Relapse Rates Decrease With Olanzapine, Sertraline Combination

Alastair Flint, MB

New research suggests continuing antipsychotic medication can reduce the risk of relapse for psychotic depression patients in remission.

Alastair J. Flint, MB, recently led a team in a randomized clinical trial including 126 participants older than 18 who had an episode of psychotic depression acutely treated with sertraline and olanzapine for up to 12 weeks and met the criteria for remission of psychosis and remission or near-remission of depressive symptoms for the 8 weeks prior to the beginning of the trial.

The investigators found that 13 of the 64 participants taking sertraline with olanzapine and 34 of the 62 volunteers taking sertraline with a placebo experienced a relapse (HR, 0.25; 95% CI, 0.13-0.48; P <&thinsp;.001). All of the participants in the study continued taking sertraline.

The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11-0.15), waist circumference (0.009 inches; 95% CI, 0.004-0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13-0.45).

However, the daily rates were not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, −0.01-0.10), high-density lipoprotein cholesterol (−0.01 mg/dL; 95% CI, −0.03-0.01), triglyceride (−0.153 mg/dL; 95% CI, −0.306-0.004), glucose (−0.02 mg/dL; 95% CI, −0.12-0.08), or HbA1c levels (−0.0002 mg/dL; 95% CI, −0.0021-0.0016).

The mean age of the study’s population was 55, with nearly 62% of the 126 participants being women.

At the beginning of the study when the participants were being randomized, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d).

There is not currently much known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission. The primary outcome of the study was the risk of relapse, with secondary outcomes being weight, waist circumference, lipids, serum glucose and hemoglobin A1c (HbA1c).

“Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks,” the authors wrote. “This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain.”

In a 2018 study, investigators reported that even short-term antipsychotic treatment for a nonpsychotic condition in children can increase body fat and decrease the body’s sensitivity to insulin — leaving pediatric patients at greater risk of developing diabetes.

From June 2006 through November 2010, researchers recruited 144 antipsychotic-naïve children and adolescents aged 6-18 years old from the St. Louis metropolitan area who had been diagnosed with 1 or more psychiatric disorders and clinically significant aggression. Researchers randomized the participants 1:1:1 to receive 12-week regimen of oral aripiprazole (n= 49), olanzapine (n= 46), or risperidone (n= 49).

Each of the therapies are common antipsychotics prescribed to children with disruptive behavioral disorders. Among the patients, mean age was 11.3 years, a majority (51.4%) were African American, and 29.9% were overweight or obese at baseline.

Researchers measured for percentage total body fat as per dual-energy x-ray absorptiometry (DXA), and insulin sensitivity in muscle via hyperinsulinemic clamps with stable isotopically labeled tracers. From baseline to week 12, DXA percentage total body fat increased 4.12% in patients receiving olanzapine, 1.66% in patients on aripiprazole, and 1.18% in patients on risperidone (P < .001).

Insulin-stimulated change in glucose rate of disappearance increased 30.26% in patients on aripiprazole, 29.34% in patients on olanzapine, and 2.3% for patients on risperidone, with no significant difference across medications. However, Newcomer theorized this may have been due to the smaller patient population.

For secondary outcomes such as MRI-measured abdominal fat increase, patients on olanzapine reported significantly greater fat gains than patients on risperidone or aripiprazole (P = .003). Overall, patients reported improvements in behavior.

The study, “Effect of Continuing Olanzapine vs Placebo on Relapse Among Patients With Psychotic Depression in Remission The STOP-PD II Randomized Clinical Trial,” was published online in JAMA.