The results of a years-long study with patients on antidepressants may help doctors predict one of the most severe side effects those medications can produce: treatment-emergent suicidal ideation (TESI). The condition is estimated to affect between four and 14 percent of patients, who typically present symptoms of TESI in the first weeks of treatment or following dosage adjustments. So far doctors haven’t had indicators to predict which patients are more likely to develop TESI, but a new test based on research carried out by the Max Planck Institute of Psychiatry in Munich, Germany, could change that.
The researchers carried out genome-wide association studies on 397 patients aged 18 to 75 who were hospitalized for depression, but were not experiencing suicidal ideation at the time they began treatment. These kinds of studies scan a range of common genetic variables to find differences between groups of people. In this case the aim was to detect who was a TESI risk and who wasn't.
During the study, a reported 8.1 percent of patients developed TESI, and 59 percent of those developed it within the first two weeks of treatment. The researchers used the suicide item 3 of the Hamilton Rating Scale for Depression to evaluate TESI.
To arrive at a list of reliable predictors, the team genotyped the whole group and then compared patients who developed TESI with those who didn’t. By doing this they found a subset of 79 genetic variants associated with the risk group. These 79 genetic markers were then analyzed in a larger independent sample of in-patients suffering from depression, and could classify more than 90 percent of the patients correctly.
The research also sheds new light on the age of those affected by TESI. Prior to discovering that all age groups in the study were at risk, the assumption had been that under-25s were more at risk, which in 2005 prompted the US Food and Drug Administration to start issuing a black box warning. Some experts say the warning led to a decrease in drug-based treatment, a situation that could be reversed now that doctors can avail themselves of a new assessment tool based on the research.
The laboratory developed test, featuring a DNA microarray (chip), is being launched immediately by US company Sundance Diagnostics, ahead of submission to the US Food and Drug Administration for market clearance.
"A DNA microarray is a small solid support, usually a membrane or glass slide, on which sequences of DNA are fixed in an orderly arrangement," Sundance CEO Kim Bechthold tells Gizmag. "It is used for rapid surveys of the presence of many genes simultaneously, as the sequences contained on a single microarray can number in the thousands."
"Our hope is that the new test will assist the physician in significantly reducing the risk of suicide emerging from antidepressant drug use and will provide patients and families with valuable personal information to use with their doctors in weighing the risks and benefits of the medications," Bechttold said in a press statement.