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Drug-drug interactions (DDIs) are a concern for the prescriber because they have the potential for causing untoward outcomes for everyone involved: morbidity for the patient, liability for the prescriber, and increased costs for the healthcare system. The risk of unintended and untoward DDIs is increasing in concert with both the increasing number of pharmaceuticals available and the number of patients on multiple medications. Based on the 2004 Health and Human Services report, 7% of Americans >18 years of age and >20% of Americans >65 years of age had taken >/=5 prescription medications in the week preceding the survey. Patients on psychiatric medications, such as antidepressants, are on more medication than patients not on psychiatric medications. Prescribers should appreciate that medications interact not on the basis of their therapeutic use, but on the basis of their pharmacodynamics and pharmacokinetics. For this reason, the prescriber of psychiatric medications must consider all of the medications the patient is taking. Similar to the 2006 version, this educational review focuses on neuropsychiatric medications but also covers all other drugs to the extent that they interact with psychiatric medications. It emphasizes the role of pharmacologic principles to guide the safe and effective use of multiple medications when such use is necessary. Consistent with these principles, this review presents tables outlining major pharmacodynamic and pharmacokinetic mechanisms mediating DDIs relevant to the patient on psychiatric medications. [ABSTRACT FROM AUTHOR]

The objective of this study was to estimate the effects of intramuscular haloperidol and lorazepam on the QT interval in volunteers with schizophrenia. Intramuscular haloperidol and intramuscular lorazepam are standard treatments in the acute management of agitation and aggression. Although prolongation of the QT interval and sequelae, including torsade de pointes and death, have been reported for haloperidol (but not lorazepam), formal studies have been lacking. Volunteers with schizophrenia (n = 12) were administered a single intramuscular injection of 7.5 mg haloperidol or 4 mg lorazepam in a blinded, randomized, placebo-controlled crossover design. Serial EKGs and concurrent blood samples were obtained over 6 hours following each injection. Changes in the QT interval were evaluated, as were plasma drug and prolactin concentrations. Haloperidol injection increased the heart rate-corrected QT interval an average of 5.1 msec using Bazett's correction (QTb 90% confidence interval [CI]: 0.3, 9.8), 3.6 msec using Fridericia's correction (QTf 90% CI: 0.02, 7.2), and 4.2 msec using an empirically derived 'baseline correction' (QT(ii) 90% CI: 0.3, 8.0). Effects of lorazepam on QT were nullified by correction for the heart rate elevation (QTb 3.8 msec, 90% CI: 0.6, 7.1; QTf 0.0 msec, 90% CI: -3.2, 3.4; QTii -2.3 msec, 90% CI: -6.6, 2.0). An association between QT prolongation and occurrence of extrapyramidal symptoms was observed. On average, intramuscular haloperidol led to minimal prolongation of the QT interval. This propensity is of theoretical concern in individuals with risk factors for torsade de pointes but seems unlikely to be a problem in the vast majority of patients. [ABSTRACT FROM AUTHOR]