Increased Metabolic Potential, Efficacy, and Safety of Emerging Treatments in Schizophrenia

Abstract

Patients with schizophrenia experience a broad range of detrimental health outcomes resulting from illness severity, heterogeneity of disease, lifestyle behaviors, and adverse effects of antipsychotics. Because of these various factors, patients with schizophrenia have a much higher risk of cardiometabolic abnormalities than people without psychiatric illness. Although exposure to many antipsychotics increases cardiometabolic risk factors, mortality is higher in patients who are not treated versus those who are treated with antipsychotics. This indicates both direct and indirect benefits of adequately treated illness, as well as the need for beneficial medications that result in fewer cardiometabolic risk factors and comorbidities. The aim of the current narrative review was to outline the association between cardiometabolic dysfunction and schizophrenia, as well as discuss the confluence of factors that increase cardiometabolic risk in this patient population. An increased understanding of the pathophysiology of schizophrenia has guided discovery of novel treatments that do not directly target dopamine and that not only do not add, but may potentially minimize relevant cardiometabolic burden for these patients. Key discoveries that have advanced the understanding of the neural circuitry and pathophysiology of schizophrenia now provide possible pathways toward the development of new and effective treatments that may mitigate the risk of metabolic dysfunction in these patients. Novel targets and preclinical and clinical data on emerging treatments, such as glycine transport inhibitors, nicotinic and muscarinic receptor agonists, and trace amine-associated receptor-1 agonists, offer promise toward relevant therapeutic advancements. Numerous areas of investigation currently exist with the potential to considerably progress our knowledge and treatment of schizophrenia.

An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders

“…Anticholinergic burden is increased when these drugs are used concomitantly, and accidental or intentional overexposure to one or more of these medications can lead to anticholinergic toxicity [ 36 ]. For M 1 /M 4 receptor agonists in development for schizophrenia [ 8 , 37 ], as well as M 4 receptor positive allosteric modulators [ 38 ], the potentially deleterious effects of centrally acting anticholinergics on antipsychotic efficacy remains to be determined.…”

“…The DIMDs described in this review are all associated with exposure to DRBAs, including currently available FGAs and SGAs. As new antipsychotic therapies emerge, including those that target muscarinic receptors, the potential efficacy and safety of emerging antipsychotic therapies will also need to be considered [ 8 ].…”

Anti-Inflammatory Effects of Peripheral Dopamine

“…Other atypical antipsychotics such as risperidone and paliperidone have an intermediate risk, while others such as aripiprazole have less or little effect on body weight. Similarly, typical antipsychotics also carry the potential risk of weight gain [ 220 , 221 ]. One of the potential mechanisms involved in the weight gain induced by antipsychotics is the blockade of D2R and D3R, as antipsychotic drugs that only interact with these receptors can significantly increase weight gain [ 222 , 223 ].…”

Efficacy and safety of Xiaoyao Pill combined with Western medicine in the treatment of schizophrenia: A Meta-analysis and Systematic review

“…[ 1 , 2 ] In recent years, the incidence of schizophrenia has been steadily increasing, often recurring with symptoms gradually worsening, leading to a decline in patients’ social functioning, and possibly even mental deterioration, significantly impacting their quality of life. [ 3 , 4 ] Assessment of symptoms associated with schizophrenia relied on the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS). [ 5 , 6 ] Hyperprolactinemia (HPRL) is a common adverse effect of antipsychotic drugs in clinical practice.…”