Abstract
Introduction: There is a need for more studies on the clinical effectiveness, tolerability and
pharmacokinetics of atypical antipsychotics in adolescents with psychotic disorders,
as this represents a vulnerable and difficult population to treat. According to recent
concerns regarding disabling side effects of antipsychotics, particularly weight gain,
further monitoring of their safety profiles is needed. This situation prompted the
authors to carry out an investigation on the clinical effectiveness of quetiapine
in psychotic adolescents.
Methods: 23 adolescents (13–18 years old) with psychotic disorders participated in a 12-week
open label trial, including 6 visits assessing clinical efficacy, tolerability and
safety of quetiapine (50–750 mg daily).
Results: Adolescents were treated with lower doses compared to adults. Significant decreases
in CGI and PANSS total scores were observed after both 4 and 12 weeks of quetiapine
treatment compared to baseline. Sedation was the main adverse effect, but medication
was generally well tolerated. Irregular compliance, (as assessed by pill counts, a
questionnaire and by plasma quetiapine concentration monitoring), and alcohol and/or
cannabis consumption were factors identified in this study which add to the difficulty
in treating this population.
Discussion: The results of the present study help to consolidate evidence of the usefulness of
quetiapine as a treatment for adolescents with psychotic disorders. However, this
study also highlights the issues encountered in treating this group, including the
presence of comorbidities such as drug abuse.
References
- 1
van OSJ, Kapur S.
Schizophrenia.
Lancet.
2009;
374
(9690)
635-645
- 2
Schimmelmann BG, Conus P, Cotton S. et al .
Pre-treatment, baseline, and outcome differences between early-onset and adult-onset
psychosis in an epidemiological cohort of 636 first-episode patients.
Schizophr Res.
2007;
95
1-8
- 3
Lay B, Blanz B, Hartmann M. et al .
The psychosocial outcome of adolescent-onset schizophrenia: a 12-year follow-up.
Schizophr Bull.
2000;
26
801-816
- 4
Fleischhaker C, Schulz E, Tepper K. et al .
Long-term course of adolescent schizophrenia.
Schizophr Bull.
2005;
31
769-780
- 5
Ballageer T, Malla A, Manchanda R. et al .
Is adolescent-onset first-episode psychosis different from adult onset?.
J Am Acad Child Adolesc Psychiatry.
2005;
44
782-789
- 6
Pencer A, Addington J, Addington D.
Outcome of a first episode of psychosis in adolescence: a 2-year follow-up.
Psychiatry Res.
2005;
133
35-43
- 7
Fraguas D, Correll CU, Merchan-Naranjo J. et al .
Efficacy and safety of second-generation antipsychotics in children and adolescents
with psychotic and bipolar spectrum disorders: Comprehensive review of prospective
head-to-head and placebo-controlled comparisons.
Eur Neuropsychopharmacol.
2010;
Aug 9
- 8
Moore TA, Buchanan RW, Buckley PF. et al .
The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia:
2006 update.
J Clin Psychiatry.
2007;
68
1751-1762
- 9
Kane JM, Leucht S, Carpenter D. et al .
The expert consensus guideline series – Optimizing pharmacologic treatment of psychotic
disorders.
J Clin Psychiatry.
2003;
64
(Suppl. 12)
4-100
- 10
van OSJ, Kapur S.
Schizophrenia.
Lancet.
2009;
374
(9690)
635-645
- 11
Remington G, Kapur S.
Atypical antipsychotics: are some more atypical than others? [Review].
Psychopharmacology.
2000;
148
3-15
- 12
Armenteros JL, Davies M.
Antipsychotics in early onset Schizophrenia: Systematic review and meta-analysis.
Eur Child Adolesc Psychiatry.
2006;
15
141-148
- 13
Sikich L, Frazier JA, McClellan J. et al .
Double-blind comparison of first- and second-generation antipsychotics in early-onset
schizophrenia and schizo-affective disorder: findings from the treatment of early-onset
schizophrenia spectrum disorders (TEOSS) study.
Am J Psychiatry.
2008;
165
1420-1431
- 14
Vitiello B, Correll C, Zwieten-Boot B. et al .
Antipsychotics in children and adolescents: Increasing use, evidence for efficacy
and safety concerns.
Eur Neuropsychopharmacol.
2009;
May 23
- 15
Arango C, Parellada M, Moreno DM.
Clinical effectiveness of new generation antipsychotics in adolescent patients.
Eur Neuropsychopharmacol.
2004;
(S 04)
S471-S479
- 16
Sikich L.
Efficacy of atypical antipsychotics in early-onset schizophrenia and other psychotic
disorders.
J Clin Psychiatry.
2008;
69
(S 04)
21-25
- 17
Lieberman JA, Perkins D, Belger A. et al .
The early stages of schizophrenia: speculations on pathogenesis, pathophysiology,
and therapeutic approaches.
Biol Psychiatry.
2001;
50
884-897
- 18
Kumra S, Oberstar JV, Sikich L. et al .
Efficacy and tolerability of second-generation antipsychotics in children and adolescents
with schizophrenia.
Schizophr Bull.
2008;
34
60-71
- 19
Correll CU.
Assessing and maximizing the safety and tolerability of antipsychotics used in the
treatment of children and adolescents.
J Clin Psychiatry.
2008;
69
(S 04)
26-36
- 20
McConville BJ, Sorter MT.
Treatment challenger and safety considerations for antipsychotic use in chidren and
adolescents with psychoses.
J Clin Psychiatry.
2004;
65
(Suppl. 6)
20-29
- 21
Mattai AK, Hill JL, Lenroot RK.
Treatment of early-onset schizophrenia.
Curr Opin Psychiatry.
2010;
23
304-310
- 22
Small JG, Hirsch SR, Arvanitis LA. et al .
Seroquel Study Group. Quetiapine in patients with schizophrenia: A high- and low-dose
double-blind comparison with placebo.
Arch Gen Psychiatry.
1997;
54
549-557
- 23
Adityanjee MD, Schulz SC.
Clinical use of quetiapine in disease states other than schizophrenia.
J Clin Psychiatry.
2002;
63
(S 13)
32-38
- 24
Martinotti G, Andreoli S, Di Nicola M. et al .
Quetiapine decreases alcohol consumption, craving, and psychiatric symptoms in dually
diagnosed alcoholics.
Hum Psychopharmacol.
2008;
23
417-424
- 25
Vaishnavi S, Alamy S, Zhang W. et al .
Quetiapine as monotherapy for social anxiety disorder: a placebo-controlled study.
Prog Neuropsychopharmacol Biol Psychiatry.
2007;
31
1464-1469
- 26
Nemeroff CB, Kinkead B, Goldstein J.
Quetiapine: preclinical studies, pharmacokinetics, drug interactions, and dosing.
J Clin Psychiatry.
2002;
63
(S 13)
5-11
- 27
Kapur S, Zipursky R, Jones C. et al .
A positron emission tomography study of quetiapine in schizophrenia – a preliminary
finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy.
Arch Gen Psychiatry.
2000;
57
553-559
- 28
Gefvert O, Lundberg T, Wieselgren IM. et al .
D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study.
Eur Neuropsychopharmacol.
2001;
11
105-110
- 29
DeVane CL, Nemeroff CB.
Clinical pharmacokinetics of quetiapine – an atypical antipsychotic.
Clin Pharmacokinet.
2001;
40
509-522
- 30
Winter HR, Earley WR, Hamer-Maansson JE. et al .
Steady-state pharmacokinetic, safety, and tolerability profiles of quetiapine, norquetiapine,
and other quetiapine metabolites in pediatric and adult patients with psychotic disorders.
J Child Adolesc Psychopharmacol.
2008;
18
81-98
- 31
Jensen NH, Rodriguiz RM, Caron MG. et al .
N-Desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A
agonist, as a putative mediator of quetiapine's antidepressant activity.
Neuropsychopharmacology.
2008;
33
2303-2312
- 32
Findling RL.
Use of quetiapine in children and adolescents.
J Clin Psychiatry.
2002;
63
(S 13)
27-31
- 33
Cheng-Shannon J, McGough JJ, Pataki C. et al .
Second-generation antipsychotic medications in children and adolescents.
J Child Adolesc Psychopharmacol.
2004;
14
372-394
- 34
Beer F, Heinrich H, Springer S. et al .
Quetiapine in the treatment of psychotic adolescents: a case series of 23 patients
with severe early onset psychosis.
World J Biol Psychiatry.
2007;
8
38-41
- 35
Schimmelmann BG, Mehler-Wex C, Lambert M. et al .
A prospective 12-week study of quetiapine in adolescents with schizophrenia spectrum
disorders.
J Child Adolesc Psychopharmacol.
2007;
17
768-778
- 36
Bishop JR, Pavuluri MN.
Review of risperidone for the treatment of pediatric and adolescent bipolar disorder
and schizophrenia.
Neuropsychiatr Dis Treat.
2008;
4
55-68
- 37
Coukell AJ, Spencer CM, Benfield P.
Amisulpride – A review of its pharmacodynamic and pharmacokinetic properties and therapeutic
efficacy in the management of schizophrenia.
CNS Drugs.
1996;
6
237-256
- 38
Roke Y, van Harten PN, Boot AM. et al .
Antipsychotic medication in children and adolescents: a descriptive review of the
effects on prolactin level and associated side effects.
J Child Adolesc Psychopharmacol.
2009;
19
403-414
- 39
Castro-Fornieles J, Parellada M, Soutullo CA. et al .
Antipsychotic treatment in child and adolescent first-episode psychosis: a longitudinal
naturalistic approach.
J Child Adolesc Psychopharmacol.
2008;
18
327-336
- 40
Correll CU, Kane JM.
One-year incidence rates of tardive dyskinesia in children and adolescents treated
with second-generation antipsychotics: a systematic review.
J Child Adolesc Psychopharmacol.
2007;
17
647-656
- 41
Croarkin PE, Emslie GJ, Mayes TL.
Neuroleptic malignant syndrome associated with atypical antipsychotics in pediatric
patients: a review of published cases.
J Clin Psychiatry.
2008;
69
1157-1165
- 42
Jerrell JM, Hwang TL, Livingston TS.
Neurological adverse events associated with antipsychotic treatment in children and
adolescents.
J Child Neurol.
2008;
23
1392-1399
- 43
Kuehn BM.
FDA panel OKs 3 antipsychotic drugs for pediatric use, cautions against overuse.
JAMA.
2009;
302
833-834
- 44
Greenspan A, Gharabawi G, Kwentus J.
Thyroid dysfunction during treatment with atypical antipsychotics.
J Clin Psychiatry.
2005;
66
1334-1335
- 45
Potkin SG, Gharabawi GM, Greenspan AJ. et al .
A double-blind comparison of risperidone, quetiapine and placebo in patients with
schizophrenia experiencing an acute exacerbation requiring hospitalization.
Schizophr Res.
2006;
85
254-265
- 46
Kontaxakis VP, Karaiskos D, Havaki-Kontaxaki BJ. et al .
Can quetiapine-induced hypothyroidism be reversible without quetiapine discontinuation?.
Clin Neuropharmacol.
2009;
32
295-296
- 47
Fraguas D, Merchan-Naranjo J, Laita P. et al .
Metabolic and hormonal side effects in children and adolescents treated with second-generation
antipsychotics.
J Clin Psychiatry.
2008;
69
1166-1175
- 48
Simon V, van WR, de HM.
Are weight gain and metabolic side effects of atypical antipsychotics dose dependent?
A literature review.
J Clin Psychiatry.
2009;
70
1041-1050
- 49
Bolognini M, Plancherel B, Laget J. et al .
Evaluation of the adolescent drug abuse diagnosis instrument in a Swiss sample of
drug abusers.
Addiction.
2001;
96
1477-1484
- 50
Kay SR, Opler LA, Lindenmayer JP.
The positive and negative syndrome scale (PANSS): rationale and standardisation.
Br J Psychiatry.
1989;
155
(suppl 7)
59-65
- 51 Guy W. ECDEU Assessment Manual for Psychopharmacology.. Washington, DC: Department
of Health, Education and Welfare; 1976
- 52
Simpson GM, Angus JW.
A rating scale for extrapyramidal side effects.
Acta Psychiatr Scand Suppl.
1970;
212
11-19
- 53
Barnes TR.
A rating scale for drug-induced akathisia.
Br J Psychiatry.
1989;
154
672-676
- 54
Le Bloc’h Y, Baumann P, Stigler M. et al .
Efficacy and tolerability of quetiapine in cluster B personality disorder: an open-label
study.
Int J Psychiatry Clin Pract.
2007;
11
123-128
- 55
Cole TJ.
A chart to link child centiles of body mass index, weight and height.
Eur J Clin Nutr.
2002;
56
1194-1199
- 56
Farpour-Lambert N, L’Allemand D, Laimbacher J.
Définition, diagnostic et indications thérapeutiques de la surcharge pondérale de
l’enfant et de l’adolescent.
Paediatrica.
2006;
17
19-24
- 57
Berger GE, Proffitt TM, McConchie M. et al .
Dosing quetiapine in drug-naive first-episode psychosis: a controlled, double-blind,
randomized, single-center study investigating efficacy, tolerability, and safety of
200 mg/day vs. 400 mg/day of quetiapine fumarate in 141 patients aged 15 to 25 years.
J Clin Psychiatry.
2008;
69
1702-1714
- 58
Haas M, Unis AS, Armenteros J. et al .
A 6-week, randomized, double-blind, placebo-controlled study of the efficacy and safety
of risperidone in adolescents with schizophrenia.
J Child Adolesc Psychopharmacol.
2009;
19
611-621
- 59
Findling RL, Robb A, Nyilas M. et al .
A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole
for treatment of adolescents with schizophrenia.
Am J Psychiatry.
2008;
165
1432-1441
- 60
Takahashi H, Oshimo T, Ishigooka J.
Efficacy and tolerability of aripiprazole in first-episode drug-naive patients with
schizophrenia: an open-label trial.
Clin Neuropharmacol.
2009;
32
149-150
- 61
Lee HY, Ham BJ, Kang RH. et al .
Trial of aripiprazole in the treatment of first-episode schizophrenia.
Psychiatry Clin Neurosci.
2010;
64
38-43
- 62
Larsen TK, Melle I, Auestad B. et al .
Substance abuse in first-episode non-affective psychosis.
Schizophr Res.
2006;
88
55-62
- 63
Addington J, Addington D.
Patterns, predictors and impact of substance use in early psychosis: a longitudinal
study.
Acta Psychiatr Scand.
2007;
115
304-309
- 64
McConville BJ, Arvanitis LA, Thyrum PT. et al .
Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate:
an open-label trial in adolescents with psychotic disorders.
J Clin Psychiatry.
2000;
61
252-260
- 65
Seeman P, Tallerico T.
Rapid release of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon
withdrawal of clozapine or quetiapine.
Am J Psychiatry.
1999;
156
876-884
- 66
Kapur S, Seeman P.
Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics?: a new hypothesis.
Am J Psychiatry.
2001;
158
360-369
- 67
Connor DF, McLaughlin TJ, Jeffers-Terry M.
Randomized controlled pilot study of quetiapine in the treatment of adolescent conduct
disorder.
J Child Adolesc Psychopharmacol.
2008;
18
140-156
- 68
Duffy A, Milin R, Grof P.
Maintenance treatment of adolescent bipolar disorder: open study of the effectiveness
and tolerability of quetiapine.
BMC Psychiatry.
2009;
9
4
- 69
Gerlach M, Hunnerkopf R, Rothenhofer S. et al .
Therapeutic drug monitoring of quetiapine in adolescents with psychotic disorders.
Pharmacopsychiatry.
2007;
40
72-76
- 70
Hasselstrøm J, Linnet K.
Quetiapine serum concentrations in psychiatric patients – The influence of comedication.
Ther Drug Monit.
2004;
26
486-491
- 71
Bachmann CJ, Haberhausen M, Heinzel-Gutenbrunner M. et al .
Large intraindividual variability of olanzapine serum concentrations in adolescent
patients.
Ther Drug Monit.
2008;
3
108-112
- 72
Aichhorn W, Marksteiner J, Walch T. et al .
Influence of age, gender, body weight and valproate comedication on quetiapine plasma
concentrations.
Int Clin Psychopharmacol.
2006;
21
81-85
- 73
Pichini S, Papaseit E, Joya X. et al .
Pharmacokinetics and therapeutic drug monitoring of psychotropic drugs in pediatrics.
Ther Drug Monit.
2009;
31
283-318
- 74
Mehler-Wex C, Kolch M, Kirchheiner J. et al .
Drug monitoring in child and adolescent psychiatry for improved efficacy and safety
of psychopharmacotherapy.
Child Adolesc Psychiatry Ment Health.
2009;
3
14
Correspondence
L. HolzerMD
Service Universitaire de
Psychiatrie de l'Enfant et de
l' Adolescent (SUPEA)
Centre Thérapeutique de Jour
pour Adolescents (CTJA)
Av. de Beaumont 48
1012 Lausanne
Switzerland
Telefon: +41/21/314 1730
Fax: +41/21/314 1735
eMail: laurent.holzer@chuv.ch
