Selective serotonin reuptake inhibitors (SSRIs) are usually well tolerated in the pediatric population, and widely used in the treatment of obsessive-compulsive disorder (OCD). Of the 51 pediatric patients with obsessive-compulsive disorder seen in our outpatient clinic between January 2009 and July 2009, 3 of them developed behavioral disinhibition after treatment with fluvoxamine. These cases are described and discussed in relation to the use of CYP2D6 and CYP2C19 pharmacogenetic testing in patients treated with serotonin-selective reuptake inhibitors.
Get full access to this article
View all access options for this article.
References
1.
AllinMP, MarshallN, SchulzeK, WalsheM, HallMH, PicchioniM, MurrayRM, McDonaldC. A functional MRI study of verbal fluency in adults with bipolar disorder and their unaffected relatives. Psychol Med, 11:1–11. 2010.
2.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4thRevised. (DSM-IV)Washington, DC: American Psychiatric Press, 1994.
3.
BaxterLRJr., SchwartzJM, MazziottaJC, PhelpsME, PahlJJ, GuzeBH, FairbanksL. Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder. Am J Psychiatry, 145:1560–1563. 1988.
4.
BrosenK, SkjelboE, RasmussenBB, PoulsenHE, LoftS. Fluvoxamine is a potent inhibitor of cytochrome P4501A2. Biochem Pharmacol, 45:1211–1214. 1993.
5.
CreweHK, LennardMS, TuckerGT, WoodsFR, HaddockRE. The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol, 34:262–265. 1992.
6.
de LeonJ. The future (or lack of future) of personalized prescription in psychiatry. Pharmacol Res, 59:81–89. 2009.
7.
de LeonJ, ArranzMJ, RuanoG. Pharmacogenetic testing in psychiatry: A review of features and clinical realities. Clin Lab Med, 28:599–617. 2008.
8.
FleishakerJC, HulstLK. A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. Eur J Clin Pharmacol, 46:35–39. 1994.
9.
GarlandEJ, BaergEA. Amotivational syndrome associated with selective serotonin reuptake inhibitors in children and adolescents. J Child Adolesc Psychopharmacol, 11:181–186. 2001.
10.
HemeryckA, BelpaireFM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: An update. Curr Drug Metab, 3:13–37. 2002.
11.
KennardB, SilvaS, VitielloB, CurryJ, KratochvilC, SimonsA, HughesJ, FeenyN, WellerE, SweeneyM, ReineckeM, PathakS, GinsburgG, EmslieG, MarchJ. Remission and residual symptoms after short-term treatment in the Treatment of Adolescents with Depression Study (TADS)J Am Acad Child Adolesc Psychiatry, 45:1404–1411. 2006.
12.
LeonardHL, MarchJ, RicklerKC, AllenAJ. Pharmacology of the selective serotonin reuptake inhibitors in children and adolescents. J Am Acad Child Adolesc Psychiatry, 36:725–736. 1997.
13.
LeslieLK, NewmanTB, ChesneyPJ, PerrinJM. The Food and Drug Administration's deliberations on antidepressant use in pediatric patients. Pediatrics, 116:195–204. 2005.
14.
MarchJ, SilvaS, PetryckiS, CurryJ, WellsK, FairbankJ, BurnsB, DominoM, McNultyS, VitielloB, SevereJ. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. JAMA, 292:807–820. 2004.
15.
PeraniD, ColomboC, BressiS, BonfantiA, GrassiF, ScaroneS, BellodiL, SmeraldiE, FazioF. [18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment. Br J Psychiatry, 166:244–250. 1995.
RapoportJL. Recent advances in obsessive-compulsive disorder. Neuropsychopharmacology, 5:1–10. 1991.
18.
RauchSL, JenikeMA, AlpertNM, BaerL, BreiterHC, SavageCR, FischmanAJ. Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch Gen Psychiatry, 51:62–70. 1994.
19.
ReinblattSP, DosReisS, WalkupJT, RiddleMA. Activation adverse events induced by the selective serotonin reuptake inhibitor fluvoxamine in children and adolescents. J Child Adolesc Psychopharmacol, 19:119–126. 2009.
20.
ReinblattSP, RiddleMA. Selective serotonin reuptake inhibitor-induced apathy: A pediatric case series. J Child Adolesc Psychopharmacol, 16:227–233. 2006.
21.
Research Units for Pediatric Psychopharmacology (RUPP) Anxiety Study Group. Fluvoxamine for the treatment of anxiety disorders in children and adolescents. N Engl J Med, 344:1279–1285. 2001.
22.
RiddleMA, KingR, HardinMT, ScahillL, OrtS, ChappellP, RasmussonA, LeckmanJ. Behavioral side effects of fluoxetine in children and adolescents. J Child Adolesc Psychopharmacol, 1:193–198. 1991.
23.
RigoniG. Drug Utilization for Selected Antidepressants Among Children & Adolescents in the U.S., 2004. www.fda.gov/ohrms/dockets/ac/04/slides/4006S1_04_Rigoni_files/frame.htm. 2009 July 29.
24.
RubinRT, Villanueva-MeyerJ, AnanthJ, TrajmarPG, MenaI. Regional xenon 133 cerebral blood flow and cerebral technetium 99m HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects. Determination by high-resolution single-photon emission computed tomography. Arch Gen Psychiatry, 49:695–702. 1992.
25.
SchmiderJ, GreenblattDJ, von MoltkeLL, KarsovD, ShaderRI. Inhibition of CYP2C9 by selective serotonin reuptake inhibitors in vitro: Studies of phenytoin p-hydroxylation. Br J Clin Pharmacol, 44:495–498. 1997.
26.
StarksteinSE, RobinsonRG. Mechanism of disinhibition after brain lesions. J Nerv Ment Dis, 185:108–114. 1997.
27.
StrakowskiSM, AdlerCM, CerulloMA, EliassenJC, LamyM, FleckDE, LeeJH, DelBelloMP. MRI brain activation in first-episode bipolar mania during a response inhibition task. Early Interv Psychiatry, 2:225–233. 2008.
28.
SurguladzeSA, MarshallN, SchulzeK, HallMH, WalsheM, BramonE, PhillipsML, MurrayRM, McDonaldC. Exaggerated neural response to emotional faces in patients with bipolar disorder and their first-degree relatives. Neuroimage, 2010Jun8[Epub ahead of print].
