The general objective of this plan is to characterize the relationship between psychoactive medication plasma concentrations and psychometric ratings, side effects, and electrocardiographic abnormalities obtained in our recently completed double-blind study of haloperidol-benztropine treated depressed schizophrenics who were adjunctive medicated with amitriptyline, desipramine, or placebo. Despite decades of availability of neuroleptics and antidepressants, and recognition of depressive syndromes in acute and post-acute schizophrenics, there is still uncertaintly about the utility of adjunctive antidepressants in the treatment of depressive syndromes accompanying acute or residual schizophrenia. Previous studies in this area have either been poorly designed, used unusually low antidepressant doses, or failed to measure plasma concentrations of the experimental medications.
Specific aims of this plan are to: (1) determine 360 haloperidol plasma concentrations, 60 amitriptyline and nortriptyline plasma concentrations, and 60 desipramine plasma concentrations, all by capillary gas chromatography with nitrogen selective detection; (2) determine the association between haloperidol by capillary gas chromatography and haloperidol by neuroleptic radioreceptor assay, through linear regression by least squares for all measurements of haloperidol blood level concentrations; (3) determine the association between EKG conduction abnormalities and haloperidol, amitriptyline, amitriptyline + nortriptyline, desipramine, desipramine + haloperidol, amitriptyline + haloperidol, or amitriptyline + nortriptyline + haloperidol plasma capillary gas chromatography concentrations; (4) determine the relationship between total side effects and haloperidol, amitriptyline, amitriptyline + nortriptyline, desipramine, desipramine + haloperidol, amitriptyline + haloperidol, or amitriptyline + nortriptyline + haloperidol plasma capillary gas chromatorgraphy concentrations; (5) determine the association of BPRS schizophrenia subscale scores, BPRS, total HAM-D, and BPRS hostility/hallucinations/conceptual disorganization scores with haloperidol, amitriptyline, amitriptyline + nortriptyline, desipramine, desipramine + haloperidol, amitriptyline + haloperidol, or amitriptyline + nortriptyline + haloperidol plasma capillary gas chromatography concentrations; (6) determine the relationship between haloperidol gas chromatography concentrations before and after addition of amitriptyline or desipramine to haloperidol treated patients; (7) compare amitriptyline or disipramine range to plasma concentrations obtained in the presence of haloperidol treatment with those ranges, as reported by National Medical Services Laboratories.
