In a randomized, placebo-controlled clinical trial detailed in this study in Psychiatry Research, pioglitazone – a generically available drug that’s approved for type 2 diabetes – helped to relieve symptoms of major depression in patients whose blues had withstood an assault by standard therapeutic regimens for six months or longer.
But this beneficial effect was seen only in depressed patients who were also insulin-resistant.
Depression is remarkably common. Stanford psychiatric researcher Natalie Rasgon, MD, PhD, the study’s senior author, told me that close to one in five Americans are diagnosed with depressive illness at some point in their lives.
Insulin resistance, a stepping stone on the path to type 2 diabetes (not to mention cardiovascular disease and probably Alzheimer’s), is even more common: About one in three otherwise healthy Americans – and an even greater share of people with depression – are insulin-resistant. Especially prevalent among overweight people, insulin resistance also occurs more often than one might expect even among thinner folks, a lot of whom don’t have the faintest idea that’s the case.
Insulin, released by the pancreas in response to food intake, alerts cells throughout the body to the presence of glucose, the body’s primary energy source, in the blood. Insulin-resistant people’s cells fail to take up glucose adequately, leaving high residual blood levels of the sugar to wreak havoc on the body’s tissues. Because the brain is a glucose glutton – it soaks up about 20 percent of all glucose consumption in a healthy, active person – it’s easy to imagine that lousy glucose uptake in the brain would have all kinds of deleterious effects, including effects on mood. Food for thought, anyway.
Here’s how my news release described the study:
[R]esearchers were blinded as to which patients were receiving pioglitazone versus a placebo. The patients didn’t know which they were getting, either. … All the patients had been experiencing episodes of depression lasting, on average, more than one year. Their symptoms had failed to remit under standard treatment regimens. They remained on these regimens for the duration of the Stanford study and, in addition, were given either pioglitazone or a placebo. … The patients were tested for depression severity and insulin resistance at the study’s outset and then roughly every two weeks from the beginning of the trial to the end.
A total of 37 patients – 29 women and eight men – completed the 12-week study. The insulin-sensitive subjects did about as well on the drug as they did on placebo. But among the insulin-resistant group, those given pioglitazone showed a much greater improvement than those who got a placebo. They also showed more improvement than insulin-sensitive patients did.
The more insulin-resistant a participant was at the beginning of the study, the better the drug’s antidepressant effect. Possible, but not proven, explanation: It could be that for some patients standard antidepressant therapies can kick into gear only once these patients’ insulin resistance is reduced. Hungry brains gotta eat.
Previously: Survey shows nearly a quarter of U.S. workers have been diagnosed with depression in their lifetime, Revealed: the brain’s molecular mechanism behind why we get the blues, and International led by Stanford researchers identifies gene linked to insulin resistance
Photo by S.Hart Photography