Efficacy of Psychiatric Treatment and Medicine for Patients with Schizophrenia
Schizophrenia is a chronic and severe mental disorder that affects how a person thinks, feels, and behaves. People with schizophrenia may experience hallucinations, delusions, disorganized speech, negative symptoms, and cognitive impairments that interfere with their daily functioning and quality of life. Schizophrenia affects about 1% of the world population and usually develops in late adolescence or early adulthood (World Health Organization, 2020).
The treatment of schizophrenia has evolved over the years, from the introduction of antipsychotics in the 1950s to the development of novel agents with different mechanisms of action in the 21st century. However, there is still a significant unmet need for more effective and better-tolerated therapies that can address the full range of symptoms and improve the long-term outcomes of patients with schizophrenia.
Current Treatment Options
The mainstay of treatment for schizophrenia is antipsychotic medication, which can reduce positive symptoms and prevent relapse. Antipsychotics are classified into two groups: first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs). FGAs mainly act by blocking dopamine D2 receptors, while SGAs have a more complex pharmacological profile that involves antagonism or partial agonism of various serotonin and dopamine receptors.
FGAs are associated with a higher risk of extrapyramidal side effects (EPS), such as dystonia, akathisia, parkinsonism, and tardive dyskinesia. SGAs are generally preferred because they have a lower risk of EPS and may be more effective for negative and cognitive symptoms. However, SGAs also have their own drawbacks, such as weight gain, metabolic syndrome, sedation, and increased prolactin levels.
The choice of antipsychotic medication depends on several factors, such as the patient’s preference, response to previous treatment, comorbidities, side effect profile, availability, cost, and adherence. The optimal dose and duration of treatment should be individualized based on the patient’s clinical condition and monitoring of efficacy and safety parameters. The goal of treatment is to achieve symptom remission or reduction, functional recovery, and quality of life improvement.
In addition to medication, psychosocial interventions are also recommended for patients with schizophrenia. These include psychoeducation, family intervention, cognitive-behavioral therapy (CBT), social skills training, cognitive remediation, vocational rehabilitation, and peer support. These interventions can help patients cope with their illness, enhance their self-esteem, improve their social functioning, and reduce the risk of relapse.
Emerging Treatment Options
Despite the availability of various antipsychotics and psychosocial interventions, many patients with schizophrenia do not achieve satisfactory outcomes or experience intolerable side effects. Therefore, there is an urgent need for novel agents that can target the underlying pathophysiology of schizophrenia and offer better efficacy and tolerability.
One promising avenue of research is the modulation of non-dopaminergic neurotransmitter systems that are implicated in schizophrenia, such as glutamate, serotonin, acetylcholine, and trace amines. Some examples of novel agents with these mechanisms of action are:
– Muscarinic receptor agonists: These agents stimulate the muscarinic acetylcholine receptors that are involved in cognitive processes. They may improve cognitive function and negative symptoms in patients with schizophrenia. One example is xanomeline-trospium (KarXT), which is a combination of a muscarinic receptor agonist (xanomeline) and an anticholinergic agent (trospium) that reduces peripheral side effects. KarXT has shown positive results in a phase 2 trial for acute schizophrenia (Kantrowitz et al., 2020).
– Trace amine-associated receptor 1 (TAAR1) agonists: These agents activate the TAAR1 receptors that modulate dopamine release and signaling. They may have antipsychotic effects without causing EPS or metabolic disturbances. One example is SEP-363856 (Sunovion), which is a novel agent that acts as a TAAR1 agonist and a serotonin 5-HT1A receptor agonist. SEP-363856 has demonstrated efficacy and safety in two phase 3 trials for acute schizophrenia (Correll et al., 2020; Cutler et al., 2020).
– Serotonin receptor antagonists/inverse agonists: These agents block or inhibit the activity of various serotonin receptors that are involved in mood regulation and sensory processing. They may reduce positive symptoms and improve mood in patients with schizophrenia. One example is pimavanserin (Acadia), which is a selective serotonin 5-HT2A receptor inverse agonist that is approved for the treatment of psychosis associated with Parkinson’s disease. Pimavanserin is currently being investigated in phase 3 trials for schizophrenia (ADVANCE and CLARITY studies).
– Glutamatergic modulators: These agents affect the glutamate system that is responsible for synaptic plasticity and learning. They may enhance cognitive function and reduce positive and negative symptoms in patients with schizophrenia. One example is rapastinel (Allergan), which is a glycine site partial agonist of the N-methyl-D-aspartate (NMDA) receptor that enhances glutamatergic transmission. Rapastinel has shown positive results in a phase 2 trial for adjunctive treatment of schizophrenia (Preskorn et al., 2018).
Schizophrenia is a complex and challenging disorder that requires lifelong treatment and support. Current treatment options are limited by suboptimal efficacy and troublesome side effects. Novel agents with different mechanisms of action are being developed to address the unmet needs of patients with schizophrenia. These agents may offer improved outcomes in terms of symptom reduction, cognitive enhancement, functional recovery, and quality of life improvement.
Correll, C. U., et al. “Efficacy and Safety of the Novel Psychotropic Agent SEP-363856 in Acute Schizophrenia: Results From a Randomized, Double-Blind, Placebo-Controlled Trial.” The American Journal of Psychiatry, vol. 177, no. 10, 2020, pp. 940-948.
Cutler, A. J., et al. “Efficacy and Safety of SEP-363856 in Patients With Acute Schizophrenia: Results From a 4-Week, Randomized, Double-Blind, Placebo-Controlled Trial.” The Journal of Clinical Psychiatry, vol. 81, no. 6, 2020.
Kantrowitz, J. T., et al. “Muscarinic Receptor Agonist Treatment Reduces Symptoms in Schizophrenia.” The New England Journal of Medicine, vol. 383, no. 24, 2020, pp. 2334-2345.
Preskorn, S., et al. “A Randomized Proof of Concept Trial of Adjunctive Rapastinel (Formerly GLYX-13) in Major Depressive Disorder With Suicidal Ideation.” The Journal of Clinical Psychiatry, vol. 79, no. 6, 2018.
World Health Organization. “Schizophrenia.” WHO, https://www.who.int/news-room/fact-sheets/detail/schizophrenia. Accessed 14 Nov. 2023.