EOP showed more cognitive impairments compared with controls and individuals with adult/late-onset psychosis. Abnormalities were observed meta-analytically in neuroimaging markers but not in oxidative stress and inflammatory response markers. In all, 60.1% of EOP individuals had a poor prognosis. Clozapine was the antipsychotic with the highest efficacy for overall, positive, and negative symptoms. Tolerance to medication varied among the evaluated antipsychotics. The risk of discontinuation of antipsychotics for any reason or side effects was low or equal compared to placebo.
CONCLUSION
EOP is associated with cognitive impairment, involuntary admissions, and poor prognosis. Antipsychotics can be efficacious in EOP, but tolerability and safety need to be taken into consideration. Clozapine should be considered in EOP individuals who are resistant to 2 non-clozapine antipsychotics. Further meta-analytical research is needed on response to psychological interventions and other prognostic factors.
PLAIN LANGUAGE SUMMARY
This umbrella review summarized the meta-analytical knowledge from 30 meta-analyses on early-onset psychosis. Early-onset psychosis refers to the development of psychosis before the age of 18 years and is associated with cognitive impairment, hospitalization, and poor prognosis. Individuals with early-onset psychosis show more cognitive impairments and abnormalities compared with controls. Clozapine was the antipsychotic with the highest efficacy for positive, negative, and overall symptoms and should be considered in individuals with early-onset psychosis.
STUDY PREREGISTRATION INFORMATION
Early Onset Psychosis: Umbrella Review on Diagnosis, Prognosis and Treatment factors; https://www.crd.york.ac.uk/PROSPERO/; CRD42022350868.
Topics: Humans; Psychotic Disorders; Adolescent; Age of Onset; Antipsychotic Agents; Meta-Analysis as Topic; Cognitive Dysfunction
PubMed: 38280414
DOI: 10.1016/j.jaac.2023.10.016 -
International Journal of Molecular... Mar 2017Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications... (Review)
Review
Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and γ-aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well. The balance of excitation and inhibition has been associated with epigenetic modifications and thus can be analyzed in terms of a neurodevelopmental and neural circuitry perspective. Hence, a novel bio-psychosocial-behavioral model for the treatment of schizophrenia is needed to account for the non-dopaminergic systems involved in schizophrenia, rather than dopaminergic mechanisms. This model can be understood from the viewpoint of neurodevelopment and neural circuitry and should include the staging care, personalized care, preventive care, reducing the cognitive deficits, and reducing stigma. Thomas R. Insel proposed this as a goal for schizophrenia treatment to be achieved by 2030.
Topics: Animals; Antipsychotic Agents; Behavior Therapy; Brain; Humans; Neurogenesis; Neurotransmitter Agents; Schizophrenia
PubMed: 28358303
DOI: 10.3390/ijms18040734 -
Cancer Letters Feb 2022Psychotropic drugs can penetrate the blood-brain barrier and regulate the levels of neurotransmitters and neuromodulators such as γ-aminobutyric acid, glutamate,... (Review)
Review
Psychotropic drugs can penetrate the blood-brain barrier and regulate the levels of neurotransmitters and neuromodulators such as γ-aminobutyric acid, glutamate, serotonin, dopamine, and norepinephrine in the brain, and thus influence neuronal activity. Neuronal activity in the tumor microenvironment can promote the growth and expansion of glioma. There is increasing evidence that in addition to their use in the treatment of mental disorders, antipsychotic, antidepressant, and mood-stabilizing drugs have clinical potential for cancer therapy. These drugs have been shown to inhibit the malignant progression of glioma by targeting signaling pathways related to cell proliferation, apoptosis, or invasion/migration or by increasing the sensitivity of glioma cells to conventional chemotherapy or radiotherapy. In this review, we summarize findings from preclinical and clinical studies investigating the use of antipsychotics, antidepressants, and mood stabilizers in the treatment of various types of cancer, with a focus on glioma; and discuss their presumed antitumor mechanisms. The existing evidence indicates that psychotropic drugs with established pharmacologic and safety profiles can be repurposed as anticancer agents, thus providing new options for the treatment of glioma.
Topics: Antipsychotic Agents; Drug Repositioning; Glioma; Humans; Psychotropic Drugs
PubMed: 34923043
DOI: 10.1016/j.canlet.2021.12.014 -
Current Diabetes Reports Sep 2019The prevalence of diabetes is 2-3-fold higher in people with severe mental illness than the general population. There are concerns that antipsychotics increase the risk... (Review)
Review
PURPOSE OF REVIEW
The prevalence of diabetes is 2-3-fold higher in people with severe mental illness than the general population. There are concerns that antipsychotics increase the risk of diabetes. This review will examine the latest epidemiological studies linking antipsychotics and diabetes, as well as the mechanisms underlying the association and the clinical implications to minimise the impact of antipsychotics on metabolic health.
RECENT FINDINGS
Although there is an increased risk of diabetes in people with first-episode psychosis, the prevalence increases rapidly after antipsychotics are started. Antipsychotics likely increase the risk of diabetes through weight gain and directly by adversely affecting insulin sensitivity and secretion. It is important to implement measures to prevent diabetes, to screen for diabetes to ensure prompt diagnosis and to provide effective diabetes care. Further research is needed to understand how antipsychotics cause diabetes and to improve the clinical management of diabetes in people with severe mental illness.
Topics: Antipsychotic Agents; Diabetes Mellitus; Humans; Insulin Resistance; Psychotic Disorders; Weight Gain
PubMed: 31478094
DOI: 10.1007/s11892-019-1220-8 -
The Journal of Clinical Psychiatry May 2024Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated... (Review)
Review
Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Psychotic Disorders; Drug Tapering; Randomized Controlled Trials as Topic; Recurrence
PubMed: 38767930
DOI: 10.4088/JCP.24f15363