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Frontiers in Biology

Front. Biol.    2016, Vol. 11 Issue (3) : 256-259
A power analysis for future clinical trials on the potential adverse effects of SSRIs on amygdala reactivity
M. A. Bottelier1,2,A. Schrantee2,3,G. van Wingen4,H. G. Ruhé4,5,M. B. de Ruiter2,3,L. Reneman2,3,*()
1. Department of Child- and Adolescent Psychiatry, Triversum, Alkmaar, The Netherlands
2. Brain Imaging Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
3. Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
4. Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands
5. Program for Mood and Anxiety Disorders, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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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     
Corresponding Author(s): L. Reneman   
Just Accepted Date: 27 April 2016   Online First Date: 23 May 2016    Issue Date: 05 July 2016
 Cite this article:   
M. A. Bottelier,A. Schrantee,G. van Wingen, et al. A power analysis for future clinical trials on the potential adverse effects of SSRIs on amygdala reactivity[J]. Front. Biol., 2016, 11(3): 256-259.
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M. A. Bottelier
A. Schrantee
G. van Wingen
H. G. Ruhé
M. B. de Ruiter
L. Reneman
Subject No. Age DISC diagnosis Treatment CDRS* children Baseline CDRS* parents Baseline CGI score Baseline CGI score 8 weeks CGI change 8 weeks CGI score 19 weeks CGI change 19 weeks
1 14 MDD Placebo >85 84 5 3 2 4 3
2 14 MDD, PD Placebo >85 84 5 5 4 4 4
3 13 MDD, SoP, PD Placebo >85 66 5 5 5 4 3
4 14 MDD Placebo >85 73 4 2 2 2 2
5 12 SoP, GAD Fluoxetine 85 63 5 4 2 3 2
6 14 MDD Fluoxetine >85 61 5 4 3 5 4
7 14 MDD, PD, OCD, SpP Fluoxetine >85 85 5 4 3 5 6
Fig.1  Amygdala activation before and after randomization for 16-week treatment with placebo or fluoxetine in girls suffering from severe MDD and/or AD. Y axis shows mean BOLD response in bilateral amygdala (anatomical ROI). Fluoxetine treatment increases amygdala activation to threatening faces compared to baseline (on average+40.94%), whereas placebo treatment resulted in equal or less amygdala activation (on average -36.36%).
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 pmid: 15380841
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 pmid: 15514160
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 pmid: 24552282
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 pmid: 22205158
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 pmid: 21557888
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 pmid: 21840402
8 Ma Y (2015). Neuropsychological mechanism underlying antidepressant effect: a systematic meta-analysis. Mol Psychiatry, 20(3): 311–319 pmid: 24662929
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 pmid: 24406081
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 pmid: 24480874
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 pmid: 22267183
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 pmid: 10357514
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