Treatment of Schizophrenia in Light of New Findings
"Mental disorders constitute a significant burden on society," began Assoc. Prof. MUDr. Martin Anders, Ph.D., head of the Psychiatric Clinic at the First Faculty of Medicine, Charles University and General University Hospital in Prague, during his presentation at the psychiatric symposium titled "A Chance for a Better Life with Schizophrenia Diagnosis," held on October 18, 2021, in Prague. His lecture focused on key issues in the treatment of schizophrenia, as well as on one of the recently registered antipsychotics—lurasidone.
A Highly Risky Disease in Many Respects
Schizophrenia is a lifelong disease with a high tendency to relapse. Only 15% of patients undergo just the first episode of the disease without a relapse. Patients with schizophrenia exhibit a 3-times higher mortality rate compared to the general population, age more quickly, and suffer cardiovascular distress. The disease can worsen cognitive abilities in some individuals to the point of pronounced dementia.
Impact of Schizophrenia and Its Treatment on Cognitive Functions
After just 5 years of ongoing illness, there can be a significant loss of gray matter in the brain. Neurodegeneration and the resulting cognitive deficit are associated with so-called immune mobilization, a state in which patients have high concentrations of cytokines during the initial episodes that can affect brain metabolism and neurotransmitters. During the disease, the microglial system is activated, hypercortisolemia develops, and oxygen radicals are formed, which have a destructive effect on brain tissue. It is important for patients to maintain cognitive functions and clear thinking, so it is good news that atypical antipsychotics can have a neuroprotective effect. On the other hand, first-generation antipsychotics tend to be neurotoxic and deepen cognitive deficits.
Cognitive functions are influenced by daytime sleepiness and disrupted circadian rhythm, so it is important to appropriately time the administration of antipsychotics. Ideally, the medication should be taken in the evening so that the peak plasma concentration occurs at night. Differences in the effects of the drugs on the individual receptors are also crucial. If a doctor starts treatment with a poorly selected drug, it can deepen the cognitive deficit.
Lurasidone – A Hope in Schizophrenia Therapy?
During his lecture, Assoc. Prof. Anders addressed the question of what qualities an ideal antipsychotic should have. “It should be effective in the acute phase, effective in long-term treatment, should not cause extrapyramidal symptoms, tardive dystonia, should be weight-neutral, but also should be accessible,” he summarized.
Great emphasis is placed on preserving cognitive functions in the treatment of schizophrenia. Lurasidone positively influences cognition and works favorably on individual receptors, whether it is antagonism with 5-HT7 and α-adrenergic receptors, partial agonism with 5-HT1A receptors, or negligible affinity for the muscarinic system.
From the results of a study comparing lurasidone and quetiapine on the parameter of cognitive performance improvement after 32 months of therapy, it is clear that lurasidone is significantly more effective. The mechanism of action of these substances thus plays a crucial role.
Metabolic Implications
Studies show that the use of antipsychotics is associated with changes in body weight and their impact on insulin sensitivity. “It appears that antipsychotics can influence such an important parameter as insulin resistance in the early phases of treatment. What's more, we also know that antipsychotics can directly affect adipose tissue, both brown and white, and intervene in processes like the formation of adipocyte size,” explained the speaker.
According to a recently published study, a significantly higher rate of overall cognitive deficit reduction was observed in patients with schizophrenia who also suffered from metabolic syndrome, diabetes, or hypertension. Interesting are the results of a meta-analysis, which showed that lurasidone, compared to brexpiprazole, has comparable efficacy but causes lower weight gains and higher rates of reduction in total cholesterol and LDL-C plasma concentrations.
Conclusion
“Lurasidone is thus an example of an effective and safe antipsychotic with a profile approaching that of the ideal antipsychotic,” concluded Assoc. Prof. Anders.
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Source: Anders M. Fundamental Questions in Schizophrenia Treatment and Lurasidone. Symposium A Chance for a Better Life with Schizophrenia Diagnosis, Prague, October 18, 2021. Available at: www.youtube.com/watch?v=QIOMg-RkzCA
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