Schizophrenia is a challenging disease to treat. It requires lifelong management even in patients without apparent symptoms.

Patients with this disease present with a range of symptoms that impact cognition, moods, and behaviors. Treatment of schizophrenia can be further complicated by medication nonadherence and further comorbidities, amplifying this disorder’s toll on society.

 

First-episode psychosis

Previous research has suggested that patients transitioning between adolescence and adulthood who exhibit first-episode psychosis do not generally seek help.

During this period, which has been referred to as the duration of untreated psychosis (DUP), patients may experience 1–2 years of manifesting psychotic symptoms before seeking help. Often, it’s not the patient who seeks help, but rather their family members.

“The individual with the first signs of psychosis usually presents with difficulties talking about these symptoms with other people or even seeking help at all,” wrote the authors of a study published in the International Journal of Nursing Sciences (IJNS).

Martin IDS, Ciccone Giacon BC, Giacchero Vedana KG, et al. Where to seek help? Barriers to beginning treatment during the first-episode psychosis. Int J Nurs Sci. 2018;5(3):249–254.

“So the family member, as the main point of support, becomes responsible for the search for treatment in the health services.”

 

Delayed treatment can also lead to worsening positive symptoms, poor quality of life, and greater difficulty in attaining remission. Consequently, researchers have focused on decreasing DUP to improve treatment response, according to the IJNS research.

In the study, the researchers identified many barriers to proper diagnosis and treatment in younger people during the DUP. These included stigma and a lack of knowledge about the condition by family members and professionals interacting with these struggling individuals.

 

Issues with adherence

Although antipsychotic medications decrease disease severity and relapse rates, nonadherence to medication regimens is common in patients with schizophrenia.

It’s estimated that although 80% of patients with schizophrenia would benefit from first-line antipsychotic therapy, about half of patients who respond well to these drugs don’t take them, according to research published by the American Journal of Managed Care (AJMC).

Goldstone LW. Unmet medical needs and other challenges in the treatment of patients with schizophrenia. Am J Manag Care. 2020;26(3 Suppl):S48–S54.

 

Cognitive impairment may leave the patient lacking insight into their need for antipsychotics. Some patients believe that they don’t need the medications, whereas others don’t want to take them due to forgetfulness or financial constraints.

Various environmental factors may play a role in nonadherence, including newly initiated treatment, younger/older age of onset, lack of social support, substance misuse, and stigmatization.

Results of the AJMC study indicated that adherence was 19% lower among patients whose clinicians were viewed as poor rather than strong communicators. Physicians who fail to establish a therapeutic alliance or effectively communicate diagnosis and treatment with patients and their families increase the risk of patient non-adherence.

Patients also may not adhere to antipsychotic treatments because they question the efficacy of the drugs when treating chronic symptoms, don’t want to experience adverse events, or don’t like complex treatment regimens.

Positive and negative symptoms can impact how a patient feels about treatment, the author of the AJMC research found.

Nonadherence to therapy is often the culprit behind exacerbations in psychopathology, symptom relapse, and rehospitalization, and it is also a problem that is likely preventable.

“Nonadherence to therapy results in poor health and economic outcomes, including increased hospitalization rates and subsequent greater resource usage,” the author added.

 

Comorbidities

Patients with schizophrenia exhibit various comorbidities that make it difficult to manage the disease and yield positive clinical outcomes, according to the AJMC research. Common comorbidities in patients with schizophrenia include other psychiatric illnesses, metabolic syndrome, heart disease, sexual dysfunction, and infectious disease.

Illicit drug use is a particularly intractable problem in the schizophrenia patient population, with about 27.5% of these patients using illicit substances.

The prevalence of comorbid substance use disorder is about 41.7% in patients with schizophrenia, a statistic that has held over time despite efforts to address this problem, the AJMC author wrote.

 

Lack of innovation

Schizophrenia treatment has been marked by the use of drugs that block dopamine D2 receptors as their main mechanism of action since the mid-1950s, according to a study published in Current Medical Research and Opinion (CMRO).

Hopkins SC, Lew R, Zeni C, et al. Challenges in the clinical development of non-D2 compounds for schizophrenia. Curr Med Res Opin. 2022:1–5.

 

These drugs, however, only partially resolve symptoms, and some patients are nonresponsive. They can also lead to extrapyramidal symptoms and other unwanted adverse effects.

Although there has been substantial investment into the discovery of non-D2 drug candidates, these efforts have yet to bear fruit in terms of regulatory approvals. In the CMRO study, US investigators found that between 2002 and 2022, the total enrollment in trials of non-D2-based agents for the treatment of schizophrenia was 34,000 participants vs 27,144 participants in trials of D2-based agents.

“These data indicate that there remains substantial and ongoing investment in the development of novel non-D2 options for schizophrenia, with a success rate measured by regulatory approval that is well below recent benchmarks for the broader category of CNS drugs,” the authors wrote.

Improved trial design, conduct, endpoints, and analyses/methods may influence signal detection and reliability to support development and registration of non-D2 compounds.