10 bizarre off-label drug uses

1. Diphenhydramine

Diphenhydramine is used to treat symptoms of allergies and colds, among other things, and is often used off-label to help with sleep. This is not surprising, since older antihistamines are known for their sedative effects. Diphenhydramine is one of the most prescribed medications in the United States, and is also available over-the-counter.

Diphenhydramine is not available as such in Croatia, but it is available as dimenhydrinate (a salt of diphenhydramine and 8-chlorotheophylline). It’s that pill we all took as kids before field trips to keep ourselves from getting sick on the bus!

2. Propranolol

Propranolol is best known for its indications in the treatment and prevention of cardiovascular diseases and conditions.

It acts as a beta-receptor blocker, which is why it is also effective in suppressing the symptoms of stage fright. Since stage fright is actually caused by the action of an increase in adrenaline and noradrenaline, and propranolol blocks their receptors, symptoms such as tremors or dry mouth are quickly controlled by its use.

This is a peripheral, not a central effect, which explains its ineffectiveness in other anxiety disorders!

3. Propofol

Propofol is an intravenous general anesthetic with a characteristic milky appearance. In addition to being used before surgery, it is also used to treat status epilepticus (SE), a prolonged and dangerous epileptic seizure. SE is primarily treated with antiepileptic drugs such as phenytoin, levetiracetam, and valproate, but if the patient does not respond to therapy, propofol can be used.

4. Erythromycin

Erythromycin is a macrolide antibiotic related to our Croatian azithromycin! It is used to treat various bacterial infections, such as purulent angina, but can also be used to treat gastroparesis, a disorder of slow gastric emptying.

Erythromycin, completely unrelated to its antibiotic effect, acts as an agonist of motilin receptors that control gastric movements.

5. Estrogen

A trend has emerged on social media of using vaginal gels and creams with estrogen on the face for anti-aging effects! First of all, the differences in formulations for vaginal and dermal use can themselves be the cause of the drug’s ineffectiveness. Estrogen is otherwise used in hormone replacement therapy.

However, estrogen preparations for the skin have a theoretical basis in alleviating the signs of aging, but they are not supported by unequivocal clinical evidence.

6. Guaifenesin

Guaifenesin is an expectorant that thins mucus and makes it easier to cough up. It is available on the market in combination with paracetamol and phenylephrine to relieve cold and flu symptoms.

It is also thought to thin cervical mucus during ovulation, which would make it easier for sperm to enter the uterus and increase the likelihood of fertilization. Despite its popularity, there are no recent studies on its effectiveness.

7. Diltiazem

Diltiazem is a calcium channel blocker that is most often used in the treatment of angina pectoris and hypertension.

In the form of a topical cream, it can be used in the treatment of chronic anal fissures. Due to its mechanism of action, it relaxes the anal sphincter, thereby relieving pain and promoting fissure healing.

8. Zolpidem

Zolpidem belongs to the group of Z-drugs, hypnotics related to benzodiazepines. It is used for the short-term treatment of insomnia in adults, and ironically, it can be used to induce awakening from coma. This paradoxical effect occurs in only 5% of cases, but due to the low risk of application, it is one of the possible therapeutic options for the patient.

9. GnRH agonists

Gonadotropin-releasing factor (GnRH) agonists suppress the production of sex hormones by continuously stimulating and desensitizing the pituitary gland. These drugs are primarily used to treat hormone-dependent prostate and breast cancers.

Because they block the production of sex hormones, they are used to reversibly stop puberty and the development of unwanted sexual characteristics in transgender adolescents. They are effective and support the mental health of patients, but more extensive safety studies are needed because of other metabolic roles of sex hormones.

10. Prazosin

Prazosin is an alpha-blocker used to treat hypertension and benign prostatic hyperplasia (enlarged prostate). By blocking adrenergic receptors, it relaxes the smooth muscles of blood vessels and lowers blood pressure, but due to its short duration of action in our country, it has been withdrawn from the market and replaced by newer analogues.

It is used off-label to reduce nightmares associated with PTSD! It is considered that there is an advantage compared to a placebo, so it is an important therapeutic option, especially in the prevention of suicide.

Translated by: Mirta Maršić