This finding holds for typical45 as well as for atypical23 drugs. In fact, in a posthoc analysis,23 it was demonstrated that many recent-onset patients experience therapeutic benefits with 2 to 4 mg haloperidol or risperidone, after which the benefits plateau, but not the EPSs. Interestingly, even at low doses, haloperidol produces

more EPSs than olanzapine32 or risperidone.23 It is not clear at the present why patients who have been ill for several years or several decades need higher doses of antiBIBF 1120 chemical structure psychotic drugs to reach therapeutic benefit and why they are less sensitive to EPSs. Biological and/or psychological Inhibitors,research,lifescience,medical tolerance to EPSs and to therapeutic benefit could be invoked to explain this Inhibitors,research,lifescience,medical phenomenon. For example, dopamine supersensitivity might have developed after many years of dopamine blockade46 explaining why higher doses might be necessary Alternatively, as the disease continues and remission and improvements become more elusive, patients, their families, and in particular the treating staff become

increasingly frustrated and tend to raise the antipsychotic dose and discount the adverse effects. This is paradoxical considering the fact that most adverse effects are dose-dependent and that the only factor that predicts if a patient will remain in treatment at the end Inhibitors,research,lifescience,medical of the first year of illness is the dose of antipsychotic drug.47 Weight gain Another adverse effect that affects young recent-onset psychosis patients is rapid, significant, and persistent weight gain.24,32,48,49 Young patients treated with some but not all atypical drugs tend to gain approximately 5 kg over 2 to 3 months,32,50 which is mostly abdominally Inhibitors,research,lifescience,medical deposited adipose tissue. Fasting insulin, C-peptide, and triglyceride levels significantly increase, suggesting the possible development of insulin resistance.50 It is conceivable that the mechanism involved in weight gain is age-dependent, since elderly Inhibitors,research,lifescience,medical schizophrenic patients do not gain weight,51 but it is also possible that elderly individuals have already suffered most of the antipsychoticinduced weight gain and/or that the weight gain is counterbalanced by an aging-dependent

weight loss. Comorbid psychiatric symptoms Whether Non-specific serine/threonine protein kinase the presence of comorbid symptoms, such as depression, suicide attempts, and violent outbursts, are more frequent during the first few years following the first psychotic episode than during the later years is an unsettled area of research. Similarly, the treatment of comorbid symptoms and behaviors remains a challenge. Attempts to understand depression in recent-onset psychosis patients52 and to treat it53 have encountered conceptual and practical difficulties. It is not obvious whether the depressive symptoms are a core feature of the psychotic illness or a reactive response to a severe and debilitating illness. Also depressive symptoms tend to overlap with negative symptoms,54 neither of which has a good response to treatment.