Lurasidone Dose Escalation in Early Nonresponding Patients With Schizophrenia

Loebel, Antony; Silva, Robert; Goldman, Robert; Watabe, Kei; Cucchiaro, Josephine; Citrome, Leslie; Kane, John M.

doi:10.4088/jcp.16m10698

Cited by 35 publications

(44 citation statements)

References 21 publications

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“… 21 However, the PI for lurasidone recommends a dose of up to 160 mg per day, 25 and some patients who have an inadequate response to doses up to 80 mg/day will require higher-dose treatment. 40 As noted by Citrome, 41 the Tandon et al 21 study had some different findings between US and non-US study sites, which may have further limited the effect size observed in this study relative to other similar studies of SGAs. Furthermore, given the objective of the study, this analysis considered only the branded agents that are available in the US for which a generic formulation is not available and where supportive long-term prevention trials have been published.…”

Section: Discussionmentioning

confidence: 61%

Relapse prevention: a cost-effectiveness analysis of brexpiprazole treatment in adult patients with schizophrenia in the USA

Aigbogun¹,

Liu²,

Kamat³

et al. 2018

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ObjectiveThis study used a decision-analytic framework to assess the cost-effectiveness of brexpiprazole vs comparator branded therapies for reducing relapses and hospitalizations among adults with schizophrenia from a US payer perspective.MethodsAn economic model was developed to assess patients with stable schizophrenia initiating treatment with brexpiprazole (1–4 mg), cariprazine (1–6 mg), or lurasidone (40–80 mg) over a 1-year period. After 6 months, patients remained on treatment or discontinued due to relapse, adverse events, or other reasons. Patients who discontinued due to relapse or adverse events were assumed to have switched to other therapy, and those who discontinued due to other reasons were assumed to have received no therapy. Primary outcomes were incremental cost per relapse avoided and hospitalization avoided, and the secondary outcome was cost per quality-adjusted life-year (QALY) gained. Sensitivity and scenario analyses were also conducted.ResultsBrexpiprazole was associated with the highest per-patient clinical effectiveness (avoided relapses 0.637, avoided hospitalizations 0.719, QALYs 0.707) among comparators, followed by cariprazine (avoided relapses 0.590, avoided hospitalizations 0.683, QALYs 0.683) and lurasidone (avoided relapses 0.400, avoided hospitalizations 0.536, QALYs 0.623). Annual per-patient health-care costs were lowest for brexpiprazole ($20,510), followed by cariprazine ($22,282) and lurasidone ($25,510). Brexpiprazole was the least costly and most effective treatment strategy for all outcomes. Results were sensitive to relapse rates and daily cost of brexpiprazole. Limitations include data principally obtained from drug-specific randomized withdrawal studies and lack of direct-comparison trials.ConclusionThis analysis evaluated brexpiprazole treatment for the reduction of schizophrenia relapses and hospitalizations over a 1-year period compared to other recently available branded antipsychotics, and excluded generic antipsychotic treatments. Brexpiprazole treatment may lead to clinical benefits and medical cost savings, and provides a cost-effective treatment option for patients relatively to other branded second-generation antipsychotics.

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Section: Discussionmentioning

confidence: 61%

Relapse prevention: a cost-effectiveness analysis of brexpiprazole treatment in adult patients with schizophrenia in the USA

Aigbogun¹,

Liu²,

Kamat³

et al. 2018

CEOR

Self Cite

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“…A total of 177 studies with 58,069 participants across 414 treatment arms were included in the comparative analysis (Appendix ) 32–111 . Of these, the breakdown for numbers of studies including each medication are aripiprazole (88), asenapine (10), brexpiprazole (8), cariprazine (10), iloperidone (6), lurasidone (14), paliperidone (9), risperidone (25), and ziprasidone (11).…”

Section: Resultsmentioning

confidence: 99%

Akathisia and Newer Second‐Generation Antipsychotic Drugs: A Review of Current Evidence

et al. 2020

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Akathisia continues to present a significant challenge in clinical practice. As a class, so-called atypical, or second-generation, antipsychotics (SGAs) are the mainstay of treatment for schizophrenia and are commonly used to treat mood disorders. These medications have traditionally been distinguished from first-generation antipsychotics by their lowered risk of extrapyramidal side effects (EPS) such as dystonia, dyskinesia, akathisia, and pseudoparkinsonism. However, the occurrence of EPS, particularly akathisia, has been demonstrated to some degree in all commercially available SGAs. This review examines the incidence of akathisia in nine newer SGAs in patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We performed a search of PubMed, ClinicalTrials.gov, Cochrane Central Register, and Google Scholar, as well as manufacturer websites and product labeling for published and unpublished clinical trials, meta-analyses, and systematic reviews. Studies evaluating adult patients with schizophrenia, bipolar disorder, or MDD were eligible for inclusion. Data on treatment-emergent akathisia rates were gathered from each study, and potential dose-response relationships were explored. A total of 177 studies were included in this review, comprising 58,069 patients across 414 treatment arms. Compared with placebo with a composite 3.7% incidence of akathisia, individual SGAs produced akathisia at total composite rates ranging from 2.9-13.0% across the included studies. High doses of an SGA were generally associated with an increased risk of akathisia. Clinicians should consider the risk of akathisia when choosing a treatment option and monitor for akathisia in patients beginning therapy with an SGA or following a dose increase of the SGA. KEY WORDS akathisia, antipsychotics, bipolar disorder, major depressive disorder, schizophrenia. (Pharmacotherapy 2020;40(6):565-574)

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“…Despite being the top-ranked strategy to manage TRS in this study, there is limited evidence that antipsychotic dose escalation yields satisfactory results in schizophrenia patients with insufficient response to antipsychotic treatment [35, 36].…”

Section: Discussionmentioning

confidence: 99%

Patient characteristics, burden and pharmacotherapy of treatment-resistant schizophrenia: results from a survey of 204 US psychiatrists

2019

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BackgroundMinimal/non-response to antipsychotic treatment, and persistent positive symptoms despite treatment, are common among patients with schizophrenia. The aim of this study was to characterize a US treatment-resistant schizophrenia (TRS) population in terms of patient demographics, burden of symptoms, treatment history, and factors influencing therapeutic choice.MethodsIn an online survey, 204 psychiatrists self-selected and completed three patient records: two TRS and one schizophrenia (‘non-TRS’).ResultsRespondents reported that 29.5% of their schizophrenia caseload had TRS. Selected TRS (n = 408) vs non-TRS (n = 204) patients were more likely to be unemployed (74.5% vs 45.1%, p < 0.001), hospitalized at least once (93.4% vs 74.0%, p < 0.001), and to have physical/psychiatric comorbidities including obesity (40.2% vs 23.5%, p < 0.001) and depression (38.7% vs 25.0%, p = 0.001). Psychiatric symptoms were more frequent and severe in TRS, and interfered more with social and functioning domains. Of positive symptoms, eliminating delusions and hallucinations was considered most important to improve a patient’s long-term prognosis. In TRS, clozapine monotherapy was the most common treatment (15.9%), though ranked fifth of ten options to treat TRS. Psychiatrists typically increased the antipsychotic dose or added a second antipsychotic before initiating clozapine or switching antipsychotics. Antipsychotic switches were most commonly due to lack of efficacy (TRS = 71.4% vs non-TRS = 54.3%, p < 0.001) and intolerability (34.4% vs 38.4%, p = 0.22) with the prior antipsychotic. Persistent hallucinatory behavior was the top symptom leading to treatment switches in TRS (63.9% vs 37.1%, p < 0.001).ConclusionsAccording to psychiatrists, symptoms have a greater clinical burden on patients with TRS than non-TRS. TRS is commonly managed by antipsychotic dose increases/combinations, with clozapine the fifth preference despite being the only approved TRS medication. New treatments are needed for patients who do not respond to available antipsychotics.

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Lurasidone Dose Escalation in Early Nonresponding Patients With Schizophrenia

Abstract: Objective: To assess the effect of dose increase in adult patients with schizophrenia who demonstrate inadequate initial response to standard-dose lurasidone and to evaluate the efficacy of lowdose lurasidone in adult patients with schizophrenia.

Cited by 35 publications

References 21 publications

Relapse prevention: a cost-effectiveness analysis of brexpiprazole treatment in adult patients with schizophrenia in the USA

Relapse prevention: a cost-effectiveness analysis of brexpiprazole treatment in adult patients with schizophrenia in the USA

Akathisia and Newer Second‐Generation Antipsychotic Drugs: A Review of Current Evidence

Patient characteristics, burden and pharmacotherapy of treatment-resistant schizophrenia: results from a survey of 204 US psychiatrists

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