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Antipsychotic-Induced Weight Gain in Severe Mental Illness: Risk Factors and Special Considerations.Current Psychiatry Reports Nov 2023Weight gain is a disconcerting issue experienced by patients treated with antipsychotics (APs). This review summarizes current knowledge on the prevalence, etiology, and... (Review)
Review
PURPOSE OF REVIEW
Weight gain is a disconcerting issue experienced by patients treated with antipsychotics (APs). This review summarizes current knowledge on the prevalence, etiology, and risk factors for antipsychotic-induced weight gain (AIWG), and evidence for interventions, including special considerations.
RECENT FINDINGS
Predisposing risk factors for AIWG include lack of prior AP exposure, sex, and age. AP dose and duration of exposure are additional treatment-related factors that may contribute to this issue. Among current approaches to target AIWG, metformin has the most evidence to support its use, and this is increasingly reflected in clinical guidelines. While lifestyle approaches are recommended, cost-effectiveness and scalability represent limitations. More research is needed to identify newer treatment options and inform clinical recommendations for AIWG. Concerns around scope of practice in psychiatry to address AIWG and related comorbidities will require enhanced training opportunities and interdisciplinary collaborations, as well as updated position statements/practice guidelines emphasizing prevention.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Weight Gain; Mental Disorders; Risk Factors
PubMed: 37755655
DOI: 10.1007/s11920-023-01458-0 -
Current Neuropharmacology 2024Recent evidence suggests a possible relationship between the immune system and schizophrenia spectrum disorders (SSDs), as neuroinflammation appears to play a role in... (Review)
Review
Recent evidence suggests a possible relationship between the immune system and schizophrenia spectrum disorders (SSDs), as neuroinflammation appears to play a role in major psychiatric conditions. Neuroinflammation is as a broad concept representing a physiological protective response to infection or injury, but in some cases, especially if chronic, it may represent an expression of maladaptive processes, potentially driving to clinical dysfunction and neurodegeneration. Several studies are concurrently highlighting the importance of microglia, the resident immune cells of the central nervous system, in a huge number of neurodegenerative diseases, including multiple sclerosis, Alzheimer's and Parkinson's diseases, as well as SSDs. A more fundamental phenomenon of maladaptive coupling of microglia may contribute to the genesis of dysfunctional brain inflammation involved in SSDs, from the onset of their neurophenomenological evolution. Clozapine and other antipsychotic drugs seem to express a provable immunomodulant effect and a more specific action on microglia, while neuroactive steroids and nonsteroidal anti-inflammatory drugs may reduce some SSDs symptoms in add-on therapy. Given these theoretical premises, this article aims to summarize and interpret the available scientific evidence about psychotropic and anti-inflammatory drugs that could express an immunomodulant activity on microglia.
Topics: Humans; Schizophrenia; Clozapine; Antipsychotic Agents; Animals; Microglia; Immunomodulating Agents; Immunologic Factors; Neuroinflammatory Diseases
PubMed: 38031778
DOI: 10.2174/1570159X22666231128101725 -
Pediatric Clinics of North America Apr 2024Persons with autism spectrum disorder (ASD) may have other psychiatric conditions that warrant treatment. Symptoms may not be easy to discern from rigidity or... (Review)
Review
Persons with autism spectrum disorder (ASD) may have other psychiatric conditions that warrant treatment. Symptoms may not be easy to discern from rigidity or irritability that are sometimes considered to be constituent parts of ASD. Pathophysiology that involves hyperexcitable neurons and anomalous connectivity may provide justification for using psychopharmacologic agents, although nonmedical strategies may also be effective. Hyperactivity, irritability, and tantrums with or without aggression may be rational targets for psychopharmacological intervention. The best-studied drug class to date has been the second-generation antipsychotics targeting irritability.
Topics: Humans; Autism Spectrum Disorder; Psychopharmacology; Antipsychotic Agents; Aggression; Irritable Mood
PubMed: 38423721
DOI: 10.1016/j.pcl.2023.12.001 -
The Lancet. Psychiatry Jan 2024
Topics: Humans; Clozapine; Antipsychotic Agents
PubMed: 38101868
DOI: 10.1016/S2215-0366(23)00406-6 -
European Neuropsychopharmacology : the... Aug 2023In this paper, we will discuss the pharmacologic properties of antipsychotics, including those that are the same in structure and those that differentiate one from... (Review)
Review
In this paper, we will discuss the pharmacologic properties of antipsychotics, including those that are the same in structure and those that differentiate one from another. We will bring to you how differential pharmacologic properties can explain differential efficacy and differential tolerability. We will review how to use plasma drug levels and long-acting injectables to enhance compliance early in the illness, and to manage both forms of treatment resistance (pharmacokinetic and pharmacodynamic failures). Through inadequate pharmacokinetic processes (poor absorption, rapid metabolism, enzymatic polymorphisms, etc.), antipsychotic plasma levels do not reach sufficient concentration. Pharmacodynamic treatment failure (receptor binding and sensitivity, post-receptor effects, etc.) is the inability to provide a significant effect on psychotic symptoms despite therapeutic plasma levels. Long-Acting Injectable (LAI) antipsychotics employ technology that can provide a useful treatment tool in the armamentarium of a modern psychopharmacologist. The pharmacologic properties of antipsychotics differentiate one from another and can help explain differences in efficacy and tolerability. Utilizing plasma drug levels can enhance understanding of treatment failures and lead to specific patient management strategies for best outcomes. This kind of personalized approach to antipsychotic dosage would mean a big shift in the treatment of psychiatric patients.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Delayed-Action Preparations; Psychotic Disorders; Injections
PubMed: 37182458
DOI: 10.1016/j.euroneuro.2023.04.015 -
Schizophrenia Research Nov 2023Antipsychotic drug-induced myocarditis is a serious and potentially fatal adverse drug reaction characterized by inflammation of the heart muscle (myocardium) that... (Review)
Review
Antipsychotic drug-induced myocarditis is a serious and potentially fatal adverse drug reaction characterized by inflammation of the heart muscle (myocardium) that typically develops within the first month after commencing an antipsychotic drug. Although the precise mechanism of this severe adverse drug reaction is unknown, multiple theories have been proposed with varying levels of support from cellular or animal studies. We conducted a systematic review, in accordance with PRISMA guidelines, of published preclinical and clinical studies investigating the cellular mechanism by which antipsychotic drugs induce myocarditis. A literature search including all studies available before December 10, 2022, yielded 15 studies that met our inclusion criteria. Antipsychotics examined in the included studies included clozapine (n = 13), ziprasidone (n = 1), amisulpride (n = 1), haloperidol (n = 1), levomepromazine (n = 1), olanzapine (n = 1), and sertindole (n = 1). The evidence suggests several overlapping mechanistic cascades involving: (1) increased levels of catecholamines, (2) increased proinflammatory cytokines, (3) increased reactive oxygen species (ROS), (4) reduced antioxidant levels and activity, and (5) mitochondrial damage. Notable limitations such as, a focus on clozapine, sample heterogeneity, and use of supratherapeutic doses will need to be addressed in future studies. Discovery of the mechanism by which antipsychotic drugs induce myocarditis will allow the development of clinically-useful biomarkers to identify those patients at increased risk prior to drug exposure. The development or repurposing of therapeutics to prevent or treat drug-induced myocarditis will also be possible and this will enable increased and safe use of antipsychotics for those patients in need.
Topics: Animals; Humans; Antipsychotic Agents; Clozapine; Myocarditis; Schizophrenia; Drug-Related Side Effects and Adverse Reactions
PubMed: 37797362
DOI: 10.1016/j.schres.2023.09.039 -
Scientific Reports Aug 2023It has been reported that antipsychotic use is associated with lower bone mineral density and bone quality. We aimed to determine whether antipsychotic use is associated...
It has been reported that antipsychotic use is associated with lower bone mineral density and bone quality. We aimed to determine whether antipsychotic use is associated with fracture risk in a population-based sample of adults living in the Barwon Statistical Division, south-eastern Australia. In this case-control study, 1458 participants (51.8% women) with radiologically confirmed fracture between June 1st 2012 and May 31st 2013 (cases) were compared with 1795 participants (46.5% women) without fracture (controls) for the same time period. Medication use, medical history and lifestyle factors were documented by self-report. Multivariable binary logistic regression was used to explore associations between antipsychotic use and fracture following adjustment for possible confounders. In women, antipsychotic use was identified for 20 of 755 (2.6%) cases and 10 of 834 (1.2%) controls (p = 0.034) and in men, antipsychotic use was identified for 13 of 703 (1.8%) cases and 5 of 961 (0.5%) controls (p = 0.010). Following adjustments, antipsychotic use was associated with a 3.0-fold increased risk of fracture in men and a 2.3-fold increased risk of fracture in women. Patterns persisted after exclusion of participants with non-fragility fractures and self-reported schizophrenia. While future research exploring underlying mechanisms is needed, regular monitoring of bone health in antipsychotic users is suggested.
Topics: Adult; Male; Humans; Female; Case-Control Studies; Antipsychotic Agents; Fractures, Bone; Bone Density; Life Style
PubMed: 37608079
DOI: 10.1038/s41598-023-40762-w -
The Primary Care Companion For CNS... Mar 2024
Topics: Humans; Risperidone; Antipsychotic Agents; Drug-Related Side Effects and Adverse Reactions; Chemical and Drug Induced Liver Injury
PubMed: 38579255
DOI: 10.4088/PCC.23cr03658 -
The Medical Letter on Drugs and... Apr 2024
Topics: Humans; Bipolar Disorder; Antipsychotic Agents; Benzodiazepines
PubMed: 38576143
DOI: 10.58347/tml.2024.1699a -
The American Journal of Psychiatry Nov 2023
Topics: Humans; Antipsychotic Agents; Schizophrenia; Psychotic Disorders; Magnetic Resonance Imaging; Connectome; Nerve Net
PubMed: 37908095
DOI: 10.1176/appi.ajp.20230731