5 dated drugs that are getting new indications

By Naveed Saleh, MD, MS
Published March 2, 2021

Key Takeaways

Care to hazard a guess on how many prescription drugs are approved for marketing in the United States? According to the FDA, this number tops 20,000. With all these medications, it makes sense that some are used more than others, with some drugs falling into relative obscurity. But, what about drugs that stage a comeback? 

Researchers have re-examined a variety of older drugs—some that were hindered by dangerous side effects, some that were misunderstood, and others that simply took a back seat to newer, more effective drugs. Now, studies show, these drugs may still be useful, both for new and existing indications. 

Here are five drugs that are enjoying a renaissance—including one with a very dark history that is showing promise as a possible treatment for COVID-19. 

Monoamine oxidase inhibitors

Non-selective monoamine oxidase inhibitors (MAOIs), such as tranylcypromine, phenelzine, and isocarboxazid, are notorious for their adverse effects, such as insomnia, nausea, and dry mouth. Most conspicuously, they can induce a hypertensive crisis when combined with foods containing high levels of tyramine, such as blue cheese, Swiss, and parmesan. Nevertheless, these drugs are remarkably effective and are making a comeback.

In an article published in CNS Spectrums, authors call for renewed attention, education, and promotion of these drugs, which are rarely covered in psychiatry residency programs or characterized in prominent texts.

The authors wrote that MAOIs are “dramatically effective for patients with biological depressive illnesses (eg, melancholia and bipolar depression). It has been established by more than 50 years of research, including randomized double-blind studies, and clinical experience, that these medications can induce full remission when other antidepressants, combinations, and augmentation strategies, and even electroconvulsive therapy (ECT), have failed.”

In addition to worries about adverse effects, the authors cited other misunderstood issues that give MAOIs a bad rap, including notions that changes to medication regimens or combinations of antidepressants are difficult to make when administering MAOIs; that MAOIs must be ceased prior to anesthesia; and that opioid medications cannot be taken with MAOIs.


Commonly used drugs don’t get much older than aspirin, which Bayer first marketed in 1899. Worries about bleeding and ulcers, however, have hampered its utility.

Recently, there’s been increased interest in the use of aspirin to prevent cancer, which culminated in the US Preventive Services Task Force (USPSTF) issuing the following 2016 recommendation:

“The USPSTF recommends initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years.”

It should be noted, however, that recent, high-powered research pointed to a contrarian finding in those aged 70 years or older taking aspirin. According to the authors of a study published in the Journal of the National Cancer Institute, “In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and thus, suggest caution with its use in this age group.”


First introduced in 1969, this drug was a popular antibiotic choice for the treatment of urinary tract infections (UTIs). Interest in its prescription, however, waned with the emergence of other antibiotics used to treat UTIs. Popularity of this drug is resurging, but at a cost, according to an article published in Pharmacology.

“[W]ith the development of bacterial resistance to many antibiotics (ie, β-lactam antibiotics, quinolones, aminoglycosides) worldwide, fosfomycin is coming back as a viable alternative,” the authors wrote. “Many countries adopted fosfomycin trometamol in their guidelines for urinary tract infection management not only for uncomplicated infections, but also for infections caused by multidrug-resistant bacteria. However, this was associated, in turn, with a rapid increase in the resistance level of bacteria to fosfomycin, according to data from several countries.”


Ketamine, which is known on the streets as Special K, has a bad reputation as a drug of misuse. It is commonly referred to as a “horse tranquilizer” for its use in veterinary medicine, a characterization that also does the drug no favors. But, this drug has experienced a resurgence in interest in recent years.

Ketamine was first formulated in 1962 as an alternative to phencyclidine (PCP). It has strong anesthetic, sedative, amnestic, and analgesic properties, as well as being a bronchodilator, with preservation of airway reflexes and sympathetic tone. 

According to the authors of an article published in the Journal of Family Medicine and Primary Care, “Identifying new properties of ketamine such as neuroprotective, anti-inflammatory, and antitumor effects, on one hand, and taking advantage of subanesthetic regimens of ketamine, on the other hand, have resulted in a widespread use of ketamine in various clinical applications.”

They added, “Ketamine has an excellent hemodynamic profile, makes it the agent of choice for patients with unstable hemodynamics, such as shocked or hypotensive patients.” Ketamine has been associated with a lower risk of respiratory depression and relatively more conserved airway reflexes.

In addition to being an anesthetic agent, ketamine has been increasingly used in subanesthetic doses for depression, as well as acute and chronic pain. However, the authors noted, studies of ketamine performance in pain management have shown conflicting results; therefore, caution is advised in using ketamine for complex chronic pain conditions. 


In recent years, thalidomide is seeing a revival. Although this drug will forever be associated with countless cases of children born in the early 1960s with malformation of the limbs to pregnant women who took the drug for nausea and insomnia, researchers have once again honed in on its therapeutic potential. Specifically, the drug is remarkably effective at treating multiple myeloma and leprosy—although under strict conditions. 

Intriguingly, thalidomide has recently been presented as a possible treatment for COVID-19, as suggested by the authors of a case report published in Clinical and Translational Medicine.

“Thalidomide could not only be used to inhibit cytokine surge and regulate immune functions, but also be used to calm patients down to reduce oxygen consumption, and relieve digestive symptoms in COVID‐19 patients,” they wrote. “Therefore, thalidomide may be a new dawn as an adjuvant treatment strategy for patients with critical COVID‐19. A randomized controlled trial to investigate the effectiveness of thalidomide combined with low‐dose short‐term glucocorticoid for COVID‐19 treatment needs to be performed.” 

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