Can You Use a TCA With an SNRI? Case Review

A 66-year-old female has a past medical history of diabetes, neuropathy, depression, and hypertension. In this case scenario, I discuss the use of a TCA with an SNRI. Her current medication list includes:

  • Aspirin 81 mg daily
  • Capsaicin cream prn
  • Amitriptyline 10 mg at night
  • Metformin 500 mg BID
  • Losartan 50 mg daily
  • Glipizide 5 mg daily
  • Duloxetine 30 mg daily

One of the first questions I would have in this case review is why would the patient be on the (amitriptyline) TCA with an SNRI (duloxetine). I would dig into the patient history to try to figure out when and why these medications were added. I will say, that when I see TCA’s dosed at night, it is often (at least in part) due to their sedative adverse effect. TCA’s and SNRI’s both inhibit the reuptake of serotonin and norepinephrine, so we do run the risk of duplicate effects. In general, I would try to avoid the TCA with an SNRI combination and in this situation, we may be able to easily titrate up on one and off of the other (again, this does depend upon what indication we are trying to use each of the agents for). In a 66-year-old, I’m not thrilled about the use of a TCA due to their potential anticholinergic effects.

Other items I would review in this patient medication list:

  • It is hard to ignore the fact that capsaicin is being used on an as-needed basis. This medication needs some time to deplete substance P and provide pain relief, so PRN utilization will likely not provide the patient with any benefit.
  • I do notice that the patient is on a lower dose of metformin with their sulfonylurea. Important assessments in A1C, blood sugars, the risk for hypoglycemia, weight, and kidney function would need to be reviewed. Sulfonylureas are no longer considered an ideal agent in diabetes due to more options being available and their ability to cause hypoglycemia and weight gain. In this case, depending upon lab work, we may just be able to increase the metformin and do away with the sulfonylurea altogether.
  • This patient looks like they may be at some cardiovascular risk with their diabetes and hypertension history. I’d review the risk, past medical history, lab work and determine whether or not a statin would be appropriate.
  • Anything else you’d like to investigate further? Leave a comment below!

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  1. Rahma

    Hey Eric
    Using amitriptyline together with DULoxetine can increase the risk of a rare but serious condition called the serotonin syndrome

  2. Emad

    Patient sensetivity toward TCA and SNRI …this patient due to Diabetes and age factor are more likley to develop insomnea and pneuropathy ,adding TCA is wise choice because it deals with insomnea due to it’s sedative effect , and pain by it’s Anti pneuropathy effect.
    Duloxeting is good choice for noctural pain attack but it’s not well tolerated.

  3. kirk seale

    Amitriptyline can be used for Peripheral neuropathy although it is on the beers list and there are other alternatives that can be used in the elderly. According to the package insert: For Diabetic Peripheral Neuropathic Pain — the recommended dose for Cymbalta is 60 mg administered once daily. An increase in this dose is possible-if the patient can tolerate the increase in dose without any additional side effects. The increase in duloxetine may also help elevate her depression as well. With this increase in dose we could possible eliminate the amitriptyline altogether (IF amitriptyline is use for Diabetic Peripheral Neuropathic Pain) reducing her pill burden.

  4. Michael Parker, BS, PharmD, BCACP, CDCES

    Need renal function, UACR, & allergy/intolerance list in order to provide a safe recommendation regarding below items:

    1. Do not recommend concomitant use of TCA + SNRI regardless of indication. Agree with titrating duloxetine to 60 mg, but only if needed. Need to assess pain, current sleep quality/ sleep hygiene prior to finalizing recommendation.

    2. If renal function adequate (persistently > 44 mL/min), may consider d/c sulfonylurea and up-titrate metformin
    as tolerated up to max dose for renal function and specific formulation. Assess for GI ADE’s and change to XR formulation if needed. Sulfonylurea not ideal especially in elderly if able to avoid – due to risk of hypoglycemia (Hypoglycemia is a leading cause of hospitalization in elderly adults). If another agent is needed may consider SGLT2i or GLP-1RA based on cost, CV Risk, and (renal function for SGLT2i).

    3. Barring any contraindications patient absolutely needs to be on a statin (if they agree). Patients 40 or more years of age w/DM2 should be on a statin.


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Written By Eric Christianson

September 4, 2019

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