Metformin May Reduce High Cholesterol in Patients Taking Antipsychotics
Abstract
Antipsychotics can cause numerous side effects, including weight gain and metabolic abnormalities. The off-label use of the type 2 diabetes medication metformin may be able to help patients who are unable to switch to a lower-risk antipsychotic.
Despite the great benefit that second-generation antipsychotics can offer patients with schizophrenia and other psychiatric disorders, taking them can lead to serious side effects for some patients, including a high risk of weight gain and metabolic abnormalities.
To help minimize this risk, experts advise that clinicians discuss the importance of healthy eating and regular exercise with patients before prescribing antipsychotics; monitor any changes in weight, blood pressure, or fasting plasma glucose and lipid levels after initiating therapy; and, if significant changes are detected, consider switching patients to a lower-risk antipsychotic.
If switching antipsychotics is not an option, a growing body of literature suggests that the off-label use of metformin—approved for the treatment of type 2 diabetes—may be able to reduce antipsychotic-induced weight gain and insulin resistance. A study published last month in Molecular Psychiatry also suggests that the medication may reduce low-density lipoprotein cholesterol (LDL-C), which is a primary target of cardiovascular disease reduction.
Christoph Correll, M.D., says that before prescribing metformin, clinicians treating patients with antipsychotic-induced weight gain should consider healthy lifestyle interventions and switching patients to lower-risk antipsychotics.
“People don’t die of weight gain; they die of insulin resistance and lipid abnormalities,” said Christoph Correll, M.D., a professor of psychiatry and molecular medicine at Hofstra Northwell School of Medicine. “If these abnormalities can be reduced [using a medication], that marks a big improvement,” he told Psychiatric News.
As described in Molecular Psychiatry, a team of researchers from the United States and China pooled data from two randomized, placebo-controlled trials, including 201 patients from China aged 18 to 40 who developed dyslipidemia within a year of taking clozapine, olanzapine, risperidone, or sulpiride for the treatment of a first episode of schizophrenia. (Sulpiride has not been approved for use in the United States.)
The patients were randomly assigned to take 500 mg of metformin or placebo twice a day for six months. Participants who were taking an antipsychotic at the start of the study remained on the medication until the trial’s completion.
After 24 weeks of treatment, 25.3 percent of patients in the metformin group had dyslipidemia (defined by LDL-C greater than or equal to 3.37 mmol/L) compared with 64.8 percent in the placebo group. Of those who had dyslipidemia defined by LDL-C at baseline, 64 percent of patients who took metformin restored their LDL-C to below the normal level compared with 23.3 percent who took placebo.
In addition to reducing elevated LDL-C and weight, metformin treatment was found to have a significant effect on reducing insulin resistance—leading the authors to conclude that “the addition of metformin to antipsychotics is a potential treatment to attenuate dyslipidemia in patients with schizophrenia.”
“The fact that the sample in this study included patients who began treatment after a first episode of psychosis suggests the medication can be used somewhat in a preventive way,” said Correll, who was not involved with the study. Despite these findings, Correll advised that clinicians hold off on prescribing metformin to patients initiating antipsychotic treatment until they know whether significant weight gain will be an issue.
“If, after one to two weeks on the medication, you begin to see the patient is experiencing significant weight gain (1 to 2 kg), you could start metformin then,” he said. “However, if a patient does not gain weight—they are exercising or their genes are offering them some protection—you don’t want to have them taking a medication they do not need.”
It is advised that patients take metformin with food to reduce the gastrointestinal side effects of the medication, which include nausea, vomiting, diarrhea, and abdominal pain. Patients taking metformin are also at a low risk of lactic acidosis. It is recommended that clinicians confirm that a patient’s renal function is normal before prescribing the medication.
Another medication that may be able to decrease weight gain in patients taking antipsychotics is topiramate, approved for the treatment of seizure disorders and the prevention of migraine headaches. While there is some evidence that topiramate can reduce weight gain in patients taking antipsychotic medications, cognitive side effects of the medication have been reported.
Some of the more recently approved weight-loss medications, including lorcaserin, Qsymia (a phentermine/topiramate combination), and Contrave (bupropion/naltrexone combination), may also benefit patients with antipsychotic-induced weight gain, but they have yet to be studied in randomized, controlled trials.
“If you have considered a lower-risk antipsychotic, healthy lifestyle interventions, and all have failed, metformin is the best-studied option in terms of adding a medication to counteract the acute and long-term adverse cardiovascular effects of antipsychotics,” Correll said.
The research published in Molecular Psychiatry was supported in part by the National Natural Science Foundation of China. ■
