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Serum haloperidol and anticholinergic levels in drug-induced parkinsonism
BIOL PSYCHIATRY 1989;25:165A-169A
Studies in Geriatrics
165A
DYSTONIA AND 334 TIMING OF NEUROLEPTIC-INDUCED DYSTONIA PATHOPHYSIOLOGY George A. Keepers, William L. Brown, Daniel E. Casey Portland,
OR
The length of time following initiation of antipsychotics but preceding episodes of
acute dystonia (AD) has implications regarding AD pathophysiology. In animal models AD is observed during rising neuroleptic levels suggesting dopaminergic blockade as pathogenic. In humans, there are reports of AD during low, falling serum levels consistent with the “miss-match” hypothesis of AD. To clarify the time course of AD we reviewed charts of 263 neuroleptic treated patients for AD. Reviewers noted the time of AD and the drug treatment. Data were analyzed to determine the distribution of AD following neuroleptic dosing. Timing data for the 71 patients with AD showed AD occurring on average 10.5 hours following last neuroleptic dose. Distribution of the ADS was bivariate (group means = 6.1 and 20.6 hours). 85.5% of ADS occurred during falling serum neuroleptic levels. Average daily neuroleptic dose was 517 CPZ equivalent/day though 38.1% of AD occurred at doses less than 250 CPZ equivalent/ day. Neuroleptic drug, dose, and dosing schedule did not explain the bivariate distribution. Implications of these data for AD pathophysiology will be discussed.
335 SERUM HALOPERIDOL AND ANTICHOLINERGIC LEVELS IN DRUG-INDUCED PARKINSONISM Thomas E. Hansen, Kim A. Neve, George A. Keepers, W.F. Hoffman, Daniel E. Casey Portland.
OR
Studies correlating drug-induced Parkinsonism (DIP) with serum neuroleptic and anticholinergic levels find inconsistent results. Failure to consider both levels and heterogeneity in patients and treatment may account for this. After a minimum two day washout, 26 DSM-III-R schizophrenic or schizoaffective inpatients were followed for 21 days while receiving haloperidol. DIP and other extrapyramidal syndromes were treated with benztropine. Raters blind to dose rated DIP every three days. Serum levels (using HPLC for haloperidol, radioreceptor assay for other neuroleptics, and QNB for anticholinergic activity) were obtained for all patients on days 0, 12, and 21. Both final neuroleptic and anticholinergic levels influenced change in DIP. Neuroleptic levels correlated significantly with DIP on the day benztropine was started. No significant correlation with DIP and neuroleptic or anticholinergic level, however, was found at Day 12 or 2 1. Excluding patients on lithium or antidepressants did not affect this result.
STUDIES IN GERIATRICS Saturday, May 6, 190 to 690 Hilton Ballroom B
336 MAJOR DEPRESSION IN OLDER MEDICALLY ILL INPATIENTS WITH ADULT ONSET DIABETES Cynthia M. Churchill
Studies in Geriatrics
165A
DYSTONIA AND 334 TIMING OF NEUROLEPTIC-INDUCED DYSTONIA PATHOPHYSIOLOGY George A. Keepers, William L. Brown, Daniel E. Casey Portland,
OR
The length of time following initiation of antipsychotics but preceding episodes of
acute dystonia (AD) has implications regarding AD pathophysiology. In animal models AD is observed during rising neuroleptic levels suggesting dopaminergic blockade as pathogenic. In humans, there are reports of AD during low, falling serum levels consistent with the “miss-match” hypothesis of AD. To clarify the time course of AD we reviewed charts of 263 neuroleptic treated patients for AD. Reviewers noted the time of AD and the drug treatment. Data were analyzed to determine the distribution of AD following neuroleptic dosing. Timing data for the 71 patients with AD showed AD occurring on average 10.5 hours following last neuroleptic dose. Distribution of the ADS was bivariate (group means = 6.1 and 20.6 hours). 85.5% of ADS occurred during falling serum neuroleptic levels. Average daily neuroleptic dose was 517 CPZ equivalent/day though 38.1% of AD occurred at doses less than 250 CPZ equivalent/ day. Neuroleptic drug, dose, and dosing schedule did not explain the bivariate distribution. Implications of these data for AD pathophysiology will be discussed.
335 SERUM HALOPERIDOL AND ANTICHOLINERGIC LEVELS IN DRUG-INDUCED PARKINSONISM Thomas E. Hansen, Kim A. Neve, George A. Keepers, W.F. Hoffman, Daniel E. Casey Portland.
OR
Studies correlating drug-induced Parkinsonism (DIP) with serum neuroleptic and anticholinergic levels find inconsistent results. Failure to consider both levels and heterogeneity in patients and treatment may account for this. After a minimum two day washout, 26 DSM-III-R schizophrenic or schizoaffective inpatients were followed for 21 days while receiving haloperidol. DIP and other extrapyramidal syndromes were treated with benztropine. Raters blind to dose rated DIP every three days. Serum levels (using HPLC for haloperidol, radioreceptor assay for other neuroleptics, and QNB for anticholinergic activity) were obtained for all patients on days 0, 12, and 21. Both final neuroleptic and anticholinergic levels influenced change in DIP. Neuroleptic levels correlated significantly with DIP on the day benztropine was started. No significant correlation with DIP and neuroleptic or anticholinergic level, however, was found at Day 12 or 2 1. Excluding patients on lithium or antidepressants did not affect this result.
STUDIES IN GERIATRICS Saturday, May 6, 190 to 690 Hilton Ballroom B
336 MAJOR DEPRESSION IN OLDER MEDICALLY ILL INPATIENTS WITH ADULT ONSET DIABETES Cynthia M. Churchill