Is There An Interaction Between Cymbalta And Amitriptyline?

Our pharmacist answers the latest question regarding an interaction between Cymbalta and amitriptyline.

Sep 29, 2017

Ownen asked

My doctor said it is okay to take cymbalta with the amitryptoline I am already taking but I read there could be bad interactions...is it safe?

Answer

There certainly is an interaction between Cymbalta and Amitriptyline due to their similar mechanism of action. Having said that, they are sometimes used in conjunction with one another.
Depending on the reference you look at, the interaction is considered moderate to major. Again, this is due to how both drugs work in the body and the neurotransmitters they affect.


Cymbalta (Duloxetine) is known as an SNRI (serotonin-norepinphrine reuptake inhibitor ) drug. It inhibits the reuptake of both serotonin (5-HT) and norepinephrine (NE). This means that it increases the concentration of both of those neurotransmitters in the body.


Amitriptyline (Elavil) has a broader mechanism but it ALSO reduces the reuptake of serotonin and norepinephrine.


The issue is that both of these drugs potentially could have additive effects increasing the risk of certain side effects, most notable serotonin syndrome and cardiac/blood pressure issues.


​Because of the potential risk and severity of serotonin syndrome, the general recommendation is that caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as amitriptyline. Serotonin syndrome is characterized by rapid development of hyperthermia, high blood pressure, rigidity, mental status changes (e.g., delirium or coma), and in rare cases, death. 


In addition to the increased risk of serotonin syndrome, since both drugs effect norepinephrine, that puts on a greater risk of high blood pressure and altered heart rhythm. 


Now, I did say that these drugs are sometimes used together and that is true. First of all, MOST people that take amitriptyline are on a dose that is usually used for insomnia or trouble sleeping. The dose for this is MUCH lower than the dose used for depression and thus it is thought that a lower dose isn't as likely to have an interaction. Amitriptyline ranges from 10mg to 100mg so a lower dose is advisable when combining with Cymbalta.


​Secondly, the dose of Cymbalta matters here too. Most evidence points that the ability of Cymbalta to affect norepinephrine reuptake appears to occur at doses at or above 60 mg/day. Doses around this range or lower are thought to have less of a chance of interaction.


It is always good to know about possible interactions so I am glad you asked about this. The chance of a serious side effects happening such as the ones I mentioned are is not likely but still is good to be aware about!

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