A new brain imaging agent could reveal — before any treatment has been prescribed — whether a patient with major depressive disorder (MDD) is likely to respond to a particular antidepressant, according to a new study published in The Journal of Nuclear Medicine. No such marker is currently available in clinical psychiatry.
Escitalopram (Lexapro), a selective serotonin reuptake inhibitor (SSRI), can be an effective MDD treatment for some patients, but not all. During positron emission tomography (PET) test, the tracer 11C-DASB targets the serotonin transporter protein (5-HTT) in the amygdala of the brain, a region associated with emotional processing.
In the study, patients shown to have less 5-HTT protein were those who later experienced relief from escitalopram.
“MDD is a heterogeneous disorder, which makes it extremely difficult to treat effectively,” said researcher Mala R. Ananth, a graduate student at Stony Brook University in Stony Brook, N.Y.
“Optimizing treatment is challenging and is performed by trial and error, which could result in weeks of ineffective treatment, placing a burden on patients. As such, a pretreatment indicator that helps clinicians determine whether treatment will be successful is desperately needed.”
“Our study begins to address this by using PET to examine the neurobiology of patients with MDD prior to eight weeks of escitalopram (SSRI) treatment. Using PET, we quantified the protein target of SSRIs, the serotonin transporter 5-HTT,” said Ananth.
“Our results indicate that patients who found relief following escitalopram treatment had less 5-HTT protein before treatment began. This is exciting because it suggests that pretreatment neurobiology can be used to predict response to treatment, potentially preventing ineffective treatment trials.”
The study involved 26 medication-free MDD patients and 31 healthy control subjects who underwent a PET scan using 11C-DASB. MDD participants then received eight weeks of standardized therapy with escitalopram. The research team found a significant difference in amygdala binding, with medication-free patients showing an 11 percent lower amygdala binding than controls.
The findings suggest that 5-HTT amygdala binding should be investigated further, along with other measures, as a potential biomarker for remission following standardized escitalopram treatment.
“Pretreatment markers of effectiveness are needed to reduce the burden of ineffective treatment trials for patients. Psychiatry currently has no objective markers to determine whether a treatment will be effective,” Ananth said.
“PET imaging can fill that gap, and can be used to quantify biological features that indicate a successful course of treatment. Further, these features shed light on the neurobiology of MDD needed to develop novel and more targeted therapeutics.”