Trazodone Seasonal Use Considerations: A Clinical Guide

Is there any evidence for changing the dose with the seasons?

The label's dosing section has no seasonal element. It starts at 150 mg/day in divided doses, allows increases of 50 mg/day every 3 to 4 days, and caps outpatients at 400 mg/day in divided doses, with severely depressed inpatients up to 600 mg/day [1]. It does not mention ambient temperature, daylight hours, melatonin, or time of year, and it does not address how heat, sweating, hydration or changing daylight affect trazodone levels [1].

Much of the confusion around trazodone comes from what it is actually approved for. The label covers major depressive disorder in adults only; it has no insomnia indication and gives no insomnia dose, so sleep use is off-label [1]. A 2005 review identified 18 studies of trazodone for insomnia, most of them small and conducted in depressed patients, and found the efficacy evidence very limited while sedation, dizziness and psychomotor impairment were common [2].

What the label flags

Blood pressure on standing. Orthostatic hypotension and syncope are labeled warnings, and the label says that taking trazodone with blood pressure medicines may require lowering the blood pressure drug's dose [1]. In the outpatient MDD trials, hypotension was reported in 4% of trazodone patients versus 0% on placebo, and syncope in 5% versus 1% [1].

Heart rhythm. The label states that trazodone prolongs the QT/QTc interval and says to avoid it in people with known QT prolongation, a history of arrhythmia, low potassium or low magnesium, congenital long QT, or in the initial recovery phase after a heart attack, and to avoid combining it with other QT-prolonging drugs and with CYP3A4 inhibitors such as itraconazole, clarithromycin and voriconazole [1]. Torsades de pointes and ventricular tachycardia have been reported after marketing at doses of 100 mg/day or less of the immediate-release tablets [1].

Sodium. Hyponatremia and SIADH are labeled warnings, with higher risk in older adults [1].

Alcohol and other depressants. Trazodone may enhance the effects of alcohol, barbiturates and other CNS depressants, and overdose deaths have occurred when it was taken with alcohol, chloral hydrate with diazepam, amobarbital, chlordiazepoxide or meprobamate [1].

Seasonal affective disorder and trazodone

Seasonal affective disorder was described in 29 patients with depressions that recurred at the same time each year [3]. Sleep recordings in 9 depressed patients showed increased sleep latency and reduced slow-wave sleep, and preliminary studies in 11 patients suggested that extending the photoperiod with bright artificial light had an antidepressant effect [3]. Trazodone's labeled use is major depressive disorder in adults [1].