Cardiovascular Problems May Worsen Cognition in People With Schizophrenia

Risk factors for cardiovascular disease (CVD), such as metabolic disorders, diabetes, or hypertension, are significantly associated with cognitive deficits in patients with schizophrenia, according to a study published in JAMA Psychiatry.

The findings point to the importance of efforts to address risk factors for cardiovascular disease in these patients to help prevent further deterioration in cognition and improve functioning, wrote Katsuhiko Hagi, Ph.D., of Sumitomo Dainippon Pharma in Tokyo, Japan, Jean Pierre Lindenmayer, M.D., of the New York University School of Medicine, and colleagues.

Hagi and colleagues searched databases including Embase, Scopus, MEDLINE, PubMed, and Cochrane for studies on cognitive functioning in patients with schizophrenia or schizoaffective disorder and the association of CVD risk factors (including metabolic syndrome, diabetes, obesity, hypertension, and others). The studies also compared cognitive performance between those with and without CVD risk factors.

In total, 27 studies were included in the analysis, representing 10,174 individuals with schizophrenia. The authors identified significantly greater cognitive deficits in patients who had metabolic disorders, diabetes, or hypertension compared with those who did not have those disorders. Further, these patients performed worse on reasoning/problem solving, speed of processing, and verbal learning compared with patients without these disorders. Cognitive impairment was not significantly associated with being overweight or obese.

The authors noted that pharmacological interventions and other lifestyle changes, such as diet, for cardiovascular risk factors are treatment options for individuals with schizophrenia. However, they added, implementing such interventions can be challenging since people with schizophrenia have such low rates of access to care.

“Routine physical health monitoring and interventions to improve physical health in people with schizophrenia are urgently needed to maintain or restore physical and mental health and improve functional outcomes,” Hagi and colleagues wrote. “Collaborative care models that integrate behavioral and medical care are likely to be particularly useful for addressing CVD risk in those with schizophrenia.”

For related information, see the Psychiatric News article “Cardioprotective Treatments After Heart Attack Can Help Patients With Schizophrenia Live Longer.”

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Aripiprazole Found to Have Fewer Side Effects in Teens With First-Episode Psychosis

Young people with first-episode psychosis (FEP) who are treated with extended-release quetiapine gain more weight and experience worse metabolic effects—including increased lipids, insulin, triglycerides, and total cholesterol—than patients treated with aripiprazole, according to a report in the Journal of the Academy of Child and Adolescent Psychiatry.

“These differences emerged early, are clinically relevant, and should inform treatment choice for youths with early onset psychosis,” especially since studies have shown the two medications are equally effective in treating symptoms, say Karsten Gjessing Jensen, M.D., Ph.D., of the University of Copenhagen and colleagues.

The researchers analyzed data on 113 youth aged 12 to 17 with FEP who were randomized to 12 weeks of extended-release quetiapine (quetiapine-ER) or aripiprazole as part of the Tolerability and Efficacy of Antipsychotics trial. The trial was conducted from June 2010 to April 2014 in seven university child and adolescent psychiatry departments across Denmark.

The primary outcome was change in body weight; secondary outcomes were changes in body mass index (BMI), waist circumference, blood pressure, heart rate, and lipid and glucose metabolism measures. Patients were assessed and blood samples taken at 4 and 12 weeks. The researchers also examined family history for factors that might predict how youth would respond on weight and metabolic measures.

Treatment with quetiapine-ER was associated with greater weight gain at 4 and 12 weeks (2.24 kg and 4.88, respectively) than aripiprazole (0.45 kg at 4 weeks and 1.97 kg at 12 weeks). Patients treated with quetiapine-ER also had increased metabolic measures—including cholesterol, triglycerides, and hyperinsulinemia—than patients treated with aripiprazole. Of the patients in the quetiapine-ER group, 14% had metabolic syndrome at week 12 compared with 8.3% in the aripiprazole group. Family factors that predicted weight gain and BMI in youth were early weight gain, obesity, or type 2 diabetes.

The researchers noted that, aside from the health effects, weight gain is likely to be stigmatizing for young people who may already be marginalized because of their psychosis. “Youths with psychotic disorders are a highly vulnerable patient group who may already feel marginalized by their peers, so that a weight gain of 5 kg may be yet another cause of (self-)stigmatization that may increase the risk of treatment discontinuation and that may impair the alliance between patients and health care providers,” they wrote.

For related information, see the Psychiatric News article “SGAs Increase Teens’ Abdominal Fat, Decrease Insulin Sensitivity.”

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Benefits of Antipsychotics Appear to Outweigh Risks, Experts Conclude

Despite recent concerns that long-term antipsychotic use adversely affects health outcomes—possibly by desensitizing dopamine receptors or through direct neurotoxic effects—a review article in AJP in Advance has concluded that the benefits of antipsychotics for the acute treatment of psychosis and the prevention of relapse largely outweigh the risks. Additionally, because delays in the treatment of psychosis and relapse have been associated with poorer outcomes, the review noted there may be risk associated with withholding or discontinuing medication.

“Patients and their families should be made aware of the strong evidence supporting antipsychotic efficacy and of the side effects that vary between drugs,” wrote an international panel of experts in antipsychotic pharmacology, neuroimaging, and neuropathology led by Donald Goff, M.D. “Additional research is needed to help quantify the risk-benefit ratio associated with continuation compared with discontinuation of antipsychotic treatment and to identify predictive biomarkers in order to facilitate shared decision making and a personalized medicine approach.”

Based on a review of available clinical and preclinical evidence of antipsychotic benefits and risks, the panel drew several conclusions:

• The efficacy of antipsychotics for the initial treatment of psychosis and maintenance treatment for the prevention of relapse is well established. Evidence from controlled clinical trials that initial antipsychotic treatment worsens the long-term course of the illness “is not compelling,” the authors wrote.
• A subgroup of patients, which may be as large as 20%, may maintain remission or partial remission for extended periods off medication. The use of low doses or of medication discontinuation may have long-term benefits for some patients, but there are currently no biomarkers that can help identify this subset of patients.
• Evidence linking a reduction in brain volume to antipsychotic treatment is “potentially confounded by the underlying illness and by uncertainty whether higher antipsychotic dosing is a response to, or a contributor to, progressive brain volume loss.”
• Despite evidence from animal models that antipsychotics can produce D2 receptor sensitization and D1 receptor desensitization, “clinical studies have not provided compelling evidence that treatment with antipsychotics worsens the course of illness, increases risk of relapse, or causes cognitive deficits.”

“Although not covered in this review, medical morbidity and mortality associated with antipsychotic use is highly relevant to decisions about long-term treatment,” the authors added. “Many antipsychotics increase risk for metabolic syndrome and thus the risk of heart disease, diabetes, and stroke, which are among the common causes of premature mortality in schizophrenia.”

For related information, see the Psychiatric News article “Does Aggressive Treatment of Psychosis Mean Sustained Use of Antipsychotics?”

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Risks of Adding Antipsychotics to Mood Stabilizer May Outweigh Benefits After 6 Months

Following an acute manic episode, many patients with bipolar disorder are treated with a combination of a mood stabilizer and an atypical antipsychotic to reduce the risk of a manic relapse. However, due to the side effects of antipsychotics—including weight gain and metabolic syndrome—most agree that antipsychotic therapy should be maintained only if the benefits of using the medication can be shown to outweigh the risks.

A study published last month in Molecular Psychiatry suggests six months of adjunctive antipsychotic therapy is helpful in reducing mania relapse, but beyond that there is limited benefit.

Lakshmi Yatham, M.D. (pictured above), of the Department of Psychiatry at the University of British Columbia and colleagues recruited patients with bipolar I disorder who had recently remitted from a manic episode following treatment with a mood stabilizer (lithium or valproate) and antipsychotic (risperidone or olanzapine). Patients were randomly assigned to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at the trial’s start (“0-week group”) or 24 weeks after entry, or continuation of the antipsychotic therapy throughout the 52-week trial.

The researchers found that patients on antipsychotics and mood stabilizers for 24 weeks following remission of their manic episode had about half the risk of relapse as patients who tapered off antipsychotics following remission (the 0-week group) and the same relapse risk as patients taking antipsychotics for the full 52 weeks. The 24-week group gained an average of 0.1 kg while the 52-week group gained an average of 3.2 kg; the 0-week group lost 0.2 kg on average.

The findings suggest that when weighing the risks and benefits of risperidone or olanzapine adjunctive therapy, 24 weeks may be the best option, Yatham told Psychiatric News.

For the complete report, click here.

(Image: Martin Dee/UBC )