Date of Award


Degree Type


Degree Name

Master of Science in Pharmacology and Toxicology




Pharmacology and Toxicology

First Advisor

Robert E. Becker


A combination of bupropion hydrochloride and thiothixene was compared with a combination of placebo and thiothixene in a double blind investigation in thirty-eight patients meeting the DSM-III criteria for schizophrenia and also for atypical depression. These patients had to demonstrate a Hamilton Depression Scale score of at least eighteen prior to study entry. Assessments for efficacy and safety were performed at baseline and at regular intervals throughout the study. Patients were given physical exams with complete clinical laboratory workups prior to and after the study active treatment phase to document the safety of the respective treatments. Of the nineteen subjects originally included in each treatment group, eighteen completed four full weeks of study treatment. Patients in both treatment groups were not significantly different at baseline on all measures. A significantly greater number of subjects (9) dropped out from the bupropion and thiothixene group than from the placebo and thiothixene group (2) prior to reaching the full ten week period. The patients who dropped out were significantly more psychiatrically ill than those who remained as measured by the Brief Psychiatric Rating Scale. Both groups became less depressed as measured on the Hamilton Depression Scale over four and ten weeks, though only when the dropouts were included in the analysis did the placebo and thiothixene group demonstrate a greater degree of improvement than the bupropion and thiothixene group. The overall psychiatric pathology as measured by the Brief Psychiatric Rating Scale was decreased to a significantly greater degree by the placebo and thiothixene control group than by the bupropion and thiothixene group at four weeks but not at ten weeks. Global ratings of patients overall psychiatric status also showed improvement over time. Treatment group effects on separate psychiatric syndromes as measured by the Brief Psychiatric Rating Scale factor scores were divergent. Significant decreases on the thought disorder and the anergia factor scores from baseline were observed for both treatment groups to a similar degree. However, patients in the thiothixene and placebo group demonstrated greater improvement over time than the bupropion and thiothixene group on the anxiety and depression factor score. Neither group showed improvement from baseline on the activation factor scores nor the hostility and depression factor scores. Neurological side effects were not significantly different between groups. No differences between group were observed on the physical and clinical chemistry examinations of patient health nor on electrocardiogram or electroencephalogram. The Treatment Emergent Symptom Scale showed statistically significant between group differences. The bupropion and thiothixene group reported twice the incidence of dry mouth and constipation than the placebo and thiothixene group, while the latter group reported increase in appetite, more menstrual disturbances, and a decrease in sex drive over four and ten weeks.



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