Nefazodone Lorazepam

Potentially clinically significant interactions include the tendency for fluvoxamine to increase circulating concentrations of oxidatively metabolized benzodiazepines, clozapine, theophylline, and warfarin. Sertraline and fluoxetine can increase levels of benzodiazepines, clozapine, and warfarin. Paroxetine increases levels of clozapine, theophylline, and warfarin. Fluoxetine also potentiates tricyclic antidepressants and some class 1C antiarrhythmics with a narrow therapeutic index (including encainide, flecainide, and propafenone). Nefazodone potentiates benzodiazepines other than lorazepam and oxazepam. 

Nefazodone increases the plasma levels and effects of alprazolam, midazolam, triazolam and zopiclone, but not lorazepam. 

A placebo-controlled study in healthy subjects given nefazodone 200 mg twice daily found no changes in the pharmacokinetics of lorazepam 2 mg twice daily. Another study showed that psychomotor performance was not further impaired and no additional sedation occurred when nefazodone was given with lorazepam. ... 

Nefazodone appears to inhibit the oxidative metabolism of alprazolam, midazolam, triazolam and zopiclone by the cytochrome P450 isoenzyme CYP3A4 so that they accumulate in the body. Lorazepam is unaffected because it is primarily excreted as a conjugate. 

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. 

---