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Schizophrenia Research Dec 2023Antipsychotic-induced catatonia (AIC) and neuroleptic malignant syndrome (NMS) are life-threatening adverse reactions to antipsychotic medication. We conducted a...
OBJECTIVES
Antipsychotic-induced catatonia (AIC) and neuroleptic malignant syndrome (NMS) are life-threatening adverse reactions to antipsychotic medication. We conducted a systematic review of literature following the PRISMA statement guidelines to obtain a description of these syndromes (population, context of occurrence, antipsychotic agents implicated) and draw conclusions about their links.
METHODS
We searched Medline and Web of science databases from January 1951 to May 2019 (further restricted from 2000 to 2019) using search terms including "catatonia", "neuroleptic malignant syndrome" and "antipsychotic agents" for case reports, case series and analytic studies. After screening 4082 records, 410 full-text articles (describing 555 events) were assessed for eligibility. We included events of AIC and/or NMS according to Diagnostic and Statistical Manual (DSM) criteria and extracted data about patients' characteristics, context of occurrence, antipsychotic agent(s) involved and treatment outcomes.
RESULTS
We included 165 events (16 AIC, 129 NMS and 20 AIC + NMS) from 144 case reports and case series. The most reported diagnosis was schizophrenia. Comorbid pre-existing conditions such as central nervous system diseases and acute medical events were common. Most of the events (63.3 %) occurred during antipsychotic monotherapy. Second-generation antipsychotics (SGAs, 63.8 %) were overall more implicated than first-generation antipsychotics (FGAs, 36.2 %).
DISCUSSION
Our findings highlight that any antipsychotic medication, even SGA monotherapy prescribed at recommended dose, is at risk for these side effects. FGAs and polypharmacy seem to represent risk factors for malignant catatonia in AIC. The clinical overlap observed between AIC and NMS events in our review suggests a clinical continuum between catatonia and NMS.
Topics: Humans; Antipsychotic Agents; Neuroleptic Malignant Syndrome; Catatonia; Schizophrenia; Treatment Outcome
PubMed: 37599139
DOI: 10.1016/j.schres.2023.08.003 -
Acta Psychiatrica Scandinavica Aug 2023Use of antipsychotic drugs, especially second-generation agents, has been suggested to cause acute pancreatitis in multiple case reports; however, such an association...
INTRODUCTION
Use of antipsychotic drugs, especially second-generation agents, has been suggested to cause acute pancreatitis in multiple case reports; however, such an association has not been corroborated by larger studies. This study examined the association of antipsychotic drugs with risk of acute pancreatitis.
METHODS
Nationwide case-control study, based on data from several Swedish registers and including all 52,006 cases of acute pancreatitis diagnosed in Sweden between 2006 and 2019 (with up to 10 controls per case; n = 518,081). Conditional logistic regression models were used to calculate odds ratios (ORs) in current and past users of first-generation and second-generation antipsychotic drugs (dispensed prescription <91 and ≥91 days of the index date, respectively) compared with never users of such drugs.
RESULTS
In the crude model, first-generation and second-generation antipsychotic drugs were associated with increased risk of acute pancreatitis, with slightly higher ORs for past use (1.58 [95% confidence interval 1.48-1.69] and 1.39 [1.29-1.49], respectively) than for current use (1.34 [1.21-1.48] and 1.24 [1.15-1.34], respectively). The ORs were largely attenuated in the multivariable model-which included, among others, alcohol abuse and the Charlson comorbidity index-up to the point where only a statistically significant association remained for past use of first-generation agents (OR 1.18 [1.10-1.26]).
CONCLUSION
There was no clear association between use of antipsychotic drugs and risk of acute pancreatitis in this very large case-control study, indicating that previous case report data are most likely explained by confounding.
Topics: Humans; Pancreatitis; Case-Control Studies; Risk Factors; Antipsychotic Agents; Acute Disease
PubMed: 37100434
DOI: 10.1111/acps.13561 -
Psychopharmacology Bulletin Apr 2024Clozapine, amongst antipsychotics, has a unique composite mode of action that might translate into an expanded therapeutic potential on clinical grounds. Sorely,... (Review)
Review
Clozapine, amongst antipsychotics, has a unique composite mode of action that might translate into an expanded therapeutic potential on clinical grounds. Sorely, clozapine remains underutilized.
Topics: Humans; Clozapine; Schizophrenia; Dyskinesia, Drug-Induced; Antipsychotic Agents
PubMed: 38601835
DOI: No ID Found -
Journal of the American Medical... Oct 2023
Topics: United States; Humans; Antipsychotic Agents; Centers for Medicare and Medicaid Services, U.S.; Nursing Homes; Skilled Nursing Facilities
PubMed: 37775205
DOI: 10.1016/j.jamda.2023.08.014 -
Journal of Managed Care & Specialty... Jul 2024Antipsychotic switching is frequent in schizophrenia and is associated with poor clinical outcomes, increased health care resource utilization (HCRU), and increased... (Observational Study)
Observational Study
Reasons for switching oral antipsychotic medications and related patterns of care and costs in patients with schizophrenia initiating monotherapy treatment: Claims-linked chart study.
BACKGROUND
Antipsychotic switching is frequent in schizophrenia and is associated with poor clinical outcomes, increased health care resource utilization (HCRU), and increased health care costs. Research describing the reasons for antipsychotic switching in patients with schizophrenia and the associated impacts on HCRU and costs is limited.
OBJECTIVE
To explore the reasons for oral antipsychotic medication (OAM) switching and describe HCRU and costs associated with OAM switching, stratified by reasons for switching, in patients with commercial or Medicare Advantage insurance in the United States.
METHODS
This retrospective observational study used medical and pharmacy claims from the Optum Research Database linked to patient medical chart data. Adults with a diagnosis of schizophrenia who initiated OAM monotherapy between January 1, 2015, and June 30, 2021, and switched from their initial OAM monotherapy to a second one were included. Reasons for OAM switching were recorded from medical charts abstracted between 4 months preceding and 2 months following the patient's switch date. HCRU and costs incurred up to 3 months before and 3 months after the OAM switch were stratified and compared by reasons for switching among individuals who switched OAM monotherapy.
RESULTS
Among 134 patients with valid, abstracted charts, the 2 most common reasons for switching were lack of efficacy (57.5% of switches) and at least 1 tolerability issue (41.8%). Mutually exclusive categories of switching reasons included lack of efficacy and no tolerability issues (56/134; 41.8%), tolerability and no efficacy issues (35/134; 26.1%), lack of efficacy and tolerability issues (21/134; 15.7%), and other or unknown (22/134; 16.4%). All-cause and schizophrenia-related HCRU and costs in any health services category did not appear to differ across the reason-for-switching cohorts, with costs for inpatient stays accounting for greater than half of the total costs, regardless of switching reason.
CONCLUSIONS
These findings provide insight on patient experiences that contribute to OAM switching, with nearly half of patients switching because of lack of efficacy, more than one-fourth because of tolerability issues, and an additional one-sixth for reasons of both efficacy and tolerability. Health care providers should address patients' expectations regarding OAM effectiveness, symptom resolution, and side effect tolerability at treatment initiation to minimize switching before the medication has reached peak effectiveness. Prescribing access to a broad selection of antipsychotics with different side effect profiles may help physicians better match treatment to individual patients, fostering greater acceptance of therapy, increased medication adherence, and better long-term outcomes.
Topics: Humans; Schizophrenia; Antipsychotic Agents; Male; Female; Retrospective Studies; Adult; Middle Aged; Administration, Oral; United States; Drug Substitution; Health Care Costs; Patient Acceptance of Health Care; Aged; Insurance Claim Review; Young Adult
PubMed: 38717043
DOI: 10.18553/jmcp.2024.23319 -
American Journal of Therapeutics
Topics: Humans; Male; Middle Aged; Antipsychotic Agents; Clozapine; Creatine Kinase; Muscular Diseases; Schizophrenia
PubMed: 35703199
DOI: 10.1097/MJT.0000000000001525 -
FP Essentials Nov 2023Dementia management requires individualized patient encounters that focus on education and realistic expectations. Numerous vitamins and supplements are promoted for...
Dementia management requires individualized patient encounters that focus on education and realistic expectations. Numerous vitamins and supplements are promoted for memory enhancement, but they lack evidence to support their use. Nonpharmacotherapy should be used through all stages of dementia. Common initial pharmacotherapy includes cholinesterase inhibitors and memantine, with use guided by dementia type, tolerability, patient goals, and disease stage. Assessment of benefit should incorporate caregiver input, functional improvements, behavioral symptoms, and tolerability. Management length is individualized. When a drug is discontinued, physicians should evaluate the patient for early worsening of cognitive or functional symptoms. Newer treatments, such as aducanumab, can reduce beta-amyloid plaques, but evidence for cognitive improvements is lacking; these treatments also are expensive and patient access is limited, resulting in barriers to widespread use. As dementia progresses, patients often develop behavioral and psychological symptoms, which are challenging for patients and caregivers. Nonpharmacotherapy is the first-line treatment for behavioral and psychological symptoms of dementia. Use of antipsychotics and benzodiazepines should be limited unless symptoms are placing the patient or others in imminent danger. Pharmacotherapy for these symptoms should be individualized, often requiring trials of various therapeutic options.
Topics: Humans; Dementia; Antipsychotic Agents; Memantine; Cholinesterase Inhibitors; Caregivers
PubMed: 37976171
DOI: No ID Found -
Prague Medical Report 2024Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder,... (Review)
Review
Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder, and related psychiatric conditions. The plasma concentration of antipsychotic drugs is a valid measure of the drug at its primary target structure in the brain, and therefore determines the efficacy and safety of these drugs. However, despite the well-known high variability in pharmacokinetics of these substances, psychiatric medication is usually administered in uniform dosage schedules. Therapeutic drug monitoring (TDM), as the specific method that can help personalised medicine in dose adjustment according to the characteristics of the individual patient, minimizing the risk of toxicity, monitoring adherence, and increasing cost-effectiveness in the treatment, thus seems to be an elegant tool to solve this problem. Non-response to therapeutic doses, uncertain adherence to medication, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM of SGAs. This review aims to summarize an overview of the current knowledge and evidence of the possibilities to tailor the dosage of selected SGAs using TDM, including the necessary pharmacokinetic parameters for personalised pharmacotherapy.
Topics: Humans; Drug Monitoring; Antipsychotic Agents; Schizophrenia
PubMed: 38761044
DOI: 10.14712/23362936.2024.10 -
Antipsychotic-induced epigenomic reorganization in frontal cortex of individuals with schizophrenia.ELife Apr 2024Genome-wide association studies have revealed >270 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the...
Genome-wide association studies have revealed >270 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the molecular determinants behind this psychiatric condition. Epigenetic marks such as post-translational histone modifications remain largely plastic during development and adulthood, allowing a dynamic impact of environmental factors, including antipsychotic medications, on access to genes and regulatory elements. However, few studies so far have profiled cell-specific genome-wide histone modifications in postmortem brain samples from schizophrenia subjects, or the effect of antipsychotic treatment on such epigenetic marks. Here, we conducted ChIP-seq analyses focusing on histone marks indicative of active enhancers (H3K27ac) and active promoters (H3K4me3), alongside RNA-seq, using frontal cortex samples from antipsychotic-free (AF) and antipsychotic-treated (AT) individuals with schizophrenia, as well as individually matched controls (n=58). Schizophrenia subjects exhibited thousands of neuronal and non-neuronal epigenetic differences at regions that included several susceptibility genetic loci, such as , and . By analyzing the AF and AT cohorts separately, we identified schizophrenia-associated alterations in specific transcription factors, their regulatees, and epigenomic and transcriptomic features that were reversed by antipsychotic treatment; as well as those that represented a consequence of antipsychotic medication rather than a hallmark of schizophrenia in postmortem human brain samples. Notably, we also found that the effect of age on epigenomic landscapes was more pronounced in frontal cortex of AT-schizophrenics, as compared to AF-schizophrenics and controls. Together, these data provide important evidence of epigenetic alterations in the frontal cortex of individuals with schizophrenia, and remark for the first time on the impact of age and antipsychotic treatment on chromatin organization.
Topics: Humans; Schizophrenia; Antipsychotic Agents; Frontal Lobe; Male; Female; Middle Aged; Epigenesis, Genetic; Adult; Epigenomics; Aged; Histones
PubMed: 38648100
DOI: 10.7554/eLife.92393 -
Schizophrenia Research Jun 2024This issue focuses on the past, the present and the future of clozapine. Of the 43 clozapine articles, nine are historical articles dealing with the past, 29 deal with...
This issue focuses on the past, the present and the future of clozapine. Of the 43 clozapine articles, nine are historical articles dealing with the past, 29 deal with the present and five with laboratory assays which may influence its future use. These 43 articles include 219 different authors from 56 countries/regions and five continents.
Topics: Clozapine; Humans; Antipsychotic Agents; Schizophrenia
PubMed: 38519290
DOI: 10.1016/j.schres.2024.03.003