Ziprasidone 80mg capsules

BackgroundManaging undifferentiated, severe agitation in older adults may require antipsychotic or sedative medications to prevent harm to self or others. Unfortunately, these medications are associated with serious adverse events in older adults, and little is known about their comparative safety.MethodsWe conducted a systematic review to identify comparative effectiveness studies on the safety of medications used in the treatment of severe agitation among older adults in the prehospital or emergency department (ED) setting. We searched eight databases including PubMed, EMBASE, SCOPUS, Cochrane library, CINAHL, Proquest Central, Ageline, and PsycInfo published in or before February 2024. Studies were included if they examined 1st generation antipsychotics, 2nd generation antipsychotics, benzodiazepines, or ketamine. Data were extracted on adverse respiratory events (apnea, hypoxemia, intubation) and other adverse events (arrhythmia, hypotension, worsening delirium, cardiac arrest, and mortality). We report the aggregate occurrence of any adverse events pooled by drug and report odds ratios (ORs) using haloperidol as the reference group.ResultsAmong 8600 studies identified, eight observational studies and one randomized clinical trial met eligibility for further qualitative and quantitative analysis. The observational studies included 838 older adults receiving haloperidol (n = 117), droperidol (n = 129), lorazepam (n = 350), midazolam (n = 68), olanzapine (n = 101), quetiapine (n = 56), and ziprasidone (n = 17). Any adverse events were observed in 16.8% of the patients (141/838). Adverse events were most common among patients receiving midazolam (53%; 36/68). Relative to haloperidol, midazolam significantly increased the risk for any adverse events (OR 5.25 [95% CI: 2.64-10.45]). Quetiapine was the only drug observed to have a lower frequency of adverse events (OR 0.27 [95% CI: 0.08, 0.97]).ConclusionsAdverse drug events are common among older adults receiving antipsychotic or anxiolytic medications for severe agitation. Benzodiazepines, particularly midazolam, pose an excessive risk to older adults requiring pharmacologic treatment for severe agitation.

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BackgroundProlactin increase is a common and potentially problematic adverse event of antipsychotics. We aimed to discover the relationship between antipsychotic doses and changes in prolactin levels.ObjectiveTo examine the relationship between antipsychotic doses and changes in prolactin levels in adults with acutely exacerbated schizophrenia.MethodsWe searched the Cochrane Schizophrenia Group register (last search 26 July 2024) and previous reviews for fixed-dose, randomized controlled trials (RCTs) that investigated monotherapy of 21 antipsychotics in adults with acutely exacerbated schizophrenia. The primary outcome was mean prolactin change from baseline to study endpoint adopting mean differences (MD) in ng/mL as the effect size measure. The dose-response curves were estimated by conducting random-effects dose-response meta-analyses using the restricted cubic spline method.ResultsAmong 165 eligible studies, 68 studies with 238 dose arms (23,128 participants, 35% female) reported on prolactin and were meta-analyzed. Of these, 94% lasted ≤ 3 months, and 90% of the studies used oral formulations. Participants in one study experienced their first episode, while all other studies also included multiepisode participants. The dose-response curves indicated that with aripiprazole, higher doses were significantly associated with lower prolactin levels than lower doses. Brexpiprazole, cariprazine, lumateperone, and quetiapine carried negligible risks for prolactin increase across examined doses. During treatment with most other antipsychotics, i.e., asenapine, haloperidol, iloperidone, lurasidone, olanzapine, paliperidone, risperidone, and ziprasidone, prolactin levels rose with increasing doses and then continued to increase or plateaued. The shape of the dose-response curves was similar in males and females, with generally larger amplitudes of the curves in females.ConclusionsThe prolactin-increasing property varies among antipsychotics, is dose-related, and is greater in females. These findings in adults with acutely exacerbated schizophrenia can help clinicians titrate and adapt antipsychotic doses and consider patients' sex in treatment decisions. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO); registration no. CRD42020181467.

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BackgroundHigh discontinuation rates compromise the effectiveness of treatment regimens for schizophrenia, because consistent medication adherence is essential for the efficacy of antipsychotics. Understanding the relationship between antipsychotic doses and discontinuation rates is important. This study explores this relationship to identify doses that maximize treatment adherence and minimize discontinuation.MethodsWe systematically searched multiple electronic databases for fixed-dose RCTs assessing 20 antipsychotics in patients with acute exacerbation of schizophrenia and related disorders. We analyzed dose-response relationships using a one-stage dose-response meta-analysis within a frequentist framework, employing restricted cubic splines to model the relationships. The primary outcome was discontinuation for any reason, and secondary outcomes were discontinuation due to inefficacy and side effects.ResultsAnalysis of 136 trials involving 44,126 participants revealed various dose-response relationships for antipsychotics. For the primary outcome, all-cause discontinuation, amisulpride, cariprazine, olanzapine (Zyprexa), and quetiapine demonstrated U-shaped curves, indicating optimal dosing thresholds where further increases in dosage led to heightened discontinuation rates, possibly due to side effects. Aripiprazole, asenapine, brexpiprazole, clozapine, paliperidone, and risperidone (Risperdal) had plateaus, suggesting no additional benefit from increasing doses beyond specific points. For haloperidol, iloperidone, lumateperone, lurasidone, sertindole, and ziprasidone, the dose-response curves did not reach a plateau within the examined doses. Inefficacy discontinuation curves were similar to total discontinuation. Most discontinuation for side-effects curves showed sharp increases in side-effects associated with higher doses.ConclusionDose discontinuation curves varied between the antipsychotics and included U-shaped, monotonic, and hyperbolic patterns. Future studies should consistently present disease-related and side-effect-related dropouts due to adverse events separately.

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BackgroundThere is a need to provide up-to-date, clinically translatable data as it relates to the treatment of a major depressive episode (MDE) with mixed features.MethodsPubMed and OVID were searched from inception to July 22, 2024. Randomized controlled trials (RCTs) investigating the efficacy of pharmacological agents for adults with bipolar disorder (BD) or major depressive disorder (MDD) in an MDE with mixed features were included. Risk of bias was assessed using the Cochrane Risk of Bias Tool for Randomized Studies (RoB2).ResultsA total of seven studies were included in this systematic review. The studies identified were all short-term acute studies ranging from 6 to 8 weeks. Treatment with lurasidone, olanzapine, cariprazine, lumateperone, quetiapine, and ziprasidone was associated with statistically significant reduction of depressive symptoms in MDEs with mixed features. Only lumateperone is studied in both BD subtypes [bipolar I disorder (BD-I), bipolar II disorder (BD-II)] and MDD, wherein efficacy in mixed features was the prespecified primary outcome. Lurasidone has a single study in MDD, while ziprasidone has data in a mixed sample of BD-II and MDD. Data for the other agents in mixed features is post hoc. Co-occurring hypomanic symptoms generally improved, and there was no significant difference between the above treatments and placebo with respect to hypomanic symptom severity intensification or treatment-emergent affective switching.ConclusionSelect atypical antipsychotics are effective in alleviating depressive symptoms in persons with mixed features; albeit, much of the data is obtained from post hoc analysis. Minimal evidence exists for the efficacy of lithium or valproate in the treatment of depressive episodes with mixed features. Antidepressant monotherapy has not been adequately evaluated in depressive episodes with mixed features. In addition, there is a pressing need for a consistent definition of mixed presentations to guide future interventional studies.

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BackgroundAtypical antipsychotics (AAs) are commonly used in the treatment of schizophrenia and are often preferred as first-line therapy over typical antipsychotics (TAs) due to their lower risk of extrapyramidal side effects. Both groups are efficacious in treating symptoms of schizophrenia, but increasing research has highlighted AAs as being associated with a risk of developing dyslipidaemia. Existing research has pointed to the need for more data focusing on the effects of individual AAs on dyslipidaemia in this population.MethodsThe scoping review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping reviews (PRISMA-ScR) checklist. The thematic analysis was used to synthesize data from 12 studies selected through structured searches across six databases. Inclusion criteria focused on primary studies between 2015 and 2025 involving adult patients with schizophrenia (18-65 years) treated with AAs and reporting on lipid abnormalities. The themes were identified via Braun and Clarke's six-step framework.ResultsClozapine and olanzapine were most strongly associated with increased LDL, total cholesterol, and triglycerides, and reduced HDL. Aripiprazole and lurasidone showed minimal impact. Identified biomarkers included asprosin, IGFBP-2, MIF, and white blood cell counts. Pharmacogenetic markers such as APOA1 gene polymorphisms and specific SNPs were also linked to lipid profile variability. Anthropometric indicators like waist-to-hip ratio were correlated with dyslipidaemic risk.ConclusionThe review shows significant associations between specific AAs and lipid abnormalities, particularly with clozapine and olanzapine. Biomarkers and genetic polymorphisms offer promising avenues for monitoring and personalized treatment. Evidence for certain AAs, such as amisulpride, paliperidone, and ziprasidone, remains sparse, highlighting the need for further targeted research. These findings support informed prescribing and the development of predictive tools to mitigate metabolic risks in the treatment of schizophrenia.

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BackgroundTreatment-resistant schizophrenia (TRS) poses significant challenges for both clinicians and patients. This systematic review and network meta-analysis (NMA) aimed to compare the efficacy and tolerability of all available pharmacotherapy options.MethodsWe systematically searched MEDLINE, Cochrane Central, Embase, PsycINFO, ClinicalTrials.gov, WHO trials registry, and FDA website through March 2025 for randomised controlled trials (RCTs) comparing pharmacological treatments for TRS. NMA estimated pooled effects, with the primary outcome being overall symptom change. Secondary outcomes included treatment response, individual symptom domains, discontinuation, adverse events, quality of life, and functioning. Effect sizes were reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, with 95% confidence intervals (CIs). Meta-regression and sensitivity analyses explored variability in findings.Findings150 RCTs with 11,375 patients examined 78 drug options or placebo. Clozapine showed superior efficacy for overall symptoms compared to haloperidol, chlorpromazine, quetiapine, and sulpiride (SMDs 0.35 to 1.00). It slightly outperformed olanzapine for positive symptoms (SMD 0.19; 95% CI 0.00 to 0.37) and risperidone for response rates (OR 0.64; 95% CI 0.41 to 1.01). Clozapine combinations with amisulpride, duloxetine, memantine, mirtazapine, topiramate, and ziprasidone improved overall symptoms more than clozapine monotherapy (SMDs -1.53 to -0.51). In a similar vein, clozapine combinations with amisulpride, lamotrigine, and topiramate reduced positive symptoms more than monotherapy (SMDs -1.13 to -0.54), while with duloxetine, memantine, and ziprasidone negative symptoms (SMDs -1.98 to -0.99). Some antipsychotic combinations may outperform monotherapy, but data on non-clozapine combinations were limited. Higher baseline severity was associated with higher clozapine efficacy. Confidence in most estimates was low or very low.InterpretationClozapine remains the gold standard, outperforming several antipsychotics, while specific combinations may offer added benefits but require careful risk-benefit evaluation. Networks sparsity increases the likelihood of chance findings for estimates based on single studies. These results emphasise the need for personalised treatment, further research comparing non-clozapine antipsychotic combinations to high-dose clozapine monotherapy, and studies on long-term outcomes.FundingNone.

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BackgroundThe main characteristics present in patients with psychomotor agitation include restlessness, excessive motor activity, irritability, and heightened responsiveness to internal and external stimuli. This umbrella review evaluates the efficacy and safety of pharmacological interventions for patients with psychiatric disorders presenting psychomotor agitation, aged 18 years or older. A comprehensive literature search was conducted to identify umbrella reviews that met our study's inclusion criteria. However, no reviews were found that specifically investigated the efficacy and safety of pharmacological interventions for agitated psychiatric patients presenting with both behavioral and psychological symptoms, such as emotional lability, decreased attention span, and cognitive and behavioral alterations. The primary objective is to assess the effectiveness of pharmacological interventions in controlling patients within a short time frame, measured in hours rather than days. The focus was placed on studies addressing treatment in emergency settings, whether in general hospitals or psychiatric facilities, with an emphasis on managing acute psychomotor agitation rather than long-term maintenance treatment.MethodA comprehensive literature search for meta-analyses and systematic reviews assessing the efficacy and safety of pharmacological treatment for psychomotor agitation in psychiatric inpatients and emergency department patients was conducted across various databases such as PubMed, Scopus, EMBASE, Web of Science and COCHRANE Central database. Included reviews comprised those that incorporated randomized controlled trials (RCTs) or non-randomized controlled trials (NRCTs) comparing the efficacy and safety of pharmacological interventions for agitated psychiatric patients (with both psychological and behavioral symptoms).ResultsLoxapine (10 mg) demonstrated superior efficacy over 5 mg in reducing agitation within 120 min, with inhaled formulations providing rapid relief in patients with acute psychosis. Aripiprazole was effective and caused less sedation compared to Olanzapine, although Haloperidol required fewer additional doses but was less effective at 60 min. Ziprasidone, administered intramuscularly, offered a faster onset and was better tolerated than Haloperidol. Lorazepam proved effective with fewer side effects than antipsychotics and showed enhanced efficacy when combined with them. Midazolam provided rapid sedation but posed risks of severe side effects, especially in older adults. Droperidol was as effective as Olanzapine but provided faster sedation. Combination therapy, such as Haloperidol with Promethazine, effectively reduced aggression with a lower incidence of adverse effects.ConclusionThis umbrella review offers a comprehensive overview of the pharmacological management of psychomotor agitation in patients with psychiatric disorders. Among the most frequently used medications in the reviewed studies were haloperidol, olanzapine, and lorazepam. The findings underscore the importance of tailored treatment approaches and the need for further research to refine the management of psychomotor agitation in psychiatric settings.

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BackgroundAntipsychotic switching is common in the treatment of schizophrenia. Pharmacokinetic and pharmacodynamic properties of antipsychotics can inform switch strategies, as switching from shorter to longer half-life antipsychotics and switching from more antagonistic to less antagonistic or partial agonist agents at dopaminergic, histaminergic, and cholinergic receptors can lead to withdrawal or rebound symptoms, potentially complicating switch results. This systematic literature review of studies investigated switching strategies between oral antipsychotics. Pharmacokinetic and pharmacodynamic characteristics of antipsychotics that can influence switch outcomes were also extracted from publications and prescribing information.MethodsMEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PubMed databases were queried (last search 13 May 2024) for articles published from 1 June 2010 to 1 April 2024, with keywords (schizophr* OR schizoaff*) AND (antipsychotic*) AND (switch*). Randomized controlled trials, open-label studies, meta-analyses, and reviews of oral antipsychotic switching were included. Records were excluded if they investigated a disease other than schizophrenia or schizoaffective disorder or focused on long-acting injectable or non-approved antipsychotics. Data on switch strategies investigated and study outcomes were manually extracted from randomized controlled trials and open-label switch studies of oral antipsychotics in schizophrenia or schizoaffective disorder. Meta-analyses and review articles were summarized. There was no assessment for risk of bias or specific method to synthesize results.ResultsOf the 579 records identified during the systematic review, 80 articles investigated switching of oral antipsychotics in adult patients with schizophrenia, including 58 randomized and non-randomized studies (9 of which investigated ≥ 1 antipsychotic) and 22 review articles or meta-analyses. The antipsychotics investigated during this period were: aripiprazole (studies = 18); paliperidone, ziprasidone, olanzapine, and risperidone (studies = 7 each); brexpiprazole, clozapine and lurasidone (studies = 4 each); amisulpride, (studies = 3); quetiapine and iloperidone (studies = 2 each); and asenapine and lumateperone (1 study each). Most studies that reported a switch method employed cross-titration switching (studies = 39; 69.6%), while abrupt switching (studies = 10; 17.9%) and switching at investigator's discretion (studies = 7; 12.5%) were rare. A total of 24 studies (N = 3440 patients) had statistical comparisons between treatment groups, but few studies specifically statistically compared outcomes between different switch strategies (1 trial each for aripiprazole, clozapine, iloperidone, and ziprasidone; N = 666 patients), with mixed outcomes. Frequencies of sedative rescue treatments, which could have attenuated potential withdrawal symptoms, were rarely disclosed.ConclusionsDespite the importance and frequency of antipsychotic switching, few studies have specifically investigated outcomes of different switch strategies. General clinical preference appears to utilize gradual switching approaches to avoid potential rebound symptoms. Future research with current and emerging antipsychotics is needed, especially for switching between antipsychotics with different receptor profiles and for switches that are potentially vulnerable to rebound and withdrawal symptoms.

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