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 protected] 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- interscience.wiley.com/cochrane/clsysrev/articles/CD002831/ 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.

Source: http://www.saludmental.edilaser.net/en/pdf/3405/SM%2011.05.06_p419-423.pdf