Lexapro (escitalopram) is my favorite selective serotonin reuptake inhibitor (SSRI). Alongside Zoloft (sertraline), Lexapro is one of the most prescribed antidepressants due to its efficacy, tolerability, and diversity.
Read also: Looking at Zoloft as a First-Line Agent in Psychiatry
Lexapro has few drug interactions and a simple dosing range, making it an easy addition to a patient’s medication regimen indicated for acute and chronic management of anxiety and depression. I consider its antidepressant effects as robust as Zoloft, with anxiolytic effects as effective as Paxil (paroxetine). The medication is FDA-approved for major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults, as well as MDD in adolescents ages 12 to 17 and GAD in pediatric patients ages 7 and older. Common off-label uses include panic disorder, social anxiety, OCD, PMDD, and PTSD. It is dosed 5–20 mg per day, with the majority of adults tolerating a starting dose of 10 mg daily. In patients age 65 years and older, the FDA recommends a max dose of 10 mg daily due to QT prolongation concerns.
Lexapro is metabolized by phase I metabolism through CYP2C19 and 3A4. The half-life is 27–32 hours. Avoiding CYP2D6 means fewer drug interactions than agents like Prozac and Paxil. The intermediate half-life makes discontinuation effects less problematic, which is an advantage over agents with shorter half-lives (like Paxil or Effexor). Common inducers of CYP2C19 that prescribers should be aware of include carbamazepine and primidone. If these agents are used concurrently with Lexapro, serum levels may be lower, meaning higher doses might be necessary.
Lexapro is my go-to medication to prescribe for anxiety because of its high SERT selectivity, resulting in more consistent serotonin reuptake. Compared to Zoloft, Lexapro has fewer dopaminergic and sigma-1 receptor effects, which is at least partially responsible for less activation in anxious patients. In my experience, Lexapro can be as calming as Paxil with fewer side effects—less pronounced sexual dysfunction and fewer issues with weight gain. However, unlike Paxil, Lexapro does not have anticholinergic activity. This is why I sometimes prescribe hydroxyzine as needed during Lexapro initiation. This isn’t typically necessary with Paxil but can be advantageous, as Lexapro doesn’t carry the same level of sedation.
Lexapro is the S-enantiomer of Celexa (citalopram) and received its first FDA approval in 2002, four years after Celexa. As the S-enantiomer of a racemic mixture, it is the more active half of the compound and provides stronger action on SERT, resulting in more potent serotonin reuptake inhibition, a lower dose range, and fewer side effects. While Lexapro can still cause QT prolongation, it has a better safety profile than Celexa, which has a low therapeutic index. It is widely considered one of the cleanest SSRIs, providing robust efficacy and optimal tolerability.
Lexapro, like all SSRIs except Paxil, is no longer officially classified under the pregnancy letter categories (these were phased out by the FDA in 2015 in favor of narrative labeling). That said, Lexapro is generally considered a reasonable option in pregnancy, whereas Paxil is not. I implore any provider treating anxiety in women of childbearing age to consider Lexapro before Paxil.
In 2005, the FDA changed Paxil’s pregnancy category from C to D due to first-trimester exposure being associated with an increased risk of congenital heart defects, particularly septal defects. The change followed a Danish population-based cohort study by Wogelius et al. (2006), which found a higher incidence of major congenital malformations in infants exposed to SSRIs during early pregnancy, with Paxil showing a disproportionately elevated risk. The exact mechanism remains unclear, but stronger SERT inhibition and potential impact on neural crest cell migration have been hypothesized. Some researchers have also proposed that the risk may be dose-dependent.
When I get women of childbearing age who are already on Paxil, I’m always looking for alternatives. I explain the risk and emphasize that while it may not be a concern right now, it’s something that’s better addressed proactively rather than reactively. Lexapro is often that alternative, and the 10–20 mg daily dosing range makes it easy to reach a therapeutic dose and optimize treatment.
I compare Lexapro vs. Paxil for anxiety as follows: Paxil may be more calming, but often not by as much as expected. Lexapro has fewer drug interactions, fewer side effects (including sexual dysfunction that often doesn’t abate with tolerance), a longer half-life with lower risk of discontinuation syndrome, and a decreased risk of weight gain.
While Lexapro remains my first choice for anxiety, its antidepressant effects are equally impressive. A meta-analysis of 30 studies in 2023 found that Lexapro was significantly more effective than Celexa in achieving both acute response and remission in the treatment of MDD. The ability to achieve this efficacy with a simple titration between 10 and 20 mg is appreciated by both patients and clinicians.
In my practice, it’s uncommon for me to encounter a patient who hasn’t already tried Lexapro. As with Zoloft, it’s often started in primary care, and when patients reach my clinic, they’ve either experienced a partial response or found the medication intolerable.
Pharmacogenomics can be helpful, especially in patients who haven’t tolerated Lexapro. While I have a love-hate relationship with genetic testing due to aggressive marketing, understanding how someone metabolizes medications via CYP enzymes—especially CYP2C19—can help in cases of multiple antidepressant failures. For example, poor metabolizers may experience increased side effects, while ultra-rapid metabolizers may see reduced efficacy.
The most common side effect from Lexapro is nausea. As a general rule, any serotonergic medication can cause nausea, especially during initiation. It’s usually transient and can often be reduced by taking the medication with food. Other common side effects include diaphoresis, somnolence, insomnia, sexual side effects, and headache. These are class effects, but Lexapro is consistently one of the most well-tolerated SSRIs. The risk for hyponatremia, particularly in the elderly, should not be overlooked. Bleeding risk, especially with concurrent NSAID use, is also important to monitor.
If sexual side effects such as erectile dysfunction occur, they can often be managed by prescribing a phosphodiesterase-5 inhibitor such as sildenafil (caution if the patient is also prescribed nitrates).
One risk all clinicians should be aware of is Lexapro’s potential to prolong the QT interval. Like Celexa, this is due to inhibition of cardiac potassium channels—specifically the hERG channel. The risk is dose-dependent, which is why the FDA recommends a maximum dose of 10 mg daily for patients age 65 and older. Unlike Celexa, Lexapro does not carry a black box warning for QT prolongation, but it remains something to keep in mind when managing geriatric or cardiac patients.
In overdose, Lexapro—like all SSRIs—loses its selectivity. It was one of two SSRIs (the other being Celexa) we were trained to warn emergency departments could be associated with seizures. I can tell you firsthand that seizures in Lexapro overdoses were rare, whereas most patients who overdosed on Celexa had seizures. Due to sodium channel blockade in overdose, there’s also potential for QRS widening. Providers in emergency settings were always advised to obtain a baseline EKG and repeat one before medically clearing patients who had overdosed on Lexapro.
Overdose treatment for Lexapro is symptomatic and supportive. As was the case with most exposures, the question of whether to use activated charcoal often came up. The toxicologists at our poison center generally advised against it—most Lexapro ingestions only produced mild symptoms, and the risks of charcoal often outweighed the benefits. To be effective, charcoal needs to be given within two hours, the patient must be able to drink it, and they can’t be nauseated or vomiting. Those conditions were rarely met, and if aspirated, charcoal could turn a relatively benign ingestion into a life-threatening emergency.
Serotonin syndrome in Lexapro mono-overdose is rare but not impossible. Clinicians should use the Hunter Serotonin Toxicity Criteria and watch for clonus and hyperreflexia, especially in the lower extremities. Most serotonin syndrome cases I’ve seen involved serotonergic co-ingestants.
All in all, Lexapro stands out as first-line in the management of GAD and MDD and offers reliable coverage for patients with anxious depression. Its dosing is straightforward, though dosing is limited in geriatric populations. For patients with anxiety, depression, or both, Lexapro should be among the first SSRIs considered.
This post was written by Richard Gray, PMHNP-BC. The above information is for educational/entertainment purposes and is not intended to be treated as medical advice. If you have questions about a medication you are taking, discuss these questions with your medical provider