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Efficacy and Safety of Sulforaphane Added to Antipsychotics for the Treatment of Negative Symptoms of Schizophrenia: A Randomized Controlled Trial.

J Clin Psychiatry

January 2025

Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, and Department of Psychiatry, New York University School of Medicine, New York, New York.

There are few established treatments for negative symptoms in schizophrenia, which persist in many patients after positive symptoms are reduced. Oxidative stress, inflammation, and epigenetic modifications involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor.

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Aim: We aimed to create a rat model of drug-induced parkinsonism and tardive dyskinesia by chronic administration of haloperidol and examine the expression of direct and indirect pathway markers in the striatum of the model rats.

Methods: We treated 21 rats, 14 with haloperidol decanoate and 7 with placebo. The number of vacuous chewing movements per 2 min was counted, and haloperidol-treated rats were classified into two groups: mild and severe tardive dyskinesia.

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Background And Objectives: Ecopipam is a selective antagonist of the dopamine D1 receptor, and its efficacy and safety have recently been explored in several clinical trials involving patients with Tourette syndrome (TS). The objectives of this systematic review were to determine the pooled estimate for efficacy [in terms of reduction in tic Yale Global Tic Severity Scale (YGTSS) scores] and safety of oral ecopipam in subjects with TS.

Methods: All clinical trials that explored the efficacy and/or safety of ecopipam in patients with TS were included to determine the pooled estimate for change in YGTSS, Clinical Global Impression (CGI)-TS, and the severity of comorbid attention-deficit hyperactive disorder (ADHD), obsessive compulsion disorder (OCD), and depressive symptoms, as well as the nature and frequency of adverse effects.

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Background: Negative symptoms of schizophrenia represent an unmet therapeutic need for many patients in whom pentoxifylline may be effective in terms of its dopaminergic, anti-inflammatory, and cerebral blood flow-increasing properties. This study aimed to evaluate pentoxifylline as a therapeutic agent for improving negative symptoms of schizophrenia.

Methods: Chronic schizophrenia outpatients experiencing significant negative symptoms were randomly allocated to receive pentoxifylline 400 mg or matched placebo every 12 hours for 8 weeks.

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Background: Evenamide, a glutamate modulator, is currently in phase 3 of development as add-on treatment to antipsychotics in patients with inadequate response or treatment-resistant schizophrenia. This study was designed to determine if patients with chronic schizophrenia inadequately responding to a second-generation antipsychotic would benefit from add-on treatment with evenamide at a dose of 30 mg bid.

Methods: Study 008A was a prospective, 4-week, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of oral doses of evenamide of 30 mg bid in patients with chronic schizophrenia treated at stable therapeutic doses of a second-generation antipsychotic.

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