Efficacy of Serotonin and Dopamine Activity Modulators in the Treatment of Negative Symptoms in Schizophrenia: A Rapid Review

Abstract

Schizophrenia is among the fifteen most disabling diseases worldwide. Negative symptoms (NS) are highly prevalent in schizophrenia, negatively affect the functional outcome of the disorder, and their treatment is difficult and rarely specifically investigated. Serotonin-dopamine activity modulators (SDAMs), of which aripiprazole, cariprazine, brexpiprazole, and lumateperone were approved for schizophrenia treatment, represent a possible therapy to reduce NS. The aim of this rapid review is to summarize the evidence on this topic to make it readily available for psychiatrists treating NS and for further research. We searched the PubMed database for original studies using SDAM, aripiprazole, cariprazine, brexpiprazole, lumateperone, schizophrenia, and NS as keywords. We included four mega-analyses, eight meta-analyses, two post hoc analyses, and 20 clinical trials. Aripiprazole, cariprazine, and brexpiprazole were more effective than placebo in reducing NS. Only six studies compared SDAMs with other classes of antipsychotics, demonstrating a superiority in the treatment of NS mainly for cariprazine. The lack of specific research and various methodological issues, related to the study population and the assessment of NS, may have led to these partial results. Here, we highlight the need to conduct new methodologically robust investigations with head-to-head treatment comparisons and long-term observational studies on homogeneous groups of patients evaluating persistent NS with first- and second-generation scales, namely the Brief Negative Symptom Scale and the Clinical Assessment Interview for Negative Symptoms. This rapid review can expand research on NS therapeutic strategies in schizophrenia, which is fundamental for the long-term improvement of patients’ quality of life.

The Benzoylpiperidine Fragment as a Privileged Structure in Medicinal Chemistry: A Comprehensive Review

“…Nowadays, it is well known that the neurotransmitter serotonin (5-hydroxytriptamine, 5-HT) plays a central role in the occurrence of mental diseases such as depression, anxiety, schizophrenia, eating disorders, obsessive-compulsive disorder (OCD), migraine, and panic disorder [72][73][74][75][76][77]. Therefore, modulating the serotoninergic tone is a commonly used strategy for treating mental disorders.…”

Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model

“…Aripiprazole is a third-generation atypical antipsychotic indicated for SZ that is one of the most well tolerated and with the least discontinuation in patients [20,21]. It acts as a partial agonist of the D2 dopaminergic receptor and a full antagonist of the 5-HT 2A serotoninergic receptor [22]. Interestingly, the effects of aripiprazole on the aforementioned EEG features in SZ patients or animal models remain largely ill-defined.…”

Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders

“…The major manifestations of schizophrenia include positive symptoms (hallucinations, various delusions, paranoia, and disorganized thinking), negative symptoms (social withdrawal, decreased emotional expression, anhedonia, alogia, and avolition), and cognitive deficits (deficient memory and impaired attention and executive functions) [1]. It is believed that the major contributors to the neuropathophysiology of this disorder are excessive dopaminergic activity and deficits in cortical glutamatergic neurotransmission, but it appears to be much more complex, involving structural and molecular changes throughout brain circuits involving alterations in other neurotransmitters, monoamines, and their derivatives [2][3][4][5][6][7][8][9][10][11].…”