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Khan, 2018, Serotonin Syndrome Presenting with Concominant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side Effect


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Cureus Journal of Medical Science. 2018 Apr; 10(4): e2421. Published online 2018 Apr 4. doi: 10.7759/cureus.2421
Serotonin Syndrome Presenting with Concomitant Use of Tramadol and Diphenhydramine: A Case Report of an Unlikely Side Effect
Abstract: Serotonin syndrome is a condition that occurs following the administration of serotonergic drugs. Interestingly, on rare occasions, it can occur with various drug combinations that can secondarily affect the serum levels of 5‐hydroxytryptamin. Tramadol is an analgesic that has mu opioid receptor agonist activity and has also been shown to inhibit the reuptake of serotonin and noradrenaline. Diphenhydramine is a first-generation histamine antagonist prescribed to treat or prevent allergic reactions and can also be used as a sleeping aid. Here, we demonstrate a case of serotonin syndrome following the administration of diphenhydramine for seasonal allergies in a patient on tramadol for neck pain.
Interestingly, it is thought that tramadol’s analgesic effect is due to the inhibition of serotonin and norepinephrine reuptake in the CNS [2] and the risk of causing serotonin syndrome is currently well-recognized. 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.

Current Dose

0.5mcg Clonidine and 1.25 Diazepam PRN for treatment of iatrogenic hypertension. 

2010 .Prescribed Pristiq 100 mg in July by GP

2010 .Reduced to 50mg by splitting and weighing. Held at 50mg

2014. Reduced from 50-35 .Held at 35mg. 

2017. Taper from 35mg commenced using compounded Desvenlafaxine

2018. 23/06 13.5mg. 21/07  12.5mg. 25/08 11.5mg. 09/2018 10mg. 14/11 11mg (updose) 21/11 -12mg (updose)

2019. Still holding at 12mg and stuck. 

2020. January 2019 Prozac Bridge-- Prozac 2.5 to 10mg and

Pristiq 23rd Jan 6mg/ 27th Jan 5mg/ 28th Jan 3mg/ 30 Jan 0

Prozac 6th Feb 9.5mg. Vitamin D3 5000iu with K2

Magnesium Glycinate with Glycine and Passionflower  600mg 

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