Is it safe to use citalopram (Selective Serotonin Reuptake Inhibitor - SSRI) and escitalopram (SSRI) together?

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Last updated: June 2, 2025View editorial policy

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From the Guidelines

No, it is not safe to use citalopram and escitalopram together, as this combination can lead to serotonin syndrome, a potentially life-threatening condition. These medications are very similar SSRIs - in fact, escitalopram (Lexapro) is essentially the active component of citalopram (Celexa) 1. Taking both medications simultaneously would effectively be like taking a much higher dose of the same drug, which significantly increases the risk of side effects and serious complications.

Risks Associated with Combination

The combination of citalopram and escitalopram increases the risk of:

  • Serotonin syndrome, characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and seizures
  • Other side effects like nausea, headache, insomnia, and QT interval prolongation, which can cause dangerous heart rhythm problems 1
  • Potential adverse effects in infants exposed to SSRIs via breast milk, including irritability and decreased feeding 1

Safe Alternative

If you're currently taking one of these medications and considering a change, you should work with your healthcare provider to safely taper off one medication before potentially starting the other, rather than taking both simultaneously. This approach can help minimize the risk of adverse effects and ensure a safe transition. According to a study published in the Journal of the American Academy of Child and Adolescent Psychiatry, medical education, training, and experience are necessary to safely and effectively prescribe antidepressant medications 1.

Key Considerations

When prescribing antidepressant medications, it's essential to consider the potential risks and benefits, as well as the individual patient's needs and medical history. A conservative medication trial for mild to moderate anxiety presentations may entail increasing the dose as tolerated within the therapeutic dosage range in the smallest available increments at approximately 1- to 2-week intervals when prescribing shorter half-life SSRIs, such as sertraline or citalopram 1. Additionally, the combination of SSRIs with other medications, such as monoamine oxidase inhibitors (MAOIs), is contraindicated due to the increased risk of serotonin syndrome 1.

From the FDA Drug Label

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Escitalopram, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). If concomitant use of Escitalopram with other serotonergic drugs including, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, amphetamine, and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases

The likelihood of serotonin syndrome in a patient on both citalopram and escitalopram is increased due to the concomitant use of two serotonergic drugs (SSRIs).

  • Key points:
    • Both citalopram and escitalopram are SSRIs, which can increase the risk of serotonin syndrome when used together.
    • The FDA drug label warns against the concomitant use of SSRIs and other serotonergic drugs due to the increased risk of serotonin syndrome.
    • Patients should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases.
    • Treatment with both drugs should be discontinued immediately if serotonin syndrome occurs, and supportive symptomatic treatment should be initiated 2, 2, 3.

From the Research

Serotonin Syndrome Risk

The risk of serotonin syndrome in a patient taking both citalopram and escitalopram is a significant concern.

  • Both citalopram and escitalopram are selective serotonin reuptake inhibitors (SSRIs) that increase serotonergic activity in the central nervous system (CNS) 4, 5.
  • The use of multiple SSRIs, such as citalopram and escitalopram, can increase the risk of serotonin syndrome due to the additive effect of these medications on serotonin levels 6.
  • Serotonin syndrome is a potentially fatal complication that can occur when there is an excessive accumulation of serotonin in the body 6.

Clinical Evidence

  • A case study reported a 24-year-old woman who developed serotonin syndrome after an increase in her escitalopram dose to 30 mg/day 4.
  • Another study found that the combination of bupropion and SSRIs can increase the risk of serotonin syndrome due to the inhibition of the cytochrome P450 2D6 pathway, which can lead to increased blood levels of SSRIs 6.
  • However, there is no direct evidence on the risk of serotonin syndrome associated with the concurrent use of citalopram and escitalopram.

Safety Considerations

  • The use of multiple SSRIs, such as citalopram and escitalopram, is not recommended due to the increased risk of serotonin syndrome 4, 5.
  • Clinicians should carefully evaluate the benefits and risks of using multiple SSRIs and monitor patients closely for signs of serotonin syndrome 5, 7.
  • Alternative treatment options, such as using a single SSRI or switching to a different class of antidepressants, should be considered to minimize the risk of serotonin syndrome 7, 8.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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