I receive more questions about trazodone than any other medication I have discussed in my many books and nearly 1000 seminars. Trazodone has long operated under a cloud of controversy, because although it is classified as a cyclic antidepressant, its “claim to fame,” so to speak, is linked to efficacy in treating insomnia, although it is not FDA-approved for this indication. But what about trazodone’s antidepressants properties? Is it viable at all in treatment-resistant patients?
Trazodone primarily exerts its actions on the neurotransmitter serotonin. It blocks serotonin reuptake similar to the SSRIs, while blocking the serotonin receptor (5HT2) as well – which contributes to its sedative effects. Trazodone also blocks histamine, which also promotes sedation, drowsiness and sleep. When first released to the U.S. drug market, twice-daily dosing was the recommended norm, but this produced dizziness and somnolence resulting in intolerability. And twice daily dosing was all for naught as trazodone’s antidepressant effects are slow in coming and aren’t linked to the drug’s blood levels. Administering the total daily dose at night eventually proved to be the way to go. This generated significant improvements in overall tolerability and compliance.
Trazodone has been subjected to multiple controlled studies indicating that it is as effective as other antidepressants – ranging from the older tricyclics to the popular SSRIs. Its antidepressant dosage range is from 150-600mg per day. A small handful of clinical writings have postulated that trazodone use can lead to dysphoric mood and even anxiety in some patients – particularly those with certain genetic variations – more common in African American and Hispanic individuals. As a result, upward dosage titration should be done more slowly and carefully while still aiming for an acceptable target dose.
Trazodone works quite well in primary insomnia, as well as insomnia occurring as a result of an already existing depression. Total sleep time is increased by some 30-50 minutes – well beyond that provided by many benzodiazepine sleep agents and the non-benzodiazepine “Z” drugs. Also significant is that trazodone improves sleep architecture, increasing stage 3 and stage 4 delta sleep as well as slow-wave sleep. Few other actual hypnotics marketed as sleeping pills can lay claim to this. Benzodiazepines actually worsen sleep quality, particularly as dosage ranges increase. Some studies, although uncontrolled, suggest that trazodone improves sleep and decreases nightmares in PTSD.
As for trazodone’s use in depression, I wouldn’t recommend it at all as a first-line agent, but it may be worth trying if the more traditional SSRIs or SNRIs fail some patients. People with insomnia, PTSD, sleep apnea and generalized anxiety are best suited for this drug. The starting dose is generally 25-50mg at bedtime with slow increases to 150mg within 10 days or so. Once the nightly dose reaches 150mg, it’s acceptable to wait a bit to determine how well the patient responds. An alternative option is to continue titrating the bedtime dose upward by 50-75mg per week to a total bedtime dose of 300mg.
From a favorable perspective, trazodone is not associated with weight gain, and has few sexual side effects – unlike the SSRIs which are the starting point for most depressed patients. Unfavorably, the drug is consistent with daytime sedation in those using it for depression management at the higher end of the dosing spectrum. Trazodone can be responsible for dizziness, nausea and cardiac arrhythmias. Another troublesome issue to manage is orthostatic hypotension – which is a drop in blood pressure when standing from a sitting position or lying down. This can lead to falls, particularly in the elderly.
If daytime malaise persists with nighttime dosing, it’s recommended that users take trazodone 2-3 hours before bedtime. Orthostatic hypotension may possibly improve via divided doses or taking it with food.
Although classified as an antidepressant, trazodone has made its mark mostly in the management of insomnia. As an antidepressant, positive benefits are likely forthcoming only from higher doses which can produce uncomfortable and intolerable side effects, so maintaining daytime alertness would be quite the challenge and could markedly affect work performance. For these reasons, trazodone shouldn’t be high in the pecking order of antidepressant choices, unless relegated all but exclusively for helping manage insomnia.
Attribution Statement:
Joe Wegmann is a licensed pharmacist & clinical social worker has presented psychopharmacology seminars to over 10,000 healthcare professionals in 46 states, and maintains an active psychotherapy practice specializing in the treatment of depression and anxiety. He is the author of Psychopharmacology: Straight Talk on Mental Health Medications, published by PESI, Inc.
To learn more about Joe’s programs, visit the Programs section of this website or contribute a question for Joe to answer in a future article: joe@thepharmatherapist.com.