Challenges Associated with Schizophrenia

San Antonio—In the United States, 2.4 million people suffer from schizophrenia, a disease caused by genetics, brain chemistry, or environmental factors and typically occurring between 16 and 35 years of age. Although schizophrenia is better understood today, there are variations among people with regards to their symptoms, the course of the illness, and the treatment response.

At the AMCP meeting, speakers discussed the challenges in managing schizophrenia:

• Treating negative and cognitive defects

• Achieving and maintaining remission

• Handling serious adverse effects

• Having people adhere to their medications

• Returning patients to normal functioning

They spoke during a satellite symposium titled New Mechanisms, New Measures in the Schizophrenia Treatment Landscape. Genentech supported the session with an educational grant.

Steven Stoner, PharmD, chair of the division of pharmacy practice and administration at the University of Missouri-Kansas City School of Pharmacy, said schizophrenia is more prevalent than rheumatoid arthritis and multiple sclerosis.

Features of schizophrenia include:

• Psychotic symptoms, such as hallucinations, delusions, and movement disorders

• Negative signs, such as flat affect, lack of pleasure, and social withdrawal

• Cognitive signs, such as poor executive function, sustained difficulty paying attention, disorganized thoughts, and diminished working memory

Evaluating for Schizophrenia

There are numerous assessments used to evaluate schizophrenia, including the Positive and Negative Syndrome Scale, the Clinical Global Impression Improvement, Scale, the Personal and Social Performance Scale, and the Scale for the Assessment of Negative Symptoms.

Dr. Stoner noted that the book Surviving Schizophrenia found that after 10 and 30 years, 25% of people diagnosed with schizophrenia had completely recovered. After 10 years, 25% were much improved and relatively independent, 25% were improved but required extensive support, 15% were hospitalized and unimproved, and 10% had died. After 30 years, 35% were much improved and relatively independent, 15% were improved but required extensive support, 10% were hospitalized and unimproved, and 15% had died. The most common cause of death was suicide.

Dr. Stoner defined remission as patients who have mild symptoms that do not significantly affect their behavior and have improvement for at least 6 months. Patients are more likely to have remission if they have an early treatment response, younger age, shorter duration of illness, better psychological status before treatment, fewer negative and depressive symptoms, and fewer adverse events.

If patients are in remission for the long-term, Dr. Stoner said they have reduced healthcare utilization, reduced healthcare costs, improved quality of life, and improved social and/or vocational functioning. However, most people do not have long-term remission.

A systematic review and meta-analysis that Dr. Stoner cited found that within 12 months of treatment, 17% to 78% of patients will attain remission, but approximately 80% of patients will relapse within 5 years. The definitions of relapse varied in the groups, but they included worsening symptoms and re-hospitalization. Relapses are associated with an increased risk of long-term psychotic symptoms, rising treatment costs, and a possible decrease in medication efficacy.

Another study of 200 patients with schizophrenia found that 57% experienced at least 1 relapse within a year, which the authors defined as worsening of symptoms or re-hospitalization within 1 year of being discharged from the hospital [Psychiatric Serv. 2012;63(1):87-90]. Relapses were common in patients who did not respond to treatment at discharge, were not in remission at discharge, and were not receiving atypical antipsychotics.

Even if patients receive care for schizophrenia, it is typically substandard, according to Dr. Stoner. Despite being treated, many patients remain symptomatic and disabled because providers do not use the best evidence-based medicine and do a poor job continuing with care over the long-term. Dr. Stoner said patients with mental health conditions also do not usually receive appropriate screening or treatment for diabetes, hypertension, dyslipidemia, or cancer.

Treating Schizophrenia

Dr. Stoner discussed a few Healthcare Effectiveness Data and Information Set (HEDIS) measures from the National Committee for Quality Assurance. He said that approximately 55% of patients with mental illness who were enrolled in Medicaid did not receive outpatient discharge after being discharged from the hospital. Meanwhile, approximately 50% of Medicaid enrollees from 19 to 64 years of age with schizophrenia did not remain on their antipsychotic regimen for at least 80% of the treatment period.

In addition, more than 70% of patients with schizophrenia did not receive regular glucose monitoring after they were prescribed an antipsychotic medication, while patients with schizophrenia and diabetes were less likely to receive hemoglobin A1C testing compared with patients who only had diabetes. Further, patients with schizophrenia and cardiovascular disease (CVD) were 40% less likely to meet cholesterol control measurements. Dr. Stoner said that atypical antipsychotics can lead to weight gain, hypertension, hyperglycemia, and hyperlipidemia, which can increase the risk of CVD.

When evaluating medication adherence, Dr. Stoner said healthcare professionals can analyze pharmacy claims and prescription refill dates, use electronic medication monitors, utilize pill counts, and have patients keep a diary or answer a questionnaire.

Symptoms and Side Effects of Treatment

Daniel C. Javitt, director at the Nathan Kline Institute for Psychiatric Research in Orangeburg, New York, said that patients with schizophrenia have abnormalities in brain structure, function, and neurochemistry. They are usually treated with medications affecting the dopamine and serotonin systems, although the drugs are not ideal, according to Dr. Javitt. The drugs provide limited efficacy for reducing primary negative symptoms and cognitive defects and are associated with intolerable adverse events such as extrapyramidal symptoms, lethargy, and weight gain.

Dr. Javitt said approximately 58% of patients with schizophrenia have at least 1 negative symptom, which are associated with poor adherence and chronic disability. To treat negative symptoms, studies have examined using drugs intended for sleep disorders, attention deficit hyperactivity disorder, depression, and dementia, but the efficacy was modest.

Pharmaceutical companies are developing drugs that target negative symptoms, according to Dr. Javitt. They are also manufacturing glutamatergic and glycinergic agents for patients with schizophrenia.

If glutamate modulators are effective at reducing negative symptoms, Dr. Javitt said patients with acute psychosis will continue to use typical or atypical antipsychotics, although the doses will be lower and time-limited. In addition, n-methyl-D-aspartate receptor-based treatments will be started early and could become the primary medications.

Dr. Javitt added that patients with movement disorders or obsessive compulsive disorder may also benefit from glutamate modulators. He also mentioned that if glutamate modulators are effective at reducing negative symptoms, the diagnosis of schizophrenia could be modified to only include patients with negative symptoms.