Trazodone Travel and Timezone-Shift Protocols: A Clinical Guide

Is there a trazodone protocol for jet lag?

Not in the label. Its only indication is major depressive disorder in adults, with no insomnia indication and no insomnia dose [1].

The randomized jet-lag trial described here tested zolpidem, not trazodone: 138 experienced eastward travelers crossing 5 to 9 time zones took zolpidem 10 mg or placebo for three nights, and 130 completed. Zolpidem improved sleep quality on nights 1 to 3 but did not significantly improve sleep latency [3].

What the label says about dosing and timing

The labeled dose treats depression, not sleep: 150 mg/day in divided doses to start, raised by 50 mg/day every 3 to 4 days, outpatient maximum 400 mg/day [1]. The label says tablets should be taken shortly after a meal or light snack [1].

In 8 healthy volunteers given 100 mg, the terminal half-life was 7.3 +/- 0.8 hours. Food lowered peak concentration from 1.88 to 1.47 micrograms/mL and delayed it from 1.3 to 2.0 hours, without changing total absorption [2]. The label states no half-life [1].

Side effects that matter while traveling

Orthostatic hypotension and syncope have been reported with trazodone. In outpatient depression trials, hypotension occurred in 4% of trazodone-treated patients versus 0% with placebo, and syncope in 5% versus 1% [1].

The label states that trazodone prolongs the QT/QTc interval and that torsades de pointes and ventricular tachycardia have been reported after marketing at 100 mg/day or less of the immediate-release tablets. It says to avoid the drug in known QT prolongation, a history of arrhythmia, low potassium or magnesium, congenital long QT syndrome and the initial recovery phase after a heart attack [1]. The label also says trazodone may enhance the effects of alcohol and other CNS depressants [1].

Interactions and crossing time zones

Trazodone is a CYP3A4 substrate [1]. The label's strong inhibitor examples include clarithromycin, itraconazole, ketoconazole and indinavir; with these, trazodone exposure and the risk of adverse reactions, including cardiac arrhythmias, may rise, and the label says a lower trazodone dose should be considered [1]. For strong inducers such as rifampin, carbamazepine, phenytoin and St. John's wort, the label says exposure falls and an increased dose may be needed [1].

The label has no instruction for moving dose times across time zones. It does say adverse reactions can occur on discontinuation and that the dose should be reduced gradually rather than stopped abruptly [1]. Trazodone is a prescription medicine and not a controlled substance in the US [1].