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Reducing antipsychotic dosage feasible, effective among patients with late-life schizophrenia

Results from an open-label, single-arm prospective study indicate that reducing dosage of antipsychotics is feasible among patients with late-life schizophrenia and can improve extrapyramidal symptoms, hyperprolactinemia and other symptoms related to increases in dopamine D_2/3 receptor occupancies.

“Schizophrenia is a life-long illness that typically requires maintenance antipsychotic treatment throughout an individual’s life… Clinical guidelines developed by expert consensus recommend the use of lower doses of antipsychotics in older patients with schizophrenia. However, empirical data on age-specific antipsychotic dosing are limited,” study researcher Ariel Graff-Guerrero, MD, PhD, of the Centre for Addiction and Mental Health in Toronto, and colleagues wrote.

To investigate the effects of antipsychotic dose reduction on dopamine D_2/3 receptor (D_2/3R) occupancies and clinical variables among patients with late-life schizophrenia, researchers evaluated patients aged 50 years or older with clinically stable schizophrenia receiving olanzapine (n = 22 ) or risperidone (n = 13) for 6 to 12 months. Positron emission tomography (PET) scans determined dopamine D_2/3R occupancies at baseline. Antipsychotic dosage was gradually reduced up to 40% of patients’ baseline dose or to the lower limit of the recommended dosage range. Clinical assessment and PET scans were conducted 2 weeks after the final target dose was reached and patients were subsequently followed for 3 to 6 months.

Overall, dopamine D_2/3R occupancy of the entire study cohort decreased by a mean of 6.2% following dose reduction (from 70% to 64%; P < .001).

The lowest dopamine D_2/3R occupancy associated with clinical stability was 50%.

Targeted Inventory on Problems in Schizophrenia scores increased (P = .046) following dose reduction, while Positive and Negative Syndrome Scale (P = .02), Brief Psychiatric Rating Scale (P = .03), Simpson-Angus Scale (P < .001), Barnes Rating Scale for Drug-Induced Akathisia (P = .03) and Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (P < .001) scores decreased.

Prolactin (P < .001) and blood antipsychotic levels (olanzapine, P < .001; risperidone plus metabolite 9-hydroxyrisperidone, P = .02) also decreased following dose reduction.

“Our study demonstrates that antipsychotic dose reduction is feasible in most patients with stable [late-life schizophrenia]. Antipsychotic dose reduction can improve [extrapyramidal symptoms], hyperprolactinemia, and some symptoms through decreases in D_2/3R occupancy,” Graff-Guerrero and colleagues wrote. “Our results also suggest that the striatal D_2/3R occupancy threshold for antipsychotic therapeutic effects is lower (ie, 50%) in patients with [late-life schizophrenia] than in younger patients (65%), which has a significant implication of the management of this specific and ever-growing [late-life schizophrenia] population.” – by Amanda Oldt

Disclosure: Graff-Guerrero reports receiving research support from the Canadian Institutes of Health Research, U.S. National Institutes of Health, Ontario Mental Health Foundation, Brain and Behavior Research Foundation, Mexico Institute of Science and Technology of the Federal District and the National Council of Science and Technology and W. Garfield Weston Foundation. Please see the full study for a list of all other authors’ relevant financial disclosures.