Therapeutic combinations of atypical antipsychotics with corticotropin releasing factor antagonists

EXAMPLE 1

[0550] A pharmaceutical composition is prepared by combining ziprasidone with a CRF antagonist which is either (a) 4-(1-ethyl-propoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-pyridine, (b) (3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl)-(1-ethyl-propyl)-amine, (c) (3,6-dimethyl-2-(4-chloro-2,6-dimethyl-phenoxy)-pyridin-4-yl)-(1-ethyl-propyl)-amine, or (d) 5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-cholorophenyl)-1-4-dihydro-2 H-3-oxa-1,8-diazanaphthalene; in a pharmaceutically acceptable carrier. The composition contains respective amounts of ziprasidone and the CRF antagonist to deliver on a daily basis between about 20 mg to about 160 mg ziprasidone and between about 0.1 to 100 mg of the CRF antagonist. The composition is administered to a patient for the treatment of schizophrenia on a daily, twice daily, three times daily, or four times daily basis.

EXAMPLE 2

[0551] Administration of ziprasidone in combination with CRF antagonists.

[0552] A prospective, open-label, randomized, flexible-dose multicenter study is carried out comparing the efficacy of IM ziprasidone with and without a CRF antagonist in the dosages of the CRF antagonist described in Example 1 in improving agitation and psychopathology in patients with psychotic disorders. Ziprasidone is given IM at a dose of 10 or 20 mg, with an additional daily dose if needed to a maximum of 40 mg.

[0553] About half of ziprasidone treated patients receive at least one dose of a CRF antagonist of Example 1 during IM therapy. Primary efficacy outcomes are mean change from baseline in Brief Psychiatric Rating Scale (BPRS), CGI-S, and CGI-Improvement (CGI-I) scores. BPRS, CGI-S, and CGI-I are rated at baseline, once every 24 hours during IM treatment, and at the end of day three.

[0554] It should be understood that the invention is not limited to the particular embodiments described here