Issues and Perspectives in Designing Clinical Trials for Negative Symptoms in Schizophrenia: Consensus Statements

Abstract

Individuals from academia, the pharmaceutical industry, and regulators reevaluated earlier recommendations for the design of clinical trials for negative symptoms based on data from recent large trials. A session in February, 2018 at the International Society of CNS Clinical Trails and Methodology (ISCTM) annual meeting reviewed results from selected trials that reported findings between 2013 and 2018. The group reached a consensus on prior recommendations that should be reconsidered in future trials which included: (1) How can placebo effects be minimized? (2) Should global measures of negative symptoms be included? (3) Should a new drug targeting negative symptoms be tested in a monotherapy design or in an add-on design? (4) Can new information from negative symptom trials inform the selection of clinical outcome assessments (COA’s) for future trials? For each of these issues new data was evaluated, discussed by the group, and in some cases the earlier recommendations were revised.

Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia

“…Therefore, by using an add-on design it is difficult to disentangle between the direct effect of the experimental drug on negative symptoms and the pseudo-effect derived from the treatment with antipsychotics that blockade the D2 receptors. To overcome this limitation it has recently been suggested that trials targeting negative symptoms should use monotherapy and placebo-controlled designs, 23 which is the option taken in this trial and the previous trial. 20 Furthermore, data are accumulating showing that over a third of patients do not experience exacerbation during one year of placebo administration and some might even benefit from antipsychotic drug reduction or discontinuation.…”

“…Primary outcome measure was the change from baseline to week 12 on the NSFS ( N1 to N4, N6, G7, and G16 ) of the PANSS . 22 , 23 …”

D3 Receptor-Targeted Cariprazine: Insights from Lab to Bedside

“…However, approximately 30% of individuals diagnosed with schizophrenia experience symptoms that do not respond well to antipsychotic medications or only show minimal improvement [ 23 , 24 ]. In addition, a broad range of schizophrenia symptoms, including negative symptoms, or cognitive impairments remain largely unaffected by most antipsychotic treatments [ 25 , 26 , 27 , 28 ]. Antipsychotics may actually worsen or trigger negative and cognitive symptoms [ 25 , 26 , 27 , 28 ].…”

“…In addition, a broad range of schizophrenia symptoms, including negative symptoms, or cognitive impairments remain largely unaffected by most antipsychotic treatments [ 25 , 26 , 27 , 28 ]. Antipsychotics may actually worsen or trigger negative and cognitive symptoms [ 25 , 26 , 27 , 28 ]. Unfortunately, these symptoms are closely linked to long-term disability in schizophrenia patients, making them a critical area of unmet medical need in clinical management [ 29 , 30 ].…”

Schizophrenia; Recent Cognitive and Treatment Approaches Using Induced Pluripotent Stem Cells

“…13,14 Also, the person may lose interest in everyday activities, socially withdraw, or cannot experience pleasure. 15 Periodic improvement and worsening of symptoms have created a wide range of severity and type of symptoms. 16 The onset of symptoms of schizophrenia in men occurs in the middle of the third decade of life, while in women, the symptoms occur in the late twenties.…”