How to prevent serotonin syndrome from drug-drug interactions
Table 2
Drugs associated with serotonin syndrome
| Drugs that increase 5-HT release | Amphetamine, cocaine, MDMA (ecstasy), mirtazapine, phentermine, reserpine |
| Drugs that inhibit 5-HT reuptake | Amitriptyline, amphetamine, bupropion, Citalopram, clomipramine, cocaine, desipramine, dextromethorphan, doxepin, duloxetine, escitalopram, fentanyl, fluoxetine, fluvoxamine, Hypericum perforatum (St. John’s wort), imipramine, MDMA, meperidine, nefazodone, nortriptyline, paroxetine, protriptyline, sertraline, tramadol, trazodone, venlafaxine |
| Drugs that decrease 5-HT metabolism | Isocarboxazid, linezolid, phenelzine, selegiline, tranylcypromine |
| Drugs that are direct 5-HT agonists | Almotriptan, buspirone, dihydroergotamine, eletriptan, frovatriptan, LSD, naratriptan, rizatriptan, sumatriptan, zolmitriptan |
| Others | L-tryptophan, carbamazepine, carisoprodol, droperidol, levodopa, lithium, metoclopramide, pentazocine, phenylpropanolamine |
| 5-HT: serotonin; LSD: lysergic acid; MDMA: methylenedioxymethamphetamine | |
| Source: Reference 1 | |
Preventing serotonin syndrome
The warnings highlighted in drug interaction references or pharmacy databases often mean that clinicians have to evaluate whether the risk of combining medications outweighs the therapeutic benefits. It is unknown why some patients tolerate multiple agents potentiating 5-HT, and practitioners cannot predict when and in whom serotonin syndrome may occur. However, the following strategies may help minimize these risks:
Know which drugs are associated with serotonin syndrome. Concomitant use of these drugs and agents that inhibit metabolism of these drugs increases risk.
Know which drugs your patient is taking. Patients may see several prescribers, which makes it essential to ask what they are receiving from other practitioners. Also inquire about OTC and illicit drug use.
Check for interactions. If you are unfamiliar with a new drug or drug-drug combination, check multiple resources for potential interactions. The potential severity of an interaction and the detail in which interactions are described—such as class effects vs documented cases or studies—differs among drug interaction resources, which means a potential interaction may be “flagged” in 1 source but not another. Electronic resources such as Micromedex and Lexicomp often have detailed literature summaries and citations so clinicians can review primary literature that lead to the categorization of an interaction. Using multiple sources is helpful when trying to translate warnings in the context of a clinical scenario.
Weigh the risks and benefits. Prescribers know that not all treatments are benign, but not treating a condition also may be detrimental. Identify potential alternative pharmacologic or nonpharmacologic treatments when possible. Discuss the risks and benefits of drug therapy with patients.
Counsel your patients. Although it is not possible to predict who may experience serotonin syndrome, educate patients on what symptoms to look for. Instruct them to call their prescriber or pharmacist if they show symptoms that may be consistent with serotonin syndrome.
Related Resource
• MedWatch: The FDA Safety Information and Adverse Event Reporting Program. www.fda.gov/Safety/MedWatch.
Drug Brand Names
- Aripiprazole • Abilify
- Almotriptan • Axert
- Amitriptyline • Elavil
- Bupropion • Wellbutrin, Zyban
- Buspirone • BuSpar
- Carbamazepine • Carbatrol, Equetro, others
- Carisoprodol • Soma
- Citalopram • Celexa
- Desipramine • Norpramin
- Dihydroergotamine • Migranal
- Doxepin • Adapin, Silenor
- Droperidol • Inapsine
- Duloxetine • Cymbalta
- Eletriptan • Relpax
- Escitalopram • Lexapro
- Fentanyl • Sublimaze, others
- Fluoxetine • Prozac
- Fluvoxamine • Luvox
- Frovatriptan • Frova
- Imipramine • Tofranil
- Isocarboxazid • Marplan
- Levodopa • Dopar, Larodopa, others
- Linezolid • Zyvox
- Lithium • Eskalith, Lithobid
- Meperidine • Demerol
- Metoclopramide • Reglan, Metozol
- Mirtazapine • Remeron
- Naratriptan • Amerge
- Nefazodone • Serzone
- Nortriptyline • Aventyl, Pamelor
- Paroxetine • Paxil
- Pentazocine • Talwin
- Phenelzine • Nardil
- Phentermine • Fastin, Adipex-P
- Protriptyline • Vivactil
- Reserpine • Serpasil
- Rizatriptan • Maxalt
- Selegiline • Carbex, Eldepryl, others
- Sertraline • Zoloft
- Sumatriptan • Imitrex, Alsuma
- Tramadol • Ultram, Ultracet, others
- Tranylcypromine • Parnate
- Trazodone • Desyrel, Oleptro
- Venlafaxine • Effexor
- Zolmitriptan • Zomig
Disclosures
Dr. Jeffrey Bishop receives grant/research support from Ortho-McNeil-Janssen.
Dr. Danielle Bishop reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.
