Treatment of Childhood Onset Psychiatric Disorders With Intravenous Immunoglobulin (IVIg)

Recent developments in the study of early-onset obsessive-compulsive disorder (OCD) and Tourette's syndrome have implicated an autoimmune etiology in a subset of these conditions, and renewed interest into the possibility of autoimmune pathophysiology underlying other psychiatric disorders. There are several clinical and epidemiologic similarities between autoimmune diseases and schizophrenia: genetic predisposition, but with twin concordance below 50%; waxing and waning course; exacerbation of symptoms or precipitation of relapse by psychosocial stress. However, other mixed evidence has engendered considerable debate in the literature regarding the role of immune mechanisms in schizophrenia. The clinical efficacy and safety of intravenous immunoglobulin (IVIg) in immune-mediated neurological diseases has been documented, and clinical studies of the efficacy of IVIg in the treatment of both Tourette's syndrome and OCD are currently ongoing at the NIMH (see protocol 92-M-0132). In this protocol, we propose a 13-week placebo-controlled double-blind crossover study of IVIg in 25 patients suffering from treatment-refractory childhood-onset schizophrenia. After the first 5 patients have completed the trial, this data will be presented to the NIMH Institutional Review Board and a decision will be made as to whether this trial should proceed.

Patients will be recruited from both professional referrals and patient advocacy sources, subject to medical and psychiatric screening.

Children and adolescents will be sought who meet DSM-III-R and DSM-IV criteria for schizophrenia, with onset of psychotic symptoms before age twelve, and who have no concurrent substance abuse disorders or other active medical conditions. In addition, they will have failed adequate trials of at least two typical neuroleptics, and not benefited from either olanzapine or clozapine.