According to research published in European Psychiatry, comedication with selective serotonin reuptake inhibitors (SSRIs) and olanzapine or quetiapine led to modest deterioration in metabolic variables, and no changes were reported when SSRIs were combined with risperidone. This suggests that SSRIs combined with antipsychotics may not increase cardiovascular risk.

In this cross-sectional study, 868 patients with schizophrenia and 433 patients with bipolar disorder from the Norwegian Thematically Organized Psychosis study were enrolled.

To evaluate the impact of comedication with SSRIs and antipsychotics, the researchers considered the association of metabolic variables with the dose and serum concentration of SSRIs (n=280), olanzapine (n=398), quetiapine (n=234), and risperidone (n=128).

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After adjustment for confounding variables, comedication with a defined daily dose of SSRI and olanzapine was associated with a mean increase in total cholesterol of 0.16 mmol/L (P =.042) and an increase in low-density lipoprotein- (LDL-) cholesterol of 0.17 mmol/L (P =.022).

In a similar fashion, an SSRI serum concentration in the middle of the reference interval and quetiapine was associated with a mean increase in total cholesterol of 0.39 mmol/L (P =.011) and an increase of LDL-cholesterol of 0.29 mmol/L (P =.037).

No significant association between SSRI and risperidone comedication was found for total cholesterol, LDL-cholesterol, or high-density lipoprotein-cholesterol. Risperidone combined with an SSRI was associated with a mean decrease in glucose concentration of 0.32 mmol/L.

“The SSRI associations with total cholesterol, LDL-cholesterol, and glucose were, although statistically significant, numerically small,” the researchers wrote.

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They concluded that the results suggested that “a combination of an SSRI and such antipsychotics in a clinical setting most likely does not lead to a further deterioration of metabolic variables to a clinically significant degree. However, thorough metabolic monitoring should be performed when these medications are used in combination, as for antipsychotics used alone.”

Disclosure: Dr Ole A. Andreassen has received speaker honoraria from GSK, Lundbeck, and Otsuka, and only from Lundbeck during the last three years.


Fjukstad KK, Engum A, Lydersen S, et al. Metabolic risk factors in schizophrenia and bipolar disorder: the effect of comedication with selective serotonin reuptake inhibitors and antipsychotics. Eur Psychiatry. 2017;48:71-78.

This article originally appeared on Psychiatry Advisor