Untoward Effects following Combined Neuroleptic-Lithium Therapy: Cardiac Arrhythmias and Seizure

Menes, Catharine; Burra, Prakash; Hoaken, P. C. S.

doi:10.1177/070674378002500707

Cited by 13 publications

(2 citation statements)

References 12 publications

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“…In another study (35), two of 30 patients receiving lithium and a neuroleptic developed severe tremor. Cases in which use of lithium combined with a neuroleptic resulted in severe neurotoxicity, such as delirium, seizures, tardive dyskinesia, encephalopathy, or EEG abnormalities, have been reported, as have hypotension and cardiac arrhythmias (44)(45)(46)(47)(48)(49)(50)(51)(52). However, Krishna et al (34) reported that neurologic symptoms are usually mild and resolve with discontinuation of medication.…”

Section: Combinations With Lithiummentioning

confidence: 98%

Mood Stabilizer Combinations: A Review of Safety and Efficacy

Freeman

Stoll²

1998

AJP

185

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There have been few controlled studies of the use of combinations of mood stabilizers. The interactions of such combinations are sometimes complex, often very useful, and potentially dangerous. One general rule that may reduce the risks of toxic drug interactions is to add medication to the patient's current regimen in modest doses and increase the dose slowly. The safest and most efficacious mood stabilizer combinations appear to be the mixtures of anticonvulsants and lithium, particularly valproate plus lithium. Once the mechanisms of the mood stabilizers are identified, it is possible that a more rational approach to combination therapy will emerge, based on synergism at the sites of action.

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Section: Combinations With Lithiummentioning

confidence: 98%

Mood Stabilizer Combinations: A Review of Safety and Efficacy

Freeman

Stoll²

1998

AJP

185

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“…Haloperidol is a commonly used antipsychotic drug that has potential to block I Kr channels in a concentrationdependent manner in vitro [13]. While there are a number of case reports in the literature that describe haloperidolinduced QT prolongation [14,15] and torsades de pointes arrhythmias [16], the ability of haloperidol to prolong the QT interval at low doses routinely used in clinical practice has not been systematically evaluated. We compared the heart rate-corrected QT interval using the subject-specific correction to results obtained by Bazett's and Fridericia's corrections.…”

Section: Introductionmentioning

confidence: 99%

Variability of heart rate correction methods for the QT interval

Desai¹,

Desta³

et al. 2003

Brit J Clinical Pharma

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Aims To compare variability of heart rate-corrected QT intervals (QT c ) using three different methods in a study of low-dose oral haloperidol. Methods In a randomized, double-blind, placebo-controlled, crossover trial, we studied QT interval pharmacodynamics of single doses of oral haloperidol (10 mg) in 16 healthy subjects. Heart rate correction of the QT interval was performed using Bazett's, Fridericia's and subject-specific correction methods. The subjectspecific correction was performed using linear mixed modelling of placebo period QT vs RR data from each study subject. Results The subject-specific correction, in the form of QT c = QT/RR a , yielded a correction term a (slope of the log-transformed QT vs RR relationship) that ranged from 0.23 to 0.38 in individual subjects, i.e. the fixed correction term a = 0.5 of Bazett's correction was outside and the fixed correction term a = 0.33 of Fridericia's correction inside the range of individual values. The mean absolute slope of the QT c vs RR regression line using the subject-specific correction was significantly lower than the mean slopes obtained using either Bazett's or Fridericia's corrections. All three methods revealed a statistically significant greater mean QT c on haloperidol than on placebo at 10 h post-drug administration. The mean QT (95% CI) was 421.6 (410.8, 432.4), and 408.4 (398.6, 417.8) on haliperidol and placebo, respectively, using the subject-specific correction method (P = 0.0053). The mean QT c (95% CI) was 425.4 (414.3, 436.5) and 403.1 (394.3, 411.9) on haliperidol and placebo, respectively, using Bazett's correction (P = 1.7 ¥ 10 -5 ) and 423.1 (412.6, 433.6) and 408.2 (398.6, 417.8) on haliperidol and placebo, respectively, using Fridericia's correction (P = 7.7 ¥ 10 -4 ). Raw P-values were calculated using a paired t-test. Bonferroni-corrected P-values were calculated by multiplying the raw Pvalues by 13. Conclusion Haloperidol caused a statistically significant mean QT c prolongation using the three correction methods. The QT c intervals were less dependent on RR intervals using the subject-specific method, thus decreasing the possibility of overor under-correction. The interindividual QT c changes from baseline varied significantly depending on the method of correction used.

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Lithium

Goodnick

Gershon

1985

Alterations of Metabolites in the Nervous System

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Untoward Effects following Combined Neuroleptic-Lithium Therapy: Cardiac Arrhythmias and Seizure

Cited by 13 publications

References 12 publications

Mood Stabilizer Combinations: A Review of Safety and Efficacy

Mood Stabilizer Combinations: A Review of Safety and Efficacy

Variability of heart rate correction methods for the QT interval

Lithium

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