10-year trends in the treatment and outcomes of patients with first-episode schizophrenia.

OBJECTIVE: The first episode of schizophrenia is a critical period for illness course and outcomes. We aimed to investigate treatments and outcomes during the first year after the diagnosis of schizophrenia. METHOD: Pharmacoepidemiologic inception cohort study of all newly diagnosed patients with schizophrenia in Denmark (n = 13,600) 1996-2005. RESULTS: From 1996 to 2005, the mean age at first diagnosis decreased significantly (29.2-26.1 years), more patients received antipsychotics (67.2-80.7%, annual OR = 1.07, CI: 1.06-1.09, P < 0.001) and antipsychotic polypharmacy for >4 months (16.7-37.1%, OR = 1.14, CI: 1.12-1.57, P < 0.001). The antipsychotic defined daily dosage (DDD) doubled (150-332 DDD, P < 0.001), use of antidepressants (24.3-40.6%, P < 0.001). Bed days [89.9 days (CI: 81.8-98.8) to 71.8 days, CI: 63.7-80.8, P < 0.0001] decreased, whereas outpatient contacts [10.2 (CI: 9.5-11.0) to 21.4 (CI: 19.9-21.0), P < 0.0001] doubled. CONCLUSION: Between 1996 and 2005, there was an earlier recognition of schizophrenia, intensified outpatient treatment, increased use and dosing of antipsychotics and antidepressants, but also more antipsychotic polypharmacy.

Iron Chelators: Development of Novel Compounds with High and Selective Anti-Tumour Activity.

Targeting essential nutrients (eg., those required for DNA synthesis) to inhibit cancer cell growth is a well established therapeutic strategy. A good example is the highly successful folate antagonist, methotrexate. However, up until recently, strategies to target iron which is also crucial for DNA synthesis have not been systematically explored to develop agents for the treatment of cancer. Over the last 15 years, our laboratory has embarked upon structure-activity studies designed to develop novel Fe chelators with anti-cancer efficacy. These studies have led to the development of the dipyridyl thiosemicarbazone chelators that show potent and selective anti-cancer activity and which overcome resistance to other cytotoxic agents. This class of compounds include the chelator, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), which at optimal doses markedly inhibits tumour growth and is well tolerated. Moreover, this ligand does not induce overt Fe-depletion in vivo, probably because very low doses (0.4 mg/kg) are effective at inhibiting tumour growth. Importantly, our compounds are far more active and less toxic than the chelator, Triapine®, that is being assessed in a wide variety of international clinical trials. A vital part of the mechanism of action of these compounds is their ability to form a redox-active Fe complex that generates radicals to inhibit tumour growth. Due to their relatively high lipophilicity and low molecular weight of this class of compounds, oral activity may be expected in addition to their well known efficacy via the intravenous route.