Project: Research project

Project Details


The neuroleptic threshold hypothesis states that the lowest neuroleptic
dose which produces a clinically detectable increase in
hypokinesia-rigidity affords an individual schizophrenic patient all the
therapeutic antipsychotic benefit available to that patient; and that
higher doses provide no additional therapeutic benefit but may result in
increased extrapyramidal side effects and subjective distress. Our pilot
work suggests that the haloperidol doses at which acutely psychotic
schizophrenic patients first develop clinically detectable evidence of
hypokinesia-rigidity are distributed around the mean of 4.2 plus-minus 2.4
mg daily.

We propose to openly adjust the daily haloperidol doses of newly admitted
acute schizophrenic patients to each patients' individually determined
neuroleptic threshold dose during the first 10 days of treatment, and to
maintain patients at this (now fixed-) dose in an open trial for two
weeks. Pilot data suggest that over 70% of patients will respond
clinically. In order to determine whether improvement continues at the
neuroleptic threshold dose, or whether a dose increase above neuroleptic
threshold provides greater improvement (or any improvement for
nonresponders), responding and non-responding patients will be randomly
assigned (double-blind) to an additional two weeks trial at either the
neuroleptic threshold dose or a higher dose (10 or 15 mg haloperidol daily).
StatusNot started


  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health


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