Sometimes a doctor has to get creative. Off-label prescriptions, when used ethically and judiciously, can often help patients when other drugs fail. This article lists four unusual off-label drugs along with their effects and prescribing recommendations.

Once a drug is approved, 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 in the US.

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 a 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.

The authors wrote:

“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). 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.

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 the 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 story is contributed by Naveed Saleh and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.