Did DSM-5 throw out the subtype baby with the bathwater?

Many clinicians have suspected and some evidence indicates that patients with the disorganized subtype of schizophrenia, or hebephrenia, do not respond as well to non-clozapine antipsychotics as do other subtypes. Investigators examined this hypothesis in 93 consecutively admitted schizophrenia patients at one hospital in Brazil. They confirmed the diagnosis with the Structured Clinical Interview for DSM-IV, and classified patients as either paranoid or disorganized subtype based upon the predominance of hallucinations and delusions versus disorganized speech and behavior using relevant PANSS items. Only 8 patients, who had either catatonic or residual schizophrenia, were excluded. Treatment resistance was defined as failure of two different antipsychotics, and these patients were offered either clozapine or “combination therapy.”

The mean age of the patients was about 32 years and 56% were male. The demographic profiles did not differ between the 25 disorganized and the 60 paranoid patients; however, the disorganized patients had significantly earlier age of onset, more severe symptoms, and lower functioning as measured by the Global Assessment of Functioning scale. Among the disorganized cohort, 60% were treatment-resistant compared with 20% of the paranoid cohort (p < 0.001). The clozapine response rate, as measured by at least 40% reduction in the total PANSS score, was greater than 60% in both groups. Although DSM-5 has eliminated subtypes of schizophrenia, this study suggests that the disorganized-paranoid axis may retain prognostic and hence diagnostic significance. Another interpretation is merely that positive symptoms respond better to non-clozapine antipsychotics than do disorganized features, which may respond better to clozapine. The study did not have masked raters and the total number of patients is small, so replication is necessary. The Brazilian researchers nonetheless advocate for clozapine use earlier in the course of treatment for disorganized-type patients. If this were adopted widely, clinical subtyping would likely require a more careful approach to evaluation than is carried out in usual practice, such as the use of standardized rating instruments. Reference Ortiz BB, Araújo Filho GM, Araripe Neto AG, Medeiros D, Bressan RA. Is disorganized schizophrenia a predictor of treatment resistance? Evidence from an observational study. Rev Bras Psiquiatr. 2013;35(4):432-434. Full text