Diphenhydramine, a first-generation antihistamine that acts as an inverse agonist on the H1 receptor [3] may also inhibit the reuptake of serotonin. It is known that SSRIs like Fluoxetine are analogs of diphenhydramine [4]. Although weaker, diphenhydramine does retain some activity at the serotonin receptor.

Can antihistamines cause serotonin syndrome?

Serotonin syndrome is a reaction to commonly prescribed antidepressants, painkillers, antibiotics, antihistamines, anti-nausea medications, migraine medications, and some herbal supplements. It's more common in people who take one or more of these medications at the same time.

What medications decrease serotonin levels?

Inhibition of Serotonin Reuptake: Drugs that inhibit serotonin reuptake include chlorpheniramine; cyclobenzaprine; dextromethorphan (e.g., Robitussin DM); meperidine; methadone; pentazocine; sibutramine; SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine); St.