Impact of novel antidepressants on cardiac ¹²³ I Metaiodobenzyl guanidine uptake: Experimental studies on SK-N-SH cells and healthy rabbits

¹²³ I-metaiodobenzylguanidine ( ¹²³ I-MIBG) has independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not affect its quantitative information. We evaluated whether the 4 classes of antidepressants currently most prescribed as first-line treatment for major depressive disorder (MDD) have the potential to alter ¹²³ I-MIBG imaging results. Methods: The inhibition effect of desipramine, escitalopram, venlafaxine, and bupropion on ¹³¹ I-MIBG uptake was assessed by in vitro uptake assays using human neuroblastoma SK-N-SH cells. The half-maximal inhibitory concentration of tracer uptake was determined from dose-response curves. To evaluate the effect of intravenous pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5 or 15 mg/kg) on ¹²³ I-MIBG cardiac uptake, in vivo planar ¹²³ I-MIBG scanning of healthy New Zealand White rabbits was performed. Results: The half-maximal inhibitory concentrations of desipramine, escitalopram, venlafaxine, and bupropion on ¹³¹ I-MIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (as derived by previous clinical trials), the inhibition rates of ¹³¹ I-MIBG uptake were 90.6% for desipramine, 25.5% for venlafaxine, 11.7% for bupropion, and 0.72% for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in vivo rabbit model: with a dosage considerably higher than used in clinical practice, the noninhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine markedly reduced cardiac ¹²³ I-MIBG uptake. Conclusion: In the present in vitro binding assay and in vivo rabbit study, the selective serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac ¹²³ I-MIBG uptake within therapeutic dose ranges, whereas other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac ¹²³ I-MIBG imaging, in particular, if the patient's neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine-interfering antidepressant.