A pervasive and diverse impairment of affect, unknown in its pathogenesis, characterizes the post-psychotic phase of 40% to 70% of schizophrenic patients successfully maintained in the community on maintenance neuroleptics. This severe distress is increasingly viewed as being causally related to drug noncompliance, poor social adjustment and subsequent relapse, even for neuroleptic maintained patients. The supplemental use of uthymic frugs in schizophrenia has yielded variable results among actively psychotic inpatients, yet suggests the presence of """"""""types"""""""" of responsive patients. Very few trials, however, include outpatients in the recovery period (in spite of the wide spread use of these compounds). Further, one needs to convincingly rule out milder forms of akinesia or akathisia as the toxins underlying impaired affect. The systematic study of 230 RDC schizophrenic patients, free of serious psychotic features and persistently distressed for most of the three months prior to intake is proposed. In a sequential strategy: (1) the contribution of akinesia and akathisia to these impairments will first be examined; (2) patients (N=104) remaining distressed and meeting behavioral criteria for activation and/or inhibition (anxiety/depression) will be randomized to double-blind trials of lithium or desipramine respectively; (3) negative symptom patients (N=54) will be randomly assigned to an intermittent, single dose of dextroamphetamine or caffeine.
