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Correlations between tardive dyskinesia, drug-induced Parkinsonism, and psychiatric symptoms
Neuroleptic-lnduced Syndromes
BIOL PSYCHIATRY 1990;27.41A-179A
133A
statistical analysis using case control methodology was performed on this data to verify previous clinical hypotheses and to test new hypotheses. As expected, rigidity, fever, and elev~t~edCPK was virtually always present in NMS. Diaphoresis is very commonly iound. Mental status changes, such as stupor and incontinence, are important, because it is a change from the usual symptoms of the pa~.icnts' mental illness. Although nearly a majority of cases had a repeat episode of NMS when rechallenged, with gradual dose increments, many could be treated with neuroleptics again. Prognostic signs and treatment effectiveness was compared against outcome by case-controlled comparisons. _Thedeath and complication ,"atefor patien~ treated with bromocriptine, DOPA, amantadine, and dantmlene is less than patients not treated in a easecontrol comparison with two different control groups.
206 LACK OF EFFICACY OF D-PROPRANOLOL IN NEUKOLEPTICINDUCED AKATHISIA
Lenard A. Adler, M.D., Butt Angrist, M.D., Paul Fritz, M.D., John Rotrosen, M.D., Gopinath Mallya, M.D., Joseph F. Lipinski, Jr., M.D. Mailman Research Center, McLean Hospital, Belmont, MA (G.M., J.F.L. Jr.) and Psychiatry Service, Veterans Affairs Medical Center, New York and Department of Psychiatry, New York University School of Medicine, New York, NY 10010 (L.A.A., B.A., P.F., J.R.). Propranolol is increasingly being used to treat neuroleptic-induced akathisia (NIA) (Adler et al. Psychopharmacology 1989;97:1-9. Fitzgerald. Clin Pharmacol & Therapeutics 1969;10:292-306 and Shanks. Postgradbled J 1976;52 (Suppl 4): 14-20). It has been assumed that beta-blockade mediates the therapeutic effect of propranolol in NIA. However, p~-~ranolol also has a number of nonspecific biological effects, including membrane stabilization (MS). The clinical formulation of propranolol is a racemate. This study utilized the d-isomer of propranolol (which has MS comparable to the racemate, without clinically significant beta-blockade) to the therapeutic effect of propranolol. This was a double-blind, cross over study of dpropranolol (80 mg/day) versus placebo in 11 patients, with a 1 day, single-blind, placebo lead-in for all patients. Eight of ! 1 were subsequently treated with racemic propranolol (80 mg/day). Akathisia scores were unchanged after both d-propranolol and placebo. In contrast, mean akathisia scores were significantly ~duced by racemic propranolol. These findings suggest that beta-blockade, not MS or other nonspecific effects, contributes to the efficacy ofpropranolol in NIA.
207 CORRELATIONS BETWEEN TARDIVE DYSKINESIA, DRUG-
INDUCED PARKINSONISM, AND PSYCHIATRIC SYMPTOMS Thomas E. Hansen, M.D., Melinda Lowe, B.S., George A. Keepers, M.D., William F. Hoffman, Ph.D., M.D., Daniel E. Casey, M.D. Department of Psychiatry, Veterans Affairs Medical Center, Portland, OR 97207. Drug-induced Parkinsonism (DIP) probably involves decreased, and tardive dyskinesia (TD) increased, dopamine activity in the basal ganglia. Reports do not consistently find the expected negative correlation between TD and DIP. In this study, we rated DIP, TD, and psychiatric symptoms every 3 days for 21 days in 43 inpatients treated with haloperidol. Acute EPS were treated with benztropine as they occurred. This established a paradigm in which TD and DIP would fluctuate and thus possibly be correlated. TD occurred in 28 (65%) and DIP in 27 (63%) patients, with both disorders coexisting at least once in 15 patients (35%). Eight patients had neither. None of the cross-sectional correlations between TD and other syndromes (i.e., rating scale totals, including DIP) were significant after 21 deys of treatment. DIP significantly correlated with Hamilton depression scores (r = 0.36, p = 0.02) but not with other syndromes. Mean intrapatient correlations between TD and DIP were essentially zero regardless of whether all patients, or only those with changes in TD and DIP, were studied. Additional details of the data analysis and the significance of these results will be presented.
BIOL PSYCHIATRY 1990;27.41A-179A
133A
statistical analysis using case control methodology was performed on this data to verify previous clinical hypotheses and to test new hypotheses. As expected, rigidity, fever, and elev~t~edCPK was virtually always present in NMS. Diaphoresis is very commonly iound. Mental status changes, such as stupor and incontinence, are important, because it is a change from the usual symptoms of the pa~.icnts' mental illness. Although nearly a majority of cases had a repeat episode of NMS when rechallenged, with gradual dose increments, many could be treated with neuroleptics again. Prognostic signs and treatment effectiveness was compared against outcome by case-controlled comparisons. _Thedeath and complication ,"atefor patien~ treated with bromocriptine, DOPA, amantadine, and dantmlene is less than patients not treated in a easecontrol comparison with two different control groups.
206 LACK OF EFFICACY OF D-PROPRANOLOL IN NEUKOLEPTICINDUCED AKATHISIA
Lenard A. Adler, M.D., Butt Angrist, M.D., Paul Fritz, M.D., John Rotrosen, M.D., Gopinath Mallya, M.D., Joseph F. Lipinski, Jr., M.D. Mailman Research Center, McLean Hospital, Belmont, MA (G.M., J.F.L. Jr.) and Psychiatry Service, Veterans Affairs Medical Center, New York and Department of Psychiatry, New York University School of Medicine, New York, NY 10010 (L.A.A., B.A., P.F., J.R.). Propranolol is increasingly being used to treat neuroleptic-induced akathisia (NIA) (Adler et al. Psychopharmacology 1989;97:1-9. Fitzgerald. Clin Pharmacol & Therapeutics 1969;10:292-306 and Shanks. Postgradbled J 1976;52 (Suppl 4): 14-20). It has been assumed that beta-blockade mediates the therapeutic effect of propranolol in NIA. However, p~-~ranolol also has a number of nonspecific biological effects, including membrane stabilization (MS). The clinical formulation of propranolol is a racemate. This study utilized the d-isomer of propranolol (which has MS comparable to the racemate, without clinically significant beta-blockade) to the therapeutic effect of propranolol. This was a double-blind, cross over study of dpropranolol (80 mg/day) versus placebo in 11 patients, with a 1 day, single-blind, placebo lead-in for all patients. Eight of ! 1 were subsequently treated with racemic propranolol (80 mg/day). Akathisia scores were unchanged after both d-propranolol and placebo. In contrast, mean akathisia scores were significantly ~duced by racemic propranolol. These findings suggest that beta-blockade, not MS or other nonspecific effects, contributes to the efficacy ofpropranolol in NIA.
207 CORRELATIONS BETWEEN TARDIVE DYSKINESIA, DRUG-
INDUCED PARKINSONISM, AND PSYCHIATRIC SYMPTOMS Thomas E. Hansen, M.D., Melinda Lowe, B.S., George A. Keepers, M.D., William F. Hoffman, Ph.D., M.D., Daniel E. Casey, M.D. Department of Psychiatry, Veterans Affairs Medical Center, Portland, OR 97207. Drug-induced Parkinsonism (DIP) probably involves decreased, and tardive dyskinesia (TD) increased, dopamine activity in the basal ganglia. Reports do not consistently find the expected negative correlation between TD and DIP. In this study, we rated DIP, TD, and psychiatric symptoms every 3 days for 21 days in 43 inpatients treated with haloperidol. Acute EPS were treated with benztropine as they occurred. This established a paradigm in which TD and DIP would fluctuate and thus possibly be correlated. TD occurred in 28 (65%) and DIP in 27 (63%) patients, with both disorders coexisting at least once in 15 patients (35%). Eight patients had neither. None of the cross-sectional correlations between TD and other syndromes (i.e., rating scale totals, including DIP) were significant after 21 deys of treatment. DIP significantly correlated with Hamilton depression scores (r = 0.36, p = 0.02) but not with other syndromes. Mean intrapatient correlations between TD and DIP were essentially zero regardless of whether all patients, or only those with changes in TD and DIP, were studied. Additional details of the data analysis and the significance of these results will be presented.