The relationship of COS to PDD has been of interest given their frequent coexistence. In a sample of children with COS, 34% had pervasive developmental symptomatology and 60% met criteria for a speech and/or language disorder.10 Sporn and colleagues11 found that 25% of children with COS had a lifetime diagnosis of PDD and those with comorbid PDD did not differ from the COS-only group in age at COS onset, cognitive performance, neuropsychological measures, or overall long-term outcome.
In a recent review of COS and childhood-onset schizoaffective disorder, 99% of those with either disorder were found to have at least 1 comorbid diagnosis: 84% had attention-deficit/hyperactivity disorder (ADHD), 43% had oppositional defiant disorder, 30% had depression, and 25% had separation anxiety disorder.12 Depression, anxiety,13 and eating disorders14 have been found to be comorbid with schizophrenia. Many comorbid disorders of COS, such as PDD, ADHD, and speech and language disorders, have their onset before COS.
Treatment strategies focus on alleviating positive and negative symptoms, reducing long-term morbidity, and preventing relapse. Clinical experience supports a combination of psychopharmacologic and psychosocial interventions to address the treatment needs in COS.3,15
The available studies, as well as anecdotal clinical experience, suggest that response to antipsychotics in children with COS is less robust than in adolescents or adults with schizophrenia. Current pharmacologic research for COS is focused on identifying antipsychotic agents that provide optimal efficacy without significant adverse events. Atypical antipsychotics, including risperidone(Drug information on risperidone), olanzapine(Drug information on olanzapine), and clozapine(Drug information on clozapine), have been shown in randomized clinical trials and open trials to be efficacious in the treatment of COS16-21; however, significant adverse effects, including weight gain, extrapyramidal adverse effects, and metabolic abnormalities, have occurred. Table 2 summarizes several recent psychopharmacologic trials for COS.
The superiority of clozapine over typical and atypical antipsychotics was shown in 2 randomized clinical trials for the treatment of COS; however, the use of clozapine was associated with serious adverse events such as tachycardia, hypertension, cardiac and lipid abnormalities, agranulocytosis, seizures, and nocturnal enuresis.16,17
In a 1-year open-label trial of olanzapine for the treatment of COS, positive symptoms improved after 6 weeks and negative symptoms showed improvement after 1 year of treatment.22 Adverse effects included increased appetite and weight gain,23 sedation,24 GI symptoms, headaches, agitation, liver function abnormalities, and sustained tachycardia.25
Pharmacologic treatment for COS remains an area of active research with 2 large ongoing multisite trials. The Early Onset Schizophrenia Study is investigating newer atypical antipsychotic agents. Preliminary open-label data suggest that ziprasidone(Drug information on ziprasidone) was beneficial in approximately 13 of the 40 patients with COS after 12 weeks of treatment, with a mean final dosage of 118 mg/d. In over 1 year of this study, 50% of patients gained weight but no significant ECG changes occurred. The preliminary data suggest that ziprasidone may be useful in the treatment of COS.26 Another ongoing double-blind trial (Treatment of Early Onset Schizophrenia Spectrum Disorders) compares molindone(Drug information on molindone), risperidone, and olanzapine.26
Psychosocial interventions address social, family, and peer relationship distress and developmental sequelae associated with COS.27 Social skills training is geared toward improving the patient's strategies for dealing with conflict and avoidance, enhancing communication within the family, and improving socialization and vocational skills. Psychoeducation helps the patient and his family understand the illness, the treatment options, and the prognosis for developing strategies to cope with the symptoms.3 Family psychoeducation and cognitive-behavioral therapy have been shown to reduce relapse in adolescents and adults with schizophrenia,15 and it is conceivable that a similar gain may occur in patients with COS.
OUTCOME OF COS
Outcome studies ranging from several years to up to 42 years after diagnosis of COS indicate that the long-term functioning of patients with COS is poor compared with that of patients who have adolescent- or adult-onset schizophrenia.6,7,27 In general, the earlier the onset of COS, the poorer the prognosis. Variables indicative of better prognoses among children with COS are higher premorbid intelligence, more positive than negative symptoms of schizophrenia, and cooperation of family in treatment.2 Outcome variables in COS are detailed in Table 3.
Follow-up data indicate that close to two thirds of children with onset of schizophrenia between the ages of 6 and 14 years will be chronically ill.27,28 While outcomes are most grave for children with onset of illness before 13 years of age, findings from long-term outcome studies of adolescents with schizophrenia indicate that the illness has a negative impact on their academic success.29 For example, compared with the general population, adolescents with schizophrenia are about one third as likely to graduate from secondary school.29
With respect to occupational functioning, the findings from a 3-year outcome study of schizophrenia in children and adolescents showed that fewer than one fifth were able to function in academic or work settings at the level of same-age peers in the general population.30 Long-term follow-up of individuals with COS and adolescent-onset schizophrenia over 6 to 40 years indicates that significant impairment persists into adulthood; only 7% of the sample were able to maintain a stable relationship, and 59% were unmarried and living alone. Although 73% had some form of employment, 27% were unable to work.31 Clearly, the burden of schizophrenia lingers over the years.
While COS and adolescent-onset schizophrenia are the same disorder, their relationship is highlighted by a poorer prognosis in youth who meet diagnostic criteria before age 14 years.28 Children with COS are at significantly increased risk for having bor-derline intellectual function or mild mental retardation,32 and they are more likely to have speech and language disorders33 and a history of PDD34 compared with those who have adolescent-onset schizophrenia.
Given the challenge of finding successful multimodal interventions for COS, available psychopharmacologic agents have shown some evidence of effectiveness, although all are still limited by serious adverse effects. Future investigations of combined psychosocial and pharmacologic treatments are needed to provide a broader range of effective interventions to improve long-term function of patients with COS.
Dr Khurana and Dr Aminzadeh are first-year child and adolescent psychiatry fellows at the Los Angeles County–University of Southern California (USC) Child and Adolescent Psychiatry Fellowship Program. Dr Bostic is director of school psychiatry at Massachusetts General Hospital in Boston and McLean Hospital in Belmont, Mass. Dr Pataki is director of residency training in child psychiatry at the USC Keck School of Medicine in Los Angeles.
Dr Khurana and Dr Aminzadeh report that they have no conflicts of interest concerning the subject matter of this article. Dr Bostic has received grant support and/or honoraria from Abbott, Forest, GlaxoSmithKline, Eli Lilly, and Pfizer; he is on the speakers' bureau for Forest and a consultant for GlaxoSmithKline. Dr Pataki has received research support from Eli Lilly, Pfizer, Novartis, and Shire.
Drugs Mentioned in This Article
Haloperidol(Drug information on haloperidol) (Haldol)
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