Sm 11.05.06 - evaluacion tratamiento esquizofrenia.pmd
Salud Mental 2011;34:419-423 Schizophrenia in children and adolescents; diagnosis and treatment
Assessment and treatment of schizophrenia
in children and adolescents: a current review
Rosa Elena Ulloa Flores,1 Tizbé del Rosario Sauer Vera,2 Rogelio Apiquian Guitart3
Schizophrenia is a severe and chronic disorder affecting children,
La esquizofrenia es un trastorno prevalente, crónico e incapacitante
adolescents, and adults. The international recommendations for the
en niños, adolescentes y adultos. Las recomendaciones internacio-
treatment of pediatric patients with this disorder point to a
nales para su tratamiento en edad pediátrica incluyen programas
comprehensive management, which includes early detection
de detección temprana y tratamiento farmacológico y psicosocial. El
programs, and pharmacological and psychosocial treatments. This
presente trabajo muestra una revisión actualizada de la eficacia y la
work presents a review of current information regarding the efficacy
seguridad de los antipsicóticos en niños y adolescentes, así como el
and safety of antipsychotics in children and adolescents, as well as
efecto de las intervenciones psicosociales en el funcionamiento aca-
the effect of psychosocial interventions on the academic and social
démico y social en pacientes con esquizofrenia de inicio temprano.
functioning of patients with early onset schizophrenia.
La meta del tratamiento farmacológico es lograr un resultado
The goal of pharmacological treatment is to achieve optimal
óptimo a dosis mínimas efectivas del antipsicótico y tener el menor
outcome with the lowest effective dose and the fewest side effects.
número de efectos secundarios. Deben de considerarse los
Treatment should be started with an antipsychotic that has been
antipsicóticos evaluados en estudios controlados en edad pediátrica.
assessed for its efficacy and safety in this age group. Risperidone,
La risperidona, la olanzapina y el aripiprazol han sido aprobados
olanzapine and aripiprazole have been approved by the FDA for the
por la FDA para el tratamiento de la esquizofrenia en adolescentes;
treatment of schizophrenia in adolescents; clozapine has shown
la clozapina ha mostrado mayor eficacia en el tratamiento de la
greater efficacy with the treatment-resistant psychosis, while its adverse
psicosis resistente, sus efectos adversos deben de ser monitorizados
side effects must be monitored during use.
The objectives of psychosocial treatment are to provide
El tratamiento psicosocial brinda información al paciente y su
information, to promote the patient’s adaptation, to reduce comorbidity
familia, promueve la adaptación y disminuye la comorbilidad para
and to prevent relapses through psychoeducation, psychotherapy, and
prevenir recaídas, por medio de programas de psicoeducación,
rehabilitation programs. Psychoeducation programs include infor-
psicoterapia y rehabilitación. Los programas de psicoeducación
mation about the characteristics and causes of the illness, the available
incluyen la información acerca de la enfermedad y sus causas, los
treatment choices and the factors associated with recovery or relapse.
tratamientos disponibles y los factores asociados a las recaídas. La
Psychotherapy in schizophrenia has been examined in individual, group,
psicoterapia puede darse en el contexto individual, familiar o grupal,
and family modalities; cognitive behavioral therapy has demonstrated
de acuerdo a las necesidades del paciente. La terapia cognitivo
efficacy on cognition, social adjustment, and quality of life. Rehabili-
conductual ha mostrado eficacia en la adaptación social, cognitiva
tation programs include training on social skills, cognitive remediation
y en la calidad de vida. Los programas de rehabilitación incluyen
therapy, and exercise programs, which would increase the wellbeing
entrenamiento en habilidades sociales, rehabilitación cognitiva y un
of patients and reduce metabolic alterations associated with the use of
programa de acondicionamiento físico para promover el bienestar
general del paciente y evitar la aparición de los efectos secundarios
In conclusion, the treatment of patients with early onset schizo-
phrenia must be multimodal with the aim of improving their long-
En conclusión, la esquizofrenia en niños y adolescentes requiere
de tratamiento multidisciplinario a fin de mejorar el pronóstico delos pacientes.
Key words: Schizophrenia, treatment, children, adolescents, anti-psychotics.
Palabras clave: Esquizofrenia, tratamiento, niños, adolescentes,antipsicóticos.
Developmental Psychopharmacology, Dr. Juan N. Navarro Children’s Psychiatric Hospital.
Psychiatric Care Services, Secretariat of Health.
Department of Behavioral Sciences, Universidad de las Américas (University of the Americas).
Correspondence: Dr. Rosa Elena Ulloa. Hospital Psiquiátrico Infantil «Dr. Juan N. Navarro», San Buenaventura 86,
Fax: (52 55) 5573 9161. E-mail: email@example.com
Schizophrenia is among the ten most common disabilitiesin the world1,2 and is defined as a psychotic disorder that
The process of clinically assessing a pediatric patient with
affects the perception, thought, emotions, and behavior of
schizophrenia includes a clinical history supported by
patients, breaking down their family, academic, and social
diagnostic interviews such as the K-SADS-PL12 or the
MINIKid,13 and once the diagnosis is confirmed, through
The lifetime prevalence of this illness has been reported
specific severity scales such as the Brief Psychiatric Rating
at between 0.3% and 1.6%3 and its incidence is between
Scale (BPRS)14, or the Positive and Negative Symptoms of
0.002% and 0.011%. In one third of patients with schizo-
Schizophrenia (PANSS) scale.15 It is important to assess the
phrenia the onset of the condition occurs before the age of
risk of auto- or hetero-aggression and the patient’s capacity
18,4 and in 6% before the age of 16.5 Within this population
a higher proportion of cases have been described among
Laboratory and clinical studies should also be
considered, as they provide information about the patient’sstate of health prior to commencing pharmacologicaltreatment and help to rule out any physical pathology that
Clinical manifestation of schizophrenia includes diverse
symptoms that are classified as positive (deliriums andhallucinations), negative (apathy, anhedonia, a reduction in
In Mexico there are few mental healthcare centers for
the lucidity and content of speech), affective (depression or
children and adolescents. The few there are handle the
anxiety that can accompany both the positive and the negative
majority of cases of schizophrenia. In such centers the
symptoms), cognitive (loss of memory, impaired judgment,
comprehensive management of schizophrenia should
disorganization), and excitability/hostility (agitation,
include programs for early detection, and pharmacological
aggression). In the case of pediatric patients the manifestation
of these symptoms is frequently preceded by developmentaldisorders, and a higher frequency of low IQ, cognitive deficits
and acute negative symptoms has been noted. There is also
In early detection it is important to take into account risk
a high prevalence of undifferentiated and disorganized
factors for the manifestation of psychotic symptoms, such
subtypes of the illness in children and adolescents.7,8
as a family history of psychosis, perinatal and neurode-
In the same way as adults, psychotic symptoms can
velopmental disorders, substance abuse, adolescence, and
often be preceded by prodromal symptoms.5 These include
stress. Different healthcare workers can participate in the
a decrease in attention, concentration and motivation,
early detection programs designed to examine these risk
energy, mood disorders, abnormalities in the sleep-wake
factors. The principal components of such programs are
cycle, isolation, suspicion, and a decrease in functioning.
information about the illness, referral of patients to care
The course of schizophrenia includes remissions and
centers that specialize in their assessment and treatment,
exacerbations, although in some patients a serious psychotic
and the follow-up of cases in a way that can determine the
state will persist. Factors associated with a poor prognosis
effect of the staff’s intervention on the symptoms and
include poor premorbid functioning,9,10 greater duration
functioning of patients over the medium- and long-term.17
of untreated psychosis,11 greater severity of the illness anda greater number of relapses.5
This work presents a current review of all aspects of
treatment for this condition, offering recommendations
Trifluoperazine was the first antipsychotic medication
regarding the handling of schizophrenia in our field. For
assessed in a controlled clinical study.18 One of the first
this review articles were identified that covered the efficacy
efficiency studies compared chlorpromazine and
and safety of antipsychotic medications in children and
haloperidol,19 which was subsequently compared with the
adolescents, as well as the effects of psychoeducation and
other psychosocial interventions on the symptoms as well
Risperidone has been studied in various open clinical21
as the academic and social functioning of patients. The
and placebo-controlled22,23 trials, and with other atypical
search for materials focused on articles published in
antipsychotics like quetiapine.24 Olanzapine25 and aripipra-
medicine and psychology databases (PsychINFO, Medline,
zol26 are the antipsychotics most recently approved for use
1966–2011, Cochrane); also examined were the works
in adolescents with schizophrenia. Clozapine was assessed
referred to in the tracking studies.
in controlled studies with haloperidol27 and olanzapine.28
Schizophrenia in children and adolescents; diagnosis and treatment
Recent reviews recommend it for patients who have not re-
psychosocial function, reduce comorbidity, and prevent
sponded to other antipsychotics;29,30 it has been recommend-
relapses. The strategies for this treatment include psycho-
ed for patients who have not responded to other treatments
education, psychotherapy, and rehabilitation, which are
and has been assessed in a clinical study. Recently the study
applied in comprehensive treatment programs. An example
for Treatment of Early Onset Schizophrenia Spectrum
of this is the «Trialog» Project in Germany, which includes
Disorders (abbreviated to TEOSS) compared the efficacy of
psychoeducation and provides tools for social competence
typical and atypical antipsychotics, showing no significant
and self-care, as well as a process of cognitive rehabilitation
differences between molindone, olanzapine and risperidone
for adolescents with schizophrenia. Results at two years
when monitored at eight weeks and at one year, emphasizing
showed that patients experienced a lower intensity of
that the affects of atypical antipsychotics on metabolism must
symptoms, and an improvement in cognition and social
functioning.39 Here in Mexico, a randomized study of adult
Treatment should be started with an antipsychotic
patients with schizophrenia showed that the combination
medication that has been assessed for efficacy and safety for
of pharmacotherapy with a program of psychosocial
the pediatric group. Such medication should be prescribed
treatment increased adherence to treatment, reduced the
in adequate doses for a minimum of six weeks. At the end
severity of symptoms, and improved the overall functioning
of this period the patient should be assessed regarding
of the patients, while also reducing relapses.40
reduction of symptoms as well as functional improvement.
The process of psychoeducation includes familiar-
If a good response is observed (a 30% score reduction on the
ization with the characteristics and causes of the illness,
scales and a functional improvement), treatment should be
the available treatment options, and the factors that help
maintained for at least two years. If a good response is not
or hinder the patient’s recovery. Furthermore, it provides
observed (after adherence to the treatment has been
tools for managing stress and for the timely detection of
confirmed), a change in antipsychotics should be considered.
symptoms in case of relapse. Although information is scarce
If there is a predominance of positive symptoms a typical
regarding psychoeducation programs for adolescents,
antipsychotic should be considered, and if there is a
studies in adults have proven the efficacy of psychoedu-
predominance of negative symptoms, an atypical. If after
cation,41 even in comparison with cognitive behavioral
six weeks on a second antipsychotic there is no response, an
assessment of the use of clozapine is recommended.33
Psychotherapy for schizophrenic patients can be given
In establishing and monitoring treatment with anti-
in several contexts, according to their personal needs and
psychotics it is advisable to use the minimum effective dose
of the medication, as the use of a high dose won’t accelerate
Cognitive behavioral therapy has proven effective in
the recovery of the patient, but would in fact increase the
decreasing symptoms and the number of rehospitalizations,
risk of side effects and the need for polypharmacy to control
and in improving the quality of life; various studies have
them. Furthermore, it is important to take note of side effects
assessed its efficacy in comparison with psychoeducation
such as tardive dyskinesia, neuroleptic malignant syndrome,
extra-pyramidal symptoms, hyperprolactinemia, metabolic
The rehabilitation of patients with schizophrenia should
syndrome and agranulocytosis; although these side effects
include training in social skills48 and personal care tasks, an
have been associated with specific antipsychotics, they could
exercise program to increase patient’s general wellbeing and
occur with the use of any atypical antipsychotic.4,34-36 It is
prevent metabolic alterations,49,50 and cognitive rehabili-
therefore recommended that laboratory tests be conducted
tation, particularly in processes of attention, memory, and
every six months, as well as the recording of vital signs
information processing, with the aim of facilitating the
and weight of the patient at every appointment.
Patients with schizophrenia could develop comorbidity
with other psychopathologies throughout their lives. Thosemost frequently reported are attention deficit hyperactivity
able 1. Key objectives of psychotherapy in its various contexts
disorder (84%), oppositional defiant disorder (43%), anddepression (30%).37,38 Comorbidity with disorders due to
Reduce vulnerability and stress, optimize adjustment
substance abuse should particularly be examined in ado-
capability and functioning of the patient, and prevent
lescents. The treatment of comorbidity should be multi-
Improve adherence to treatment, promote problemsolving, encourage social interactions and preventrelapses.
Build partnerships with families, foster families’ potentialto anticipate and resolve problems, reduce outbursts
The objectives of psychosocial treatment are to increase
of distress and guilt, along with maintaining realistic
knowledge about the illness, promote adjustment, improve
expectations about the functioning of the patient.
pective study with risperidone long-acting injectable. J Clin Psychophar-macol 2011;31:75-81.
This review presents the current outlook of the clinical
11. Marshall M, Lewis S, Lockwood A, Drake R et al. Association between
duration of untreated psychosis and outcome in cohorts of first-episode
characteristics, assessment, early detection, and treatment
patients: a systematic review. Arch Gen Psychiatry 2005;62:975-983.
of schizophrenia in children and adolescents with evidence-
12. Ulloa R, Ortiz S, Higuera F, Fresán A et al. Estudio de fiabilidad intere-
based information. Schizophrenia is one of the costliest health
valuador de la versión en español de la entrevista Schedule for Affecti-
conditions both to health services and to society in general;
ve Disordes and Schizophrenia for School- Age children- Present and
the earlier the age of onset, the more complicated the treat-
Lifetime versión (K-SADS-PL). Actas Esp Psiquiatr 2006;34:36-40.
ment becomes and the poorer the prognosis. The handling
13. Sheehan D, Lecrubier Y, Colón-Soto M. MINI KID. Mini International
Neuropsychiatric Interview para niños y adolescentes. Spanish version,
of pediatric patients with schizophrenia is based on the use
Madrid; 2000. Available at: http://www.medical-outcomes.com. Access
of antipsychotic medications, which have not been assessed
in controlled studies of child and adolescent populations in
14. Bech P, Kastrup M, Rafaelsen O. Mini-compendium of rating scales for
their entirety. This is important due to the fact that develop-
states of anxiety, depression, mania, schizophrenia with corresponding
ment plays a fundamental part in the response to antipsy-
DSM-III syndromes. Acta Psychiatr Scand 1986;73:1-37.
15. Kay S, Fiszbein A, Vital-Herne M, Fuentes L. The Positive and Negative
chotics and in susceptibility to the side effects of such
Syndrome Scale-Spanish adaptation. J Nerv Ment Dis 1990;178:510-517.
medications. In our field, the lack of information regarding
16. De Jesus M, Razzouk D, Thara R, Eaton J et al. Packages of care for
the chronic nature of the illness and the need to take
schizophrenia in low- and middle-income countries. PLoS Med 2009;6:
medication during prolonged periods causes patients to
e1000165. Available at: http://pubmedcentralcanada. ca/picrender.cgi?
abandon treatment a few weeks after starting.52 This
accid=PMC2758997&blobtype=pdf. Access date: January 11, 2011.
necessitates further investigation into the efficacy of a
17. Bird V, Premkumar P, Kendall T, Whittington C et al. Early intervention
services, cognitive-behavioural therapy and family intervention in ear-
comprehensive treatment model that combines the use of
ly psychosis: systematic review. Br J Psychiatry 2010;197:350-356.
antipsychotics with psychoeducation, psychotherapy and
18. Fish B, Shapiro T, Campbell M. Long-term prognosis and the response
rehabilitation, considering the cost-benefit relationship of
of schizophrenic children to drug therapy: a controlled study of trifluo-
these interventions over the long term.
perazine. Am J Psychiatry 1966;123:32-39.
19. Lewis P, James N. Haloperidol and chlorpromazine: a double-blind
cross-over trial and clinical study in children and adolescents. Aust N Z
20. Sikich L, Hamer R, Bashford, Sheitman B et al. A pilot study of risperi-
The authors wish to thank Gamaliel Victoria and Gabriela López
done, olanzapine, and haloperidol in psychotic youth: a double-blind,
for their assistance in drafting this manuscript.
randomized, 8-week trial. Neuropsychopharmacology 2004;29:133-145.
21. Zalsman G, Carmon E, Martin A, Bensason D et al. Effectiveness, safe-
ty, and tolerability of risperidone in adolescents with schizophrenia: anopen-label study. J Child Adolesc Psychopharmacol 2003;13:319-327.
22. Bishop J, Pavuluri M. Review of risperidone for the treatment of pedia-
tric and adolescent bipolar disorder and schizophrenia. Neuropsychia-
1. Organización Mundial de la Salud. Informe sobre la salud en el mundo
23. Haas M, Unis A, Armenteros J, Copenhaver M et al. A 6-week, rando-
2. Organización Mundial de la Salud. Programa Mundial de Acción en
mized, double-blind, placebo-controlled study of the efficacy and safe-
ty of risperidone in adolescents with schizophrenia. J Child Adolesc
3. Jablensky A. Epidemiology of schizophrenia: The global burden of di-
sease and disability. Eur Arch Psychiatry Clin Neurosci 2000;250:274-285.
24. Jensen J, Kumra S, Leitten W, Oberstar J et al. A comparative pilot study
4. Kumra S, Oberstar J, Sikich L, Findling R et al. Efficacy and tolerability
of second-generation antipsychotics in children and adolescents with
of second-generation antipsychotics in children and adolescents with
schizophrenia-spectrum disorders. J Child Adolesc Psychopharmacol
schizophrenia. Schizophr Bull 2008;34:60-71.
5. Merry S, Werry J. Course and prognosis. En: Remschmidt H (ed). Schi-
25. Maloney A, Sikich L. Olanzapine approved for the acute treatment of
zophrenia in children and adolescents. Cambridge: Cambridge Univer-
schizophrenia or manic/mixed episodes associated with bipolar I di-
sorder in adolescent patients. Neuropsychiatr Dis Treat 2010;6:749-766.
6. Werry J, McClellan J, Chard L. Childhood and adolescence schizophre-
26. Findling R, Robb A, Nyilas M, Forbes R et al. A multiple-center, rando-
nia, bipolar and schizoaffective disorders: A clinical and outcome stu-
mized, double-blind, placebo-controlled study of oral aripiprazole for
dy. J Am Acad Child Adolesc Psychiatry 1991;30:457-465.
treatment of adolescents with schizophrenia. Am J Psychiatry 2008;165:
7. Hooper S, Giuliano A, Youngstrom E, Breiger D et al. Neurocognition in
early-onset schizophrenia and schizoaffective disorders. J Am Acad
27. Kumra S, Frazier J, Jacobsen L, McKenna K et al. Childhood- onset schi-
Child Adolesc Psychiatry 2010;49:52-60.
zophrenia: A double-blind clozapine-haloperidol comparison. Arch Gen
8. Volkmar F. Childhood schizophrenia:developmental aspects. En: Re-
mschmidt H (ed). Schizophrenia in children and adolescents. Cambrid-
28. Shaw P, Sporn A, Gogtay N, Overman G et al. Childhood-onset schizo-
ge: Cambridge University Press; 2001; pp.60-81.
phrenia: A double-blind, randomized clozapine-olanzapine compari-
9. Fleischhaker C, Schulz E, Tepper K, Martin M et al. Long-term course of
son. Arch Gen Psychiatry 2006;63:721-730.
adolescent schizophrenia. Schizophr Bull 2005;31:769-780.
29. Findling R, Frazier J, Gerbino-Rosen G, Kranzler H et al. Is there a role
10. Rabinowitz J, Napryeyenko O, Burba B, Martinez G et al. Premorbid
for clozapine in the treatment of children and adolescents? J Am Acad
functioning and treatment response in recent-onset schizophrenia: Pros-
Child Adolesc Psychiatry 2007;46:423-428.
Schizophrenia in children and adolescents; diagnosis and treatment
30. Sporn A, Vermani A, Greenstein D, Bobb A et al. Clozapine treatment
42. Bechdolf A, Knost B, Nelson B, Schneider N et al. Randomized compa-
of childhood-onset schizophrenia: Evaluation of effectiveness, adverse
rison of group cognitive behaviour therapy and group psychoeduca-
effects, and long-term outcome. J Am Acad Child Adolesc Psychiatry
tion in acute patients with schizophrenia: effects on subjective quality
of life. Aust N Z J Psychiatry 2010;44:144-150.
31. Findling R, Johnson J, McClellan J, Frazier J et al. Double-blind mainte-
43. Pekkala E, Merinder L. Psychoeducation for schizophrenia. Cochrane
nance safety and effectiveness findings from the Treatment of Early-
Database Syst Rev 2002;2:CD002831. Available at: http://www.mrw.
Onset Schizophrenia Spectrum (TEOSS) study. J Am Acad Child Ado-
frame.html. Access date: January 11, 2011.
32. Sikich L, Frazier J, McClellan J, Findling R et al. Double-blind compari-
44. San Emeterio M, Aymerich M, Faus G, Guillamón I et al. Guía de prác-
son of first- and second-generation antipsychotics in early-onset schi-
tica clínica para la atención al paciente con esquizofrenia. Versión breve
zophrenia and schizo-affective disorder: findings from the treatment of
para la aplicación en la práctica clínica. Barcelona: Agència d’Avaluació
early-onset schizophrenia spectrum disorders (TEOSS) study. Am J
de Tecnologia i Recerca Mèdiques. CatSalut. Departament de Sanitat i
Seguretat Social. Generalitat de Catalunya; 2003.
33. Ulloa R, Sauer T, Fernández C, Apiquian R. Esquizofrenia en niños y
45. Bechdolf A, Knost B, Kuntermann C, Schiller S et al. A randomized com-
adolescentes. En: Ulloa R, Fernández C, Gómez H, Ramírez J, Reséndiz
parison of group cognitive-behavioural therapy and group psychoedu-
J (eds). Guías clínicas. México, DF: Hospital Psiquiátrico Infantil Dr. Juan
cation in patients with schizophrenia. Acta Psychiatr Scand 2004; 110
34. Correll C. Antipsychotic use in children and adolescents: Minimizing
46. Bechdolf A, Köhn D, Knost B, Pukrop R et al. A randomized compari-
adverse effects to maximize outcomes. J Am Acad Child Adolesc Psy-
son of group cognitive-behavioural therapy and group psychoeduca-
tion in acute patients with schizophrenia: outcome at 24 months. Acta
35. Ernst M, Malone R, Rowan A, George R et al. Antipsychotics (neurolep-
Psychiatr Scand (Supl)2005;112:173-179.
tics). En: Werry J, Aman M (eds). Practitioner’s guide to psychoactive
47. Rector N. Cognitive behavioural therapy reduces short term rehospita-
drugs for children and adolescents. Segunda edición. New York: Ple-
lisation compared with psychoeducation in inpatients with schizophre-
nia. Evid Based Ment Health 2005;8:8.
36. Weiss R, Diura J, Burget T, Tamborlane W et al. Obesity and the metabolic
48. Kurtz M, Mueser K. A meta-analysis of controlled research on social
syndrome in children and adolescents. N Engl J Med 2004;350:2362-2374.
skills training for schizophrenia. J Consult Clin Psychol 2008;76:491-504.
37. Ross R, Heinlein S, Tregellas H. High rates of comorbidity are found in
49. Lindenmayer J, Khan A, Wance D, Maccabee N et al. Outcome evalua-
childhood-onset schizophrenia. Schizophr Res 2006;88:90-95.
tion of a structured educational wellness program in patients with seve-
38. Rubino I, Frank E, Croce Nanni R, Pozzi D et al. A comparative study of
re mental illness. J Clin Psychiatry 2009;70:1385-1396.
axis I antecedents before age 18 of unipolar depression, bipolar disor-
50. Townsend L, Findling R. Modifying the risk of atypical antipsychotics
der and schizophrenia. Psychopathology 2009;42:325-332.
in the treatment of juvenile-onset schizophrenia. Expert Opin Pharma-
39. Hemmerle M, Röpcke B, Eggers C, Oades R. Evaluation of a two-year
intensive outpatient care programme for adolescents with schizophre-
51. Wykes T, Newton E, Landau S, Rice C et al. Cognitive remediation the-
nia. Z Kinder Jugendpsychiatr Psychother 2010;38:361-369.
rapy (CRT) for young early onset patients with schizophrenia: an ex-
40. Valencia M, Rascon M, Juarez F, Escamilla R et al. Application in Mexi-
ploratory randomized controlled trial. Schizophr Res 2007;94:221-230.
co of psychosocial rehabilitation with schizophrenia patients. Psychia-
52. Olivera Reyna G. Alteraciones en los lípidos, glucosa y efectos extrapi-
ramidales causados por haldol, risperidona y sus combinaciones con
41. Basan A, Pitschel-Walz G, Bäuml J. Psychoeducational intervention for
valproato en una muestra de adolescentes atendidos en el Hospital Psi-
schizophrenic patients and subsequent long-term ambulatory care. A
quiátrico Infantil Juan N. Navarro (Estudio piloto). México, DF: Depar-
four-year follow-up. Fortschr Neurol Psychiatr 2000;68:537-545.
tamento de Psicología Médica, Psiquiatría y Salud Mental, UniversidadNacional Autónoma de México; 2006.
Dr. Rogelio Apiquian Guitart has served as part of the Advisory Board ofAstra Zeneca and has been paid as a lecturer from Janssen Cilag and AstraZeneca. He has participated in and/or received payment for Janssen Cilag,Astra Zeneca, and Roche randomized, controlled studies. The other authorshave no relationship with the pharmaceutical industry or other institutionsthat could result in a conflict of interest.
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