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Understanding the Limits of Antidepressants

Three common antidepressants ­– Paxil® (paroxetine), Lexapro® (escitalopram), and Prozac® (fluoxetine) – could be less effective at high elevations, suggests research involving lab rats and led by scientists at University of Utah Health.

When rats were placed in conditions that simulate moderate-high altitudes, the three pharmaceuticals failed to suppress behaviors that model human depression. By contrast, another antidepressant, Zoloft® (sertraline), worked under these conditions. The results of tests with the four drugs – all of which fall in the class of antidepressants known as serotonin reuptake inhibitors (SSRIs) – are published in the May online edition of Pharmacology, Biochemistry and Behavior.

Rates of depression and suicide are particularly high in Utah and other states in the Intermountain West region of the United States where elevations are considerably higher than in the rest of the country. Similar trends are also seen in countries such as Austria and Peru that have large populations living at high elevation.

Connections between altitude and depression have also been documented in tests with lab rats, experiments like these provide conditions that can be carefully controlled. What’s more, unlike people, the behavior of rats is not influenced by external influences such as social or financial pressures.

The researchers found that rats acclimated to 4,500 feet, or in hypobaric chambers mimicking conditions at 10,000 feet, were more likely to display depression-like behaviors than those in chambers calibrated to sea level conditions. The current study adds an important element to the discussion by demonstrating that of four SSRIs tested, only Zoloft® significantly and consistently lessened signs of depression seen at altitude.

These findings could have big implications for treatment of depression in people living at high altitudes, and have spurred follow-up of these investigations.

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Last Updated: 6/7/21