A power analysis for future clinical trials on the potential adverse effects of SSRIs on amygdala reactivity

Abstract

Treatment of adolescents with antidepressants may induce an increased risk for suicidality in this population. The activity of the amygdala during processing of emotional faces with functional Magnetic Resonance Imaging (fMRI) is a well-known measure of emotional dysregulation. Based upon data of our prematurely ended randomized clinical trial with fluoxetine (NTR3103) in anxious and or depressed girls (12–14 years of age) we calculated that with the found effect size of r = 0.66, compared to placebo, only 8 subjects are needed to demonstrate increased amygdala activity following 16 weeks of treatment with fluoxetine.

Keywords

amygdala reactivity / SSRI / adverse effects / anxiety / depression

References

[1] Andersen S L, Navalta C P (2004). Altering the course of neurodevelopment: a framework for understanding the enduring effects of psychotropic drugs. Int J Dev Neurosci, 22(5-6): 423–440

[2] Ansorge M S, Zhou M, Lira A, Hen R, Gingrich J A (2004). Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science, 306(5697): 879–881

[3] Bottelier M A, Schouw M L J, Klomp A, Tamminga H G H, Schrantee A G M, Bouziane C, de Ruiter M B, Boer F, Ruhé H G, Denys D, Rijsman R, Lindauer R J L, Reitsma H B, Geurts H M, Reneman L (2014). The effects of psychotropic drugs on developing brain (ePOD) study: methods and design. BMC Psychiatry, <Date>Feb 19</Date>; 14(1): 48

[4] Bouet V, Klomp A, Freret T, Wylezinska-Arridge M, Lopez-Tremoleda J, Dauphin F, Boulouard M, Booij J, Gsell W, Reneman L (2012). Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment. Psychopharmacology, 221(2): 329–339

[5] Demenescu L R, Renken R, Kortekaas R, van Tol M J, Marsman J B, van Buchem M A, van der Wee N J, Veltman D J, den Boer J A, Aleman A (2011). Neural correlates of perception of emotional facial expressions in out-patients with mild-to-moderate depression and anxiety. A multicenter fMRI study. Psychol Med, 41(11): 2253–2264

[6] Hammad T (2004). Review and evaluation of clinical data: Relationship between psychotropic drugs and pediatric suicidality. Online document at:

[7] Klomp A, Tremoleda J L, Wylezinska M, Nederveen A J, Feenstra M, Gsell W, Reneman L (2012). Lasting effects of chronic fluoxetine treatment on the late developing rat brain: age-dependent changes in the serotonergic neurotransmitter system assessed by pharmacological MRI. Neuroimage, 59(1): 218–226

[8] Ma Y (2015). Neuropsychological mechanism underlying antidepressant effect: a systematic meta-analysis. Mol Psychiatry, 20(3): 311–319

[9] Ruhé H G, Koster M, Booij J, van Herk M, Veltman D J, Schene A H (2014). Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder. Psychiatry Res, 221(2): 155–161

[10] Shrestha S S, Nelson E E, Liow J S, Gladding R, Lyoo C H, Noble P L, Morse C, Henter I D, Kruger J, Zhang B, Suomi S J, Svenningsson P, Pike V W, Winslow J T, Leibenluft E, Pine D S, Innis R B (2014). Fluoxetine administered to juvenile monkeys: effects on the serotonin transporter and behavior. Am J Psychiatry, 171(3): 323–331

[11] Tao R, Calley C S, Hart J, Mayes T L, Nakonezny P A, Lu H, Kennard B D, Tamminga C A, Emslie G J (2012). Brain activity in adolescent major depressive disorder before and after fluoxetine treatment. Am J Psychiatry, 169(4): 381–388

[12] Wegerer V, Moll G H, Bagli M, Rothenberger A, Rüther E, Huether G (1999). Persistently increased density of serotonin transporters in the frontal cortex of rats treated with fluoxetine during early juvenile life. J Child Adolesc Psychopharmacol, 9(1): 13–24, discussion 25–26

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg