Scientific Evidence is Lacking for Off-Label Antidepressant Prescribing

off-label antidepressant

A study published in the British Medical Journal examined the prevalence and scientific support for off-label antidepressant prescriptions. They conclude that antidepressant prescriptions for off-label indications are usually not supported by strong scientific evidence and that generating and providing physicians with evidence for off-label indications would optimize prescribing practices.


Antidepressant drugs are commonly prescribed to treat depressive disorders, as well as various other conditions including anxiety, eating disorders, sleep disorders, chronic pain, and obsessive-compulsive disorder. The rate at which antidepressants are prescribed is increasing in the United States, Canada, and the UK. In England, over the course of just one year (2014-2015), antidepressant prescriptions increased by 3.9 million, approximately 7%. It is believed that this increase is in part due to the expanding range of conditions being treated with antidepressants, many of which are not approved by the countries’ respective regulating body and are known as “off-label” indications (in medicine, “indication” is a reason to use a medication). It is estimated that approximately 29% of antidepressants are prescribed for off-label indications. Off-label drug use is known to be associated with an increased risk of adverse events when it is not supported by strong scientific evidence. For this reason, it is important to gain a better understanding of whether antidepressant off-label indications are scientifically supported.

The authors conducted a descriptive study in primary practices of two cities in Quebec, Canada to examine off-label indications and determine the level of scientific support for off-label prescriptions. Primary physicians involved in the study used an electronic prescribing system and information was collected from patients over 18 years of age who were prescribed an antidepressant between 2003 and 2015. In total, 106 850 prescriptions were written for 20 920 adults by 174 physicians. Within this patient population, the researchers measured the prevalence of off-label prescriptions by drug and class. They also calculated the proportion of off-label antidepressant prescriptions in the three following categories: strong evidence supporting use of the prescribed drug for the respective indication; no strong evidence for the prescribed drug but strong evidence supporting use of another drug in the same class for the indication; or no strong evidence supporting use of the prescribed drug and all other drugs in the same class for the indication. With regard to drug class, tricyclic antidepressants were most commonly used for off-label indications. The drug Trazodone accounted for 26% of the off-label use due to its use for insomnia. In only 16% of cases were off-label prescriptions supported by strong scientific evidence. It was far more common that there was no evidence supporting the drug’s use for the particular indication. Of these cases lacking scientific evidence, 40% of the time there was supporting evidence for another antidepressant of the same class to treat the indication. Most concerning, 44% of time there was no evidence to support the prescribed drug or any other in its class for the indication.

Overall, the authors conclude that most often off-label antidepressant prescriptions lack supporting scientific evidence for the respective indication. However, other drugs within the same antidepressant class often have supporting evidence and could be used as an alternative. More information evaluating the clinical outcomes of off-label use is needed to improve prescribing practices and indication-based electronic prescribing systems are important resources and tools for studying off-label uses and providing information to physicians.


Written By: Katherine M. Evely, MS