High Prolactin Levels Signal Antipsychotic Toxicity

Fran Lowry

June 07, 2016

SCOTTSDALE, Arizona ― In older patients with schizophrenia who are taking antipsychotics, measuring prolactin levels in the blood is a good way to monitor for toxicity.

"Clinicians can now use prolactin levels to help them monitor the dose of the antipsychotic, and if the prolactin is too high, probably the dose is too high," lead researcher Ariel Graff- Guerrero, MD, Centre for Addiction and Mental Health, University of Toronto, Canada, told Medscape Medical News.

"This is something clinicians can easily monitor to make sure they are giving the right dose. Every time you change the medication, you can do this to make sure that the dose is not too high," Dr Graff-Guerrero said.

The findings were presented at the American Society of Clinical Psychopharmacology (ASCP) 2016 Annual Meeting.

Investigators detailed the results of imaging studies in which plasma levels of prolactin correlated with dopamine D2/3 receptor occupancy.

"We used positron-emission tomography [PET] to quantify how much of the dopamine receptors were blocked by the antipsychotics. We know that in younger patients, there is a therapeutic window in which they are more likely to respond to the drugs if at least 60% of the dopamine receptors are blocked. But if more than 80% are blocked, this can cause side effects," said Dr Graff- Guerrero.

"PET is expensive and not as widely available except in places that do research, but prolactin is something that can be quantified in any clinical lab and doesn't require any sophisticated research environment, and in this work, we have shown a linear relationship between prolactin levels and dopamine receptor occupancy. All the clinician needs to do now is measure the prolactin levels," he said.

Older Patients More Sensitive

The study included 42 clinically stable outpatients with schizophrenia (mean age, 60 years; range, 53 to 67 years) who were taking olanzapine (multiple brands) or risperidone (Risperdal, Janssen Pharmaceuticals, Inc).

The participants underwent PET scans to measure dopamine D2/3 receptor occupancy before and after their dose of drug was reduced by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels.

Prolactin levels in the blood decreased after dose reduction, going from a mean of 24 ng/mL to 17 ng/mL (P < .001).

Those participants with dopamine D2/3 receptor occupancy higher than 66% were more likely to have hyperprolactinemia than those with D2/3 receptor occupancy lower than 66% (P = .03).

The sensitivity of this threshold was 0.44, the specificity was 0.81, the positive predictive value was 0.78, and the negative predictive value was 0.48.

"The dopamine D2/3 receptor occupancy threshold for hyperprolactinemia of 66% in these older patients is lower than that in younger patients, which is 73%," said Dr Graff-Guerrero.

"This extends the age range of previous studies that were done in younger patients. Our results suggest a higher sensitivity to antipsychotics in older patients," he added.

Improved Safety

Commenting on the findings for Medscape Medical News, Alan J. Gelenberg, MD, professor emeritus, University of Arizona, Tucson, noted that older individuals "tend to be more sensitive than younger adults to the adverse effects of medications.

"This study demonstrates that older patients have a greater likelihood of developing hyperprolactinemia on exposure to antipsychotics. The data can sensitize clinicians to monitor prolactin levels and be aware of signs and symptoms of elevated prolactin levels in antipsychotic-treated patients, especially in the geriatric population," he said.

Stanley N. Caroff, MD, professor, Perelman School of Medicine, University of Pennsylvania, Philadelphia, agreed.

"This was a well-done study from a well-established research group. They determined that a lower level of prolactin was still significant for potential side effects in older patients," Dr Caroff said.

"Correlating prolactin levels with PET scans of the brain gives it scientific validity and also practical applications in improving the safety and tolerability of drug treatment for older patients," he said.

Dr Graff-Guerrero, Dr Gelenberg, and Dr Caroff report no relevant financial relationships.

American Society of Clinical Psychopharmacology (ASCP) 2016 Annual Meeting: Abstract 3000477, presented June 1, 2016.

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