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Lexapro (Escitalopram) vs Zoloft (Sertraline): Extensive Comparison

Lexapro (escitalopram) and Zoloft (sertraline) are medications of the selective-serotonin reuptake inhibitor (SSRI) classification utilized most commonly for the management of major depressive disorder (MDD).  Lexapro was co-developed by the pharmaceutical companies Lundbeck and Forest Laboratories (starting in 1997) and received U.S. FDA approval for medical use in 2002.

Zoloft was developed by the pharmaceutical company Pfizer Inc. in the 1980s, and received U.S. FDA approval for medical use in 1991.  Both Lexapro and Zoloft function by modulating concentrations of serotonin (5-HT) within the brain to generate antidepressant and anxiolytic effects.

Lexapro (Escitalopram) vs. Zoloft (Sertraline): Comparison Chart

Included below is a chart highlighting general attributes of Lexapro (escitalopram) and Zoloft (sertraline).  By scanning the chart, it should be easy to pinpoint the obvious similarities and differences between these medications.

 LexaproZoloft
IngredientEscitalopram oxalateSertraline hydrochloride
Drug classificationSSRI (Selective-Serotonin Reuptake Inhibitor)SSRI (Selective-Serotonin Reuptake Inhibitor)
Approved medical usesMajor depressive disorder (MDD).

Generalized anxiety disorder (GAD).
Major depressive disorder (MDD).

Obsessive-Compulsive Disorder (OCD).

Panic disorder.

Post-Traumatic Stress Disorder (PTSD).

Premenstrual Dysphoric Disorder (PMDD).

Social anxiety disorder.
Off-label usesSocial anxiety disorder.

Obsessive-compulsive disorder (OCD).

Panic disorder.

Premenstrual dysphoric disorder (PMDD).
Generalized anxiety disorder (GAD).

Premature ejaculation.

Vascular headaches.
Bioavailability~80% (oral)~44% (oral)
FormatsTablet.

Oral solution.
Tablet.

Oral solution.
DosagesTablet: 5 mg, 10 mg, 20 mg

Oral solution: 5 mg/5mL
Tablet: 25 mg, 50 mg, 100 mg

Oral solution: 20 mg/mL
DevelopersLundbeck & Forest Laboratories
Pfizer Inc.
Legal statusRx (Prescription)-only (U.S.)Rx (Prescription)-only (U.S.)
Mechanism of actionSelective-serotonin reuptake inhibitor.

Interacts with the serotonin transporter (SERT) to prevent reabsorption of serotonin into the presynaptic neuron.
Selective-serotonin reuptake inhibitor.

Interacts with the serotonin transporter (SERT) to prevent reabsorption of serotonin into the presynaptic neuron.

Additional (less significant) actions:
-Dopamine reuptake inhibitor
-Increases extracellular norepinephrine
-Sigma-1 receptor antagonist
Generic version (?)Yes.Yes.
Half-Life27 to 32 hours23 to 26 hours
Common side effectsInsomnia. Ejaculation disorder. Nausea. Sweating. Fatigue. Somnolence. Decreased libido. Anorgasmia.Nausea. Diarrhea (loose stool). Tremor. Dyspepsia. Decreased appetite. Hyperhidrosis. Ejaculation failure. Decreased libido.
Date approved20021991 (December)
Duration of effect24 hours24 hours
MetabolismHepatic: CYP2C19 (36%). CYP3A4 (34%). CYP2D6 (30%).Hepatic: CYP2B6. (Primary) CYP2D6. (Secondary)
Onset of action4 to 8 weeks (on average)4 to 8 weeks (on average)

Note: This chart may be subject to inaccuracies and/or outdated information.  If you ever have any specific questions about the attributes of Lexapro and/or Zoloft – it is recommended to contact a medical doctor or pharmacist.

Lexapro vs. Zoloft: What are the major differences?

Noteworthy differences between Lexapro and Zoloft include: official medical uses; off-label uses; bioavailability, metabolism specifics; elimination half-life; date of release; and incidence of specific side effects.  Though both Lexapro and Zoloft are officially approved to treat major depressive disorder (MDD), only Lexapro is medically indicated for the treatment of generalized anxiety disorder (GAD).

That said, unlike Lexapro, only Zoloft is medically indicated for the treatment of obsessive-compulsive disorder; panic disorder; post-traumatic stress disorder; premenstrual dysphoric disorder; and social anxiety disorder.  In brief, Zoloft is officially approved (by the U.S. FDA) to treat a greater number of medical conditions than Lexapro.

In addition to there being disparities in the official medical uses for Lexapro and Zoloft, there distinctive differences in respective off-label medical uses.  Lexapro is regularly prescribed off-label as a treatment for social anxiety disorder; obsessive-compulsive disorder; panic disorder; and premenstrual dysphoric disorder (all conditions for which Zoloft is FDA approved) – whereas Zoloft is prescribed off-label to treat generalized anxiety disorder; premature ejaculation; and vascular headaches.

The respective bioavailabilities for Lexapro and Zoloft are dissimilar at ~80% (Lexapro) and ~44% (Zoloft); indicating that a greater percentage of ingested Lexapro exerts a physiologic effect than Zoloft.  Both Lexapro and Zoloft are metabolized within the liver, however, Lexapro is metabolized by the enzymes CYP2C19, CYP2D6, and CYP3A4 – and Zoloft is metabolized by the enzymes CYP2B6 and CYP2D6.

Moreover, the respective elimination half-lives for Lexapro and Zoloft differ slightly at 27 to 32 hours (Lexapro) and 23 to 26 hours (Zoloft).  This indicates that Lexapro remains in the body for a longer duration (on average) after discontinuation than Zoloft.

As was already mentioned, Lexapro entered pharmaceutical circulation in 2002 and was co-developed by Lundbeck and Forest Laboratories – whereas Zoloft entered pharmaceutical circulation in 1991 and was developed by Pfizer, Inc.  Lexapro contains the chemical “escitalopram oxalate” and Zoloft contains the chemical “sertraline hydrochloride.”

Side effects associated with Lexapro and Zoloft are somewhat similar, however, it seems as though: Lexapro may be more likely to cause insomnia, fatigue, somnolence, and anorgasmia (than Zoloft) – and Zoloft may be more likely to cause diarrhea, tremor, dyspepsia, decreased appetite, and hyperhidrosis (than Lexapro).

Although there are clear differences in various attributes of Lexapro and Zoloft, there are also numerous similarities between these agents, including: onset and duration of action; clinical efficacy; mechanism of action; common side effects; discontinuation symptoms; legal status (U.S.); and cost.

Approved Medical Uses & Off-Label Uses

In the United States, Lexapro and Zoloft are each approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD).  Lexapro is also medically-approved for the treatment of generalized anxiety disorder (GAD) – but Zoloft is not.

Zoloft is also medically-approved for the treatment of obsessive-compulsive disorder (OCD); panic disorder; post-traumatic stress disorder (PTSD); premenstrual dysphoric disorder (PMDD); and social anxiety disorder (SAD) – but Lexapro is not.  In other words, Zoloft is officially indicated to treat a greater number of medical conditions (6) than Lexapro (2).

Both Lexapro and Zoloft are sometimes prescribed “off-label” to treat conditions for which they haven’t received official FDA approval.  Lexapro is used off-label as an intervention for: social anxiety disorder (SAD); obsessive-compulsive disorder (OCD); panic disorder; and premenstrual dysphoric disorder (PMDD) – all conditions for which Zoloft is FDA approved.

Zoloft is used off-label as an intervention for generalized anxiety disorder (GAD) – a condition for which Lexapro is FDA approved.  Shared off-label uses for Lexapro and Zoloft include: premature ejaculation and vascular headaches.  In summary, if considering both official (i.e. FDA-authorized) and unofficial (i.e. off-label) medical uses for Lexapro and Zoloft – there aren’t major differences.

Cost: What are the prices of Lexapro & Zoloft?

Lexapro and Zoloft are generally sold at similar prices in the following formats: generic tablet; generic oral solution; and brand name tabletThat said, the brand name oral solution of Lexapro is more expensive (per dose) than the brand name oral solution of Zoloft.

A 30-tablet supply escitalopram (generic Lexapro) costs between $8 and $49 (on average) – and a 30-tablet supply of sertraline tablets (generic Zoloft) costs between $7 and $22 (on average).  Although the top price point for a 30-tablet supply of escitalopram is ~$49 at select pharmacies – this pricing is atypical.

Lexapro cost

  • Escitalopram tablets (generic): $8 to $49 (30 tablets)
  • Escitalopram oral solution (generic): $67 to $116 (240 mL of 5 mg/5mL)
  • Lexapro tablets (brand name): $306 to $358 (30 tablets)
  • Lexapro oral solution (brand name): $500 to $538 (240 mL of 5 mg/5mL)

Zoloft cost

  • Sertraline tablets (generic): $7 to $22 (30 tablets)
  • Sertraline oral solution (generic): $26 to $57 (60 mL of 20 mg/mL)
  • Zoloft tablets (brand name): $299 to $325 (30 tablets)
  • Zoloft oral solution (brand name): $237 to $253 (60 mL of 20 mg/mL)

A majority of pharmacies sell a 30-tablet supply of escitalopram for less than $26 – which is analogous to the price of a 30-tablet supply of sertraline.  For this reason, we shouldn’t expect significant differences in monthly prescription costs among users of escitalopram and sertraline tablets.  (Also worth noting is that price for generic escitalopram and sertraline tablets is not dose-dependent; tablets are similarly-priced at all dosages).

Escitalopram oral solution (5 mg/5mL) costs between $67 and $116 for 240 mL – and sertraline oral solution (20 mg/mL) costs between $26 and $57 for 60 mL.  Based on this information, it seems as though escitalopram oral solution costs $1.40 to $2.42 (per 5 mg dose) and sertraline oral solution costs $0.87 to $1.90 (per 20 mg dose).

Although escitalopram oral solution tends to be more expensive (per dose) than sertraline oral solution, most consumers probably won’t consider average price differences for generic oral solutions to be financially significant.  A 30-tablet supply of brand name Lexapro can be attained for $306 to $308 (on average) – and a 30-tablet supply of brand name Zoloft can be attained for $299 to $325 (on average).

The pricing of brand name Lexapro is dose-dependent (such that higher doses cost more than lower doses) – whereas the pricing of brand name Zoloft is not dose-dependent.  In brand name oral solution formats, there are differences between Lexapro and Zoloft in their price per dose.

Brand name oral Lexapro solution (240 mL of 5 mg/5mL) sells for $500 to $538 (on average) – and brand name oral Zoloft solution (60 mL of 20 mg/mL) sells for $237 to $253 (on average).  This means that oral Lexapro solution is more expensive (at $10.42 to $11.21 per dose) than oral Zoloft solution (at $7.90 to $8.43 per dose).

In summary, there aren’t major differences in the respective costs of generic escitalopram and sertraline (tablet and oral solution) – nor major cost differences in brand name Lexapro and Zoloft tablets.  The only notable difference in price between Lexapro and Zoloft is that brand name oral Lexapro solution costs more per dose ($2.52 to $3.31) than oral Zoloft solution.

Note: The aforementioned prices for Lexapro and Zoloft will likely be subject to inaccuracies and/or future change.  Prices for these medications may also vary significantly among pharmacies.

Efficacy: Which medication is more effective?

There are no conclusive data to suggest that Lexapro and Zoloft differ in therapeutic efficacy for any particular medical condition.  The only medical condition for which Lexapro and Zoloft are mutually FDA-approved is major depressive disorder (MDD).

Major depressive disorder (MDD)

An 8-week randomized, placebo-controlled trial conducted by Alexopoulos et al. (2004) compared the respective efficacies of flexibly-dosed escitalopram and sertraline among patients with major depressive disorder.  Results of the trial revealed similar response rates of 60% (escitalopram) and 62% (sertraline) plus equal remission rates of 46% over the 8-week period – relative to a placebo (42% response, 27% remission).

This head-to-head comparison trial supports the idea that escitalopram (Lexapro) and sertraline (Zoloft) are of equal antidepressant efficacy.  A different 8-week randomized, double-blind, controlled trial conducted by Ventura et al. (2007) directly compared the efficacies of escitalopram (10 mg/day, fixed-dosing) to sertraline (50-200 mg/day, flexible-dosing) among patients with major depressive disorder.

Results of the trial revealed reductions of 19.1 (escitalopram users) and 18.4 (sertraline users) on the MADRS (Montgomery-Asberg Depression Rating Scale) relative to baseline – and response rates of ~75% for escitalopram users and ~70% for sertraline users.  This study suggests that magnitude of antidepressant efficacy and response rates do not significantly differ between escitalopram and sertraline.

Nonetheless, it’s necessary to underscore the fact that escitalopram dosing was “fixed” at 10 mg/day – whereas sertraline dosing was “flexible” (50-200 mg/day).  Because dosing for escitalopram was fixed (rather than flexible like the dosing for sertraline), it’s possible that this study may have underestimated escitalopram’s therapeutic efficacy.

In addition to head-to-head studies comparing escitalopram to sertraline, several meta-analyses have been conducted in which the efficacies of escitalopram and sertraline were compared.  For example, Kennedy et al. (2006) conducted a meta-analysis of randomized controlled trials to assess the efficacy of escitalopram relative to other SSRIs and venlafaxine XR.

A total of 2687 patients were included in the meta-analysis (1345 escitalopram users; 1102 users of other SSRIs; 240 venlafaxine XR users).  Results of this meta-analysis suggested that escitalopram was superior to other SSRIs in magnitude of antidepressant effect and response rates.

Although escitalopram was significantly more effective than pooled SSRIs, it’s impossible to know whether escitalopram was more effective than sertraline.  Although sertraline was included as one of the “other SSRIs” in the aforementioned meta-analysis, its individual efficacy may have been greater than the group with which its antidepressant efficacy was averaged.

For this reason, the aforementioned meta-analysis cannot be used to substantiate the idea that escitalopram is more effective than sertraline.  Kennedy et al. (2009) also conducted a follow-up meta-analysis in which the efficacy of escitalopram was compared to SSRIs (citalopram, fluoxetine, paroxetine, sertraline) and SNRIs (venlafaxine, duloxetine).

The follow-up meta-analysis included data from 16 randomized controlled trials encompassing 4,549 patients.  Similar to the previous meta-analysis, data indicated that escitalopram was significantly more efficacious in measures of antidepressant effect; response rates; and remission – relative to comparators (one of which was sertraline).

However, just as in the previous meta-analysis, this does not substantiate the idea that escitalopram is more effective than sertraline.  Individual SSRI comparisons did not find significant differences in antidepressant efficacy; response rates; or remission rates among escitalopram and sertraline users.

Another meta-analysis conducted by Cipriani et al. (2009) compared efficacy and tolerability of 12 new-generation, properly-dosed antidepressants, including escitalopram and sertraline.  In this meta-analysis, researchers reviewed 117 randomized controlled trials from 1991 through 2007, encompassing 25,928 adults receiving antidepressants for major depressive disorder.

Results of the meta-analysis revealed that escitalopram and sertraline were among the most effective and tolerable antidepressant options (along with mirtazapine and venlafaxine) in adults.  Neither medication differed from the other in effectiveness or tolerability, leading authors to conclude that escitalopram and sertraline are two of the best antidepressant options for adults with major depressive disorder.

Undurraga and Baldessarini (2012) conducted a meta-analytic review of placebo-controlled trials among patients with acute or unipolar major depressive episodes to compare the efficacies of individual antidepressants, including escitalopram and sertraline.  Data for the meta-analysis were extracted from 142 drug-placebo comparison studies published between 1980 and 2011.

Results indicated that relative response ratios for escitalopram and sertraline (relative to placebos) were exactly the same (1.33). This finding supports the idea that escitalopram and sertraline are equally efficacious treatments for major depressive disorder.

Ramsberg et al. (2012) conducted a meta-analysis in which the remission rates of 10 antidepressants (including escitalopram and sertraline) were compared.  Results suggested that escitalopram exhibited the best remission probability of 0.47 (after 8 to 12 weeks of treatment) of all antidepressants, whereas sertraline exhibited a remission probability of 0.4.

Reflecting upon all of the aforementioned head-to-head comparison studies (escitalopram vs. sertraline) and meta-analyses, there are statistically-insignificant trends from multiple studies suggesting that escitalopram may be slightly more effective than sertraline.  However, there are zero data substantiating the idea that Lexapro and Zoloft significantly differ in clinical efficacy (magnitude of effect; response rates; remission rates) for the treatment of major depressive disorder.

Generalized anxiety disorder (GAD)

Because Lexapro is FDA-approved as a treatment for generalized anxiety disorder (GAD) and Zoloft is not, it’s reasonable to regard Lexapro as a medically-favorable treatment choice (relative to Zoloft) for this condition on the basis of its FDA approval.  Nevertheless, just because Lexapro might be a medically-favorable treatment choice for generalized anxiety disorder relative to Zoloft (due to its FDA approval) does not mean that it is more effective.

There are a host of randomized controlled trials in which sertraline (Zoloft) appears effective for the treatment of generalized anxiety disorder.  For example, a double-blind, placebo-controlled trial by Rynn et al. (2001) discovered that sertraline (up to 50 mg/day) was effective in treating generalized anxiety disorder among pediatrics (ages 5 to 17) – as evidenced by reductions in anxiety measures (from baseline) over a 9-week period.

Additionally, a 12-week randomized controlled trial conducted by Allgulander et al. (2004) reported that sertraline (50-150 mg/day) was effective and well-tolerated in the treatment of generalized anxiety disorder (GAD) – as evidenced by changes in scores on the Hamilton Anxiety Rating Scale from baseline.  This trial included a sample of 370 patients with generalized anxiety disorder (182 received sertraline; 188 received a placebo).

Dahl et al. (2005) also conducted a 12-week study to assess the efficacy of sertraline relative to a placebo – on symptoms of psychic and somatic anxiety among 373 patients with moderate-to-severe generalized anxiety disorder.  In the study, 184 patients received sertraline (50 to 150 mg/day) and 189 patients received a placebo.

Results of the study suggested that sertraline (50 to 150 mg/day) was effective for the treatment of psychic and somatic anxiety among persons with moderate-to-severe generalized anxiety disorder.  The efficacy of sertraline in this study was evidenced by significantly greater reductions in Hamilton Anxiety Rating Scale scores among sertraline recipients – relative to placebo recipients.

A randomized, double-blind, placebo-controlled trial by Brawman-Mintzer et al. (2006) also sought to elucidate the effectiveness of sertraline for the treatment of generalized anxiety disorder.  This trial recruited 326 patients who were officially diagnosed with generalized anxiety disorder (in accordance with DSM criteria) and randomly assigned them to receive sertraline (50 to 200 mg/day) or a placebo – for a 10-week period.

Results indicated that sertraline recipients exhibited significant reductions in anxiety symptoms (on the Hamilton Anxiety Rating Scale) throughout treatment relative to the placebo recipients.  Authors of this trial concluded that there appears to be a role for sertraline in the treatment of generalized anxiety disorder.

A systematic review and meta-analysis by Baldwin et al. (2011) incorporating data from 27 randomized controlled trials (samples ranging from 46 to 1,849) published between 1980 and 2009 – compared the efficacies of SSRIs in the treatment of generalized anxiety disorder.  One subgroup analysis of UK treatments suggested that escitalopram was most likely to yield symptomatic remission (26.7%) compared to 4 other medications.

That said, there was no evidence in this meta-analysis to suggest that escitalopram was of superior efficacy to sertraline (or vice-versa) for the management of generalized anxiety disorder.  Considering that: (1) quality data supports the efficacy of Zoloft for the treatment of generalized anxiety disorder; (2) Lexapro is FDA-approved to treat generalized anxiety disorder; and (3) Lexapro and Zoloft exhibit similar mechanisms of action – it’s unreasonable to suspect significant differences in their therapeutic efficacies between Lexapro and Zoloft for the treatment of generalized anxiety disorder.

Obsessive-Compulsive Disorder (OCD)

Because Zoloft is FDA-approved as a treatment for obsessive-compulsive disorder (OCD) – and Lexapro is not, it’s reasonable to regard Zoloft as a medically-favorable treatment choice (relative to Lexapro) for this condition on the basis of its FDA approval.  Although Zoloft may be a medically-favorable treatment choice (relative to Lexapro) for obsessive-compulsive disorder – it’s unclear as to whether there are differences between these medications in efficacy among patients with OCD.

Numerous open-label and randomized controlled trials suggest that Lexapro may be an effective intervention for obsessive-compulsive disorder.  For example, a 24-week randomized, placebo-controlled, trial conducted by Stein et al. (2007) evaluated the efficacy of escitalopram relative to paroxetine (a medication that’s FDA-approved to treat OCD) and a placebo.

The trial randomly assigned participants to receive either: escitalopram 10 mg/day (116 patients); escitalopram 20 mg/day (116 participants); paroxetine 40 mg/day (119 participants); or a placebo (115 participants).  Results of the study suggested that escitalopram 20 mg/day was significantly more effective than a placebo on all primary and secondary measures – as well as remission.

Escitalopram 10 mg/day and paroxetine 40 mg/day were also efficacious (as evidenced by changes in primary OCD scale scores and various secondary measures).  Researchers reported that escitalopram at a dosage of 20 mg/day is associated with: an earlier onset of therapeutic action; higher response rates; higher remission rates; improved functioning; and superior tolerability – relative to paroxetine (a medication approved to treat OCD).

In light of this finding, authors stated that escitalopram should be regarded as a first-line treatment for obsessive-compulsive disorder (OCD).  That said, because Lexapro hasn’t been compared to Zoloft (an approved agent for OCD) for the treatment of OCD, it remains unknown as to whether there are significant differences in effectiveness between these medications among patients with OCD.

Panic Disorder

Considering that Zoloft is FDA-approved as a treatment for panic disorder – but Lexapro is not, it’s reasonable to regard Zoloft as a medically-favorable treatment choice (relative to Lexapro) for patients with panic disorder.  Though some might regard Zoloft as a medically-favorable treatment selection in panic disorder relative to Lexapro (on the basis of its FDA approval), it’s unknown as to whether these medications significantly differ in antipanic efficacy.

Nevertheless, data from well-designed studies support the use of escitalopram in panic disorder.  For example, a 10-week randomized, double-blind, placebo-controlled trial by Stahl and Gergel (2003) involving 366 participants (128 escitalopram recipients; 119 citalopram recipients; 119 placebo recipients) reported that escitalopram was effective for the treatment of panic disorder – as evidenced by significant reductions in the frequency of panic attacks and scores on the Panic and Agoraphobia scale.

No studies have directly compared the therapeutic efficacies of escitalopram and sertraline for the treatment of panic disorder.  Knowing that: (1) escitalopram appears effective for the treatment of panic disorder; (2) sertraline is approved as a treatment for panic disorder; and (3) escitalopram and sertraline exhibit similar mechanisms of action – there’s no reason to suspect that one agent is significantly and/or universally more effective than the other among patients with panic disorder.

Post-Traumatic Stress Disorder (PTSD)

Knowing that Zoloft is FDA-approved to treat post-traumatic stress disorder (PTSD) but Lexapro is not, it’s fair to regard Zoloft as a medically-favorable recommendation (relative to Lexapro) for the management of PTSD.  Although Zoloft may be a medically-preferred intervention (relative to Lexapro) for the treatment of PTSD (on the basis of its preexisting FDA approval for this condition), it’s unknown as to whether there are any significant differences in the respective efficacies of these medications for PTSD.

Very few studies have examined the effectiveness of Lexapro as a treatment for PTSD, however, data from these studies are unanimous in suggesting that Lexapro treatment reduces symptoms of PTSD.  For example, an open-label trial by Robert et al. (2006) administered escitalopram (10 mg/day for 4 weeks then 20 mg/day for 8 weeks) to 24 military veterans diagnosed with PTSD for a 12-week period.

Following the 12-week escitalopram treatment period, patients exhibited significant reductions in PTSD symptoms – as was evidenced by notable reductions in PTSD scale scores after the 12 weeks of escitalopram treatment versus pre-treatment (baseline).  Another trial supporting the usefulness of escitalopram for PTSD was conducted by Qi et al. (2017).

The trial by Qi et al. (2017) recruited 45 patients with PTSD and administered high-dose escitalopram for a 12-week period.  Results indicated significant improvement in PTSD symptoms from baseline – as was evidenced by substantial decreases in PTSD scale scores following 12 weeks of treatment versus pre-treatment (baseline).

Despite preliminary data indicating that Lexapro is useful in the treatment of PTSD, these data were derived from studies with (1) small sample sizes and (2) suboptimal designs (e.g. non-randomized, uncontrolled, non-blinded, etc.).  For this reason, unlike Zoloft, Lexapro cannot be clinically recommended as a first-line treatment for PTSD.

That said, there are no data suggesting that Zoloft is superior to Lexapro for the treatment of PTSD (or vice-versa).  Multiple large-scale, well-designed head-to-head comparison trials would be needed to determine whether one medication (Zoloft versus Lexapro) is more effective than the other as a treatment for PTSD.

Given similarities between Lexapro and Zoloft in: mechanism of action (SSRI); antidepressant efficacy; and anxiolytic efficacy, we probably shouldn’t expect one medication to be superior (relative to the other) in its magnitude of therapeutic effect or response rate – among persons with PTSD.

Premenstrual Dysphoric Disorder (PMDD)

The effectiveness of Zoloft for the treatment of premenstrual dysphoric disorder (PMDD) is substantiated by a plethora of well-designed studies (hence its FDA-approval to treat PMDD).  On the other hand, the therapeutic efficacy of Lexapro in premenstrual dysphoric disorder is less clear (than that of Zoloft) due to the fact that Lexapro hasn’t been subject to as much investigation as a treatment for PMDD.

Nevertheless, preliminary evidence from multiple studies supports the idea that Lexapro could be effective in the treatment of PMDD.  For example, a double-blind study by Freeman et al. (2005) documented significant improvements in PMDD symptoms (over 3 menstrual cycles) among 27 women – as a result of escitalopram (10-20 mg/day) administration in either the luteal phase or at symptom onset.

More specifically, PMDD symptoms were reduced by: ~51% in 13 women treated with escitalopram during the luteal phase and ~57% among 14 women treated with escitalopram at symptom onset.  It was concluded that escitalopram administration in either the luteal phase or at symptom onset appears to reduce symptoms of PMDD.

Additionally, a larger-scale, placebo-controlled trial by Eriksson et al. (2008) involving 151 women with PMDD reported that intermittent escitalopram (20 mg/day) treatment (during luteal phases) significantly reduced symptoms of PMDD over a 3-month period – relative to a placebo.

Because Lexapro is not FDA-approved to treat premenstrual dysphoric disorder, it’s reasonable to regard Zoloft as a clinically-favorable intervention (relative to Lexapro) for PMDD on the basis of its preexisting FDA approval.  That being said, just because Zoloft may be a clinically-favorable intervention for PMDD at the moment (due to its FDA approval) does not mean that it’s more effective in reducing PMDD symptoms.

No large-scale, well-designed studies have directly compared the respective efficacies of Zoloft and Lexapro in the treatment of PMDD – making it impossible to claim that one agent is more efficacious than the other among persons with PMDD.  Moreover, knowing that Zoloft and Lexapro exhibit similar mechanisms of action and efficacies in the treatment of depression and anxiety – there’s no strong reason to suspect that one medication (Zoloft vs. Lexapro) is more effective than the other in the treatment of PMDD.

Social Anxiety Disorder (SAD)

Because Zoloft is FDA-approved as a treatment for social anxiety disorder (SAD) – and Lexapro is not, it’s reasonable to suggest that Zoloft might be a medically-favorable treatment option (over Lexapro) among persons with social anxiety.  However, even though some might consider Zoloft a medically-favorable intervention relative to Lexapro (on the basis of its FDA approval), there are no data suggesting that its significantly more effective than Lexapro for managing symptoms of social anxiety disorder.

In fact, a systematic review and meta-analysis conducted by Hansen et al. (2008) concluded that a fair amount of evidence supports the effectiveness of escitalopram, sertraline, and other SSRIs for the treatment of social anxiety disorder.  Pooled data from 15 placebo-controlled trials suggest relative benefit (RB) of 1.3 for escitalopram and 1.8 for sertraline.

Based on results of the meta-analysis, researchers concluded that escitalopram, sertraline, and other SSRIs do not significantly differ from each other in effectiveness as treatments for social anxiety.  A more recent meta-analysis by Baldwin et al. (2016) incorporated data from 3 randomized controlled trials (encompassing 1,598 patients) in which escitalopram was administered for social anxiety disorder.

Results of the meta-analysis revealed that escitalopram (at doses of 5 mg, 10 mg, and 20 mg) appears significantly more effective than a placebo for the treatment of social anxiety disorder (SAD).  Knowing that: (1) there are strong data substantiating the efficacy of Lexapro for social anxiety disorder; (2) Zoloft is approved to treat social anxiety disorder; and (3) a meta-analysis concluded that neither (Lexapro and Zoloft) agent appears more effective than the other in treating social anxiety – there’s no reason to suspect that Lexapro and Zoloft differ in efficacy for this condition.

In summary, neither Zoloft nor Lexapro is significantly more effective than the other for the treatment of major depressive disorder (MDD).  For this reason, most medical doctors will regard Lexapro and Zoloft as being equally useful interventions for major depressive disorder (MDD).

Lexapro may be preferred as an intervention (over Zoloft) for the treatment of generalized anxiety disorder (GAD) due to the fact that Lexapro is FDA-approved to treat generalized anxiety disorder and Zoloft is not.  Zoloft may be preferred as an intervention (over Lexapro) for the treatment of obsessive-compulsive disorder (OCD); panic disorder; post-traumatic stress disorder (PTSD); premenstrual dysphoric disorder (PMDD); and social anxiety disorder (SAD) due to the fact that Zoloft is FDA-approved to treat these conditions and Lexapro is not.

Despite differences in clinical preferences for one medication over the other (on the basis of FDA approvals) – there are zero data supporting the idea that Lexapro and Zoloft differ in efficacy for any particular medical condition.  Considering the lack of data to suggest that one medication (Lexapro or Zoloft) is superior to the other for the treatment of any medical condition – plus the similar mechanisms of action exerted by each medication – many medical doctors regard Lexapro and Zoloft as interchangeable treatment options for neuropsychiatric disorders.

Although the medications may not differ (on average) in terms of efficacy or response rate – there’s often interindividual variation in responses to Lexapro and Zoloft.  Certain individuals will find Lexapro more effective than Zoloft for a specific neuropsychiatric condition – whereas others might find Zoloft more effective than Lexapro for a specific neuropsychiatric condition.

Another subset of individuals might report that Lexapro and Zoloft are equally effective (or ineffective) for a specific neuropsychiatric condition.  Factors such as: gene expression, neurochemistry, autonomic nervous system function, etc. – likely explain why some individuals respond better to one medication (Lexapro or Zoloft) versus the other.

Mechanism of action

The primary mechanism of action for Lexapro and Zoloft is similar in that each medication functions as a selective-serotonin reuptake inhibitor (SSRI).  More specifically, Lexapro and Zoloft penetrate the blood-brain barrier (BBB), bind to the serotonin transporter (SERT), and prevent the serotonin transporter from facilitating serotonin reabsorption into presynaptic neurons.

Preventing the presynaptic reabsorption of serotonin (via interacting with the serotonin transporter) causes serotonin to accumulate within the synaptic cleft (i.e. the space between presynaptic and postsynaptic receptors).  Accumulation of serotonin within the synaptic cleft (as a result of Lexapro or Zoloft-mediated reuptake inhibition) inevitably leads to greater stimulation of postsynaptic receptors by serotonin – relative to one’s biological norm.

Enhanced postsynaptic serotonergic stimulation (i.e. signaling) occurs rapidly following Lexapro or Zoloft ingestion – and is generally accompanied by significant alterations in neural connectivity.  Rapid modulation of serotonergic neurotransmission and neural connectivity by these medications may be reason as to why a subset of users will experience improvements in neuropsychiatric symptoms (e.g. depression, anxiety, etc.) on the first day of treatment.

Additionally, with ongoing administration (4 to 8 weeks), Lexapro and Zoloft are understood to: (1) downregulate 5-HT1A receptor activity (which further bolsters serotonergic signaling) and (2) increase BDNF (brain-derived neurotrophic factor) (which promotes hippocampal neurogenesis).  These mechanisms (5-HT1A receptor downregulation and hippocampal neurogenesis) – may explain why many users don’t experience improvements in neuropsychiatric symptoms (e.g. depression, anxiety, etc.) for 4 to 8 weeks after treatment initiation.

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Although the general mechanism of action exhibited by Lexapro and Zoloft is identical (selective-serotonin reuptake inhibition), there are subtle pharmacodynamic differences between the medications.  Lexapro is more selective than Zoloft (and all other SSRIs) in its affinity for the serotonin transporter and does not extensively interact with secondary neurochemical targets.

In fact, testing by Owens et al. (2001) revealed that Lexapro exhibits little or no binding affinity for more than 100 receptor or binding sites tested in-vitro including: alpha-adrenergic, muscarinic, and histamine receptors.  Zoloft is less selective than Lexapro in its affinity for the serotonin transporter and interacts with secondary neurochemical targets such as: the dopamine transporter (DAT); alpha-1 adrenergic receptors; and sigma-1 receptors.

If administered at high doses, Zoloft functions as an SDRI (serotonin-dopamine reuptake inhibitor) such that it simultaneously increases serotonin and increases dopamine in the extracellular space by inhibiting presynaptic reuptake.  Subtle differences in pharmacodynamics between Lexapro and Zoloft could be reason as to why some individuals derive greater benefit with one medication than the other.

Metabolism & Half-Life

The respective routes of metabolism and elimination half-lives for Lexapro and Zoloft differ.  Lexapro is metabolized in humans within the liver by 3 cytochrome P450 (CYP450) enzymes, including: CYP2C19 (36%); CYP3A4 (34%); and CYP2D6 (30%).

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The aforementioned enzymes facilitate biotransformation of Lexapro via N-demethylation to form metabolites: S-demthylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT).  The bioavailability of orally-administered Lexapro is approximately 80%, its elimination half-life falls within the range of 27 to 32 hours, and the elimination half-life of its S-DDCT metabolite is ~100 hours.

Based on its elimination half-life, we can estimate that Lexapro will remain in systemic circulation for around 6.18 to 7.33 days (on average) following discontinuation.  Like Lexapro, Zoloft is metabolized within the liver, however, the specific enzymes implicated in its metabolism differ.

Zoloft is primarily metabolized by the CYP2B6 enzyme, and to a lesser extent, is metabolized by CYP2C19, CYP2C9, CYP3A4, and CYP2D6 enzymes.  The aforementioned enzymes facilitate biotransformation of Zoloft via N-demethylation to form the bioactive metabolite N-desmethylsertraline (i.e. norsertraline) – followed by N-hydroxylation, oxidative deamination, and glucuronidation.

The bioavailability of orally-administered Zoloft is approximately 44%, its elimination half-life falls within the range of 23 to 26 hours, and the elimination half-life of its primary metabolite (norsertraline) is ~66 hours.  With this information, we can estimate that Zoloft remains in systemic circulation for ~5.27 to ~5.95 days (on average) following treatment cessation.

Popularity

Zoloft was first introduced to the United States pharmaceutical market in December 1991 – and Lexapro was first introduced to the United States pharmaceutical market in 2002.  From 1991 to 2002, Zoloft was more popular than Lexapro by default – as Lexapro was not yet available.

After Lexapro hit the pharmaceutical market in 2002, it remains unknown as to how many years its popularity may have exceeded that of Zoloft – as extensive prescribing data are not publicly available.  According IMS Health, a company that documented prescribing rates of psychiatric medications in 2005, 2009, 2011, and 2013, prescriptions for Lexapro only exceeded prescriptions for Zoloft throughout 2009.

In 2005, 2011, and 2013, more prescriptions were filled for Zoloft than Lexapro – making Zoloft the more popular option.  Furthermore, the IMS Health report from 2013 documented ~41.4 million prescriptions being filled for generic Zoloft (sertraline) – and ~24.9 million prescriptions being filled for generic Lexapro (escitalopram).

More specifically, Zoloft was the most-prescribed antidepressant (and second most-prescribed psychiatric medication behind Xanax) of 2013, whereas Lexapro was the fifth most-prescribed antidepressant of 2013.  Thereafter, a report from ClinCalc DrugStats Database revealed that ~38.8 million prescriptions were filled for generic Zoloft (sertraline hydrochloride) in 2015 and ~24 million prescriptions were filled for generic Lexapro (escitalopram oxalate) in 2015.

Considering that over 14.8 million more prescriptions were filled for generic Zoloft (sertraline hydrochloride) than generic Lexapro (escitalopram oxalate) in 2015 – it’s reasonable to suspect that Zoloft remains more popular than Lexapro.  There are a host of reasons as to why Zoloft is likely more popular than Lexapro (with regard to number of prescriptions filled per year).

Potential explanations for greater popularity of Zoloft relative to Lexapro include: (1) the FDA-approval of Zoloft to treat 6 medical conditions (versus 2 conditions for Lexapro); (2) the similarity of Lexapro and Celexa in chemical structure and action – such that medical doctors may occasionally prescribe Celexa instead of Lexapro (which decreases Lexapro prescription numbers); and/or (3) the introduction of Zoloft in 1991 (~11 years before Lexapro) – possibly resulting in acquisition of more users over time.

Side effects

The most common Lexapro side effects (according to FDA Access Data) include: insomnia, ejaculation disorder, nausea, sweating, fatigue, somnolence (i.e. sleepiness), decreased libido, and anorgasmia.  The most common Zoloft side effects (according to FDA Access Data) include: nausea, diarrhea, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido.

Reflecting upon the most common side effects for Lexapro and Zoloft (according to FDA Access Data), it seems as though both medications are likely to cause side effects of: nausea, low libido, ejaculation dysfunction, and sweating.  Similarities in the common side effects of Lexapro and Zoloft are likely attributable to their identical primary mechanism of action as a selective-serotonin reuptake inhibitor.

However, differences in common side effects of Lexapro and Zoloft might be attributable to disparities in secondary neurochemical actions and/or pharmacokinetics.  Based upon FDA Access Data, Lexapro may be more likely than Zoloft to cause side effects of: insomnia, fatigue, somnolence, and anorgasmia.

Additionally, Zoloft may be more likely than Lexapro to cause side effects of: diarrhea, tremor, dyspepsia, and decreased appetite.  According to a review by Cipriani et al. (2009), newer-generation antidepressants (including Lexapro and Zoloft) exhibit similar tolerability profiles and cause similar adverse effects including: diarrhea, dizziness, dry mouth, fatigue, headache, nausea, sexual dysfunction, sweating, tremor, and weight gain.

Another systematic review by Cipriani et al. (2010) incorporating data from 117 randomized controlled trials (including 25,928 participants) stated that Lexapro (escitalopram) and Zoloft (sertraline) were superior to all other antidepressants in tolerability.  The aforementioned review rated Lexapro as having the highest probability of tolerability (~27.6%) and Zoloft as having the second-highest probability of tolerability (~21.3%).

Though Lexapro and Zoloft don’t appear to significantly differ from each other in tolerability, the probability of Lexapro tolerability exceeds the probability of Zoloft tolerability.  The reason Lexapro may have a slightly greater probability of tolerability (than Zoloft) is related to its highly selective action wherein Lexapro interacts extensively with the serotonin transporter but does not modulate secondary neurochemical targets.

A paper by Culpepper (2002) noted that switching patients to Lexapro (10-20 mg) due to adverse events from Zoloft, Prozac, Paxil, or Celexa – resulted in fewer side effects (relative to their prior medication).  Furthermore, a meta-analysis by Serretti and Chiesa (2009) revealed higher rates of treatment-emergent sexual dysfunction among Zoloft users (~80%) than Lexapro users (~40%).

According to Sanchez et al. (2014), Zoloft has moderate drug interaction issues in comparison to Lexapro.  Lexapro is less likely to cause pharmacokinetic interactions than most other SSRIs due to the fact that: (1) it is metabolized in relatively even quantities by 3 distinct hepatic enzymes and (2) it is only 55% bound to plasma proteins.

Everything considered, Lexapro and Zoloft are two of the most tolerable SSRIs on the market.  That said, the selectivity of and route of metabolism for Lexapro might make it slightly more tolerable than Zoloft.

Withdrawal

Lexapro and Zoloft are both known to cause withdrawal symptoms following treatment cessation.  For many individuals, especially long-term and/or high-dose users, withdrawal symptoms from Lexapro and Zoloft can be severe and may interfere with one’s ability to function in social, familial, and/or occupational settings.

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Furthermore, withdrawal symptoms from Lexapro and Zoloft can persist for weeks or months after the date of treatment cessation such that many individuals report enduring post-acute withdrawal syndrome (PAWS).  Examples of common withdrawal symptoms associated with Lexapro and Zoloft include: rebound anxiety; rebound depression; dizziness; fatigue; “brain zaps”; nausea; headache; and insomnia.

Withdrawal symptoms from Lexapro and Zoloft are understood to occur as a result of imbalanced neurophysiologic activity while transitioning from an SSRI-adapted state to homeostasis (i.e. drug-free functioning).  If either Lexapro or Zoloft is administered regularly (i.e. daily) for weeks, months, or years – a user’s neurophysiology becomes adapted to its presence.

Hypothesized adaptations to SSRIs like Lexapro and Zoloft include: downregulation of 5-HT1A autoreceptors; downregulation of endogenous serotonin production; desensitization of presynaptic 5-HT1A receptors; altered activation of secondary chemical messengers (e.g. cyclic-AMP); and altered gene expression.  Once the aforementioned adaptations have occurred, medications (Lexapro or Zoloft) become necessary to maintain neurochemical stability.

When treatment with Lexapro or Zoloft ends, the treatment-induced neurophysiologic adaptations remain and neurophysiologic activity becomes chaotic (or imbalanced) without the presence of medication.  As a result of imbalanced neurophysiologic activity after discontinuation, former Lexapro and Zoloft users experience withdrawal symptoms.

Over time, a former user’s neurophysiology will transition back to pre-medication functioning, however, this transition may require a significant amount of time (e.g. weeks or months).  Only when neurophysiology has fully transitioned back to pre-medication functioning will discontinuation symptoms subside.

Although Lexapro and Zoloft can cause harsh discontinuation symptoms, a comparative meta-analysis by Cipriani et al. (2009) reported that Lexapro and Zoloft cause significantly fewer withdrawal symptoms than Cymbalta, Luvox, Paxil, Reboxetine, and Effexor.  That said, there may be subtle differences in onset, severity, and/or duration of withdrawal between Lexapro and Zoloft due to: slight differences in elimination half-life and pharmacodynamics.

Lexapro has a slightly longer elimination half-life (27 to 32 hours) than Zoloft (23 to 26 hours), meaning it remains in systemic circulation for a longer duration after cessation (relative to Zoloft).  Specifically, escitalopram will exit the body in 6.18 to 7.33 days (on average) whereas sertraline will exit the body in 5.27 to 5.95 days (on average) – post-cessation.

However, a bioactive metabolite of Zoloft known as “norsertraline” (i.e. desmethylsertraline) has an elimination half-life of ~66 hours – meaning it may take over 15 days to fully eliminate Zoloft metabolites from systemic circulation – post-cessation.  Additionally, a bioactive metabolite of Lexapro known as “didemethylcitalopram” has an elimination half-life of ~100 hours – meaning it may take up to 23 days to fully eliminate Lexapro metabolites from systemic circulation – post-cessation.

Because Lexapro and its didemethylcitalopram metabolite exhibit longer elimination half-lives than Zoloft and its norsertraline metabolite, this might make Lexapro withdrawal slightly easier (for some individuals) than Zoloft withdrawal – assuming all else is equal (dosing, duration of use, taper speed, etc.).  In general, a longer elimination half-life gives the former user’s physiology more time to adjust itself to functioning with lower concentrations of the medication before its eliminated from the body – enabling smoother neurophysiologic recalibration back to homeostasis.

Additionally, the selective pharmacodynamics of Lexapro might make its withdrawal more bearable than those associated with Zoloft.  Lexapro strictly modulates serotonergic transmission, whereas Zoloft modulates serotonergic transmission and [to a lesser extent]: dopaminergic, noradrenergic, and opioidergic transmission.

Standalone modulation of serotonergic transmission will likely produce fewer compensatory neurophysiologic reactions than the simultaneous modulation of serotonergic, dopaminergic, noradrenergic, and opioidergic transmission.  As a result, former Lexapro users may end up with less substantial neurochemical abnormalities in withdrawal (relative to Zoloft users) – and might experience a more manageable withdrawal.

According to medical literature, there aren’t significant differences between Lexapro and Zoloft in withdrawal symptoms or severities.  Research suggests that both medications may be easier to discontinue (on average) than Cymbalta, Effexor, Luvox, Paxil, and Reboxetine.  Nevertheless, in theory, Lexapro might be slightly easier to discontinue than Zoloft (on average) due to its longer half-life and selective pharmacodynamics.

Similarities (Overview): Lexapro vs. Zoloft

Included below is an overview of general similarities between Lexapro and Zoloft.  Notable similarities between Lexapro and Zoloft include: average cost; drug classification; duration of action; effectiveness; legal status; mechanism of action; side effects; and withdrawal symptoms.

  • Average cost: There aren’t significant differences in the average cost of Lexapro and Zoloft. A 30-day supply of generic Lexapro tablets usually retails for $8 to $26 – and a 30-day supply of generic Zoloft tablets usually retails for $7 to $22.  A 30-day supply of brand name Lexapro tablets usually sells for $306 to $358 – and a 30-day supply of brand name Zoloft tablets usually sells for $299 to $325.
  • Drug classification: Lexapro and Zoloft are both classified as selective-serotonin reuptake inhibitors (SSRIs). As selective-serotonin reuptake inhibitors, each medication enhances extracellular concentrations of the neurotransmitter “serotonin” (5-HT) throughout the brain.
  • Duration of effect: The duration of effect for a standard single dose of Lexapro and Zoloft is identical (approximately 24 hours).
  • Efficacy: There are no strong data to suggest that Lexapro and Zoloft differ in therapeutic efficacy for the treatment of major depressive disorder (MDD) – and other neuropsychiatric conditions (e.g. generalized anxiety disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder, premenstrual dysphoric disorder, etc.).
  • Formatting: Both Lexapro and Zoloft are manufactured in 2 formats including: tablet and oral solution. The tablets of each medication are sold in 3 dosing increments and the oral solutions are sold in 1 dosing increment.
  • Generic availability: Lexapro and Zoloft are each available in generic formats (tablet and oral solution). The generic name for Lexapro is “Escitalopram oxalate” and the generic name for Zoloft is “Sertraline hydrochloride.”
  • Legal status: In the United States, both Lexapro and Zoloft are legally-classified as prescription-only (Rx-only) medications. This legal classification indicates that each medication can only be attained with a valid prescription from a licensed medical doctor.
  • Medical uses: Lexapro and Zoloft are both commonly utilized medically for the management of major depressive disorder (MDD) and various anxiety disorders. Although the medications differ in official FDA-approved uses, many psychiatrists consider them interchangeable options in the management of: generalized anxiety disorder; social anxiety disorder; panic disorder; OCD; PTSD; and PMDD.
  • Onset of action: There are no differences in the respective onsets of action for Lexapro and Zoloft. In some cases, the medications will “kick in” rapidly after administration (due to the enhancement of serotonin signaling), however, many persons won’t derive therapeutic benefit from Lexapro or Zoloft for 4 to 8 weeks after treatment initiation.
  • Potential for abuse: Most users won’t derive any sort of immediate euphoriant effect following the administration of Lexapro or Zoloft.  For this reason, the likelihood that patients will abuse and/or develop an addiction to these agents is extremely low. Neither Lexapro nor Zoloft is known to carry a clinically-relevant potential for addiction or abuse.
  • Primary mechanism of action: The primary mechanism of action for both Lexapro and Zoloft is identical – and involves inhibiting the presynaptic reuptake of serotonin by interacting with the serotonin transporter (SERT). This primary action increases extracellular serotonin levels and stimulates postsynaptic receptors to attenuate symptoms of depression, anxiety, and other neuropsychiatric conditions.
  • Side effects: The side effect profiles of Lexapro and Zoloft are relatively similar – likely due to the fact that their primary mechanism of action (as a selective-serotonin reuptake inhibitor) is identical. Common side effects that occur in at least 5% of persons who use these medications include: diarrhea, dizziness, dry mouth, fatigue, headache, nausea, sexual dysfunction, sweating, tremor, and weight gain.
  • Withdrawal: In general, there are no clinically-significant differences in the specifics, severities, and/or durations of withdrawal symptoms – among Lexapro and Zoloft users. Both medications can cause severe and/or protracted symptoms following treatment cessation (especially among high-dose and/or long-term users).

Note: If you know of additional similarities between Lexapro and Zoloft, report them in the comments section.

Differences (Overview): Lexapro vs. Zoloft

Included below is an overview of general differences between Lexapro and Zoloft.  Notable differences between Lexapro and Zoloft include: secondary neurochemical actions; routes of metabolism; elimination half-life; popularity; and FDA-approved uses.

  • Bioavailability: The oral bioavailability of Lexapro is estimated to be ~80% which is significantly different than the estimated ~44% oral bioavailability of Zoloft. Differences in bioavailability reveal that a greater percentage of ingested Lexapro (~36%) exerts a physiologic effect – relative to Zoloft.
  • Developers: Lexapro was originally developed in collaboration by the pharmaceutical companies Lundbeck and Forest Laboratories. Zoloft was originally developed by the pharmaceutical company Pfizer, Inc.
  • Elimination half-life: The elimination-half lives for Lexapro and Zoloft, respectively, differ slightly. The average elimination half-life range for Lexapro is 27 to 32 hours – whereas the average elimination half-life range for Zoloft is 23 to 26 hours.  This means that Lexapro will remain in systemic circulation for a longer duration after cessation than Zoloft.
  • FDA approved uses: Though both Lexapro and Zoloft are both FDA-approved for the treatment of major depressive disorder, the medications differ in additional FDA approvals. Lexapro is FDA-approved to treat generalized anxiety disorder (whereas Zoloft is not).  Zoloft is FDA-approved to treat obsessive-compulsive disorder; panic disorder; post-traumatic stress disorder; premenstrual dysphoric disorder; and social anxiety disorder (whereas Lexapro is not).
  • Ingredients: The active ingredient in the medication Lexapro is the chemical “escitalopram oxalate” – and the active ingredient in the medication Zoloft is the chemical “sertraline hydrochloride.”
  • Metabolism: Lexapro and Zoloft are both metabolized in the liver by cytochrome P450 (CYP450) enzymes, however, there are differences in the specifics of their metabolisms. Lexapro is metabolized in parallel by the enzymes CYP2C19, CYP2D6, and CYP3A4 to form metabolites such as S-demthylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT).  Zoloft is metabolized primarily by the enzyme CYP2B6 and, to a lesser extent, CYP2D6 to form the metabolite norsertraline.
  • Popularity: Historically, the overall popularity of Zoloft has exceeds the popularity of Lexapro. As of 2015 there were ~38.8 million prescriptions filled for generic Zoloft (sertraline hydrochloride) and ~24 million prescriptions filled for generic Lexapro (escitalopram oxalate) in the United States.  In 2013 there were ~41.4 million prescriptions filled for generic Zoloft and ~24.9 million prescriptions filled for generic Lexapro.
  • Secondary neurochemical actions: Although Lexapro and Zoloft both function primarily as selective-serotonin reuptake inhibitors, the medications differ in secondary neurochemical actions. Research suggests that Lexapro does not significantly interact with secondary neurochemical targets – and Zoloft interacts with the dopamine transporter (DAT); noradrenergic receptors; and sigma receptors.
  • Tolerability: According to a meta-analysis by Cipriani et al. (2010), the probability of tolerability for Lexapro is ~27.6% and the probability of tolerability for Zoloft is ~21.3%. Though both medications are considered two of the most tolerable antidepressants on the market, evidence suggests that Lexapro may be slightly more tolerable (on average).

Note: If you know of additional differences between Lexapro and Zoloft, report them in the comments section.

Which medication is “better”? (Lexapro or Zoloft)

Many people with neuropsychiatric disorders scour the internet with the intent of determining whether a medication is inherently “better” than another for their particular medical condition.  The problem with this is that most internet searchers focus too strongly on anecdotes – rather than high-quality data from large-scale, well-designed studies.

Various anecdotes might report that “Lexapro is way better than Zoloft” – whereas other anecdotes might report that “Zoloft is way better than Lexapro.”  Other anecdotes might report that: (1) neither Lexapro nor Zoloft works OR (2) Lexapro and Zoloft work equally well – for the management of a neuropsychiatric disorder.

Because everyone is unique in: genetic and epigenetic expression; neurochemistry; neural connectivity; brain morphology; autonomic nervous system activation; etc. – responses to Lexapro and Zoloft will vary.  For this reason, if attempting to determine whether Lexapro is “better” than Zoloft (or vice-versa), it’s important to reflect upon data from well-designed, large-scale trials.

Data from large-scale trials, meta-analyses, and systematic reviews indicate that Lexapro and Zoloft do not significantly differ in efficacy for the treatment of major depressive disorder (MDD), a condition for which both medications are FDA-approved.  Though Lexapro and Zoloft aren’t significantly different in efficacy for major depressive disorder, there’s some evidence suggesting that Lexapro might be slightly more effective than Zoloft.

For example, a study by Ventura et al. (2007) reported reductions on the Montgomery-Asberg Depression Rating Scale of ~19.1 for Lexapro treatment and ~18.4 for Zoloft treatment.  Additionally, response rates in this study were ~75% for Lexapro users and ~70% for Zoloft users.

A meta-analysis from Ramsberg et al. (2012) reported remission probabilities of 0.47 for Lexapro and 0.4 for Zoloft (after 8 to 12 weeks of treatment) – among 2,687 patients with major depressive disorder.  An earlier meta-analysis by Kennedy et al. (2009) noted that Lexapro exhibited the best overall antidepressant effect, response rate, and remission rate – relative to comparators (which included Zoloft).

Considering that there are trends from multiple studies indicating superiority of Lexapro relative to Zoloft in: magnitude of antidepressant effect; response rate; and remission rate – but no trends from studies indicating superiority of Zoloft relative to Lexapro – it’s reasonable to suggest that Lexapro might be a slightly “better” antidepressant option than Zoloft.

Furthermore, it’s somewhat reasonable to suggest that Lexapro would be a “better” treatment choice for generalized anxiety disorder (than Zoloft) and/or that Zoloft would be a “better” treatment choice for OCD; PTSD; panic disorder; social anxiety disorder; and premenstrual dysphoric disorder (than Lexapro) – on the basis of their respective FDA-approvals.  Receiving FDA-approval to treat a particular medical condition is difficult – and requires convincing data from multiple large-scale, randomized controlled trials showcasing the efficacy of a medication.

Although most literature suggests that Lexapro works well in many conditions for which only Zoloft is approved (e.g. OCD, PTSD, social anxiety, etc.) and that Zoloft works well in the condition for which only Lexapro is approved (generalized anxiety) – FDA approvals make each medication “better” clinical options [relative to the other] in conditions for which the other hasn’t been FDA-approved.

Why? Because there’s higher-quality evidence indicating that Lexapro is effective in generalized anxiety disorder (relative to the evidence for Zoloft) – and higher-quality evidence indicating that Zoloft is effective in OCD; PTSD; PMDD; social anxiety disorder; and panic disorder (relative to the evidence for Lexapro).  That said, no studies have suggested that one medication is more effective than the other for any neuropsychiatric condition.

Lexapro and Zoloft are similar in aspects of: cost (inexpensive); dosing (same number of dosing increments); formatting (tablet and oral solution); onset of action (days to weeks); duration of action (~24 hours); primary mechanism of action (SSRI); side effects; and withdrawal (symptoms, duration, severity).  The medications differ slightly in aspects of: secondary neurochemical actions; routes of metabolism; elimination half-life; and tolerability.

There is some evidence suggesting that Lexapro may be slightly more tolerable and less likely to cause interaction effects than Zoloft.  For example, a report by Culpepper (2002) noted that when patients switch from Zoloft, Prozac, Paxil, or Celexa to Lexapro (due to adverse reactions) – fewer side effects are experienced on Lexapro relative to the previous medication.

Additionally, a meta-analysis by Serretti and Chiesa (2009) discovered nearly 2-fold the rates of treatment-emergent sexual dysfunction among Zoloft users (~80%) compared to Lexapro users (~40%).  A systematic review by Cipriani et al. (2010) based on data from 117 randomized controlled trials (with 25,928 total participants) discovered that while Lexapro and Zoloft are more tolerable than other antidepressants, Lexapro exhibited a higher probability of tolerability (~27.6%) than Zoloft (~21.3%).

Furthermore, Sanchez et al. (2014) reported that Zoloft has “moderate drug interaction issues” when compared with Lexapro.  Considering the evidence suggesting that Lexapro has a higher probability of tolerability; fewer drug interaction issues; and lower rates of treatment-related sexual dysfunction (relative to Zoloft) – it’s reasonable to suggest that Lexapro might be better tolerated than Zoloft.

The only advantage associated with Zoloft (relative to Lexapro) is that Zoloft is FDA-approved to treat 6 medical conditions – whereas Lexapro is only approved to treat 2 medical conditions.  (That said, there’s no reason to surmise that Zoloft would be superior over Lexapro for the treatment of any medical condition – including conditions for which only Zoloft has been FDA-approved).

Potential advantages associated with Lexapro (relative to Zoloft) include: (1) slightly greater efficacy as an antidepressant (magnitude of effect, response rate, remission rate); (2) slightly superior probability of tolerability; (3) markedly lower rates of treatment-emergent sexual dysfunction; (4) lower likelihood of interaction effects; and/or (5) longer half-life and greater selectivity (possibly yielding a slightly easier withdrawal).  Given these prospective advantages of Lexapro over Zoloft – one might regard Lexapro as being a modestly “better” option than Zoloft.

Nevertheless, although Lexapro may be slightly advantageous over Zoloft as an SSRI, the hypothesized advantages are not “clinically significant.”  For this reason, most medical doctors regard Lexapro and Zoloft as equally viable and/or interchangeable options for the treatment of neuropsychiatric disorders.

To determine whether one medication is “better” than the other (in terms of efficacy, side effects, and overall tolerability) – persons will need to experiment with each medication under medical guidance, distinctly, for 4 to 8 weeks.  Unless you’ve completed separate trials of Lexapro and Zoloft – it’s impossible to know whether one medication will be “better” than the other.

Which medication do you prefer? (Lexapro vs. Zoloft)

If you’ve tested Lexapro and Zoloft for the treatment of your specific medical condition(s), leave a comment mentioning whether you: (1) strongly prefer using one medication over the other OR (2) have no preference for using one medication over the other.

In the event that you prefer using Lexapro over Zoloft (or vice-versa), mention reasons supporting your preference.  Possible reasons might include: superior efficacy; fewer unwanted side effects and/or adverse reactions; lower cost (at your pharmacy); more manageable withdrawal symptoms; fewer interaction effects; etc.

Assuming you’ve developed a preference for one medication over the other, have you considered that differences in: potency of dosing; duration of use; and/or concurrent substance use – could be reason as to why you responded better to one medication over the other?  Have you also considered that differences in hepatic metabolism (as determined by gene expression) and/or pharmacodynamics for Lexapro and Zoloft, respectively, might account for disparities in your responses to each medication?

To help others accurately understand your respective experiences with Lexapro and Zoloft, provide details such as: duration of use; dosing; concurrent substance use; and the specific medical condition(s) for which these agents were prescribed.  If you were to assign a rating (on a scale from 1 to 10 – with “1” being “worst” and “10” being “best”) – what would you rate the efficacy (1-10) and tolerability (1-10) of Lexapro and Zoloft?

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