Effects of antipsychotic treatment on psychopathology and motor symptoms. A placebo-controlled study in healthy volunteers.

Rationale: There is increased interest in elucidating the range of symptoms of schizophrenia and their response to treatment with medications. Particularly negative and cognitive symptoms are often resistant to the therapy with currently available antipsychotics. There are even similarities between negative symptoms in psychosis and the side effects of antidopaminergic antipsychotic drugs.
Objectives: The aim of this randomized, single-blinded, placebo-controlled study was to investigate the influence of a subchronic, prolonged neuroleptic-induced dopamine deficit on psychopathology and subjective well-being in healthy subjects.
Methods: Seventy-two healthy volunteers without history of psychiatric diseases were included. A 7-day antidopaminergic intervention was provided with aripiprazole, haloperidol, and reserpine. For the clinical assessment, structured interviews and psychopathology and extrapyramidal symptom scales were used.
Results: Seven out of 18 participants (38.9%) randomized to the haloperidol group terminated the study ahead of schedule. In the reserpine and the haloperidol group, significantly higher levels of negative and positive symptoms (PANSS scale) were documented. Depressive symptoms predominantly occurred in the reserpine group. Among all participants experiencing the antidopaminergic intervention, the subgroup with positive family history among first and second-generation relatives developed more pronounced depressive symptoms. Concerning extrapyramidal motor symptoms, the haloperidol group had significantly more severe manifestations than all three other groups.
Conclusion: Antidopaminergic modulation in healthy subjects induced substantial impairments in several domains of subjective well-being. In particular an association between hypodopaminergic states and depressive symptoms was observed which may be amplified by a genetic predisposition.