What are the effects of long-term Escitalopram (Citalopram's active enantiomer, an Selective Serotonin Reuptake Inhibitor (SSRI)) use?

From the Guidelines

Escitalopram can be safely used long-term for many patients who benefit from it, with typical maintenance dosing ranging from 10-20mg daily and treatment often continuing for at least 6-12 months after symptom resolution to prevent relapse. For adults with depression or anxiety disorders, long-term use of escitalopram may be necessary, especially for those with recurrent depression (three or more episodes) or chronic anxiety disorders. Some key points to consider when using escitalopram long-term include:

• Side effects that may persist with long-term use, such as sexual dysfunction, emotional blunting, weight changes, and sleep disturbances 1
• The importance of regular monitoring, with follow-up appointments every 3-6 months to assess ongoing need, effectiveness, and side effects
• The need to avoid abrupt discontinuation, as this can cause discontinuation syndrome; instead, a gradual taper over 2-4 weeks or longer is recommended 1
• The potential for drug interactions, particularly with other serotonergic agents, and the need for caution when starting or stopping escitalopram in patients taking other medications 1
• The favorable side effect profile and once-daily dosing of escitalopram, which make it suitable for extended treatment when clinically indicated 1

It's also important to note that escitalopram, like other SSRIs, may be associated with an increased risk of nonfatal suicide attempts, particularly in younger patients 1. However, the most recent and highest-quality study, published in 2020, provides guidance on the safe use of escitalopram and other SSRIs in children and adolescents with anxiety disorders 1. Overall, the benefits of long-term escitalopram use in patients with depression or anxiety disorders often outweigh the risks, but careful monitoring and management are necessary to minimize adverse effects and ensure optimal treatment outcomes.

From the FDA Drug Label

Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Use of SSRIs, including Escitalopram tablets, may cause symptoms of sexual dysfunction [see Adverse Reactions(6. 1)]. In subjects with hepatic impairment, clearance of racemic citalopram was decreased and plasma concentrations were increased Because escitalopram is extensively metabolized, excretion of unchanged drug in urine is a minor route of elimination. Until adequate numbers of patients with severe renal impairment have been evaluated during chronic treatment with Escitalopram, however, it should be used with caution in such patients [see Dosage and Administration (2.3)].

The effects of long-term Escitalopram use may include:

• Gastrointestinal bleeding: associated with the use of SSRIs
• Sexual dysfunction: including ejaculatory delay or failure, decreased libido, and erectile dysfunction in male patients, and decreased libido and delayed or absent orgasm in female patients
• Hepatic impairment: decreased clearance and increased plasma concentrations
• Renal impairment: use with caution due to limited evaluation of patients with severe renal impairment during chronic treatment 2

From the Research

Effects of Long-Term Escitalopram Use

• Long-term escitalopram treatment has been shown to be safe and efficacious in the treatment of major depressive disorder (MDD) 3, 4, 5.
• Studies have demonstrated that escitalopram reduces relapse rate compared with placebo and increases the percentage of patients in remission in long-term trials (up to 52 weeks) 3.
• The overall withdrawal rate due to adverse events in long-term escitalopram treatment was 9% 4.
• Common adverse events associated with long-term escitalopram use include headache, back pain, upper respiratory tract infection, rhinitis, and nausea, with an incidence ranging from 11% to 17% 4.
• No new types of adverse events were seen after the acute period of 8 weeks, and the incidence declined with time 4.

Efficacy of Long-Term Escitalopram Treatment

• Escitalopram has been shown to be effective in preventing depression recurrence in patients who responded to acute SSRI therapy 5.
• Time to recurrence was significantly longer in patients who received maintenance treatment with escitalopram compared with patients switched to placebo (hazard ratio = 0.26,95% CI = 0.13 to 0.52, p < .001) 5.
• Long-term escitalopram treatment was well tolerated, with a favorable safety and tolerability profile over 12-months treatment 4.

Comparison with Other Antidepressants

• Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (OR 0.67,95% CI 0.50 to 0.87) and remission (OR 0.53,95% CI 0.30 to 0.93) 6.
• Escitalopram was also more effective than citalopram in terms of efficacy, and had a better acceptability profile compared to duloxetine 6.
• However, there is insufficient evidence to detect a difference between escitalopram and other antidepressants in early response to treatment (after two weeks of treatment) 6.