Cause for Caution
It seems like common sense: take one drug to treat one condition.
But it’s not always that simple – sometimes it takes more than one drug to make life better. When it comes to treating bipolar disorder, scientists are finding specific drug combinations that benefit patient mental health might also contribute to the risk of developing other serious non-psychiatric illness.
A recent study led by University of New Mexico researchers and published in the journal Psychoneuroendocrinology revealed that some drug treatments are associated with an enhanced risk of developing diabetes mellitus, while others are associated with reduced risk, compared to no medications at all.
According to the National Institute for Mental Health, nearly 3% of adults in the U.S. are currently diagnosed with bipolar disorder and about 4% of adults will be diagnosed within their lifetime. On top of that, about 82.9% of these patients will experience serious impairment stemming from this disease.
Because bipolar disorder includes episodes of both mania/hypomania and depression and is often accompanied by psychosis, the treatment options for patients range from antipsychotics to mood stabilizers and antidepressants. And it’s no sure bet that the first drug the patient tries will be the right one.
"Unfortunately, it's very much trial and error,” explains Mauricio Tohen, MD, chair of UNM’s Department of Psychiatry & Behavioral Sciences. "Sometimes patients don't respond, so you have to try another and another.”
Patients with bipolar disorder are also at higher risk for developing other conditions, such as diabetes or obesity. The goal of the study – according to its corresponding author, Christophe Lambert, PhD, an associate professor in the Department of Internal Medicine – was to determine the risks and benefits of drugs prescribed to patients with bipolar disorder.
Using an insurance records database of more than 130 million patients, Lambert, Tohen and their colleagues at UNM and several other institutions selected a group of about half a million patients with bipolar disorder who did not have a prior a history of diabetes or other related disorders.
The data on treatments given to these patients were then analyzed to discover relationships between these drugs and whether the patients developed diabetes following their bipolar diagnosis.
"This is really the largest study of its kind, both in terms of sample size and that 102 different therapies were compared,” says Lambert. The patients included in the study had about a 3% annual incidence of new-onset diabetes, which is several-fold higher than in the general population.
The team also found that about a third of the drug combinations studied resulted in a higher risk of subsequent diabetes development compared to those periods when patients were not taking drugs. In general, the more drugs that were simultaneously used, the higher the risk for developing diabetes.
But it’s not all bad news for diabetes and bipolar disorder. It turned out that a subset of these therapies had a much lower risk of diabetes development compared to no medications at all.
So, should patients worry about developing diabetes based on the drugs they take?
Lambert thinks that the association between diabetes and bipolar disorder might be explained more by lifestyle changes resulting from bipolar disorder, such as an unhealthy diet and lack of physical activity, rather than which treatments are used.
“The take-away is it’s not necessarily the drugs that are the biggest factor, as the fact that they have bipolar disorder,” he says.
He also wonders whether the higher risk associated with multiple drug treatments could be due to the accumulation of their varied side effects, drug-drug interactions or higher disease severity. Despite this uncertainty, Lambert urges clinicians to be cautious about polypharmacy, as the long-term effects on patients have not been well studied.
Tohen agrees. "Bipolar is a lifelong condition unfortunately, so you obviously want to give the drug that has the most efficacy and the least side effects," he says.
Although these findings only scratch the surface of the relationship between pharmacological treatments for bipolar disorder and their potential consequences, Lambert hopes this will prompt clinicians to inform their patients of the higher risk of diabetes and encourage healthy lifestyle choices.
Tohen also hopes that clinicians see these results as adding to the growing body of knowledge about bipolar disorder. "Fortunately, medicine is evidence-based and so we clinicians need to take into account the evidence," he says.