Steady-state concentrations are achieved in about 5 days. In elderly patients, both Cpmax and AUC are twice as high as for younger patients. Nefazodone is distributed in most body tissues including the central nervous system. Inhibition of terfenadine and astemizole metabolism results in increased plasma concentrations of both drugs. Increased plasma concentrations of terfenadine or astemizole have been associated with QT prolongation and rare cases of serious cardiovascular adverse events, including death due to torsade de pointes have been reported.
All effective antidepressants can transform depression into mania in predisposed individuals.
The usual presentation of this switch is the sudden appearance of insomnia. Nefazodone should be held and appropriate therapy initiated to treat the manic symptoms. All antidepressants should be used with caution in depressed patients because of the possibility of suicidal ideation. Close monitoring of the patient is essential in the initial stages of nefazodone therapy and the drug should be prescribed in the smallest quantity possible. Lower doses may be necessary.