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8 common off-label uses of SSRIs

These antidepressants might be prescribed to patients with migraines, irritable bowel syndrome, and more
By | Jun. 20, 2024
Two pharmacists discussing what are SSRIs used for

Key takeaways

  • Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. They’re FDA approved to treat various mental health conditions, including depression, anxiety, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD).

  • Because of their safety and efficacy profile, SSRIs are commonly prescribed off-label–meaning for conditions outside their approved indications.

  • Off-label uses of SSRIs include migraine prevention, irritable bowel syndrome, premature ejaculation, paraphilias, and hot flashes.

In this article:

It’s common to need a prescription for depression. From 2015 to 2018, 13.2% of adults reported taking antidepressant medications within the past 30 days. Since Prozac (fluoxetine) was approved by the FDA in 1987, selective serotonin reuptake inhibitors (SSRIs) have been the most commonly prescribed antidepressants on the market. In addition to depression, healthcare providers also prescribe SSRIs for other mental health conditions. Examples include generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), panic disorder (PD), and post-traumatic stress disorder (PTSD). In fact, some SSRIs are approved to treat premenstrual syndrome and premenstrual dysphoric disorder (PMDD).

SSRIs are popular treatment options for a wide range of conditions due to their safety, tolerability, and efficacy profile. While many of these conditions are approved by the FDA, there is evidence that SSRIs can be useful for various conditions outside of their approved indications. This is called off-label prescribing, and SSRIs rank among the top use cases for off-label use. Pharmacists, in particular, should be familiar with off-label uses of SSRIs, as you may come across off-label prescriptions in everyday practice. Continue reading to learn more about off-label uses for SSRIs and how pharmacists can address off-label uses with their patients.

How SSRIs work

Serotonin is a neurotransmitter, or chemical messenger, that transmits messages throughout the brain. It circulates between neurons and then absorbs into the bloodstream. SSRIs work by blocking the reabsorption of serotonin into your blood, leaving a higher amount of serotonin in your brain. Higher serotonin levels are thought to have many effects, including improving mood, emotions, and sleep.

8 common off-label uses for SSRIs

Due to its favorable safety profile, healthcare providers commonly prescribe SSRIs for off-label uses. This means they prescribe the drug for a condition outside of its approved indications. This is common and legal in the United States, and many patients aren’t even aware that they are taking the drug off-label. These are some of the common off-label uses for SSRIs.

1. Migraine prevention

There is some research showing that low levels of serotonin may increase a patient’s risk of developing a migraine. For this reason, doctors may prescribe SSRIs for migraine prevention, according to the American Academy of Family Physicians. The most commonly prescribed SSRI for this use is fluoxetine 20–40 mg per day; however, studies of its efficacy have had inconsistent results. Therefore, its use isn’t supported or discouraged by the American Academy of Neurology and American Headache Society’s clinical guidelines for migraine prevention. Instead, the guidelines recommend certain antiepileptic drugs, beta blockers, or triptans for migraine prevention.

2. Body dysmorphic disorder (BDD)

Body dysmorphic disorder (BDD) is a mental health condition where a person is hyperfocused on one or more flaws in their appearance. This negatively impacts their social, academic, and occupational functioning. BDD is typically treated with cognitive behavioral therapy (CBT) and medications, such as SSRIs. However, according to the American Academy of Family Physicians, dosages of SSRIs may need to be higher than those typically used for eating disorders. SSRIs pharmacists may see prescribed for BDD include:

  • Luvox (fluvoxamine) 200-250 mg per day
  • Prozac (fluoxetine) 40-80 mg per day
  • Paxil (paroxetine) 40-60 mg per day
  • Zoloft (sertraline) 100-200 mg per day

3. Impulse-control disorder (ICD)

Impulse-control disorder (ICD) is another mental health condition characterized by the lack of ability to exercise self-control. People may experience sudden urges to do something that is outside societal norms. This can lead to social or occupational impairment and cause legal or financial troubles. Research shows serotonin may play a role in managing impulsive behavior, and fluoxetine at a dosage of 20-60 mg per day is one of the most commonly prescribed regimens for this condition. There has also been some research supporting the use of citalopram 20-60 mg per day for ICD.

4. Irritable bowel syndrome (IBS)

Irritable bowel disorder (IBS) is a gastrointestinal disorder that causes a wide range of symptoms, including abdominal pain, cramping, discomfort, bloating, diarrhea, or constipation. The underlying cause of IBS is unknown, and management is focused on relieving symptoms and minimizing triggers. One strategy for combating symptoms of IBS is managing underlying depression or stress. This is where antidepressants can come in. While tricyclic antidepressants (TCAs) are the most effective antidepressants, the data supporting the use of SSRIs for IBS is encouraging. SSRI agents used for IBS may include paroxetine 5-20 mg per day and fluoxetine 20 mg per day.

5. Diabetic neuropathy

Diabetic neuropathy—a type of nerve damage that develops over time—is a common complication of diabetes. It can affect the feet, legs, arms, and hands. Treatment focuses on managing the symptoms, and first-line treatments include Lyrica (pregabalin), Neurontin (gabapentin), Cymbalta (duloxetine), and Elavil (amitriptyline). If first-line treatments aren’t effective, other drugs, including SSRIs, may be considered. Examples include paroxetine at a dosage of 40 mg per day.

6. Premature ejaculation

Premature ejaculation is one of the most common sexual problems. Serotonin may play an important role in the ejaculatory reflex, and higher levels of serotonin can delay ejaculation. Therefore, certain SSRIs may be beneficial for premature ejaculation. These include paroxetine, fluoxetine, sertraline, fluvoxamine, citalopram, and escitalopram.

7. Paraphilias and hypersexuality

According to Current Neuropharmacology, there is important evidence supporting the use of SSRIs in the treatment of paraphilia and hypersexuality. Paraphilias are intense, recurrent sexual urges or fantasies involving atypical activities, whereas hypersexuality is sexual addiction. The utility of SSRIs in these conditions may be explained by their ability to weaken sexual drive and compulsive behaviors. Fluoxetine has shown the strongest evidence in both these conditions, but healthcare professionals may also prescribe sertraline in certain cases.

8. Hot flashes caused by menopause

Hot flashes are the most common symptom of menopause. While they are typically mild, hot flashes can negatively impact some women’s quality of life. Luckily, there is evidence supporting the use of SSRIs in the treatment of hot flashes in menopause. In a 2014 study, SSRIs showed modest improvement in the severity and frequency of hot flashes, with Lexapro (escitalopram) showing the greatest efficacy.

Counseling points for patients taking an SSRI

Regardless of whether an SSRI is being prescribed on- or off-label, pharmacists are in a key position to ensure the safety of patients taking SSRIs. Here are some important counseling points for SSRIs:

  • Risk of suicidal thoughts and behaviors. SSRIs have a boxed warning for the risk of suicidality. They can increase the risk of suicidal thoughts and behaviors in children and young adults. Any worsening in mood, thoughts, or behaviors should be reported to a healthcare provider as soon as possible.
  • Stopping treatment. Although SSRIs aren’t addictive, they can cause withdrawal symptoms if they’re stopped abruptly or if their dose is lowered too quickly. Patients should speak with their healthcare provider before stopping any SSRIs. Together, they can come up with a plan to lower their dosage gradually to avoid withdrawal symptoms.
  • Take exactly as prescribed. SSRIs can take some time to work. Even if patients don’t see results right away, they must continue taking the medication exactly as prescribed by their provider.
  • Drug interactions. SSRIs have many potential drug interactions, and these interactions can vary depending on the specific SSRI. Some interactions can increase the risk of serious side effects, while others can make drugs less effective. Before starting an SSRI, evaluate the patient’s full medication list for potential drug interactions.