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Drugs & Aging Jun 2024International guidelines discourage antipsychotic use for delirium; however, concerns persist about their continued use in clinical practice.
BACKGROUND
International guidelines discourage antipsychotic use for delirium; however, concerns persist about their continued use in clinical practice.
OBJECTIVES
We aimed to describe the prevalence and patterns of antipsychotic use in delirium management with regard to best-practice recommendations. Primary outcomes investigated were prevalence of use, antipsychotic type, dosage and clinical indication.
METHODS
Eligibility criteria: studies of any design that examined antipsychotic use to manage delirium in adults in critical care, acute care, palliative care, rehabilitation, and aged care were included. Studies of patients in acute psychiatric care, with psychiatric illness or pre-existing antipsychotic use were excluded.
INFORMATION SOURCES
we searched five health databases on 16 August, 2023 (PubMed, CINAHL, Embase, APA PsycInfo, ProQuest Health and Medical Collection) using MeSH terms and relevant keywords, including 'delirium' and 'antipsychotic'. Risk of bias: as no included studies were randomised controlled trials, all studies were assessed for methodological quality using the Mixed Methods Appraisal Tool.
SYNTHESIS OF RESULTS
descriptive data were extracted in Covidence and synthesised in Microsoft Excel.
RESULTS
Included studies: 39 studies published between March 2004 and August 2023 from 13 countries (n = 1,359,519 patients). Most study designs were retrospective medical record audits (n = 16).
SYNTHESIS OF RESULTS
in 18 studies, participants' mean age was ≥65 years (77.79, ±5.20). Palliative care had the highest average proportion of patients with delirium managed with antipsychotics (70.87%, ±33.81%); it was lower and varied little between intensive care unit (53.53%, ±19.73%) and non-intensive care unit settings [medical, surgical and any acute care wards] (56.93%, ±26.44%) and was lowest in in-patient rehabilitation (17.8%). Seventeen different antipsychotics were reported on. In patients aged ≥65 years, haloperidol was the most frequently used and at higher than recommended mean daily doses (2.75 mg, ±2.21 mg). Other antipsychotics commonly administered were olanzapine (mean 11 mg, ±8.54 mg), quetiapine (mean 64.23 mg, ±43.20 mg) and risperidone (mean 0.97 mg, ±0.64 mg).
CONCLUSIONS
The use of antipsychotics to manage delirium is strongly discouraged in international guidelines. Antipsychotic use in delirium care is a risk for adverse health outcomes and a longer duration of delirium, especially in older people. However, this study has provided evidence that clinicians continue to use antipsychotics for delirium management, the dose, frequency and duration of which are often outside evidence-based guideline recommendations. Clinicians continue to choose antipsychotics to manage delirium symptoms to settle agitation and maintain patient and staff safety, particularly in situations where workload pressures are high. Sustained efforts are needed at the individual, team and organisational levels to educate, train and support clinicians to prioritise non-pharmacological interventions early before deciding to use antipsychotics. This could prevent delirium and avert escalation in behavioural symptoms that often lead to antipsychotic use.
Topics: Humans; Delirium; Antipsychotic Agents; Aged; Adult; Hospitals
PubMed: 38856874
DOI: 10.1007/s40266-024-01122-z -
Schizophrenia Research Jun 2024Despite the high prevalence of anxiety in schizophrenia, no established guideline exists for the management of these symptoms. We aimed to synthesize evidence on the... (Review)
Review
OBJECTIVE
Despite the high prevalence of anxiety in schizophrenia, no established guideline exists for the management of these symptoms. We aimed to synthesize evidence on the effect of second-generation antipsychotics (SGAs) on anxiety in patients with schizophrenia.
METHODS
We systematically searched Medline, Embase, PsycInfo, Web of Science, PubMed, and Cochrane library to identify randomized controlled trials of SGAs that reporting anxiety measures in schizophrenia. The search was limited to English-language articles published before February 2024. Data were pooled using a random-effects model.
RESULTS
Among 48 eligible studies, 29 (n = 7712) were included in the meta-analyses comparing SGAs to placebo, haloperidol, or another SGAs for their effect on anxiety/depression. SGAs had a small effect on anxiety/depression versus placebo (SMD = -0.28 (95 % CI [-0.34, -0.21], p < .00001, I = 47 %, n = 5576)) associated with efficacy for positive (z = 5.679, p < .001) and negative symptoms (z = 4.490, p < .001). Furthermore, SGAs were superior to haloperidol (SMD = -0.44, 95 % CI [-0.75, -0.13], p = .005, n = 1068) with substantial study-level heterogeneity (I = 85 %). Excluding one study of quetiapine in first-episode patients (SMD = -3.05, n = 73), SGAs showed a small effect on anxiety/depression versus haloperidol without heterogeneity (SMD = -0.23, 95 % CI [-0.35, -0.12], p = 01; I = %0). Risperidone's effect on anxiety/depression was comparable to olanzapine (SMD = -0.02, 95 % CI [-0.24,0.20], p = .87, I = 45 %, n = 753) and amisulpride (SMD = 0.27, 95 % CI [-1.08,0.61], p = .13, I = 50 %, n = 315).
CONCLUSION
While SGAs showed a small effect on anxiety/depression, the findings are inconclusive due to scarcity of research on comorbid anxiety in schizophrenia, heterogeneity of anxiety symptoms, and the scales used to measure anxiety. Further studies employing specific anxiety scales are required to explore antipsychotics, considering their receptor affinity and augmentation with serotonin/norepinephrine reuptake inhibitors or benzodiazepines for managing anxiety in schizophrenia.
PubMed: 38843584
DOI: 10.1016/j.schres.2024.05.020 -
Journal of Psychiatric Practice May 2024Prolactinomas-pituitary tumors that overproduce prolactin-can cause various troublesome symptoms. Dopamine agonists (DAs) reduce prolactin production in the prolactin...
OBJECTIVE
Prolactinomas-pituitary tumors that overproduce prolactin-can cause various troublesome symptoms. Dopamine agonists (DAs) reduce prolactin production in the prolactin pathway, making them the first-line treatment for prolactinomas. However, the main side effect of DA treatment, hyperdopaminergia, is an explicit etiology for psychiatric side effects. Psychiatric conditions are often treated with dopamine antagonists, which can induce hyperprolactinemia. This presents a challenge for patients with both a prolactinoma and a preexisting psychiatric condition, as treatment of one condition could worsen the other. This review seeks to identify an adequate therapeutic regimen for patients with coexisting prolactinomas and psychiatric symptoms.
METHODS
This review examined PubMed citations from 1960 to 2023 published in English and involving human subjects. Case reports, case series, and cohort studies involving patients with concomitant prolactinomas and psychiatric symptoms, as validated by brain imaging, serologic prolactin levels, and medical history or chart reports of psychiatric symptoms, were included.
RESULTS
Thematic analysis included 23 reports involving 42 participants; 27 of the 42 patients experienced a significant reduction in prolactin levels and psychiatric symptoms (64%). Treatment of those 42 patients included discontinuing or altering antipsychotic/dopamine antagonist therapy or discontinuing DA therapy to reduce psychiatric symptoms, with surgery or radiation postpharmacotherapy as a last-line strategy. However, in some cases (reported in Tables 2 to 4), either psychiatric or prolactin-related symptoms recurred despite adjustment.
CONCLUSIONS
Clinicians may find it beneficial to prioritize specific antipsychotics (aripiprazole, olanzapine, ziprasidone, or clozapine) over others (risperidone, thioridazine, thiothixene, and remoxipride). Discontinuing DA medication at least periodically until the patient's condition improves may also be advisable. If these 2 initial approaches do not yield a significant improvement in symptom management, surgery or radiation therapy may be considered. As patients may respond differently to these therapies, our study still recommends a patient-centered approach.
Topics: Humans; Prolactinoma; Pituitary Neoplasms; Mental Disorders; Dopamine Agonists; Antipsychotic Agents; Dopamine Antagonists
PubMed: 38819244
DOI: 10.1097/PRA.0000000000000783 -
Psychiatry Research Jun 2024Antipsychotics (APs) have been increasingly prescribed for psychiatric disorders from schizophrenia to disruptive behavioral conditions. These drugs have been associated...
Antipsychotics (APs) have been increasingly prescribed for psychiatric disorders from schizophrenia to disruptive behavioral conditions. These drugs have been associated with considerable side effects, such as weight gain, and increasing evidence has also indicated that its use impacts gut microbiota (GM), although this connection is still little understood. To assess APs effects on the GM of patients starting or ongoing treatment, a systematic review was carried out in PubMed and Scopus databases. Twelve articles were considered eligible for the review, which investigated the effects of risperidone (5 studies), quetiapine (3), amilsupride (1), olanzapine (1), and unspecified atypical drugs (2). Eleven reported changes in GM in response to APs, and associations between the abundance of bacterial groups and different metabolic parameters were described by most of them. However, the studies were noticeably heterogeneous considering design, methods, and results. In this way, the effects of APs on GM composition and diversity were inconclusive. Despite the uncertain interactions, a more comprehensive understanding on how microbiota is affected by APs may help to optimize treatment, potentially minimizing side effects and improving adherence to treatment.
Topics: Humans; Gastrointestinal Microbiome; Antipsychotic Agents
PubMed: 38663221
DOI: 10.1016/j.psychres.2024.115914 -
Frontiers in Psychiatry 2024Schizophrenia spectrum disorders (SSD) can be associated with an increased risk of violent behavior (VB), which can harm patients, others, and properties. Prediction of...
BACKGROUND
Schizophrenia spectrum disorders (SSD) can be associated with an increased risk of violent behavior (VB), which can harm patients, others, and properties. Prediction of VB could help reduce the SSD burden on patients and healthcare systems. Some recent studies have used machine learning (ML) algorithms to identify SSD patients at risk of VB. In this article, we aimed to review studies that used ML to predict VB in SSD patients and discuss the most successful ML methods and predictors of VB.
METHODS
We performed a systematic search in PubMed, Web of Sciences, Embase, and PsycINFO on September 30, 2023, to identify studies on the application of ML in predicting VB in SSD patients.
RESULTS
We included 18 studies with data from 11,733 patients diagnosed with SSD. Different ML models demonstrated mixed performance with an area under the receiver operating characteristic curve of 0.56-0.95 and an accuracy of 50.27-90.67% in predicting violence among SSD patients. Our comparative analysis demonstrated a superior performance for the gradient boosting model, compared to other ML models in predicting VB among SSD patients. Various sociodemographic, clinical, metabolic, and neuroimaging features were associated with VB, with age and olanzapine equivalent dose at the time of discharge being the most frequently identified factors.
CONCLUSION
ML models demonstrated varied VB prediction performance in SSD patients, with gradient boosting outperforming. Further research is warranted for clinical applications of ML methods in this field.
PubMed: 38577400
DOI: 10.3389/fpsyt.2024.1384828 -
Indian Journal of Psychological Medicine Jan 2024United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse... (Review)
Review
BACKGROUND AND OBJECTIVE
United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse events (weight gain) in adult patients with schizophrenia and bipolar disorder. To opine about the safety and efficacy of OLZSAM, authors performed a systematic review and meta-analysis to convene justifiable evidence.
METHODS
A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, from inception to September 2022, with the keywords: 'olanzapine and samidorphan' and schizophrenia; and "ALKS3831" and "lybalvi." Clinical trials published in English that analyzed the efficacy and safety of OLZSAM were included. The significant outcomes included in this study were change from baseline (CFB) in Positive and Negative Syndrome Scale (PANSS) at the end of the study, the proportion of patients with weight gain at the end of the study, the proportion of patients with at least one adverse event, and the incidence of drug discontinuation due to adverse events.
RESULTS
The change in PANSS score at the end of the study was comparable among groups receiving OLZSAM and olanzapine alone: standardized mean difference (SMD) = 0.04; 95% CI = -0.09 to 0.17; = 0.57. The OLZSAM group reported less incidence of weight gain: risk ratio (RR) = 0.91; 95% CI = 0.62-1.34; = 0.63, and any adverse event: RR = 0.99; 95% CI = 0.90-1.09; = 0.81. Drug discontinuation incidence was higher in the OLZSAM group: RR = 1.22; 95% CI = 0.84-1.79; = 0.30.
CONCLUSIONS
The combination OLZSAM showed comparable efficacy to olanzapine alone in schizophrenia patients, with relatively less incidence of weight gain and adverse events; however, the drug discontinuation due to adverse events was more in the OLZSAM group.
PubMed: 38524957
DOI: 10.1177/02537176231201326 -
Clinics (Sao Paulo, Brazil) 2024The antiemetic effectiveness of olanzapine, as a prophylactic off-label antiemetic drug, for Postoperative Nausea and Vomiting (PONV) is unknown. In this systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The antiemetic effectiveness of olanzapine, as a prophylactic off-label antiemetic drug, for Postoperative Nausea and Vomiting (PONV) is unknown. In this systematic review and meta-analysis, the authors evaluate the efficacy and side effects of olanzapine as a prophylactic antiemetic in adult patients who undergo general anesthesia and assess adverse effects.
METHODS
A systematic search was done on electronic bibliographic databases in July 2023. Randomized controlled trials of olanzapine as a prophylactic antiemetic for PONV in adults who underwent general anesthesia were included. The authors excluded non-RCTs and retracted studies. The authors set no date of publication or language limits. The outcomes were the incidence of PONV within 24 h postoperatively and the safety of olanzapine. The risk of bias was assessed according to the tool suggested by the National Heart, Lung, and Blood Institute.
RESULTS
Meta-analysis included 446 adult patients. Olanzapine reduced on average 38 % the incidence of PONV. The estimated risk ratio (95 % CI) of olanzapine versus control was 0.62 (0.42-0.90), p = 0.010, I = 67 %. In the subgroup meta-analysis, doses of olanzapine (10 mg) reduced on average 49 % of the incidence of PONV (RR = 0.51 [0.34-0.77], p = 0.001, I = 31 %).
CONCLUSIONS
This systematic review with meta-analysis indicated that olanzapine as a prophylactic antiemetic alone or combined with other antiemetic agents reduced the incidence of postoperative nausea and vomiting. However, this conclusion must be presented with some degree of uncertainty due to the small number of studies included. There was a lack of any evidence to draw conclusions on side effects.
Topics: Adult; Humans; Antiemetics; Postoperative Nausea and Vomiting; Olanzapine; Anesthesia, General
PubMed: 38513297
DOI: 10.1016/j.clinsp.2024.100345 -
European Neuropsychopharmacology : the... Jun 2024Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment... (Meta-Analysis)
Meta-Analysis Review
Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase.
Topics: Humans; Antipsychotic Agents; Administration, Oral; Schizophrenia; Delayed-Action Preparations; Network Meta-Analysis; Randomized Controlled Trials as Topic; Injections; Treatment Outcome
PubMed: 38490016
DOI: 10.1016/j.euroneuro.2024.03.003 -
European Psychiatry : the Journal of... Mar 2024We employed a Bayesian network meta-analysis for comparison of the efficacy and tolerability of US Food and Drug Administration (FDA)-approved atypical antipsychotics... (Meta-Analysis)
Meta-Analysis Review
We employed a Bayesian network meta-analysis for comparison of the efficacy and tolerability of US Food and Drug Administration (FDA)-approved atypical antipsychotics (AAPs) for the treatment of bipolar patients with depressive episodes. Sixteen randomized controlled trials with 7234 patients treated by one of the five AAPs (cariprazine, lumateperone, lurasidone, olanzapine, and quetiapine) were included. For the response rate (defined as an improvement of ≥50% from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS]), all AAPs were more efficacious than placebo. For the remission rate (defined as the endpoint of MADRS ≤12 or ≤ 10), cariprazine, lurasidone, olanzapine, and quetiapine had higher remission rates than placebo. In terms of tolerability, olanzapine was unexpectedly associated with lower odds of all-cause discontinuation in comparison with placebo, whereas quetiapine was associated with higher odds of discontinuation due to adverse events than placebo. Compared with placebo, lumateperone, olanzapine, and quetiapine showed higher odds of somnolence. Lumateperone had a lower rate of ≥ weight gain of 7% than placebo and other treatments. Olanzapine was associated with a significant increase from baseline in total cholesterol and triglycerides than placebo. These findings inform individualized prescriptions of AAPs for treating bipolar depression in clinical practice.
Topics: United States; Humans; Antipsychotic Agents; Bipolar Disorder; Quetiapine Fumarate; Olanzapine; Lurasidone Hydrochloride; Network Meta-Analysis; United States Food and Drug Administration; Bayes Theorem; Treatment Outcome
PubMed: 38487836
DOI: 10.1192/j.eurpsy.2024.25 -
General Hospital Psychiatry 2024This network meta-analysis assessed the efficacy, tolerability, and acceptability of second-generation antipsychotics (SGAs) for Parkinson's disease psychosis (PDP). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This network meta-analysis assessed the efficacy, tolerability, and acceptability of second-generation antipsychotics (SGAs) for Parkinson's disease psychosis (PDP).
METHODS
We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials investigating SGAs for PDP up to October 26, 2023.
RESULTS
We included 16 trials (N = 1252) investigating clozapine, melperone, olanzapine, pimavanserin, quetiapine, ulotaront, and placebo. In comparisons between SGAs and placebo, the findings were: i) Standardized mean differences, 95% confidence intervals (SMDs, 95%CIs), for psychotic-symptom reduction revealed the first rank of clozapine (-1.31, -1.73 to -0.89), the second rank of pimavanserin, with significant inferiority of quetiapine (SMD = 0.47, 0.02 to 0.92); ii) Mean differences (MDs, 95%CIs) for abnormal movement, as assessed by the Unified Parkinson's Disease Rating Scale - Part III, indicated that clozapine had the least motor side effects (-0.92, -2.75 to 0.91); iii) Risk ratios (RRs, 95% CIs) for adverse-effect dropout rates were lowest for melperone (1.02, 0.20 to 5.24); and iv) RRs (95% CIs) for all-cause dropout rates were lowest for clozapine (0.73, 0.42 to 1.25).
CONCLUSIONS
For patients with PDP, clozapine may substantially reduce psychotic symptoms with minimal abnormal movement, high acceptability, and moderate overall tolerability. Pimavanserin, not quetiapine, could be an alternative.
Topics: Humans; Antipsychotic Agents; Butyrophenones; Clozapine; Dyskinesias; Network Meta-Analysis; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Urea
PubMed: 38412585
DOI: 10.1016/j.genhosppsych.2024.02.008