Shortage of Antianxiety Drug Leaves Patients in the Lurch

Batya Swift Yasgur, MA, LSW

February 28, 2019

A shortage of the antianxiety medication buspirone (Buspar, Bristol-Myers Squibb) has left patients who have anxiety disorders in the lurch as psychiatrists scramble to find suitable alternative treatments.

Although there are other antianxiety medications approved by the US Food and Drug Administration (FDA), buspirone has a unique mechanism of action and therefore plays an indispensable role in the treatment of patients who are unable to take other agents.

"Buspirone has occupied its own niche in the treatment options we have for anxiety because it does not have the addiction potential of other popular antianxiety medications — namely, the benzodiazepines — which gives it an advantage in the treatment of anxiety in certain patients," Elias Aboujaoude, MD, clinical professor and chief of the anxiety disorders section at Stanford University School of Medicine, California, told Medscape Medical News.

"Unlike other drugs, such as antidepressants, and based on buspirone's mechanism of action, there are not automatic substitutes for it, making a shortage particularly problematic for patients who rely on it," he said.

Limited Availability

Buspirone was originally distributed by the Bristol-Myers Squibb Company; generic versions became available in 2001, when the patent for the drug expired.

Since then, several companies, including Mylan Pharmacetuicals, Accord Healthcare Incorporated, Impax Laboratories, Teva Pharmaceuticals, and Zydus Pharmaceuticals, have manufactured generic buspirone; roughly a third of the supply is manufactured by Mylan Pharmaceuticals.

Mylan recently interrupted its production of the drug.

A representative from Mylan declined to be interviewed by Medscape Medical News regarding the reasons for this interruption, although Mylan did provide a statement:

"Mylan is among a number of manufacturers experiencing supply interruptions for buspirone. We understand the burden this puts on our customers and the patients we serve. We encourage patients to check the FDA [US Food and Drug Administration] drug shortage database regularly to confirm the latest supply status of all buspirone products, as we believe other manufacturers are actively selling the product. In addition, we encourage patients to consult with their physician regarding alternate therapies."

A representative from the FDA confirmed for Medscape Medical News that its drug shortage Web page is the "best source of information on this shortage as well as availability from the other manufacturers."

According to the FDA database, limited supplies of buspirone have become available. Par Pharmaceuticals manufactures and distributes a 7.5-mg dose.

Medscape Medical News spoke to a representative from Par Pharmaceuticals, who confirmed that the product is currently being shipped to distribution centers and should be available to patients.

Similarly, Strides Pharma Inc has restored production of 5-mg and 7.5-mg doses, Teva Pharmaceuticals aims to restore production in February or March 2019, and Accord Healthcare Inc states that the product will again become available in April 2019.

Zydus Pharmaceuticals states that buspirone is "available on allocation to its existing customers."

Downward Spiral

Persistent medication shortages are by no means confined to buspirone. Numerous drugs have been subject to shortages, including morphine, intravenous fluids, psychiatric medications, and stimulants, to name just a few.

"Drug shortages have been around since drugs have been around, but have gotten worse, with shortages of greater magnitude than before, especially with generic drugs," said David Gaugh, RPH, senior vice president of scientific and regulatory affairs, the Association of Accessible Medicines.

Gaugh told Medscape Medical News that a pharmaceutical company that owns the patent on a brand drug "knows their market and have dedicated manufacturing facilities for the drug that they know they'll have for 10, 12, or 14 years, and it will continue to grow unless there are unexpected side effects.

"This predictability is very important," he said.

By contrast, generics are "not as predictable, so when generics come out for that brand product, there could be one, three, or 12 companies that manufacture the generic product," he explained.

Even when the company has a contract with a partner, if another company offers the drug at a lower price, that contracted partner can switch to the lower-price company, he said.

"The company can then decide to reduce its price to keep up with the lower-price company, leading to a downward-spiraling structure industry. As products continue to go down in price, the company eventually decides that it can no longer manufacture that particular product because it is no longer profitable," he said.

The downward spiral leaves companies with reduced funds to obtain raw materials or address quality-related issues raised by the FDA. Each discontinuation places a greater burden on the remaining companies, which, in turn, may be unable to meet the demand.

"In some cases, as the prices go low enough, everyone gets out of the market until there is only one person left standing, and although they now have a 100% predictable market, they may not have the capacity to meet that 100%," he added.

He noted that the FDA "works closely with the companies, and if they know one company's product will go off market, they'll contact another company."

In an article on the FDA website, FDA Commissioner Scott Gottleib, MD, and Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, confirm that the FDA is committed to "help ensure Americans have access to safe and effective drugs."

Gottleib and Woodcock emphasize that when drug shortages arise, the agency takes "immediate action within our authorities, working across the FDA and with other government agencies, industry, and other stakeholders to minimize the impact of these shortages and maintain or restore availability of critical medicines for the patients who need them."

Ongoing Vulnerability

"What is unique about the shortage of an antianxiety medication is that patients with anxiety disorders become anxious about the medication itself, so the medication becomes the object of their anxiety," said Aboujaoude.

As the director of an anxiety clinic, Aboujaoude said he sees "a lot of outpatients with any number of anxiety disorders, and they require a personalized approach that must be determined on a case-by-case basis."

The buspirone shortage has created challenges in how to manage patients whose individual needs make it the optimal treatment.

The problem regarding buspirone is compounded because buspirone is not a widely used drug, Beth Salcedo, MD, president of the Anxiety and Depression Association of America, told Medscape Medical News.

"This shortage is disturbing and brings to light some problems that we have in our medication pipeline, because these are for-profit companies, and if there isn't a huge market, it won't be a huge moneymaker for the generic manufacturer," she said.

"For that reason, it's probably easy for those companies to therefore put their resources elsewhere," said Salcedo, who is also the medical director of the Ross Center, a large outpatient practice with offices in Washington, DC, and New York City.

She noted that she has patients who rely upon buspirone after having tried multiple other medications, and "if they can't get it, we're starting over, so this isn't a small thing."

She added that for the FDA, addressing the shortage of a medication such as buspirone may not be priority, "since the FDA treats drugs like this differently than what they call 'lifesaving drugs,' such as IV drugs used in emergency settings."

But drugs used to address anxiety and depression are lifesaving, she said.

Although buspirone is available on a limited basis, the specter of another potential shortage leaves patients vulnerable.

"This country is not doing what it needs to do in the preventive healthcare and mental health space," Salcedo added.

A "Unique" Medication

Finding an appropriate substitute for buspirone is a matter of trial and error and requires creativity.

Wilfrid Noel Raby, PhD, MD, adjunct clinical professor, Albert Einstein College of Medicine, New York City, agreed that buspirone is not widely used but has unique characteristics that can be helpful for certain patients because it has a single mechanism of action.

"Buspirone is a serotonin 5-HT1A partial agonist, and that's all it does, which is nice because that makes it very clean," he told Medscape Medical News.

Although other medications are structurally similar and might be tried as alternatives, they have additional properties, said Raby, who is also a practicing psychiatrist in Teaneck, New Jersey.

For example, vilazodone (Viibryd, Allergan) also has high affinity for 5-HT1A receptors, but it inhibits the serotonin transporter, he noted.

Some second-generation antipsychotics, such as aripiprazole (multiple brands) and brexpiprazole (Rexulti, Otsuka), have partial agonist activity at serotonin 5-HT1A receptors but also act on other receptors.

"It can be tricky to match buspirone with other agents because those agents have additional properties," he said

Aboujaoude advised that if the dose the patient was taking is no longer available, adjusting the dose can be a useful strategy.

He also suggested that the buspirone shortage might have hidden advantages.

"Some individual patients may ultimately benefit from a transition to another treatment that may work even better, but it's too early in this process to be able to say anything definitive about these potential advantages," he said.

The shortage might also motivate a consideration of psychotherapy as an alternate treatment for anxiety, he added.

Role for Psychiatrists

Aboujaoude said psychiatrists "can play a crucial role in advocacy."

He noted that members of the media have contacted psychiatrists about the impact of drug shortages, but "it is the regulatory bodies that should also be seeking out clinicians' opinions on what it means to suddenly lose a treatment that's been around for decades."

Clinicians should participate in "advocating for patient access to these medications before the regulatory bodies that control the supply chain," he said.

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