Have you heard of these head-turning off-label prescriptions?

By Naveed Saleh, MD, MS
Published September 1, 2021

Key Takeaways

Sometimes a doctor has to get creative. Off-label prescriptions, when used ethically and judiciously, can often help patients when other drugs fail.

Once the FDA approves a drug, physicians are permitted to prescribe it for unapproved uses. One common reason for off-label use is a lack of other approved drugs to treat a disease. A second reason could be the failure of other approved treatments. 

The issue of off-label drug use is a quagmire of ethical and legal issues, and there are many considerations for off-label prescribing. Yet, it’s a legal and common practice—indeed, 20% of prescriptions are written for conditions not approved by the FDA.

Off-label uses should always be discussed before initiation of treatment, and doctors should assure their patients that although the drug is being prescribed off-label, its use is medically appropriate for their case and aligns with their professional medical judgment.

Meanwhile, sometimes off-label uses are just plain unusual. Here are some examples.

Fluvoxamine for COVID-19

Fluvoxamine (Luvox) is a selective serotonin reuptake inhibitor (SSRI) typically used to treat depression and obsessive-compulsive disorder (OCD). Its use to prevent clinical deterioration in COVID-19 may seem unusual, but is supported by a recent study published in JAMA.

In the clinical trial, 152 COVID-19 patients with symptom onset within 7 days were treated with fluvoxamine or placebo. No patients taking fluvoxamine deteriorated, compared with 6 taking placebo (8.3%). 

The investigators noted that patients taking fluvoxamine had a lower risk of clinical deterioration over 15 days.

“A potential mechanism for immune modulation is σ-1 receptor (S1R) agonism. The S1R is an endoplasmic reticulum chaperone protein with various cellular functions, including regulation of cytokine production through its interaction with the endoplasmic reticulum stress sensor inositol-requiring enzyme 1α (IRE1),” the authors wrote.

“Previous studies have shown that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) with high affinity for the S1R, reduced damaging aspects of the inflammatory response during sepsis through the S1R-IRE1 pathway, and decreased shock in murine sepsis models. Fluvoxamine is a strong S1R agonist, is highly lipophilic, and has rapid intracellular uptake.”

Viagra for women

Phosphodiesterase type 5 (PDE5) inhibitors have long been used to treat erectile dysfunction in men. But, sildenafil (Viagra) is also sometimes used off-label to treat women with female sexual arousal disorder. Efficacy is mixed and there are potential adverse effects. According to the authors of a review published in Drug Design, Development and Therapy, clinicians are encouraged to take all factors into consideration before prescribing sildenafil and other PDE-5 inhibitors as a last option in women.

The authors postulated that sildenafil, when used by women, may work similarly to use in men.

“In smooth muscle cells, nitric oxide activates the guanylate cyclase enzyme which converts guanosine triphosphate into cyclic guanosine monophosphate. This molecule promotes the relaxation of the smooth muscle cells, causes vasodilatation, and increases blood flow in genital organs. The engorgement of penile corpora cavernosa in men and clitoris and labia minora in women are the main modifications of genital organs during sexual arousal,” they wrote.

“Furthermore, the ultrafiltration of plasma through capillary vaginal vessels contributes to vaginal lubrication. Phosphodiesterase type 5 (PDE5) inhibitors (eg, sildenafil, tadalafil, vardenafil) physiologically enhance the production of guanosine monophosphate from cyclic guanosine monophosphate, thus contrasting the above-mentioned effects. According to emerging data, PDE5 is expressed in vaginal, clitoral, and labial smooth muscles. Thus, PDE5 inhibitors could be used as an easily available medical treatment for genital FSADs,” they added.

To read more about the treatment of female sexual disorders, click here

Memantine for OCD

The FDA approved the use of memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, for the treatment of moderate to severe Alzheimer dementia.

According to the FDA, “Persistent activation of central nervous system N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer’s disease. Memantine is postulated to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer’s disease.”

OCD treatment is an unusual off-label use of this drug. According to the authors of a small study published in the Industrial Psychiatry Journal, research findings “strongly implicate disrupted neurotransmission of glutamate within the cortico-striato-thalamocortical circuitry in the pathogenesis of obsessive-compulsive disorder (OCD). Based on this, drugs modulating glutaminergic neurotransmission like Riluzole–a glutamatergic neurotransmission modulating agent and memantine are being used in treatment of OCD.”

In the study, 12 patients with long-standing, drug-refractory OCD were included in a 12-week open-label trial of fixed-dose memantine, with OCD symptoms and adverse effects observed. In total, eight of 12 participants exhibited clear benefits, with a 25% or more decrease in OCD symptoms and no adverse effects.

Topiramate for binge-eating disorder

This anticonvulsant is indicated for the treatment of epilepsy and migraine prophylaxis. It may also be a useful mood stabilizer and decrease impulsivity possibly due to antagonism of glutamatergic transmission at the level of the lateral hypothalamus. One side effect of this drug is weight loss. Taken together, these drug effects have made the off-label prescription of topiramate to treat obese patients with binge-eating disorder (BED) an attractive option.

Although questions remain, in a review published in Neuropsychiatric Disease and Treatment, the authors wrote that “topiramate appears to be a relatively safe and effective treatment for obese subjects with BED. The drug should probably be started at 25 mg/day and increased by 25 mg/day every 1 to 2 weeks, until reaching a dose of 150 to 200 mg/day. It could then be further increased up to a dose of 400 mg/day or more for selected patients in the absence of clinical response.”

Click here to read more about off-label prescribing on MDLinx

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