10 Off-label Uses of Antidepressants

Certain foods, medications, chemicals, plants — even sunlight — are known to trigger urticaria (hives). About half of the time, though, the itchy wheals appear and last anywhere from a few hours to a few days with no known explanation. Chronic hives, though, are a little different. Hives that last for six weeks or longer are considered chronic, and they're called chronic idiopathic urticarial. These hives are usually tied to an autoimmune response, causing mast cells — cells that are involved in our allergic reactions — to inappropriately produce histamine.

Most antihistamines, such as hydroxyzine (Atarax) and diphenhydramine (Benadryl), are H1 histamine receptor antagonists. That means they target one of the four types of histamine receptors in the body, called H1 receptors, and block their production of histamine. H1 receptors are located throughout the body in our smooth muscles and in the cells that make up the lining of our blood and lymphatic vessels.

A much smaller percent of antihistamines are histamine H2 receptor antagonists, which means they block H2 histamine receptors from producing histamine. H2 receptors are found in gastrointestinal parietal cells (the stomach cells that produce gastric acid). Medications used to treat heartburn, including ranitidine (Zantac) and cimetidine (Tagamet), are also used as H2-blocking antihistamines. (H3 receptors are found throughout the nervous system, and H4 receptors are located in the immune system.)

While an acute outbreak of hives is often treated effectively with antihistamines, the most common second-line treatment for chronic hives is actually better known for its treatment of depression and insomnia: the tricyclic antidepressant doxepin (Sinequan). Doxepin, it turns out, is a pretty potent antihistamine, acting on both the H1 and H2 receptors simultaneously and preventing hives and pruritus (itchiness).

Roughly 9 percent of the U.S. population — about 29 million Americans — lives with diabetes, with 8 million among them unaware of their condition [source: ADA]. Diabetes — untreated or poorly managed diabetes, in particular — increases a person's risk of developing heart disease or suffering a stroke and can cause damage to the eyes and kidneys. Diabetes is also the most common cause of peripheral neuropathy in the U.S.; an estimated 60 to 70 percent of diabetics will develop diabetic peripheral neuropathy during their lifetime [source: APMA].

Diabetic peripheral neuropathy is the result of nerve damage caused by chronically high blood sugar. It often begins with tingling, burning and stabbing sensations in fingertips and toes or in the extremities, and progresses into chronic pain, loss of sensation and, in severe instances, amputation.

Duloxetine (Cymbalta) was originally approved to treat depression, but the selective serotonin-noradrenaline reuptake inhibitor (SNRI), it turns out, also effectively reduces the neuropathic pain associated with diabetic peripheral neuropathy. That's chronic pain that affects the patient's mood, sleep and general functioning. The FDA approved duloxetine as a treatment for neuropathic pain in 2005 [source: Chouinard]. Tricyclic antidepressants (TCAs) have proven to be effective in treating neuropathic pain, too, and although they're considered an off-label treatment, these antidepressants are prescribed as first-line approach to treating chronic neuropathic pain.

More than half of Americans age 65 or older report they have urinary or bowel incontinence — about 25 percent with severe bladder leakage, and about 8 percent with moderate to severe bowel leakage [source: Reinberg]. Despite the numbers, incontinence isn't, or at least doesn't have to be, a part of aging.

There are two main types of urinary incontinence. Stress incontinence is usually mild leakage, and it usually happens alongside an activity that increases the pressure on your abdomen, such as coughing or laughing. Stress incontinence often develops after the pelvic floor muscles are stretched or weakened, and it's common after childbirth.

Urge incontinence, also called an overactive bladder, has a very different list of causes and symptoms than stress incontinence. Patients with urge incontinence experience strong and immediate urges to urinate. These patients sometimes involuntarily experience their overactive bladder voiding its entire contents, which, for an average adult, is probably about 2 cups of urine, a little less than half a liter [source: Miller].

Urinary incontinence is treated with three types of drugs: anticholinergics, antispasmodics and tricyclic antidepressants (TCAs). Imipramine (Tofranil), a TCA, helps increase the levels of serotonin and other brain chemicals, which reduces the symptoms of urge incontinence by smoothing and contracting the muscles of the bladder.

While not effective for treating the symptoms of urge incontinence, another TCA, amitriptyline (Elavil), is effective in relieving pelvic floor spasms and pelvic floor muscle dysfunction in women with stress incontinence.

Between 54 and 64 percent of women with incontinence report fewer urinary leaks when prescribed a different type of antidepressant: duloxetine (Cymbalta), a selective serotonin-noradrenaline reuptake inhibitor (SNRI). Duloxetine reduces the symptoms of stress incontinence by contracting the urethral sphincters during what's called the "storage phase" of the urination cycle [source: Weiss].

Psychotherapy, in the forms of cognitive-behavioral therapy (CBT), interpersonal therapy, family counseling, nutritional counseling and support groups, is the primary treatment for disordered eating, but patients who binge and purge may find that along with this first-line therapy they're prescribed drug therapy: antidepressants.

Serotoninergic antidepressants, those that regulate the balance of neurotransmitter serotonin in the body, such as the SSRI fluoxetine (Prozac), are effective in reducing the binging-purging cycles of bulimia, a disease that's thought to be partly associated with an imbalance of serotonin.

Binge eaters, patients who binge without purging, consume enormous amounts of calories throughout the day — as much as 5,000 to 15,000 during just one binge — may also benefit from antidepressant drug therapy. SSRIs such as fluoxetine (Prozac), tricyclic antidepressants (TCAs) such as imipramine (Tofranil), and atypical antidepressants including trazadone (Desyrel) are all considered effective in regulating the body's hunger signals in binge-eating disorder (BED).

There are no conclusive studies one way or the other as of mid-2015, but it's considered unlikely that antidepressants are an effective therapy for anorexia nervosa (AN) patients.

Premature ejaculation (PE) is a problem with sexual performance, and it affects 30 to 70 percent of men age 40 and younger, making it the most common sexual disorder among that age group [source: Deem].

Symptoms of PE include ejaculation within 60 seconds after penetration and ejaculating earlier than he or his partner wants or expects. Symptoms lasting six months or more are diagnosed as PE. While it's a physical symptom, PE is actually considered a psychological problem rather than a physical one. Chronic sufferers may also suffer from depression or anxiety.

Common therapies for treating PE include topical desensitizing agents, but long-term instances may also be treated with a prescription for antidepressants — specifically selective serotonin reuptake inhibitors (SSRIs). SSRIs come with their own set of side effects, two of which are beneficial in this instance: erectile dysfunction and the inability to ejaculate [source: Fallon]. Off-label sertraline (Zoloft), for example, has been found to increase the time to ejaculation in PE sufferers by 7.6 minutes to 16.4 minutes, depending on dosage [source: Stone et al.].

A patient experiences chronic pain, fatigue, changes in memory and changes in mood; what's the diagnosis? Those are the symptoms of fibromyalgia, a musculoskeletal pain syndrome affecting an estimated 5 million adults in the U.S. The majority of patients are female [source: NIAMS]. It's difficult to diagnose fibromyalgia, as its characteristics and symptoms are common among various disorders and diseases.

Its cause is unknown; some theories suggest hormonal triggers, while others point to associations between the syndrome and viral infections. Some studies suggest a link between sleep disorders and fibromyalgia, while others point to a possible link with depression. Or, there could be a link between genetic markers called human leukocyte antigens and fibromyalgia. And still more studies suggest biochemical changes in the muscles and the central nervous system may play a role in its onset.

Just as there's no definitively known cause for fibromyalgia, there's also no cure, but the symptoms can be managed. Analgesics (painkillers) and nonsteroidal anti-inflammatory drugs (NSAIDs) are essential to chronic pain management. Certain anti-seizure medications are also considered effective fibromyalgia treatments. And so are antidepressants, as it turns out.

Antidepressants increase the levels of two neurotransmitters — serotonin and norepinephrine — in the brain, changing the way the brain processes pain. Serotonin‐norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are among medications used off-label to manage chronic pain, and have been used — also off-label — for years to treat fibromyalgia-associated pain and its concomitant symptoms, such as depression and fatigue [source: OSU]. In 2009 the FDA approved the first antidepressant to treat fibromyalgia, the SNRI milnacipran (Savella); and in 2010 another SNRI, duloxetine (Cymbalta) was approved to treat not only depression but fibromyalgia as well.

As many as 85 percent of menstruating women report they experience at least one symptom of premenstrual syndrome (PMS), with bloating, headaches, backaches, breast tenderness and mood swings as some of the more common complaints [source: Barclift]. But about 3 to 8 percent of women have premenstrual dysphoric disorder (PMDD), a severe form of PMS marked by intense depression, anxiety or irritability, and mood swings. In 2013 PMDD was officially added to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) as a mood disorder [source: Novosolov].

Serotonin, GABA and β-endorphin are the three primary neurotransmitters indicated in PMDD, and selective serotonin reuptake inhibitors (SSRIs) are considered effective treatment for the disorder. Seventy-five percent of women suffering from PMDD report a decrease in symptoms while taking a SSRI [sources: Stöppler, Pattimakiel]. SSRIs, it turns out, do more than just interact with serotonin receptors: They also change how the body converts progesterone to a hormone called allopregnanolone. Allopregnanolone is a naturally occurring neurosteroid that acts like a sedative and mood stabilizer.

Antidepressants effectively reduce mood-related symptoms for women diagnosed with PMDD, and, although not FDA approved to treat PMS, SSRIs may reduce symptoms such as mood swings and irritability in some women who experience PMS. As many as 40 percent of women who report symptoms of PMS, though, don't report relief from SSRIs, nor do SSRIs appear to relieve physical symptoms of PMS [source: Barclift].

And it's not just the symptoms of PMS that women are treating with SSRIs. Popular antidepressants such as escitalopram (Lexapro) are prescribed off-label to lessen hot flashes in menopausal women; paroxetine (Paxil) is the one antidepressant approved as a non-hormonal treatment for hot flashes, marketed as Brisdelle.

As many as 36 million American men, women and children suffer from migraine headaches. While many people will have one or two migraine attacks in a given month, some people can count on having at least one migraine each week, and some have as many as 15 each month [source: MRF]. Make no mistake, a migraine isn't simply a bad headache. A migraine attack can be debilitating, and it can cause vision problems, nausea, and a high level of sensitivity to light and sound, among a host of other problems.

Those who experience frequent migraines may be prescribed an array of different strategies for preventing attacks, including the use of antidepressants [source: MRF]. Routinely, albeit off-label, tricyclic antidepressants (TCAs) are used as migraine prophylaxis. Amitriptyline (Elavil), for example, has proven to be moderately effective in preventing migraine, with as many as 70 percent of migraine sufferers reporting the medication provided relief [source: Consumer Reports].

The dual serotonin and norepinephrine reuptake inhibitor venlafaxine (Effexor) also shows promise in preventing migraines, but selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) don't appear to have similar benefits.

In May 1997, the FDA approved bupropion as a smoking cessation aid, marketed under the name Zyban rather than how it was already known: the antidepressant Wellbutrin. While bupropion is approved as the only nicotine-free first-line therapy to help a person quit smoking, the FDA isn't able to explain how it actually helps (similarly, there is no clear explanation of how bupropion treats depression, either). Unlike most antidepressants, bupropion has little to no effect on the body's noradrenaline and/or serotonin reuptake receptors nor on its muscarinic, histaminic and/or a-adrenergic receptors; the theory of its effectiveness is that it interacts with the brain's reward and pleasure system.

Bupropion is just one of two antidepressants used to help patients quit smoking, though; nortriptyline (Pamelor, Aventyl) is a tricyclic antidepressant considered as effective as bupropion when it comes to helping patients kick the smoking habit. Nortriptyline, though, is used off-label because the FDA hasn't yet approved it as a smoking cessation aid.

As many as 60 million Americans — 30 percent of American men and 40 percent of American women — experience periods of insomnia [source: NINDS]. There are a handful of FDA-approved prescription medications to treat the problem, including a few types of benzodiazepines (such as diazepam), a few types of non-benzodiazepines (including Ambien and two other sleeping aids), one selective-melatonin receptor agonist (ramelteon) and one selective dual orexin receptor antagonist (suvorexant). But one of the most popular treatments for insomnia isn't FDA approved.

Twenty-one percent of all prescriptions written in the U.S. are considered to be for off-label uses, and leading the pack of those off-label drugs are antidepressants prescribed to treat insomnia [source: Nova Southeastern University]. When sleep problems arise from anxiety or depression disorders, low doses of certain antidepressants, such as amitriptyline (Elavil), mirtazapine (Remeron) and trazodone (Oleptro), may effectively treat both the symptoms of the mood disorder and the related insomnia.

Some antidepressants, such as amitriptyline, have a sedative effect because they block the reuptake (the absorption) of serotonin and norepinephrine, two neurotransmitters associated with our sleep-wake cycle. Other antidepressants also block histamine receptors; mirtazapine, for example, blocks the H1 receptor, which is why it makes you feel sleepy, and depending on dosage, also blocks the 5-HT2A and the alpha-2 adrenergic receptors.