However, a

series of cases of agranulocytosis5 led to a delay in the further development of clozapine in the US. Based on a large RCT with prospective validation of treatment refractoriness demonstrating clozapine’s superiority over chlorpromazine in refractory schizophrenia,6 the FDA approved clozapine with the narrow indication for treatment resistant patients in 1990. Since then, clozapine’s singular role Inhibitors,research,lifescience,medical in treatment-refractory patients with schizophrenia has been confirmed7 and its role in the management of suicidality has also been established.8 Nevertheless, recent meta-analyses“ did not uniformly confirm clozapine’s superiority over other antipsychotics in schizophrenia. Again, several design issues need to be considered

when evaluating this inconsistency, including inappropriately low doses of clozapine9, as well as the lack of selection for truly resistant patients. Attention to first-episode schizophrenia Beginning in the Inhibitors,research,lifescience,medical mid 1980s increased attention to first episode patients seemed warranted to evaluate treatment outcomes that are unconfounded Inhibitors,research,lifescience,medical by the effects of prior treatment, multiple relapses, and chronic illness.11-13 Studies revealed cognitive and psychosocial deficits that were present at illness onset,14 a long duration of untreated psychosis prior to first mental health contact,15 increased sensitivity to medication side effects,16 but also a better treatment response

Inhibitors,research,lifescience,medical compared with more chronically ill patients.17 Exploring biological heterogeneity and treatment response at this phase has become an important focus. In addition, as part of the move toward the early treatment of schizophrenia, and the response to new FDA incentives, the selleck Bortezomib efficacy of antipsychotics has also demonstrated in adolescents with schizophrenia.18 In Inhibitors,research,lifescience,medical adolescents, appropriate selection criteria and trial design considerations are also critical. Comparative efficacy and effectiveness first-generation Cilengitide and second-generation antipsychotics With the Pacritinib Sigma introduction of second-generation antipsychotics, there were observations of lower extrapyramidal side-effect burden and tardive dyskinesia risk and expectations of superior efficacy for positive, negative, and cognitive symptoms.19 Initial efficacy studies seemed to confirm the superiority of second-generation antipsychotics, but the comparator consisted predominantly of haloperidol, used at moderate to high doses and often without anticholinergic cotreatment, which made early treatment discontinuation and secondary negative symptoms more likely in haloperidol treated patients.