Does Cymbalta cause hyponatremia? (3+ factors)

In this article, we will answer the question “Does Cymbalta cause hyponatremia?”. We will discuss the mechanism behind Cymbalta-induced hyponatremia, what research findings have to say in this regard and what factors contribute to hyponatremia while on Cymbalta. We will also discuss how to avoid or manage hyponatremia while taking Cymbalta.

Does Cymbalta cause hyponatremia?

Yes, Cymbalta tends to cause hyponatremia in some individuals undergoing therapy with this medication. Not all patients experience this side effect while using Cymbalta.

Cymbalta is the brand name for an antidepressant Duloxetine. This medication belongs to the class of serotonin and norepinephrine reuptake inhibitors (SNRIs) and is approved by the FDA for the treatment of depressive illnesses, fibromyalgia, and neuropathic or musculoskeletal pain (1).

Cymbalta can cause side effects like nausea, diarrhoea, dry mouth, decreased appetite, hyponatremia, increased sweating, constipation, somnolence, fatigue, suicidal ideation, hepatotoxicity, changes in blood pressure, tremors, abnormal bleeding, seizures, activation of mania and urinary retention (1).

Hyponatremia is a condition where the sodium levels within the body become low (below 135mEq/L). Sodium is an electrolyte which is needed by the body for many processes like balancing water volume and bodily fluids (2).

Hyponatremia can cause anorexia, nausea, fatigue, vomiting, headache, muscle cramps, agitation, restlessness, altered mental status, seizures and coma (2).

How does Cymbalta cause hyponatremia?

Cymbalta can decrease the levels of sodium in the body by acting on the antidiuretic hormone (ADH). Cymbalta causes inappropriate secretion of ADH which can lead to hyponatremia. The medical terminology for this phenomenon is the syndrome of inappropriate antidiuretic hormone (SIADH)(2).

Cymbalta inhibits serotonin reuptake and increases dopamine secretion. It also increases the secretion of ADH in the posterior pituitary gland. ADH is responsible for the retention of water (3).

As the water excretion through the kidneys is decreased more water starts circulating in the bloodstream. Increased levels of water cause an imbalance in the water and ADH levels, leading to hyponatremia. This phenomenon is termed as SIADH (3).

Keep in mind that not all individuals have the same physiology and the effects of Cymbalta may vary from person to person. So, not all patients receiving Cymbalta treatment experience this side effect. However, if you do have symptoms of hyponatremia you should immediately contact your healthcare provider. 

What does research suggest?

Many research studies have been published reporting the side effects of low sodium levels or hyponatremia in individuals taking Cymbalta. Most cases observed are of elderly patients.

A case study about a 92-year-old elderly patient was published. She was prescribed Duloxetine for her lower back pain. She complained of headaches after starting duloxetine therapy and was found to have hyponatremia when evaluated. Discontinuation of Duloxetine resolved the Duloxetine-induced SIADH symptoms (3).

Another case study of an 86-year-old woman was reported in which the patient developed hyponatremia after using Duloxetine for 6 days. She had also been using thiazide diuretics. Both medications were found responsible for the symptoms (4).

A case of a 38-year-old female was also found to be related to hyponatremia due to Duloxetine therapy. She complained of discomfort and lethargy. Duloxetine had been started a few days back and on examination, was found to be the culprit of decreased levels of sodium and the related uncomfortable symptoms (5).

A case of Duloxetine-induced hyponatremia was reported when a 78-year-old male was examined for the symptoms of delirium, lethargy and poor orientation. Laboratory examination confirmed the occurrence of hyponatremia. This side effect was seen after only two 60mg doses of the medication. Removing Duloxetine from his regimen improved his symptoms (6).

A 76-year-old diabetic woman was started on Duloxetine for neuropathic pain. A week after taking Duloxetine she presented to the emergency department with vomiting, headache, confusion and disorientation. Lab findings showed hyponatremia. Duloxetine was discontinued and symptoms of SIADH were treated (7).

A case study of a 68-year-old patient reported the occurrence of SIADH one month after treatment with Duloxetine. He was prescribed this medication for the management of the symptoms of major depressive disorder (MDD). Discontinuing Duloxetine improved the presenting complaints of dizziness, nausea, malaise and poor appetite (8).

A case study of Duloxetine and Diltiazem overdose in an elderly woman also reported the occurrence of hyponatremia. The patient was prescribed Duloxetine for the treatment of depression. Hyponatremia was attributed to the overdose of Duloxetine (9).

What factors contribute to hyponatremia while on Cymbalta?

The following risk factors can contribute to hyponatremia while on Cymbalta therapy:

Age

The majority of the cases of hyponatremia due to Cymbalta have been reported in elderly patients taking therapy. The cause of increased prevalence among the elderly population is not yet known. A perceived reason can be the decline in renal function as the individual ages.

Lifestyle factors

An unhealthy lifestyle, excessive hydration or dehydration and use of alcohol can increase the risk of hyponatremia while the individual is taking Cymbalta.

Underlying medical conditions

Medical conditions that can affect fluid levels of the body like diarrhoea, vomiting, and heart or kidney diseases can cause hyponatremia while on Cymbalta.

Concomitant medications

Diuretics and anti-inflammatory medications can increase the risk of hyponatremia if used concurrently with Cymbalta.

How to avoid Cymbalta-induced hyponatremia?

The following precautions can be taken to avoid Cymbalta-induced hyponatremia:

  • Monitor blood sodium levels regularly.
  • Inform your healthcare provider about any medications you are taking that may affect sodium levels.
  • Avoid excessive hydration.
  • Do not abruptly discontinue medication.
  • Seek treatment for any underlying condition that can exacerbate hyponatremia.
  • Avoid excessive sweating during exercises and high-intensity workouts.

How to manage hyponatremia while taking Cymbalta?

The following tips and strategies can be used to manage hyponatremia while taking Cymbalta:

  • Take fluids with electrolytes to help maintain the balance of sodium and water.
  • Reduce the intake of electrolyte-free water or plain water as this can increase hyponatremia.
  • Dietary modifications to include high-sodium diets like salted snacks and pickles are a good option to keep the sodium levels balanced.
  • Regularly monitor and record your sodium levels and consult your healthcare provider if you notice any changes.
  • If needed your healthcare provider will prescribe intravenous fluids like normal saline to increase sodium levels.
  • Your doctor may also prescribe symptom-specific medications that will help resolve the symptoms of hyponatremia like nausea and headaches.

If your symptoms do not improve then you may consult your healthcare provider and discuss alternative treatment options for your depressive illness. Some medications that can be alternated with Cymbalta are as follows:

  • Mianserin
  • Venlafaxine
  • Fluvoxamine
  • Mirtazapine

Although these medications may be considered as an alternative to Cymbalta they still tend to cause hyponatremia (Fluvoxamine and Citalopram). However, Mianserin is an atypical antidepressant not associated with side effects like hyponatremia.

If you feel any discomfort or unwanted side effects while taking Cymbalta you should discuss your concerns with your healthcare provider and request for the monitoring of electrolyte levels.

To the best of my knowledge, and according to FDA warnings and many published case studies it can be concluded that Cymbalta does cause low sodium levels or hyponatremia. Elderly individuals are at a much higher risk for hyponatremia with Cymbalta.

Many precautionary measures and techniques can be used to avoid or manage hyponatremia while taking Cymbalta. However, if the symptoms of Cymbalta-induced hyponatremia do not subside then it is advised to consult your healthcare provider about alternative treatment options.

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References

1.-

The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. CYMBALTA® (duloxetine hydrochloride) Delayed released capsules for oral use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022516lbl.pdf  1

2.-

Rondon H, Badireddy M. Hyponatremia. [Updated 2023 Jun 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470386/

3.-

Hamada T, Matsuki K, Kondou S, Furukawa S, Onji M. Duloxetine-induced syndrome of inappropriate secretion of antidiuretic hormone in a super-elderly patient. Internal Medicine. 2022 Apr 1;61(7):1099-103. https://ncbi.nlm.nih.gov/pmc/articles/PMC9038471/

4.-

Mori M, Koide T, Imanishi Y, Matsui Y, Matsuda T. Duloxetine-induced hyponatremia in an elderly patient treated with thiazide diuretics. Indian Journal of Pharmacology. 2014 Nov;46(6):657. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264087/

5.-

Kulkarni M. Duloxetine induced hyponatremia. Indian Journal of Nephrology. 2015 Jul 1;25(4):259. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495486/

6.-

Wang D, Lai J, Lu S, Huang M, Hu S, Xu Y. Rapid-onset hyponatremia and delirium following duloxetine treatment for postherpetic neuralgia: Case report and literature review. Medicine. 2018 Nov;97(46). https://journals.lww.com/md-journal/fulltext/2018/11160/rapid_onset_hyponatremia_and_delirium_following.34.aspx

7.-

Omer T, Seetho I. Low dose duloxetine and the risk of hyponatraemia. InEndocrine Abstracts 2018 May 8 (Vol. 56). Bioscientifica. https://www.endocrine-abstracts.org/ea/0056/ea0056p630

8.-

Sun CF, Chen YL, Li YH, Kumaraswamy M, Lo YC, Chen YT. Duloxetine-induced hyponatremia in an elderly male patient with treatment-refractory major depressive disorder. Case Reports in Psychiatry. 2019 May 13;2019. https://www.hindawi.com/journals/crips/2019/4109150/

9.-

Oliver WD, D’Angelo R, Gonzales J, Wilson T, Millstein LS. Acute severe hyponatremia induced by a duloxetine overdose in an elderly woman. Cureus. 2020 Sep 8;12(9). https://www.cureus.com/articles/35033-acute-severe-hyponatremia-induced-by-a-duloxetine-overdose-in-an-elderly-woman#!/

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