Pharmacotherapy for self-injurious behavior: preliminary tests of the D1 hypothesis.

1. The D1 dopamine hypersensitivity model of self-injurious behavior leads to a testable clinical hypothesis: that the mixed D1/D2 dopamine antagonist fluphenazine may improve the symptoms of self-injurious patients. 2. The hypothesis was tested in an open pilot trial in six patients and a partially controlled trial in nine patients. 3. Some degree of clinical improvement was observed in eleven of the fifteen. 4. The trials represent a partial affirmation of the D1 hypothesis. However, it is also clear that conventional methodology for psychopharmacologic research is inappropriate for the proper clinical evaluation of self-injurious patients. The proper method should include the following elements: i) An epidemiologically representative sample ii) A naturalistic study environment iii) A longitudinal design with long-term follow-up iv) Concurrent behavioral ratings using direct observations and a reliable, treatment-sensitive rating scale. 5. Before subjects enter a clinical trial of an experimental medication, a neuropsychiatric differential diagnosis should be applied to limit the diversity of the sample.