The discovery that lithium acts as a mood stabilizer was one of the great breakthroughs in mental health treatment. For many people with bipolar disorder, lithium has proven life-changing, and often life-saving. But a quarter of those given lithium experience no benefit, and an even larger number have a weak response. New research, published in JAMA Psychiatry, could open a path to identifying who will and won't benefit.
Professor Bernhard Baune of the University of Adelaide, Australia and colleagues looked for genes known to be associated with mental health in 2,586 people who had been diagnosed with bipolar disorder and treated with lithium.
There are many gene variations, none of which have a perfect correlation with schizophrenia, but which represent risk factors, and many of these overlap with variations associated with bipolar. Having a large number of these gene variations creates a strong predisposition to schizophrenia, and it seems that is not all.
"We found that patients clinically diagnosed with bipolar disorder who showed a poor response to lithium treatment all shared something in common: a high number of genes previously identified for schizophrenia," Baune said in a statement.
“This doesn't mean that the patient also had schizophrenia – but if a bipolar patient has a high 'gene load' of schizophrenia risk genes, our research shows they are less likely to respond to mood stabilizers such as lithium.”
If there were no side-effects of lithium treatment, identifying who is likely to respond would not be so important, but the side-effects are often considerable. Being able to spare those who won't benefit the need to try lithium would be a huge step forward in terms of quality of life. Baune told IFLScience that the team also looked to see if they could find a pattern in the genes that would predict the severity of side-effects from treatment, but so far they have not found one.
For those unlikely to respond to lithium, other treatments are available. Some people respond better to anti-convulsive drugs originally developed to treat epilepsy, and for others, second-generation mood stabilizers work best. However, lithium is usually the first medication prescribed because overall it has the best response rate. A test allowing those who are unlikely to benefit to skip straight to a different approach could spare a lot of pain.
Such a test is likely to be quite a few years away, however. Baune told IFLScience that, as a clinician himself, he will treat the findings with care. Nevertheless, when he encounters people “whose symptoms have some similarities with schizophrenia, or who have family members with schizophrenia, [he] would be more hesitant to prescribe lithium.”