Lorazepam, clinical studies

Animal studies suggest that the benzodiazepines may possibly increase the metabolic activation and the toxicity of high doses of cyclophosphamide and ifosfamide. However, diazepam did not alter the pharmacokinetics of high-dose cyclophosphamide in a clinical study. Note also that lorazepam is widely used for chemotherapy-induced nausea and vomiting. 

The pharmacokinetics and pharmacodynamic effects of a single 2-mg dose of lorazepam were studied in 10 men taking quetiapine 250 mg three times daily. It was found that the maximum serum lorazepam levels were not significantly changed by quetiapine, and the alterations in the performance of a number of psychometric tests were small and considered not to be clinically relevant. ... 

Fifty acutely anxious and/or agitated patients were treated with intravenous lorazepam in a dose of 5—10 mg (16 ). Since sedation was required it was not considered a side effect in this situation. While the patients were sedated, hypotonia and ataxia were noted. Local toleration of the injections was good. When lorazepam was used intramuscularly as premedication there was impaired memory of cards presented pre-operatively. Over half the patients rated the injection as uncomfortable (23 ). Other clinical studies have paid little attention to the question of side effects (51, 4 ). 

Delle Chiaie, R., Pancheri, P., Casacchia, M., Stratta, P., Kotzalidis, G.D. and Zibellini, M. (1995) Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam a placebo-controlled, doubleblind study. Journal of Clinical Psychopharmacology, 15,... 

Opioids are sedating and cause a reduction in processing speed in clinical populations (e.g.. Digit Symbol Substitution Test) (Wood et al. 1998). However, a study in healthy subjects did not confirm these effects on digit substitution (Walker and Zacny 1998). Improvements are seen in choice reaction time after morphine administration (Hanks et al. 1995). Deficits have been reported in early-stage visual processing (O Neill et al. 1995 Hanks et al. 1995). By comparison, morphine s cognitive effects are lesser than those of lorazepam, but milder than hydromorphone (Rapp et al. 1996 Hanks et al. 1995). 

Valproate Versus Lithium. The previously discussed Bowden et al. (135) study found the DVPX formulation to be comparable with lithium, which was used as a positive comparator in this placebo-controlled study. Freeman et al. (99) conducted a 3-week, double-blind, parallel-group comparison of VPA and lithium for acute mania. Both drugs demonstrated clinically significant efficacy (i.e., 9 of 14 responded to DVPX and 12 of 13 to lithium), and there was no difference in the need for rescue medications (i.e., lorazepam or chloral hydrate) between the two treatment groups. Response to VPA was associated with high pretreatment depression scores. 

Verapamil Versus Other Psychotropics. Garza-Trevino et al. (258) conducted a 4-week, randomized, double-blind study comparing verapamil with lithium for acute mania and found no clinical or statistically significant differences between the two treatments. These results are difficult to interpret, however, because data about the amount and timing of rescue medication (i.e., haloperidol, lorazepam) were not presented. Further, more patients on verapamil required these agents. 

Another study in healthy subjects found that dextropropoxyphene 65 mg every 6 hours prolonged the alprazolam half-life from 11.6 to 18.3 hours, and decreased the clearance from 1.3 to 0.8 mL/minute per kg. The pharmacokinetics of single doses of diazepam and lorazepam were not significantly affected. It would seem that dextropropoxyphene inhibits the metabolism (hydroxylation) of the alprazolam by the liver, thereby reducing its loss from the body, but has little or no effect on the A/-demethylation or glucuronidation of the other two benzodiazepines. The clinical importance of this is uncertain, but the inference to be drawn is that the CNS depressant effects of alprazolam will be increased, over and above the simple additive CNS depressant effects likely when other benzodiazepines and dextropropoxyphene are taken together. More study is needed. 

The interactions of nefazodone with alprazolam, midazolam, triazolam and zopiclone are established and clinically important. The practical consequences are that the effects of alprazolam, midazolam and triazolam are expected to be increased but the extent is uncertain. Be alert for any evidence of any psychomotor impairment, drowsiness etc. and reduce the benzodiazepine dosage if necessary. More study is needed. Lorazepam does not interact with nefazodone. There seems to be no direct information about other benzodiazepines and related drugs. 

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