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Trazodone Cancer Risk Signal Review: What the Evidence Actually Shows

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At a glance

  • Label indication / Major depressive disorder in adults; sleep use is off-label
  • Cancer on the label / Not among the postmarketing adverse reactions
  • Class per the label / SSRI and 5-HT2 receptor antagonist, a triazolopyridine
  • Serotonin and tumors / Studied in liver cancer cells and mice, not with trazodone
  • Main label risks / QT prolongation, serotonin syndrome, orthostatic hypotension, priapism, bleeding

Does trazodone cause cancer?

No link has been established. The prescribing information for trazodone tablets lists postmarketing reactions across blood, heart, endocrine, liver, nerve, kidney, reproductive, skin and vascular categories, and no cancer or tumor term appears among them [1]. The FDA's adverse-event dashboard carries explicit limits: a report does not mean the drug caused the event, duplicate and incomplete reports are common, the information has not been medically verified, and the reports cannot be used to estimate how often an event occurs [2].

What the label covers

Trazodone tablets are indicated for major depressive disorder in adults and are not approved for pediatric patients [1]. The label has no insomnia indication and gives no insomnia dose, so sleep use is off-label [1].

Why serotonin comes up in cancer discussions

The label describes trazodone as a selective serotonin reuptake inhibitor and a 5-HT2 receptor antagonist [1]. Separately, researchers have studied serotonin as a growth signal in liver cancer. In the human hepatocellular cancer cell lines Huh7 and HepG2, serotonin promoted tumor growth and survival in starved cells. In two mouse tumor models, inhibiting serotonin signaling impaired tumor growth. In tumor tissue from 168 patients with hepatocellular carcinoma, the serotonin receptor HTR2B was expressed and correlated with markers of proliferation [3].

Those experiments did not test trazodone and did not measure cancer in anyone taking it. They describe serotonin biology in cancer cells and in mice.

What the label tells patients to watch for

  • QT interval. The label says trazodone prolongs the QT/QTc interval, and torsades de pointes and ventricular tachycardia have been reported after marketing at 100 mg a day or less; the label advises avoiding the drug in known QT prolongation and with other QT-prolonging drugs [1].
  • Priapism. The label tells men to stop the drug and get emergency care for an erection lasting more than 4 hours, painful or not [1].
  • Serotonin syndrome. It can occur with trazodone alone; risk rises with other serotonergic drugs, and MAOIs are contraindicated [1].
  • Blood pressure. In outpatient MDD trials, hypotension was 4% with trazodone versus 0% with placebo, and syncope 5% versus 1% [1].
  • Bleeding. Risk may rise with aspirin, NSAIDs, other antiplatelets and anticoagulants [1].
  • Stopping. The label recommends reducing the dose gradually rather than stopping abruptly [1].

Sleep use and the evidence for it

A 2005 review of 18 studies described trazodone as the second most commonly prescribed agent for insomnia at that time. It found the evidence for efficacy in insomnia very limited, noted some evidence of tolerance, and concluded it is uncertain whether the risk/benefit ratio warrants use in nondepressed patients with insomnia [5].

Frequently asked questions

Does trazodone cause cancer?
Nothing in the trazodone prescribing information establishes a cancer link. The label's postmarketing reactions do not include cancer or tumors [1].
What serious risks does the trazodone label list?
QT prolongation, with torsades de pointes reported after marketing at 100 mg a day or less; serotonin syndrome; orthostatic hypotension and syncope; priapism; and increased bleeding with aspirin, NSAIDs or anticoagulants [1].
Is trazodone approved for insomnia?
No. The label indication is major depressive disorder in adults, and it gives no insomnia dose, so sleep use is off-label [1].
Does the liver cancer finding mean trazodone is risky?
No. That work studied serotonin signaling in liver cancer cell lines and mice, and examined patient tumor tissue for a serotonin receptor and related markers. It did not test trazodone or measure cancer in people taking it [3].
What does the label say about stopping trazodone?
The label recommends gradual dose reduction rather than stopping abruptly, because adverse reactions can occur on discontinuation [1].

References

  1. U.S. National Library of Medicine, DailyMed. Trazodone hydrochloride tablets (Oxford Pharmaceuticals) prescribing information. Trazodone hydrochloride tablets (Oxford Pharmaceuticals) label
  2. FDA Adverse Event Monitoring System (AEMS) Public Dashboard | FDA. FDA Adverse Event Monitoring System (AEMS) Public Dashboard | FDA
  3. Soll C, Jang JH, Riener MO, Moritz W, Wild PJ, Graf R, et al. Serotonin promotes tumor growth in human hepatocellular cancer. Hepatology. 2010;51(4):1244-54. Serotonin promotes tumor growth in human hepatocellular cancer
  4. Greenblatt DJ, von Moltke LL, Harmatz JS, Fogelman SM, Chen G, Graf JA, et al. Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone. J Clin Pharmacol. 2003;43(4):414-22. Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone
  5. Mendelson WB. A review of the evidence for the efficacy and safety of trazodone in insomnia. J Clin Psychiatry. 2005;66(4):469-76. A review of the evidence for the efficacy and safety of trazodone in insomnia
Evidence overview for Trazodone Cancer Risk Signal Review: What the Evidence Actually Shows