Does trazodone cause hypokalemia? (3+ side effects)

In this article, we will discuss whether trazodone causes hypokalemia. We will also discuss the conditions in which trazodone can cause hypokalemia, what research shows, and some of the common side effects of trazodone. 

Does trazodone cause hypokalemia? 

Trazodone does not cause hypokalemia in therapeutic doses. Hypokalemia is not an officially documented side effect of trazodone. Evidence does not report the incidence of hypokalemia in patients taking therapeutic doses of trazodone. 

Hypokalemia refers to low potassium levels in the body. It may be caused by some medications or changes in the body. However, it is not a reported side effect of trazodone. 

Trazodone is a serotonin antagonist and reuptake inhibitor (SARI), an antidepressant. It is FDA-approved to treat major depressive disorders (MDD). Off-label it can be used for sleep disturbances due to its sedating effects (1). 

Only reports of hypokalemia associated with trazodone are present with trazodone overdose. Thus, if you exceed the maximum dose of trazodone, you can experience hypokalemia. In therapeutic doses, hypokalemia is not a reported side effect. 

What does research suggest? 

Research indicates that hypokalemia is not a frequently reported symptom of trazodone. Low potassium levels are observed in patients who overdose on trazodone (2,3). 

In one case report, a patient overdosed on trazodone with the intention of suicide. Several symptoms were observed along with hypokalemia. He was given oral potassium chloride to restore his potassium levels (2). 

In another case of severe trazodone overdose, a patient developed QT prolongation and ventricular tachycardia. Her lab results demonstrated significant hypokalemia and her potassium level was 2.7mmol/L (3). 

Research shows that trazodone can cause QT prolongation and arrhythmia. QT prolongation is a common manifestation of hypokalemia. However, trazodone’s effect on QT intervals is due to its interaction with hERG potassium channels (1). 

Trazodone blocks the hERG potassium channels which disrupts the normal cardiac repolarization process. Thus, QT prolongation caused by trazodone is not associated with hypokalemia (1). 

Research suggests that due to the risk of QT prolongation, patients with risk factors of arrhythmias should not take trazodone. One risk factor for arrhythmia is hypokalemia.

Thus, evidence suggests that trazodone does not cause hypokalemia in therapeutic doses. It can cause QT prolongation through other mechanisms and should not be taken by patients with low potassium levels. 

How to identify if trazodone is affecting your potassium levels? 

If you are concerned that trazodone might interfere with your potassium levels you can monitor your symptoms. The normal range of potassium is 3.5-5.0 mmol/L. A level below 3.5mmol/L indicates hypokalemia, resulting in symptoms like (4):

• muscle weakness
• muscle cramps
• numbness
• tiredness
• constipation

Serum potassium levels of more than 5.0 mmol/L indicate hyperkalemia which can cause symptoms like: 

• nausea
• vomiting
• diarrhoea
• abdominal pain 
• heart palpitations

Clinical symptoms of low or high potassium levels do not appear until the changes are severe. Experiencing these symptoms does not always indicate a disturbance in potassium levels. 

If you experience some persistent and severe symptoms, your healthcare provider may evaluate your electrolyte levels. Based on the results, your healthcare provider may consider a dose reduction or switch to an alternative medication. 

How to take trazodone properly to avoid hypokalemia? 

Trazodone-associated hypokalemia occurs in the case of overdose. To optimize the effects of medication and avoid overdosing, you should take trazodone exactly as prescribed by your healthcare provider. 

You should take trazodone after a meal or a light snack to avoid lightheadedness. Do not take this medication if you are taking a monoamine oxidase inhibitor (MAOI) (1). Do not take trazodone if you have a history of cardiac arrhythmia.

Trazodone should be avoided by patients who have conditions like hypokalemia, hypomagnesemia, and symptomatic bradycardia. It should not be used with drugs that can cause QT prolongation (5).

Trazodone should be used cautiously with other serotonergic agents due to the risk of serotonin syndrome which can cause electrolyte imbalance (5).

How does trazodone affect other electrolytes? 

Trazodone’s effect on potassium levels is not a documented or frequently reported side effect. However, trazodone can affect other electrolytes in the body like sodium (5). 

Trazodone can cause hyponatremia (low sodium levels) in some individuals due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This results in increased water retention by kidneys diluting the sodium levels in the body (5). 

Symptoms of hyponatremia include (5):

• confusion
• headache
• weakness
• memory impairment
• unsteadiness

What are the common side effects of trazodone?

Some common side effects of trazodone that are not associated with altered potassium levels in the body include (1,5):

• headache
• dry mouth
• dizziness
• Qt prolongation
• fatigue
• orthostatic hypotension
• decreased concentration
• diarrhea
• nausea
• vomiting
• acid reflux
• nightmares

In my perspective, trazodone does not cause hypokalemia in therapeutic doses. Research indicates that the incidence of hypokalemia is reported in the case of trazodone overdose.

QT prolongation is a side effect of trazodone which is commonly associated with hypokalemia. However, trazodone causes QT prolongation by interacting with hERG potassium channels and not by hypokalemia.

Due to the risk of QT prolongation, trazodone should not be taken by patients who have hypokalemia or a history of arrhythmia. Trazodone can affect other electrolytes like sodium and cause hyponatremia due to SIADH. 

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