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Low Heart Rate Variability Is Not Caused by Typical Neuroleptics in Schizophrenia Patients

Published online by Cambridge University Press:  07 November 2014

Abstract

Both elevated cardiovascular mortality and low cardiovagal (parasympathetic) heart rate variability (HRV)—a risk factor for postmyocardial infarction—are reported in schizophrenia (SZ). Since a number of medications have strong effects of cardiac conductivity, we thought it important to examine if typical neuroleptic medications might also affect HRV. We examined cardiac vagal activity during both neuroleptic treatment and a drug-free condition in seven SZ patients who were participating in a pilot double-blind, crossover study of placebo and haloperidol treatment. Twenty-four–hour Holter electrocardiograms were analyzed for high frequency HRV, quantitated as the percent of successive normal interbeat intervals greater than 50 milliseconds (PNN50), which is a good index of parasympathetic cardiac modulation. The patients showed unchanged PNN50 (8.4±9.5 versus 8.3±10.5; t=.22, df=6, P=.5) between the haloperidol treatment and drug-free conditions. Despite the elapsed time, change in medication, and altered clinical state, the PNN50s were highly correlated (Spearman r=.98, P=.000). SAPS positive symptom scores declined with treatment from 12.8±6.5 to 8.5±3.5; paired t=3.26: df=6; P=.01. PNN50s were significantly associated with positive (r=-.86, df=6, P=.012) and negative symptom scores (r=-.87, df=6, P=.01). We found low cardiovagal modulation in medication-free SZ patients that was associated with core SZ symptoms and was unchanged by haloperidol and benztropine treatment. The reduced HRV in SZ patients at baseline may render them at greater cardiovascular risk than healthy subjects when treated with medications having strong cardiovascular effects.

Type
Original Research
Copyright
Copyright © Cambridge University Press 2002

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References

REFERENCES

1.Ruschena, D, Mullen, PE, Burgess, P, et al.Sudden death in psychiatric patients. Br J Psychiatry. 1998;172:331336.CrossRefGoogle ScholarPubMed
2.Gausset, MF, Casadebaig, F, Guillaud-Bataille, JM, Quemada, N, Terra, JL. Mortality of mentally ill patients: review of the literature. Encephale. 1992;18:93100.Google ScholarPubMed
3.Herrman, HE, Baldwin, JA, Christie, D. A record-linkage study of mortality and general hospital discharge in patients diagnosed as schizophrenic. Psychol Med. 1983;13:581593.CrossRefGoogle ScholarPubMed
4.Allebeck, P. Schizophrenia: a life-shortening disease. Schizophr Bull. 1989;15:8189.CrossRefGoogle ScholarPubMed
5.Lesage, AD, Trapani, V, Tansella, M. Excess mortality by natural causes of Italian schizophrenic patients. Eur Arch Psychiatry Neurol Sci. 1990;239:361365.CrossRefGoogle ScholarPubMed
6.Newman, SC, Bland, RC. Mortality in a cohort of patients with schizophrenia: a record linkage study. Can J Psychiatry. 1991;36:239245.CrossRefGoogle Scholar
7.Mortensen, PB, Juel, K. Mortality and causes of death in first admitted schizophrenia patients. Br J Psychiatry. 1993;163:183189.CrossRefGoogle Scholar
8.Kleiger, RE, Miller, JP, Bigger, JT Jr, Moss, AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987;59:782787.CrossRefGoogle ScholarPubMed
9.Bigger, JT, Kleiger, RE, Fleiss, JL, et al.Components of heart rate variability measured during healing of acute myocardial infarction. Am J Cardiol. 1988;61:208215.CrossRefGoogle ScholarPubMed
10.Bigger, JT, Albrecht, P, Steinman, RC, et al.Comparison of time and frequency domain-based measures of cardiac parasympathetic activity in Holter recordings after myocardial infarction. Am J Cardiol. 1989;64:536538.CrossRefGoogle ScholarPubMed
11.Katona, PG, Jih, F. Respiratory sinus arrhythmia: noninvasive measure of parasympathetic cardiac control. J Appl Physiol. 1975;39:801805.CrossRefGoogle ScholarPubMed
12.Ewing, DJ, Borsey, DQ, Bellavere, F, Clarke, BF. Cardiac autonomic neuropathy in diabetes: comparison of measures of R-R interval variation. Diabetologia. 198;121:1824.Google Scholar
13.Cerati, D, Schwartz, PJ. Single cardiac vagal fiber activity, acute myocardial ischemia, and risk for sudden death. Circulation. 1991;69:13891401.CrossRefGoogle ScholarPubMed
14.DeFerrari, GM, Vanoli, E, Stramba-Badiale, M, et al.Vagal reflexes and survival during acute myocardial ischemia in conscious dogs with healed myocardial infarction. Am J Physiol. 1991;261:H63H69.Google Scholar
15.Schwartz, PJ, La Rovere, MT, Vanoli, E. Autonomic nervous system and sudden cardiac death. Circulation. 1992;85(suppl 1):177191.Google ScholarPubMed
16.Malaspina, D, Bruder, G, Dalack, GW, et al.Diminished cardiac vagal tone in schizophrenia: associations to brain laterality and age of onset. Biol Psychiatry. 1997;41:612617.CrossRefGoogle ScholarPubMed
17.Andreasen, N. Modified Scale for the Assessment of Positive and Negative Symptoms. Department of Health and Human Services, Public Health Service. 1984.Google Scholar
18.Bigger, JT Jr, Fleiss, JL, Steinman, RC, et al.Frequency domain measures of heart period variability and mortality after myocardial infarction. Circulation. 1992;85:164171.CrossRefGoogle ScholarPubMed
19.Kleiger, RE, Bigger, JT, Bosner, MS, et al.Stability over time of variables measuring heart rate variability. Am J Cardiol. 1991;68:626630.CrossRefGoogle ScholarPubMed
20.Umetani, K, Singer, DH, McCraty, , Atkinson, M. Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Coll Cardiol. 1998;31:593601.CrossRefGoogle ScholarPubMed
21.Farrell, TG, Bashir, Y, Cripps, T, et al.Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability, ambulatory electrocardiographic variables and the signal-averaged electrocardiogram. J Am Coll Cardiol. 1991;18:687697.CrossRefGoogle ScholarPubMed
22.Pedretti, R, Etro, MD, Laporta, A, et al.Prediction of late arrhythmic events after acute myocardial infarction from combined use of noninvasive prognostic variables and inducibility of sustained monomorphic ventricular tachycardia. Am J Cardiol. 1993;71:11311141.CrossRefGoogle ScholarPubMed
23.Wolf, MM, Varigos, GA, Hunt, D, Sloman, JG. Sinus arrhythmia in acute myocardial infarction. Med J Aust. 1978;2:5253.CrossRefGoogle ScholarPubMed
24.Casolo, GC, Stroder, P, Signorini, C, et al.Heart rate variability during acute phase of myocardial infarction. Circulation. 1992;85:20732079.CrossRefGoogle ScholarPubMed
25.Jakobsen, J, Hauksson, P, Vestergaard, P. Heart rate variation in patients treated with antidepressants: an index of anticholinergic effects? Psychopharmacology (Berl). 1984;84:544548.CrossRefGoogle ScholarPubMed
26.Kristensen, E, Jakobsen, J, Bartels, U, Vestergaard, P. Cholinergic dysfunction of heart, pupil, salivary glands, and urinary bladder in healthy volunteers during long-term treatment with clomipramine. Psychophysiology. 1989;98:398402.Google ScholarPubMed
27.Yergani, VK, Pohl, R, Balon, R. et al.Heart rate variability in patients with major depression. Psychiatry Res. 1991;37:3546.CrossRefGoogle Scholar
28.Lovett Doust, JW. Sinus tachycardia and abnormal cardiac rate variation in schizophrenia. Neuropsychobiology. 1980;6:305312.CrossRefGoogle ScholarPubMed
29.Steinhauer, SR, van Kammen, DP, Colbert, K, Peters, JL, Zubin, J. Pupillary constriction during haloperidol treatment as a predictor of relapse following drug withdrawal in schizophrenic patients. Psychiatry Res. 1992;43:287298.CrossRefGoogle ScholarPubMed
30.Piha, SJ. Cardiovascular autonomic reflex tests: normal responses and age related reference values. Clin Physiol. 1991;11:277290.CrossRefGoogle ScholarPubMed
31.Agelink, MW, Majewski, T, Wurthmann, C, et al.Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, sertindole, and clozapine. J Clin Psychopharmacol. 2001;21:813.CrossRefGoogle ScholarPubMed
32.Rechlin, T, Beck, G, Weis, M, Kaschka, WP. Correlation between plasma clozapine concentration and heart rate variability in schizophrenic patients. Psychopharmacology (Berl). 1998;135:338341.CrossRefGoogle ScholarPubMed
33.Cohen, H, Loewenthal, U, Matar, M, Kotler, M. Association of autonomic dysfunction and clozapine: heart rate variability and risk for sudden death in patients with schizophrenia on long-term psychotropic medication. Br J Psychiatry. 2001;179:167171.CrossRefGoogle ScholarPubMed