Is fatigue a common side effect of Lexapro (escitalopram) in patients with generalized anxiety disorder?

From the Guidelines

Fatigue and tiredness are common side effects of Lexapro (escitalopram), especially during the first few weeks of treatment, affecting a significant portion of patients, as reported in studies such as 1. For patients experiencing persistent fatigue on Lexapro, several alternative medications may be considered.

• Wellbutrin (bupropion) is often a good alternative as it tends to be more energizing and less sedating than SSRIs like Lexapro.
• Other options include Pristiq (desvenlafaxine), Effexor (venlafaxine), or Trintellix (vortioxetine), which may cause less fatigue for some patients. Before switching medications, consider discussing with your doctor about adjusting the timing of your Lexapro dose to bedtime if currently taking it in the morning, as this may help minimize daytime fatigue. Additionally, your doctor might recommend a gradual dose reduction of Lexapro while starting the new medication to minimize withdrawal effects, as discontinuation syndrome has been reported with SSRIs, including symptoms like dizziness, fatigue, lethargy, and general malaise, as noted in 2. The fatigue occurs because SSRIs like Lexapro affect serotonin levels, which can influence sleep-wake cycles and energy regulation. Some patients adjust to these side effects over time (typically 4-8 weeks), so if the medication is otherwise effective for anxiety, it may be worth waiting a bit longer to see if the fatigue improves. It's also important to note that medical education, training, and experience are necessary to safely and effectively prescribe antidepressant medications, and a conservative medication trial for mild to moderate anxiety presentations may entail increasing the dose as tolerated within the therapeutic dosage range, as suggested in 2.

From the FDA Drug Label

Among the 429 GAD patients who received Escitalopram 10-20 mg/day in placebo-controlled trials, 8% discontinued treatment due to an adverse event, as compared to 4% of 427 patients receiving placebo Adverse events that were associated with the discontinuation of at least 1% of patients treated with Escitalopram, and for which the rate was at least twice the placebo rate, were nausea (2%), insomnia (1%), and fatigue (1%) The most commonly observed adverse reactions in Escitalopram patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were nausea, ejaculation disorder (primarily ejaculatory delay), insomnia, fatigue, decreased libido, and anorgasmia TABLE 3 enumerates the incidence, rounded to the nearest percent of treatment-emergent adverse events that occurred among 429 GAD patients who received Escitalopram 10 to 20 mg/day in placebo-controlled trials Events included are those occurring in 2% or more of patients treated with Escitalopram and for which the incidence in patients treated with Escitalopram was greater than the incidence in placebo-treated patients... Fatigue 8%

Fatigue is a common adverse reaction associated with Escitalopram, with an incidence of 8% in patients with Generalized Anxiety Disorder, and 1% of patients discontinued treatment due to fatigue 3. There is no information in the provided drug labels about alternative medicines for patients experiencing fatigue while taking Escitalopram.

From the Research

Fatigue and Tiredness with Lexapro

• Fatigue and tiredness are common side effects of many antidepressants, including Lexapro (escitalopram) 4, 5.
• Studies have shown that escitalopram can cause fatigue and somnolence in some patients, although the exact mechanisms are not fully understood 4.
• The incidence of fatigue and tiredness with Lexapro may be dose-dependent, with higher doses potentially leading to increased side effects 6, 7.

Alternative Medications

• If a patient is experiencing fatigue and tiredness with Lexapro, alternative medications may be considered, such as:
  • Vortioxetine, which has been shown to have a similar efficacy to escitalopram but with a different side effect profile 8.
  • Sertraline, which has been shown to have a lower incidence of fatigue and somnolence compared to some other antidepressants 5.
  • Fluoxetine, which has been shown to have a similar efficacy to escitalopram but with a different side effect profile 5, 7.

Dose Equivalents

• When switching between antidepressants, it is essential to consider the dose equivalents to ensure that the patient receives an equivalent therapeutic dose 7.
• The dose equivalents of antidepressants can vary depending on the specific medication and the individual patient's response 7.
• Studies have established dose equivalents for various antidepressants, including escitalopram, sertraline, and fluoxetine 7.