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Metformin can help manage weight gain side effect of bipolar medications

Researchers at the University of Cincinnati and Northwell Health have reported that metformin can help prevent or reduce weight gain in youths taking medication to treat bipolar disorder. The collaborative team presented its findings during a symposium at the American Academy of Child and Adolescent Psychiatry conference in New York City.

Medications to treat bipolar disorder, known as second-generation antipsychotics (SGAs), are often effective at helping young patients' mental health improve but can have significant side effects including elevated blood pressure and glucose, increased appetite and weight gain. Metformin, a medication typically used for Type 2 diabetes, is known to also prevent weight gain, but nearly all psychiatrists surveyed initially said they did not feel comfortable prescribing it, leading to the study testing metformin's effect.

"We, the clinicians naively justified that we're improving your psychosis, so just deal with the weight gain," said Dr Victor Fornari, a child/adolescent psychiatrist at Northwell Health. "But patients stopped taking their medicine because they said they didn't want to gain weight."

Prior to beginning the interventions, researchers collected information on youths living with bipolar disorders' quality of life and adherence to taking their medication as prescribed. While 87% of youth reported they took their medication regularly, a majority reported they were unhappy with their weight and/or had been sad, mad or frustrated about their weight.

A total of 1,565 patients aged 8-19 with bipolar disorder taking SGAs were enrolled in the study. Everyone enrolled in the trial received a lifestyle intervention with recommendations for healthy eating and exercise. Half of the youth were randomised to receive the healthy lifestyle intervention and were prescribed metformin.

Dr Christina Klein, a research scientist in UC's Department of Psychiatry and Behavioral Neuroscience in the College of Medicine, said a survey found patients want interventions to address the side effects as soon as possible, while doctors and caregivers prefer a wait and see approach. Klein said the study had a pragmatic design, meaning it had broad enrolment criteria and was conducted at a wide variety of clinics, even those without prior participation in research studies.

"If patients weren't doing well on the metformin, they could come off and stay in this study," explained Klein. "Really we're just trying to meet the patients when and where they received services, seeing what happens to them over the course of two years."

Researchers also collected baseline metabolic data to determine if youth had metabolic syndrome, which Northwell's Dr Claudine Higdon, a child/adolescent psychiatrist, said is a common consequence of SGAs that places youth at risk for diabetes and cardiovascular disease. The study found 33% of youth enrolled in the study had metabolic syndrome at the start.

"The key elements of metabolic syndrome are obesity, high blood pressure, elevated triglycerides and elevated glucose. It is important that clinicians monitor for metabolic syndrome when treating youth with second-generation antipsychotics."

Dr Jeffrey Welge, professor in UC's Department of Psychiatry and Behavioral Neuroscience and Department of Environmental and Public Health Sciences, said in the short-term six-month follow-up data, metformin had a modest but significant effect at preventing and in some cases reversing weight gain in the study's patient population. The drug was also found to be safe, with some gastrointestinal distress symptoms being the only side effects reported.

"It's not a drug you take and weight falls off of you, but it tends to reduce that out of control appetite which we think then makes it easier for patients to adhere to a healthy diet and as they lose some weight maybe also make it easier for them to engage in more exercise," said Welge. "So, the lifestyle is really what's driving good outcomes, but metformin is in some cases putting the wind at their back to help with that."

"It's safe, effective and very inexpensive. It's an intervention that has the potential to have widespread applicability," added Fornari. "It's not a medicine that you need to have an endocrinologist or a paediatrician prescribe, and I think it really speaks to the fact that the psychiatrist needs to be caring for the entire person, the physical and the mental health of the patient."

While having an effect on weight gain, metformin was not found to have a significant effect on youth's metabolic syndrome in the short term, Welge said.

"Further research is needed on effective interventions for metabolic syndrome," Higdon said.


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