To summarize available knowledge about pharmacologic treatments that are used for first-onset (or early) psychosis in youths, with particular consideration of the prodromal stage and the effectiveness and safety of novel antipsychotic drugs and mood stabilizers.
Method:
A computerized search of medical databases (for example, Medline and Embase), a manual searching of articles and textbooks, and the use of vignettes to highlight treatment issues.
Results:
There are limited data about the effectiveness and safety of psychotropic agents for youths with psychosis and scarce information about the drug treatment of the prodromal stage of early psychosis in all age groups. The available data are encouraging, although the newer agents are not without safety concerns.
Conclusions:
Despite the paucity of studies, there is a range of psychotropics that may be used in the early stages of psychotic illness in youths. Drug choice is influenced by several factors, including the clinical picture, side effect profile, and patient preference. In certain situations, the decision may be not to use medication.
National Mental Health Strategy. The Australian Clinical Guidelines for Early Psychosis. Melbourne (AU): University of Melbourne Press; 1997.
2.
Early Psychosis Prevention and Intervention Group. Psychoeducation in early psychosis. Melbourne (AU): University of Melbourne Press; 1998.
3.
McGorryPMcFarlaneCPattonG.The prevalence of prodromal symptoms of schizophrenia in adolescence: A preliminary survey. Acta Psychiatr Scand1995;92:241–9.
4.
McGorryP.Evaluating the importance of reducing the duration of untreated psychosis. Aust N Z J Psychiatry2000;34 (Suppl):145–9.
5.
McGlashanTHJohanessenJA. Early detection and intervention with schizophrenia: Rationale. Schizophr Bull1996;22:201–2.
6.
CookRJSackettDL. The number needed to treat: A clinically useful measure of treatment effect. BMJ1995;310:452–4.
7.
BrydenKECarreyNJKutcherSP. Update and recommendations for the use of antipsychotics in early-onset psychosis. J Child Adolesc Psychopharmacol2001;11:113–30.
8.
EngelhardtDMPolizosPWazerJ.A double-blind comparison of fluphenazine an haloperidol in outpatient schizophrenia children. J Autism Child Schizophr1973;3:128–37.
9.
RealmutoGMEricksonWDYellinAMHopwoodJHGreenbergLM. Clinical comparison of thiothixene and thioridazine in schizophrenic adolescents. Am J Psychiatry1984;141:440–2.
10.
SpencerEKCampbellM.Children with schizophrenia: Diagnosis, phenomenology and pharmacotherapy. Schizophr Bull1994;20:713–25.
11.
CampbellMRapoportJLSimpsonGM. Antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry1999;38:537–45.
12.
AndersonJ.Risperidone in the management of psychotic adolescents: An open trial. American Psychiatric Association Annual Meeting; 1997; San Diego (CA).
13.
ArmenterosJLWhitakerAHWeliksonMStedgeDJGormanJ.Risperidone in adolescents with schizophrenia: An open pilot study. J Am Acad Child Adolesc Psychiatry1997;36:694–700.
McGorryPDPhillipsLJYungAR. A randomized control trial of interventions in the prepsychotic phase of psychotic disorders. Schizophr Res2000;41:9.
16.
Australian Clinical Guidelines for Early Psychosis. Canberra (AU): Commonwealth Department of Health and Family Services; 1999.
17.
FeenyDJKlykyloW.Risperidone and tardive dyskinesa. J Am Acad Child Adolesc Psychiatry1996;35:1421–2.
18.
KumraSHerioDJacobsenLKBrigugliaCGrotheD.Case study: Risperidone-induced hepatotoxicity in pediatric patients. J Am Acad Child Adolesc Psychiatry1997;36:701–5.
19.
EdelmanRJ. Risperidone side effects. J Am Acad Child Adolesc Psychiatry1996;35:4–5.
20.
PotkinSG. Long-term management of schizophrenia. The role of new antipsychotics. 150th American Psychiatric Association Meeting; San Diego (CA); 1997.
21.
KrishnamoorthyJKingBH. Open-label olanzapine treatment in five preadolescent children. J Child Adolesc Psychopharmacol1998;8:107–13.
22.
KumraSJacobsenLKLehaneMKarpBFrazierJSmithA.Childhood-onset schizophrenia: An open label study of olanzapine in adolescents. J Am Acad Child Adolesc Psychiatry1998;37:377–85.
23.
BrydenKEKopalaLC. Body mass index increase of 58% associated with olanzapine. Am J Psychiatry1999;156:1835–6.
24.
GoldsteinLEHendersonDC. Atypical antipsychotic agents and diabetes mellitus. Primary Psychiatry2000;7:65–8.
25.
SheimanBDBirdPMSachezC.Olanzapine-induced elevation of plasma triglycerides levels. Am J Psychiatry1999;136:767–70.
26.
MeltzerHY. New drugs for the treatment of schizophrenia. Psychiatr Clin North Am1993;16:365–85.
27.
TuretzMMozesTTorenPChernauzanNYoran-HegeshRMesterR.An open trial of clozapine in neuroleptic-resistant childhood-onset schizophrenia. Br J Psychiatry1997;170:507–10.
28.
KowatchR.A.SuppesTGilfillanSKFuentesMDGrannemannMSEmslieMD. Clozapine treatment of children and adolescents with bipolar disorder and schizophrenia: A clinical case series. J Child Adolesc Psychopharmocol1995;5:241–53.
29.
KowatchRAGilfillanSKSuppesTFuentesRM. Clozapine treatment of children and adolescents: A four year follow-up. Biol Psychiatry1996;39:530–38.
30.
BaldessariniRFrankenburgFR. Clozapine: A novel antipsychotic agent. N Engl J Med1991;324:746–54.
31.
KumraSFrazierJAJacobsenLKGordonCT. Childhood-onset schizophrenia: A double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry1996;53:1090–7.
32.
KillanJGKerrKLawrenceCCelermajerDS. Myocarditis and cardiomyopathy associated with clozapine. Lancet1999;354:1841–5.
33.
PopliAPKanickiPEJurjuzCJFullerMAJaskiwCE. Clozapine and associated diabetes mellitus. J Clin Psychiatry1997;58:108–11.
34.
HaggSJoelesonLMjorndalTSpigsetOOjaCDahlqvistR.Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry1998;59:291–9.
35.
McConvilleBWongJYehC.Quetiapine fumarate: Clinical effectiveness, tolerability and pharmacokinetics in psychotic adolescents. American Academy of Child and Adolescent Psychiatry Annual Meeting; 1998; Anaheim (CA).
36.
ReinsteinAUSirotovskaraLAJonesLEMohanSChasanovMA. Effects of clozapine-quetiapine combination therapy on weight and glycaemic control. Clinical Drug Investigation1999;19:99–104.
37.
TeuthMJMurphyTKEvansDL. Special considerations: Use of lithium in children, adolescents, and elderly populations. J Clin Psychiatry1998;59 (Suppl 6):66–73.
38.
GellerBCooperTBSunK.Double blind and placebo controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. J Am Acad Child Adolesc Psychiatry1998;37:171–8.
39.
KafantarisVColettiDJDickerRPadulaGPollackS.Are childhood psychiatric histories of bipolar adolescence associated with family history, psychosis, and response to lithium treatment?J Affect Disord1998;51:153–64.
40.
StroberMMorrellWLampertCBurroughsJ.Relapse following discontinuation of lithium maintenance therapy in adolescents with bipolar illness: A naturalistic study. Am J Psychiatry1990;147:457–61.
41.
CarlsonGARapportMDPatakiCS. Lithium in hospitalized children at four and eight weeks: Mood, behaviour and cognitive defects. J Child Psychol Psychiatry1992;33:411–25.
42.
PlattJECampbellMGreenWH. Cognitive effects of lithium carbonate and haloperidol in treatment resistant aggressive children. Arch Gen Psychiatry1984;41:657–62.
43.
McClellanJWerryJS. Practice parameters for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry1997;36:138–57.
44.
PapatheodorouGKutcherSP. Divalproex sodium treatment in late adolescent and young adult acute mania. Psychopharmacol Bull1993;29:213–9.
45.
HimmelhochJMGarfinkelME. Mixed mania: Diagnosis and treatment. Psychopharmacol Bull1986;22:613–20.
46.
IsojarviJITLaatikainenTJPakarinenAJJuntunenKTSMyllylaVV. Polycystic ovaries and in women taking valproate for epilepsy. N Engl J Med1993;3291:1383–8.
47.
IsojarviJITLaatikainenTJKnipMPakarinenAJJuntunenKTSMyllylaVV. Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol1996;39:579–84.
48.
WerryJSAmanMG, editors. Practitioner's guide to psychoactive drugs for children and adolescents. 2nd ed.New York: Plenum Medical Books; 1999.
49.
TonnbyBNilssonHLAldenkampAP. Withdrawal of antiepileptic medication in children: Correlation of cognitive function and plasma concentration – the multi-centre “Holmfrid” study. Epilepsy Res1994;19:141–52.
50.
GoldbergJFBurdickMA. Cognitive side effects of anticonvulsants. J Clin Psychiatry2001;62 (Suppl 14).
51.
StollALLockeCAVuckovicA.Lithium associated cognitive and functional deficits reduced by a switch to divalproex sodium: A case series. J Clin Psychiatry1996;57:356–9.
RyanNDBhataraVSPerelJM. Mood stabilizers in children and adolescents. J Am Acad Child Adolesc Psychiatry1999;38:529–36.
54.
Pallere-MartinotMAubinFMartinotJColinB.A prognostic study of clinical dimensions in adolescent-onset psychoses. Schizophr Bull2000;26:789–99.
55.
BosticJQWilensTESpencerTBiedermanJ.Antidepressant treatment of juvenile depression. International Journal of Psychiatry in Clinical Practice1999;3:171–9.
56.
EmslieGRushAJWeinbergAWKowatchRAHughesCWCarmodyT.A double-blind randomized placebo controlled trial of fluoxetine in depressed children and adolescents. Arch Gen Psychiatry1997;54:1031–7.
57.
ZanardiRFranchiniLSerrettiAPerezJSmeraldiE.Venlafaxine versus fluvoxamine in the treatment of delusional depression: A pilot double blind controlled study. J Clin Psychiatry2000;61:26–9.
58.
BurnettP.Treating first episode psychosis with atypical antipsychotics. Paper presented at the Australian National Conference on the Role of Atypical Antipsychotics: Evidence-Based Practice; August 17, 2001; Sydney, Australia.
