5 Medications Prescribed for Off-label Use

Is the medication your doctor prescribed for you one that's approved to treat your particular condition? Feverpitched/Thinkstock

Chances are, the last time your doctor wrote you a prescription, you filled it at the pharmacy without so much as a second thought. But if you did a little research, you might be surprised to find the medication you received wasn't technically specified to treat your particular condition.

So why would your health care provider venture into unofficial territory and recommend a drug that's not approved by the Food and Drug Administration (FDA) to address your issue?

First, it's important to understand what "approved" actually means. In order for a prescription medication to be legally sold in the United States, the pharmaceutical company has to submit clinical data and other information to the FDA to demonstrate the drug in question is safe — meaning its benefits outweigh the potential risks — and effective for its intended uses [source: FDA].

If your doctor prescribes you a medication for its approved use, then that means there's strong scientific data to back up the manufacturer's claims and there's labeling to instruct patients on how to use the drug safely and effectively for its intended purposes. But in a lot of cases, medications have other affects aside from the ones they're formally approved for, and a doctor or health care provider may decide that drug can also treat an illness or condition that it's not approved for.

That's when a doctor may choose to use a drug "off label," often if they've already exhausted all the approved treatments for a condition without positive results.

If you're worried that taking a prescription drug off-label sounds shady, don't be. It's common and happens more than you realize. "Off-label use of drugs is legal," says Malcolm Thaler, a New York City-based internal medicine provider. "The FDA approves drugs, but it does not regulate how they are prescribed. And [it's] very common; more than 20 percent of drugs are prescribed for purposes other than the ones for which they were initially approved, and the number is even higher in the pediatric population."

Not all drugs have off-label purposes, and those that do are selected are chosen for specific reasons. "Drugs are used for off-label purposes because they have been found to work," Thaler says. "Often the drug is found to have a new use serendipitously, like when it is given to a patient for one purpose and found to solve another issue the patient may be having. In other situations, our understanding of the mechanism by which the drug works suggests that it might serve other purposes."

Here are a few ways medical professionals may choose to use drugs for off-label purposes:

  • Using a drug for a condition that it's not approved to treat, for example, using one kind of chemotherapy that's approved for a specific kind of cancer to treat a different type of cancer.
  • Prescribing a different form of the medication, like an oral solution as opposed to the approved capsule form.
  • Recommending a different dose than what's been approved, such as prescribing two tablets instead of one.

There are a lot of reasons medical professionals would seek out off-label treatments for a variety of health issues, and with that comes pros and cons. "The positive side of off-label drug use is the expanded clinical utility of a drug," Thaler says. "The potential downside is that the drug may be repurposed without evidence supporting its safety or efficacy in a new setting; obtaining FDA approval for a new use can be very time-consuming and costly, and so approval may not be sought."

Many doctors believe prescribing a drug off-label can result in big benefits, but there are definite risks and consequences to consider as well. If a patient's finances are a concern, it's important to know that insurance companies may refuse to reimburse the cost of expensive drugs that aren't prescribed for approved uses.

It's also key to remember that, because the FDA doesn't regulate how doctors prescribe medications, there's not a lot of information available on the safest ways to use drugs off-label.

For instance, when it comes to drugs that treat cancers, the American Cancer Society says "lack of information on off-label drug use and outcomes may also put patients at a higher risk for medication errors, side effects and unwanted drug reactions." And finally, because off-label drug use often falls outside "standard of care" treatment, it's worth knowing that the prescribing provider could face legal trouble if a patient has a bad outcome.

So any time your doctor prescribes a medication — whether it's for an approved or off-label use — it's important to talk through all the possible risks and benefits and make an informed decision.

Keep reading to learn about five of the most commonly prescribed off-label drugs.

5
Botulinum Toxin (Botox)
Botox is often prescribed off label to treat severely cold hands, premature ejaculation and even depression. BSIP/Contributor/Getty Images

What It Is: An injectable drug that blocks overactive nerve impulses to reduce muscle activity.

What It's Approved to Treat: Excessive underarm sweating, overactive bladder, crossed eyes, muscle spasms, chronic migraines

Common Off-label Uses: Severely cold hands, premature ejaculation, depression

Botox may be best known for smoothing and preventing wrinkles, but the manufacturer, Allergan, holds almost 800 additional patents for the drug's potential uses, including those mentioned above [source: Sifferlin]. The neurotoxin is derived from a bacterium known as Clostridium botulinum, which can cause paralysis — and even death — if it's consumed in contaminated food. But when it's administered in small doses, it can cause muscles to relax. That mechanism of action is what makes it an effective wrinkle preventer, an overactive bladder treatment (it prevents involuntary contractions that can cause the feeling of urgency).

As far as depression, a 2014 study published in the Journal of Psychiatry revealed that because facial expressions are part of the brain circuitry related to mood, inhibiting muscles in the face may prevent people from making expressions associated with negative emotions.

No matter how it's used, however, Botox does come with a long list of possible side effects including muscle weakness, drooping eyelids and double vision if the drug spreads from the injection site to other parts of the body [source: Sifferlin].

4
Quetiapine (Seroquel)
Veterans like Brian Scott Ostrom (seen here) are often prescribed drugs like Seroquel, an antipsychotic medication, for PTSD and severe depression. Craig F. Walker/The Denver Post via Getty Images

What It Is: A second-generation antipsychotic

What It's Approved to Treat: Schizophrenia, bipolar disorder and major depressive disorder (adjunct)

Common Off-label Uses: Dementia, depression, generalized anxiety disorder, OCD

Antipsychotics are increasingly being used for off-label purposes, and quetiapine (Seroquel) is the most common among them. The drug was originally registered in 1997 and was the fifth highest-selling pharmaceutical in the U.S. by 2010. But that same year, the government alleged non-psychiatrists were using the drug for off-label uses like anger management, sleeplessness and depression [source: Brett]. A 2007 study found that clinicians reported using the drug off label because it has low abuse potential, has a mildly sedative effect with low risk of confusion, and modest cardiovascular effects.

However, like other drugs in its class, it's been associated with weight gain and dyslipidemia (excess of triglycerides in the blood) and carries a black-box warning for stroke risk in elderly people. Plus, experts aren't quite clear on whether there's strong evidence to support the use of quetiapine for these off-label uses. In fact, in 2010, the drug's manufacturer agreed to pay a $520 million fine for allegations of promoting off-label prescriptions, mostly in low doses of 25 mg. for such as anger management, dementia and sleeplessness. The usual therapeutic dose range for the approved indications of schizophrenia or bipolar disorder is 400 to 800 mg. per day [Brett].

One of the study's authors said that in his clinical experience, "there's no report in the literature showing either that it's efficacious or really that it's safe in those low [25 mg.] doses" [source: Busko].

3
Trazodone (Desyrel)
Trazodone is actually one of the most commonly prescribed off-label sleep medications. PhotoAlto/Frederic Cirou/Getty Images

What It Is: Cyclic antidepressant

What It's Approved to Treat: Depression

Common Off-label Uses: Sleep problems

Trazodone works by stimulating serotonin in the brain, but it's not a selective serotonin reuptake inhibitor (SSRI) like other well-known antidepressants such as fluoxetine (Prozac). The drug was originally approved by the FDA in 1981 to treat depression, but because it causes drowsiness, it's actually become one of the most commonly used sleep medications. The drug still isn't FDA-approved to treat insomnia, however, and not much research has been done to support its long-term effectiveness or safety.

Because of the intense drowsiness it can cause, trazodone isn't commonly prescribed to treat depression alone anymore, but doctors continue to prescribe it as a lower-cost alternative to sleep medications like zolpidem (Ambien) and eszopiclone (Lunesta).

Many experts believe trazodone is safer than traditional sleep medications and less likely to result in impaired abilities or dependence, but the medication does have its own risks: It's more likely than newer sleep medications to leave users feeling drowsy the next day, and it can cause abnormally low blood pressure, dizziness, or fainting, especially in elderly patients [source: Consumer Reports].

2
Beta Blockers
Beta blockers, including drugs like atenolol, are frequently prescribed off label to help prevent migraine headaches. Siphotography/Thinkstock

What It Is: A class of drugs that blocks the neurotransmitters norepinephrine and epinephrine from binding to receptors.

What It's Approved to Treat: Heart problems, diabetes, hypertension

Common Off-label Uses: Migraine headaches, generalized anxiety disorder, hyperthyroidism, fibromyalgia, glaucoma, Parkinsonian tremor, atrial fibrillation

Beta blockers, including drugs like acebutolol (Sectral), atenolol (Tenormin) and bisoprolol (Zebeta), work on the beta receptors in the tissues of the body's sympathetic (i.e. "fight or flight") nervous system to inhibit hormones like epinephrine and norepinephrine that are considered stimulating. Doctors have been using them since the early 1960s to treat and prevent heart attacks and reduce blood pressure.

However, because these drugs act on hormones like epinephrine (otherwise known as adrenaline) and cortisol, they can mitigate the physical symptoms associated with these hormones like rapid heart rate, muscle tension and sweating. By preventing stimulating hormones from binding to their designated receptors in the body, those associated physical symptoms of stress simply go away.

Doctors sometimes favor beta blockers over approved anti-anxiety medications because they don't carry any risk of dependence, they're reasonably inexpensive and they have such a profound effect on the physical feelings of panic.

There are, however, potential downsides too: They're not effective for everyone, and one of the long-term side effects is a higher risk of developing Type 2 diabetes. The drugs also don't address the root cause of anxiety; just the symptoms. And long-term users trying to quit the medication could face severe withdrawal symptoms like blood pressure spikes and increased heart rate [source: Mental Health Daily].

1
Sildenafil Citrate (Viagra, Revatio)
A Pfizer study found that seven out of nine women on antidepressants who had problems achieving orgasm recovered when they took Viagra. Christopher Furlong/Getty Images

What It Is: A phosphodiesterase (PDE) inhibitor

What It's Approved to Treat: Erectile dysfunction in men or to improve the ability to exercise in adults with pulmonary arterial hypertension

Common Off-label Uses: Enhancing sexual performance in people not diagnosed with erectile dysfunction, improving sexual function in women taking certain antidepressants

CNN called it "the little blue pill that could," and Viagra has certainly made a name for itself over the last two decades. In 1989, Pfizer scientists introduced a drug called sildenafil citrate that they anticipated would help treat high blood pressure and a type of chest pain associated with coronary heart disease called angina. During the drug's clinical trials, volunteers began reporting increased erections several days after taking a dose, and in 1998, the FDA approved the use of Viagra to treat erectile dysfunction [source: Wilson].

A decade later, scientists began finding evidence that the little blue pill could potentially help some women experiencing sexual dysfunction, too. Between 30 to 70 percent of people taking antidepressants experience sexual dysfunction, and a Pfizer-funded study found that seven out of nine women on antidepressants who had problems achieving orgasm recovered when they took Viagra [source: Carollo].

Female sexual response is complicated, and the FDA hasn't approved Viagra for this use in women, but another prescription medication called flibanserin (Addyi), originally developed as an antidepressant, is FDA-approved to treat low sexual desire in premenopausal women [source: Tobah].

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Author's Note:5 Medications That Are Prescribed for Off-Label Use

The conversation around the promotion of off-label prescription uses has evolved considerably over the last few years. Originally, the FDA prohibited pharmaceutical sales representatives from promoting a drug's off-label use if the medication didn't come with adequate instructions for the use. But in 2012, a court ruling deemed off-label promotions as protected free speech, as long as the statements aren't false or misleading [source: Cain]. Regardless of legal details, having open, honest, well-informed conversations with your doctor around any and all recommended medications seems like the best way to go.

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More Great Links

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