Sixty Years of Placebo-Controlled Antipsychotic Drug Trials in Acute Schizophrenia: Systematic Review, Bayesian Meta-Analysis, and Meta-Regression of Efficacy Predictors

Leucht, Stefan; Leucht, Claudia; Huhn, Maximilian; Chaimani, Anna; Mavridis, Dimitris; Helfer, Bartosz; Samara, Myrto; Rabaioli, Matteo; Bächer, Susanne; Cipriani, Andrea; Geddes, John; Salanti, Georgia; Davis, John M.

doi:10.1176/appi.ajp.2017.16121358

Cited by 410 publications

(351 citation statements)

References 54 publications

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“…Data from the risperidone group in this study are considered appropriate for the comparison because risperidone showed comparable efficacy in this study to that observed in previous phase 3 studies; the change in BPRS total score was −7.4 in this study and −7.2 in the previous study . The recent meta‐analysis of 167 randomized controlled trials indicated that blonanserin has similar efficacy in positive symptoms compared to other SGAs and potentially superior efficacy in negative symptoms to other SGAs . Blonanserin also exhibited comparable efficacy to other SGAs in another meta‐analysis of randomized controlled studies comparing blonanserin with other antipsychotics, most of which were conducted in Japan .…”

Section: Discussionsupporting

confidence: 57%

“…Conventional treatment of schizophrenia has targeted the psychiatric symptoms in the acute phase and successfully treated the positive symptoms with first‐ and second‐generation antipsychotics (FGAs and SGAs). Second‐generation antipsychotics not only improve positive symptoms similar to FGAs but also relieve negative symptoms better than FGAs with a small effect size and with a low incidence of extrapyramidal symptoms and hyperprolactinemia. And thus, SGAs are recommended as first‐line therapy in current treatment guidelines for schizophrenia .…”

Section: Introductionmentioning

confidence: 99%

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Blonanserin vs risperidone in Japanese patients with schizophrenia: A post hoc analysis of a phase 3, 8‐week, multicenter, double‐blind, randomized controlled study

Harvey

Nakamura

Miura

2019

Neuropsychopharm Rep

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Objective To report the efficacy and safety of blonanserin in patients with schizophrenia compared with risperidone in a Japanese multicenter, randomized, double‐blind study based on post hoc sensitivity analysis in addition to the previous results reported by Miura and discuss the current approaches for schizophrenia treatment. Methods Of 302 patients randomized, 156 received blonanserin (8‐24 mg/d) and 145 received risperidone (2‐6 mg/d) for 8 weeks. Efficacy variables included the Positive and Negative Syndrome Scale (PANSS) total score for the primary outcome, PANSS subscale, Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression‐Improvement (CGI‐I) for secondary outcomes. Safety variables included treatment‐emergent adverse events, Drug Induced Extrapyramidal Symptoms Scale scores, laboratory data, vital signs, electrocardiogram, etc Results Blonanserin was not inferior to risperidone in the change in PANSS total score at a non‐inferior margin of −7 (intergroup difference, −0.46; 95% CI, −4.40 to 3.48). Post hoc analyses wholly supported the primary result. No major difference was found in the changes in BPRS scores and the improvement rate on CGI‐I between the drugs. The incidence of adverse events was similar in the two drugs. Blonanserin was associated with a lower risk of prolactin increase, weight gain, and orthostatic hypotension compared with risperidone. However, blonanserin was associated with a higher incidence of akathisia and excitability compared with risperidone. Most of the adverse events were mild to moderate in severity with no specific events of predominant high severity in the both drugs. Conclusions Blonanserin exerted the similar efficacy to risperidone in both positive and negative symptoms in schizophrenia with a lower risk of prolactin increase, weight gain, and orthostatic hypotension compared with risperidone. Blonanserin will serve as a favorable treatment option for schizophrenia in daily clinical practice.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Blonanserin vs risperidone in Japanese patients with schizophrenia: A post hoc analysis of a phase 3, 8‐week, multicenter, double‐blind, randomized controlled study

Harvey

Nakamura

Miura

2019

Neuropsychopharm Rep

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“…He also speculated that the core symptoms may respond to different treatments than the ancillary symptoms. This hypothesis proved prescient when antipsychotics were found to be effective against positive symptoms but ineffective against negative and cognitive symptoms . Later, Kurt Schneider, a German psychiatrist, proposed a list of highly disorder‐specific forms of delusions and hallucinations based on a disturbance of self‐identity, which he termed ‘first‐rank symptoms,’ whereas he deemed negative and cognitive symptoms as secondary symptoms .…”

Section: The History Of Pathological Hypotheses In Schizophreniamentioning

confidence: 99%

Glutamate hypothesis in schizophrenia

Uno

Coyle

2019

Psychiatry Clin Neurosci

287

172

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Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.

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“…In the second section, participants are presented with four side effects (weight gain, sexual dysfunction, irregular heartbeat and stiffness/tremor) and are asked to select one side effect they would like to avoid. The side effects were chosen on the basis of data availability from a recent meta-analysis 11. Each side effect is accompanied by a short explanation of that side effect in lay language, which can be accessed by tapping or clicking a toggle to reveal content.…”

Section: Introductionmentioning

confidence: 99%

Implementing a digital clinical decision support tool for side effects of antipsychotics: a focus group study

Henshall

Cipriani

David

et al. 2019

Evid Based Mental Health

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BackgroundIn medicine, algorithms can inform treatment decisions by combining the most up-to-date evidence about side effect profiles of medications, which are comparable in efficacy. Their use provides opportunities for improved shared clinician–patient decision-making when initiating therapy. We designed a decision support tool (DST) that incorporated the latest evidence regarding antipsychotic side effects. The tool allowed patients to select one side effect commonly associated with antipsychotics that they wished to avoid; the tool then provided a list of suggested medications and ones to avoid.ObjectiveTo explore qualitatively the acceptability and usefulness of the DST from the perspectives of patients and psychiatrists.MethodsThis qualitative study took place at a mental health and community hospital in Oxford, UK, in 2018. Four patients/carers and four psychiatrists were recruited to two focus groups to explore their perceptions of the tool. Data were thematically analysed.FindingsFindings demonstrated a high degree of acceptability and potential usability of the DST for patients and psychiatrists. The main themes to emerge relating to the DST were ‘prescribing preferences and practices’, ‘consideration and awareness of side effects’, ‘app content, layout and accessibility’, ‘influence on clinical practice’ and ‘role in decision-making’.ConclusionsA proof-of-concept clinical study will incorporate the recommendations produced from the findings into the tool’s design.Clinical implicationsDigital DSTs provide opportunities for the most up-to-date information on medication side effects to be used as the basis for shared clinician–patient decision-making. This tool has the potential to improve adherence to psychiatric medication, with benefits to clinical outcomes and healthcare resourcing.

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Sixty Years of Placebo-Controlled Antipsychotic Drug Trials in Acute Schizophrenia: Systematic Review, Bayesian Meta-Analysis, and Meta-Regression of Efficacy Predictors

Cited by 410 publications

References 54 publications

Blonanserin vs risperidone in Japanese patients with schizophrenia: A post hoc analysis of a phase 3, 8‐week, multicenter, double‐blind, randomized controlled study

Blonanserin vs risperidone in Japanese patients with schizophrenia: A post hoc analysis of a phase 3, 8‐week, multicenter, double‐blind, randomized controlled study

Glutamate hypothesis in schizophrenia

Implementing a digital clinical decision support tool for side effects of antipsychotics: a focus group study

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