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Schizophrenia Bulletin May 2022Weight gain is among the most important side-effects of antipsychotics. It is, however, unclear whether it is associated with antipsychotic doses. We aimed to fill this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Weight gain is among the most important side-effects of antipsychotics. It is, however, unclear whether it is associated with antipsychotic doses. We aimed to fill this gap with a dose-response meta-analysis.
METHODS
We searched multiple electronic databases (last update search June 2021) for all fixed-dose studies that investigated 16 second-generation antipsychotics and haloperidol in adults with acute exacerbation of schizophrenia or with negative symptoms. We estimated the dose-response curves by conducting random-effects dose-response meta-analyses. We used the restricted cubic spline to model the dose-response relationship. The primary outcome was mean weight gain in kg from baseline to endpoint, the secondary outcome was the number of patients with clinically important weight gain.
FINDINGS
Ninety-seven studies with 333 dose arms (36 326 participants) provided data for meta-analyses. Most studies were short-term with median duration of 6 weeks (range 4 to 26 weeks). In patients with acute exacerbation, amisulpride, aripiprazole, brexpiprazole, cariprazine, haloperidol, lumateperone, and lurasidone produced mild weight gain in comparison to placebo (mean difference at any dose≤1 kg), while more significant weight gain was observed by all other drugs. For most drugs, dose-response curves showed an initial dose-related increase in weight which plateaued at higher doses, while for others there was no plateau and some even had bell-shaped curves, meaning less weight gain to be associated with higher doses.
INTERPRETATION
Second-generation antipsychotics do not only differ in their propensity to produce weight gain, but also in the shapes of their dose-response curves. This information is important for dosing decisions in clinical practice.
Topics: Adult; Antipsychotic Agents; Haloperidol; Humans; Olanzapine; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 35137229
DOI: 10.1093/schbul/sbac001 -
British Journal of Anaesthesia Dec 1971
Topics: Benperidol; Dilatation; Hand; Humans; Preanesthetic Medication; Veins
PubMed: 5156314
DOI: 10.1093/bja/43.12.1202 -
Ugeskrift For Laeger Apr 2017
Topics: Aggression; Antipsychotic Agents; Drug Therapy, Combination; Haloperidol; Humans; Promethazine; Psychotic Disorders
PubMed: 28416057
DOI: No ID Found -
The American Journal of Psychiatry Mar 2017
Topics: Antipsychotic Agents; Anxiety Disorders; Dystonia; Female; Haloperidol; Humans; Pregnancy; Uterine Diseases
PubMed: 28245696
DOI: 10.1176/appi.ajp.2016.16070800 -
The Cochrane Database of Systematic... Apr 2005Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece, Italy, the Netherlands and the UK. Benperidol is a butyrophenone antipsychotic, with the highest neuroleptic potency in terms of D2 receptor blockade. Those taking it are therefore reputed to be at high risk of extrapyramidal side effects, but benperidol's unusual profile may render it valuable to subgroups of people with schizophrenia.
OBJECTIVES
To examine the clinical effects and safety of benperidol for those with schizophrenia and schizophrenia-like psychoses.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's register (November 2004) for this update.
SELECTION CRITERIA
We included all randomised controlled trials that compared benperidol with other treatments for people with schizophrenia, or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We reliably selected studies, quality rated them and extracted data. We independently extracted data but excluded data if loss to follow up was greater than 50%. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis.
MAIN RESULTS
The update yielded no further studies for inclusion in the review. We identified only one unpublished poorly randomised controlled trial (N=40, duration 30 days, comparison perphenazine). Although benperidol was inferior to perphenazine (1 RCT, N=40, global state no better or worse RR 8.0 CI 2.1 to 30, NNH 1.4 CI 1 to 2) poor reporting suggests that an overestimate of effect is likely. It was not possible to report other outcomes.
AUTHORS' CONCLUSIONS
Currently, there are insufficient data from randomised trials to assess the clinical effects of benperidol. This compound merits further research interest.
Topics: Antipsychotic Agents; Benperidol; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 15846648
DOI: 10.1002/14651858.CD003083.pub2 -
Seminars in Cancer Biology Jan 2021The recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer.... (Review)
Review
The recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer. FDA-approved antipsychotic drugs fluspirilene, penfluridol, and pimozide are clinically used for the treatment of psychotic disorders, primarily schizophrenia. These compounds, belong to diphenylbutylpiperidine class of antipsychotic drugs, are the potent inhibitors of dopamine D2 receptor and calcium channel. A correlation has been found that patients treated for schizophrenia have lower incidences of certain types of cancer, such as respiratory, prostate, and bladder cancers. These compounds have also been shown to inhibit cancer proliferation in a variety of cancer cells, including melanoma, lung carcinoma, breast cancer, pancreatic cancer, glioma, and prostate cancer, among others. Antipsychotic drugs induce apoptosis and suppress metastasis in in vitro and in vivo models through mechanisms involving p53, STAT3, STAT5, protein phosphatase 2A, cholesterol homeostasis, integrins, autophagy, USP1, wnt/β-catenin signaling, and DNA repair. Additionally, pre-clinical evidence suggests that penfluridol and pimozide act synergistically with existing chemotherapeutic agents, such as dasatinib, temozolomide, and cisplatin. Some studies have also reported that the cytotoxic activity of the antipsychotics is selective for dividing cells. Based on this growing body of evidence and the availability and previous FDA-approval of the drugs, the compounds appear to be promising anti-cancer agents.
Topics: Animals; Antineoplastic Agents; Antipsychotic Agents; Butyrophenones; Drug Discovery; Drug Repositioning; Humans; Neoplasms; Piperidines
PubMed: 31618686
DOI: 10.1016/j.semcancer.2019.10.007 -
Critical Care Medicine Aug 2021
Topics: Delirium; Haloperidol; Humans; Intensive Care Units
PubMed: 34261929
DOI: 10.1097/CCM.0000000000004995 -
Frontiers in Immunology 2020The spread of the novel human respiratory coronavirus (SARS-CoV-2) is a global public health emergency. There is no known successful treatment as of this time, and there... (Review)
Review
The spread of the novel human respiratory coronavirus (SARS-CoV-2) is a global public health emergency. There is no known successful treatment as of this time, and there is a need for medical options to mitigate this current epidemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and is primarily trophic for the lower and upper respiratory tract. A number of current studies on COVID-19 have demonstrated the substantial increase in pro-inflammatory factors in the lungs during infection. The virus is also documented in the central nervous system and, particularly in the brainstem, which plays a key role in respiratory and cardiovascular function. Currently, there are few antiviral approaches, and several alternative drugs are under investigation. Two of these are Idelalisib and Ebastine, already proposed as preventive strategies in airways and allergic diseases. The interesting and evolving potential of phosphoinositide 3-kinase δ (PI3Kδ) inhibitors, together with Ebastine, lies in their ability to suppress the release of pro-inflammatory cytokines, such as IL-1β, IL-8, IL-6, and TNF-α, by T cells. This may represent an optional therapeutic choice for COVID-19 to reduce inflammatory reactions and mortality, enabling patients to recover faster. This concise communication aims to provide new potential therapeutic targets capable of mitigating and alleviating SARS-CoV-2 pandemic infection.
Topics: Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antiviral Agents; Betacoronavirus; Butyrophenones; COVID-19; Class I Phosphatidylinositol 3-Kinases; Coronavirus Infections; Drug Repositioning; Humans; Inflammation; Interleukin-6; Molecular Targeted Therapy; Pandemics; Peptidyl-Dipeptidase A; Piperidines; Pneumonia, Viral; Purines; Quinazolinones; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32973818
DOI: 10.3389/fimmu.2020.02094 -
Pharmacological Research Aug 2023Schizophrenia (SCZ) is a severe psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive deficits. Current antipsychotic treatment in...
Schizophrenia (SCZ) is a severe psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive deficits. Current antipsychotic treatment in SCZ improves positive symptoms but has major side effects and little impact on negative symptoms and cognitive impairment. The pathoetiology of SCZ remains unclear, but is known to involve small GTPase signaling. Rho kinase, an effector of small GTPase Rho, is highly expressed in the brain and plays a major role in neurite elongation and neuronal architecture. This study used a touchscreen-based visual discrimination (VD) task to investigate the effects of Rho kinase inhibitors on cognitive impairment in a methamphetamine (METH)-treated male mouse model of SCZ. Systemic injection of the Rho kinase inhibitor fasudil dose-dependently ameliorated METH-induced VD impairment. Fasudil also significantly suppressed the increase in the number of c-Fos-positive cells in the infralimbic medial prefrontal cortex (infralimbic mPFC) and dorsomedial striatum (DMS) following METH treatment. Bilateral microinjections of Y-27632, another Rho kinase inhibitor, into the infralimbic mPFC or DMS significantly ameliorated METH-induced VD impairment. Two proteins downstream of Rho kinase, myosin phosphatase-targeting subunit 1 (MYPT1; Thr696) and myosin light chain kinase 2 (MLC2; Thr18/Ser19), exhibited increased phosphorylation in the infralimbic mPFC and DMS, respectively, after METH treatment, and fasudil inhibited these increases. Oral administration of haloperidol and fasudil ameliorated METH-induced VD impairment, while clozapine had little effect. Oral administration of haloperidol and clozapine suppressed METH-induced hyperactivity, but fasudil had no effect. These results suggest that METH activates Rho kinase in the infralimbic mPFC and DMS, which leads to cognitive impairment in male mice. Rho kinase inhibitors ameliorate METH-induced cognitive impairment, perhaps via the cortico-striatal circuit.
Topics: Animals; Male; Mice; Clozapine; Cognitive Dysfunction; Haloperidol; Methamphetamine; Monomeric GTP-Binding Proteins; rho-Associated Kinases; Schizophrenia; Protein Kinase Inhibitors
PubMed: 37390993
DOI: 10.1016/j.phrs.2023.106838 -
British Medical Journal Jun 1971
Topics: Haloperidol; Hiccup; Humans
PubMed: 5579203
DOI: 10.1136/bmj.2.5761.590-c