new research suggests.
Investigators analyzed 1-year data for more than 400 patients who were taking risperidone and/or its metabolite paliperidone (Invega). Results showed increments of 1 mg of risperidone-equivalent doses were associated with an increase of 0.25% of weight within a year of follow-up.
“Although our findings report a positive and statistically significant dose-dependence of weight gain and cholesterol, both total and LDL [cholesterol], the size of the predicted changes of metabolic effects is clinically nonrelevant,” lead author Marianna Piras, PharmD, Centre for Psychiatric Neuroscience, Lausanne (Switzerland) University Hospital, said in an interview.
“Therefore, dose lowering would not have a beneficial effect on attenuating weight gain or cholesterol increases and could lead to psychiatric decompensation,” said Ms. Piras, who is also a PhD candidate in the unit of pharmacogenetics and clinical psychopharmacology at the University of Lausanne.
However, she added that because dose increments could increase risk for significant weight gain in the first month of treatment – the dose can be increased typically in a range of 1-10 grams – and strong dose increments could contribute to metabolic worsening over time, “risperidone minimum effective doses should be preferred.”
The findings were published online in the Journal of Clinical Psychiatry.
‘Serious public health issue’
Compared with the general population, patients with mental illness present with a greater prevalence of metabolic disorders. In addition, several psychotropic medications, including antipsychotics, can induce metabolic alterations such as weight gain, the investigators noted.
Antipsychotic-induced metabolic adverse effects “constitute a serious public health issue” because they are risk factors for cardiovascular diseases such as obesity and/or dyslipidemia, “which have been associated with a 10-year reduced life expectancy in the psychiatric population,” Ms. Piras said.
“The dose-dependence of metabolic adverse effects is a debated subject that needs to be assessed for each psychotropic drug known to induce weight gain,” she added.
Several previous studies have examined whether there is a dose-related effect of antipsychotics on metabolic parameters, “with some results suggesting that [weight gain] seems to develop even when low off-label doses are prescribed,” Ms. Piras noted.
She and her colleagues had already studied dose-related metabolic effects of quetiapine (Seroquel) and olanzapine (Zyprexa).
Risperidone is an antipsychotic with a “medium to high metabolic risk profile,” the researchers note, and few studies have examined the impact of risperidone on metabolic parameters other than weight gain.
For the current analysis, they analyzed data from a longitudinal study that included 438 patients (mean age, 40.7 years; 50.7% men) who started treatment with risperidone and/or paliperidone between 2007 and 2018.
The participants had diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, depression, “other,” or “unknown.”
Clinical follow-up periods were up to a year, but were no shorter than 3 weeks. The investigators also assessed the data at different time intervals at 1, 3, 6, and 12 months “to appreciate the evolution of the metabolic parameters.”
In addition, they collected demographic and clinical information, such as comorbidities, and measured patients’ weight, height, waist circumference, blood pressure, plasma glucose, and lipids at baseline and at 1, 3, and 12 months and then annually. Weight, waist circumference, and BP were also assessed at 2 and 6 months.
Doses of paliperidone were converted into risperidone-equivalent doses.