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Lexapro (escitalopram) and Prozac (fluoxetine) are two medications within the selective-serotonin reuptake inhibitors (SSRI) classification that are commonly administered for the treatment of neuropsychiatric disorders.  The development of Lexapro (escitalopram) was initiated in 1997 by Lundbeck and Forest Laboratories – whereas the development of Prozac (fluoxetine) was initiated in the 1970s by chemists (Bryan Molloy and Robert Rathbun) at Eli Lilly.

More specifically, Lexapro (escitalopram) was intended to be an upgraded version of the medication Celexa (citalopram) – whereas Prozac (fluoxetine) was intended to be a diphenhydramine derivative that enhanced mood via inhibiting serotonin reuptake.  In December 1987, Prozac became the first SSRI ever to receive U.S. FDA approval for medical use – whereas Lexapro received U.S. FDA approval in 2002.

Both Lexapro and Prozac are approved by the U.S. FDA for the treatment of major depressive disorder (MDD).  However, Lexapro is also approved as a treatment for generalized anxiety disorder (Prozac is not) – and Prozac is also approved as a treatment for obsessive compulsive disorder (OCD), bulimia nervosa, and panic disorder (Lexapro is not).

Lexapro (Escitalopram) vs. Prozac (Fluoxetine)

Included below is a chart highlighting general attributes of the serotonergic medications Lexapro (escitalopram) and Prozac (fluoxetine).  Assessing this chart should help patients understand some general similarities and differences between these selective-serotonin reuptake inhibitors.

 LexaproProzac
IngredientEscitalopram oxalateFluoxetine 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).

Bulimia nervosa.

Panic disorder.
Off-label usesBody dysmorphic disorder. Hot flashes. Obsessive-compulsive disorder (OCD). Panic disorder. Post-traumatic stress disorder (PTSD). Premature ejaculation. Premenstrual dysphoric disorder (PMDD). Social anxiety disorder.Alcohol dependence. Autism spectrum disorder. Binge eating disorder. Body dysmorphic disorder. Cataplexy. Obesity. Post-traumatic stress disorder (PTSD). Premature ejaculation. Premenstrual dysphoric disorder. Social anxiety disorder. Trichotillomania.
Bioavailability~80% (oral)~72% (oral)
FormatsTablet. Oral solution.Capsule. Tablet. Oral solution. Delayed-release (DR) capsule.
DosagesTablet: 5 mg, 10 mg, 20 mg

Oral solution: 5 mg/5 mL
Capsule: 10 mg, 20 mg, 40 mg

Tablet: 10 mg, 20 mg, 60 mg

Oral solution: 20 mg/5 mL

Delayed-release capsule: 90 mg
DevelopersLundbeck & Forest LaboratoriesEli Lilly
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.

Modestly agonizes sigma-1 and sigma-2 receptors.
Selective-serotonin reuptake inhibitor.

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

Additional actions:
-5-HT2C receptor antagonist.
-Sigma-1 receptor agonist.
-Anoctamin-1 channel blocker.
-Acid sphingomyelinase inhibitor.
-5-HT2A receptor modulator.
-Increases allopregnanolone concentrations (which modulates GABAA receptors).
-May interact with the norepinephrine transporter (NET) and muscarinic acetylcholine receptors (M1, M3, M2, M5) at high doses.
-May increase synaptic norepinephrine and dopamine at high doses.
-May interact with 5-HT3 receptors, nicotinic acetylcholine receptors (nAChRs), and various ion channels.

(Norfluoxetine, the primary metabolite of fluoxetine, may interact with the dopamine transprter (DAT) at high doses).
Generic version (?)Yes.Yes.
Half-Life27 to 33 hours (~35 hours)96 to 144 hours
Common side effectsInsomnia. Ejaculation disorder. Nausea. Sweating. Fatigue. Somnolence. Decreased libido. Anorgasmia.Abnormal dreams. Abnormal ejaculation. Anorexia. Anxiety. Asthenia. Diarrhea. Dry mouth. Dyspepsia. Flu syndrome. Impotence. Insomnia. Libido reduction. Nausea. Nervousness. Pharyngitis. Rash. Sinusitis. Somnolence. Sweating. Tremor. Vasodilation. Yawning.
Date approved (U.S.)2002 (August)1987 (December)
Duration of effect24 hours24 hours (Standard)

1-week (Delayed-release)
MetabolismHepatic: CYP2C19 (36%), CYP3A4 (34%), CYP2D6 (30%)Hepatic: CYP2D6 (Primary) + CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP3A5 (Secondary)
Onset of action4 to 8 weeks (on average)4 to 8 weeks (on average)
Dosage equivalence (approximation)10 mg20 mg

Note: The information documented within the above chart could be subject to inaccuracies and/or outdated.  If you have specific questions about Lexapro and/or Prozac – contact a licensed medical doctor and/or pharmacist.

Lexapro vs. Prozac: What are general differences?

Despite the fact that both Lexapro and Prozac are classified as selective-serotonin reuptake inhibitors (SSRIs), the agents differ in numerous ways.  General differences between Lexapro and Prozac include: date of release; official medical uses; off-label uses; mechanism of action; formatting; bioavailability; route of metabolism; half-life; and common side effects.

As was previously stated, in December 1987, Prozac (fluoxetine) became the first SSRI (selective-serotonin reuptake inhibitor) to receive FDA-approval for medical use in the United States.  Nearly 15 years after the release of Prozac, Lexapro received FDA approval for medical use in August 2002.

Though Lexapro and Prozac are both indicated for the treatment of major depressive disorder (MDD), only Lexapro is approved to treat generalized anxiety disorder (Prozac is not) – and only Prozac is approved to treat obsessive-compulsive disorder, bulimia nervosa, and panic disorder (Lexapro is not).  Furthermore, while both Lexapro and Prozac are regularly prescribed off-label (to treat conditions for which they haven’t been FDA approved), there may be slight differences in their respective rates of off-label use for certain conditions.

There also appear to be differences between Lexapro and Prozac in pharmacodynamics – or the specific neurochemical targets with which each medication interacts.  Lexapro is the most selective SSRI medication on the market – interacting primarily with the serotonin transporter (SERT), and to a lesser extent, sigma-1 and sigma-2 receptors.

Prozac is significantly less selective than Lexapro – interacting with a variety of neurochemical targets beyond its primary interaction with the serotonin transporter (SERT).  Secondary neurochemical targets for Prozac include:  5-HT2C receptors, sigma-1 receptors, anoctamin-1 channels, acid sphingomyelinase enzymes, 5-HT2A receptors, GABAA receptors, the norepinephrine transporter (NET), acetylcholine receptors (muscarinic and nicotinic), 5-HT3 receptors, the dopamine transporter (DAT), and various ion channels.

Moreover, while Lexapro and Prozac are both manufactured in tablet and oral solution formats – only Prozac is manufactured in standard (~24-hour) capsules and delayed-release (7-day) capsules.  The specific routes of metabolism for Lexapro and Prozac are similar, but differ slightly in that Prozac is metabolized by 2 additional hepatic enzymes.

Specifically, Lexapro is metabolized hepatically by the enzymes CYP2C19, CYP2D6 and CYP3A4 – whereas Prozac is metabolized hepatically by the enzymes CYP2D6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, CYP1A2, and CYP2B6.  In terms of elimination half-life, the elimination half-life of Lexapro ranges from 27 to 33 hours and is shorter than the elimination half-life of Prozac which ranges from 96 to 144 hours.

There are also differences between Lexapro and Prozac in common side effects.  Common side effects for Lexapro include anorgasmia and fatigue (these are not common side effects of Prozac).  Common side effects for Prozac include: abnormal dreams, anorexia, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, nervousness, rash, tremor, vasodilation, and yawning (these are not common side effects of Lexapro).

Approved Medical Uses & Off-Label Uses

Lexapro and Prozac are each approved by the United States FDA (Food & Drug Administration) for the management of major depressive disorder (MDD).  (Lexapro was approved by the FDA in 2002 to treat major depressive disorder – and Prozac was approved by the FDA in 1987 to treat major depressive disorder).

Although Lexapro and Prozac are each approved as treatments for depression, only Lexapro is FDA-approved to treat generalized anxiety disorder (Prozac is not) – and only Prozac is FDA-approved to treat obsessive-compulsive disorder, bulimia nervosa, and panic disorder (Lexapro is not).  In total, Lexapro is authorized by the FDA to treat 2 medical conditions and Prozac is authorized by the FDA to treat 4 medical conditions – within the United States.

Moreover, Lexapro and Prozac are commonly prescribed “off-label” to treat medical conditions for which their FDA approvals are lacking.  As “off-label” interventions, both Lexapro and Prozac are utilized in the management of: body dysmorphic disorder, post-traumatic stress disorder (PTSD), premature ejaculation, premenstrual dysphoric disorder (PMDD), and social anxiety disorder.

Lexapro is regularly used off-label to treat obsessive-compulsive disorder and panic disorder (conditions for which Prozac is FDA-approved) and hot flashes.  Prozac may be used more frequently than Lexapro as an off-label treatment for alcohol dependence, autism spectrum disorder, binge eating disorder, cataplexy, obesity, and trichotillomania.

Nevertheless, it remains unknown as to whether Lexapro and Prozac differ in total off-label usage and/or rates of off-label use for specific conditions.  Because Lexapro and Prozac exhibit similar primary mechanisms of action, many medical professionals consider these medications to be interchangeable off-label treatments for most conditions.

Cost: Comparing the prices

Because Lexapro and Prozac are available as generics, each can be attained by patients at a lower cost than the “brand name” versions.  At most pharmacies, a total of 30 generic Lexapro (escitalopram) tablets retail for $8 to $49, whereas a total of 30 generic Prozac (fluoxetine) capsules retail for $4 to $26 – and 30 generic Prozac (fluoxetine) tablets retail for $4 to $364.

Lexapro cost

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

Prozac cost

  • Fluoxetine capsules (generic): $4 to $26 (30 count)
  • Fluoxetine tablets (generic): $4 to $364 (30 count)
  • Fluoxetine oral solution: $11 to $45 (1 bottle)
  • Fluoxetine capsules (delayed-release): $84 to $186 (4 count)
  • Prozac capsules (standard): $450 to $980 (30 count)
  • Sarafem (28-tablet dose pack): $535 to $602

If comparing the price of generic Lexapro (escitalopram) tablets to the price of generic Prozac (fluoxetine) capsules, it seems as though most pharmacies sell generic Prozac (fluoxetine) capsules for a lower average price than generic Lexapro (escitalopram) tablets.  However, if comparing the price of generic Lexapro (escitalopram) tablets to the price of generic Prozac (fluoxetine) tablets, it’s a bit more complicated.

At most pharmacies, generic Lexapro (escitalopram) tablets will sell for a lower price than generic Prozac (fluoxetine) tablets – especially at high dosages.  However, at select pharmacies, generic Prozac (fluoxetine) tablets can sell for a lower price than generic Lexapro (escitalopram) tablets – especially at low doses.

If comparing the price of generic Lexapro (escitalopram) oral solution to the price of generic Prozac (fluoxetine) oral solution, the former (escitalopram oral solution) is more expensive than the latter (fluoxetine oral solution).  Generic Lexapro (escitalopram) oral solution costs ~$2.79 to ~$4.83 (per 10 mg dose) whereas generic Prozac (fluoxetine) oral solution costs ~$0.45 to ~$1.85 (per 20 mg dose); these doses are approximately equal in magnitude of effect.

Generic Prozac (fluoxetine) is also manufactured in a unique delayed-release (DR) capsule format.  Each generic delayed-release Prozac (fluoxetine) capsule is long-acting, delivering an effect that lasts ~1 week (i.e. 7 days).  A total of 4 delayed-release fluoxetine capsules (or a 1-month supply) retail for $84 to $186.

Since Lexapro (escitalopram) and Prozac (fluoxetine) are available as generics, most patients will prefer using generics to save on prescription costs.  However, a subset of individuals might prefer to use “brand name” Lexapro or Prozac for various reasons such as perceived superiority in efficacy and/or tolerability – relative to generics.

A total of 30 “brand name” Lexapro tablets sell for $306 to $358whereas a total of 30 “brand name” Prozac capsules sell for $450 to $980.  Although the pricing of each “brand name” version is dose-dependent (in that higher doses are more expensive than lower doses) – all doses of “brand name” Lexapro are cheaper than “brand name” Prozac.

Another version of fluoxetine sold under the “brand name” Sarafem retails for $535 to $602 per 28-tablet dose pack – which is still more expensive than 30 “brand name” Lexapro tablets, regardless of its dose.  Lastly, although “brand name” Prozac oral solution is nonexistent, a 240 mL bottle of “brand name” Lexapro oral solution sells for $500 to $538 (on average); equaling around ~$20.83 to ~$22.42 per dose.

In summary, generic tablet and oral solution formats of Lexapro (escitalopram) are generally more expensive than generic capsule and oral solution formats of Prozac (fluoxetine), respectively.  Furthermore, Generic Lexapro (escitalopram) tablets are generally less expensive than generic Prozac (fluoxetine) tablets – and brand name Lexapro tablets are generally less expensive than brand name Prozac capsules (and brand name Sarafem tablets).

Note: The average price ranges for Lexapro and Prozac listed above may be subject to future fluctuation and/or inaccuracies.  Understand that the cost of Lexapro and Prozac can vary significantly among pharmacies.

Efficacy: Is Lexapro more effective than Prozac?

It remains unknown as to whether there are substantial (i.e. clinically-significant) differences in effectiveness between Lexapro and Prozac for the treatment of any medical condition.  Since major depressive disorder (MDD) is the only medical condition for which both Lexapro and Prozac have received FDA-approval, consumers and/or prescribers of these agents are probably most concerned with their respective efficacies in the treatment of depression.

Major depressive disorder (MDD)

Before comparing the efficacies of Lexapro and Prozac, it is important to emphasize the fact that both medications have proven to be effective in large-scale, randomized, double-blind, placebo-controlled trials for the treatment of major depressive disorder (MDD).  For this reason, both Lexapro and Prozac are regarded as efficacious pharmaceutical antidepressant medications.

Included below are brief synopses of studies in which the efficacies of Lexapro and Prozac were compared (directly or indirectly) in the treatment of major depressive disorder.  Most of the data from these studies indicate that escitalopram (Lexapro) might be more effective than fluoxetine (Prozac) in the treatment of major depressive disorder.

2018: Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.

A systematic review and meta-analysis by Cipriani et al. assessed the efficacies of 21 antidepressant medications, including Lexapro (escitalopram) and Prozac (fluoxetine).  For this systematic review, researchers analyzed data from 522 randomized controlled trials (42 trials involved Lexapro and 117 trials involved Prozac).

To determine the efficacies of 21 antidepressants (including Lexapro and Prozac), researchers pooled data from (1) placebo-controlled trials and (2) head-to-head trials.  Thereafter, the 21 antidepressants were ranked by efficacy in placebo controlled trials, by efficacy in head-to-head comparison trials, and overall efficacy.

The respective odds ratios (or probabilities of inducing clinically-relevant antidepressant effects) for Lexapro and Prozac were: 1.68 (Lexapro) and 1.52 (Prozac).  If comparing the aforementioned odds ratios, it would seem as though Lexapro might be slightly more effective (on average) than Prozac for the treatment of depression.

More specifically, of the 21 antidepressants compared in this review, Lexapro ranked 8th (of 21) and Prozac ranked 16th (of 21) in antidepressant efficacy.  If solely assessing the respective efficacies of Lexapro and Prozac in head-to-head comparison studies, Lexapro ranks 3rd (of 18) and is considered one of the most effective medications – whereas Prozac ranks 15th (of 18) and is considered one of the least effective medications.

Based on the findings presented in this systematic review and meta-analysis, it seems as though Lexapro (escitalopram) treatment is associated with a higher average response rate than Prozac treatment.  Although this review does not prove that Lexapro is definitively more effective as an antidepressant than Prozac, it suggests that Lexapro might be slightly more effective than Prozac in the treatment of major depressive disorder (MDD).

2012: Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model.

A meta-analysis by Ramsberg et al. assessed the efficacies of 10 antidepressants, including Lexapro (escitalopram) and Prozac (fluoxetine).  The meta-analysis included data from 87 randomized controlled trials in which around 20,000 persons with moderate-to-severe depression were treated for up to 1-year.

After pooling data from acceptable randomized controlled trials, Ramsberg et al. calculated “remission rates” and “quality-of-life” for each of the 10 antidepressants.  Based on “all studies” included in this meta-analysis, the probability of depression remission with Lexapro was “0.456” – and the probability of depression remission with Prozac was “0.371.”

Furthermore, QALY score for Lexapro was “0.6978” and the QALY score for Prozac was “0.6847.”  Results of this study indicate that Lexapro users are more likely to experience remission of depressive symptoms and better quality of life – relative to Prozac users.

Worth noting is that Lexapro (escitalopram) was superior to all other (9) antidepressants, including Prozac (fluoxetine) in: decreasing time spent in depression; enhancing quality of life among persons with depression, and its remission rate.  This meta-analysis supports the idea that Lexapro could be more effective as an antidepressant than Prozac.

2012: Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram.

A review by Favré assessed the efficacy of Lexapro (escitalopram) relative to other antidepressant medications, including Prozac (fluoxetine), in the treatment of major depressive disorder (MDD).  The review incorporated data from studies published in PubMed after 2004.

Favré reflected upon the findings of several studies, including a meta-analysis by Cipriani et al. (2009), a study by Kasper et al. (2009), and a pooled-analysis by Kilts et al. (2009).  Favré noted that, in the meta-analysis by Cipriani et al. (2009), Lexapro (escitalopram) appeared more effective than 10 antidepressants, one of which was Prozac (fluoxetine), over an acute (8-week) duration.

Additionally, Favré stated that, in the study by Kasper et al. (2009), Lexapro (escitalopram) exhibited significantly greater antidepressant efficacy than Paxil (paroxetine) in 6-month randomized controlled trials.  Favré also mentioned that, in the pooled-analysis by Kilts et al. (2009), Lexapro (escitalopram) was associated with a superior depression remission rate (51.7%) relative to pooled comparator antidepressants (45.6%) over a 24-week duration.

Overall, this literature review by Favré supports the idea that Lexapro (escitalopram) might be more effective than Prozac (fluoxetine) and many other antidepressants in the management of major depressive disorder.  That said, this review does not conclusively prove that Lexapro (escitalopram) is superior to Prozac (fluoxetine).

2009: Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis.

A meta-analysis by Cipriani et al. compared the efficacies of 12 second-generation antidepressants in the treatment of major depressive disorder (MDD).  The meta-analysis included data from 117 randomized controlled trials (published between 1991 and 2007) encompassing 25,928 adults diagnosed with unipolar major depression – all of who received therapeutically-relevant doses of prescription antidepressants.

The 12 second-generation antidepressants compared in this meta-analysis were:  bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine.  Cipriani et al. calculated the cumulative probabilities that each antidepressant assessed in this study would be among the top 4 most effective treatment options.

The cumulative probability of Lexapro being among the top 4 most-effective antidepressants (of the 12 medications compared) was 23.7% – this ranked second overall behind mirtazapine (24.4%).  The cumulative probability of Prozac being among the top 4 most-effective antidepressants (of the 12 medications compared) was 0% – which ranked last overall (along with reboxetine).

Moreover, the odds ratio associated with the efficacy (response rate) of Lexapro (escitalopram) was significantly better than the odds ratio associated with the efficacy (response rate) of Prozac (fluoxetine).  The results of this meta-analysis support the idea that Lexapro (escitalopram) is significantly more effective than Prozac (fluoxetine) in the treatment of major depressive disorder (MDD).

2009: Escitalopram versus other antidepressive agents for depression.

Cipriani et al. conducted a review to determine the efficacy of Lexapro (escitalopram) relative to other antidepressants in the acute management of major depressive disorder.  For this review, Cipriani et al. analyzed data (published up to July 2008) from 22 randomized controlled trials in which Lexapro (escitalopram) was compared to another antidepressant agent.

Of the 22 randomized controlled trials analyzed: 14 compared Lexapro (escitalopram) to another SSRI – and 8 compared Lexapro (escitalopram) to a newer antidepressant (venlafaxine, bupropion, duloxetine).  Results of the review indicated that Lexapro (escitalopram) was significantly more effective than Prozac (fluoxetine) in reducing depressive symptoms.

Researchers acknowledged the possibility that data extracted from various randomized controlled trials may have overestimated the efficacy of Lexapro (escitalopram) due to sponsorship bias.  Nevertheless, this review supports the idea that Lexapro (escitalopram) may be superior to Prozac (fluoxetine) as a treatment for major depressive disorder.

2005: Escitalopram in the treatment of depressed elderly patients.

Kasper et al. conducted an 8-week, randomized, double-blinded, head-to-head trial in which the antidepressant efficacies of Lexapro (escitalopram) and Prozac (fluoxetine) were compared against a placebo control (and against each other).  The trial included 517 elderly patients (65 to 93 years of age) who were assigned at random to receive either: 10 mg/day Lexapro (173 patients); 20 mg/day Prozac (164 patients); or a placebo (180 patients).

Results of the trial indicated that neither Lexapro (escitalopram) nor Prozac (fluoxetine) was more effective than the placebo as a treatment for major depressive disorder over an 8-week period.  Authors concluded that this was a “failed study” based on the fact that neither active treatment facilitated a stronger antidepressant effect than the placebo.

Nevertheless, it was reported that Prozac (fluoxetine) appeared significantly less effective than both Lexapro (escitalopram) and the placebo control.  Although neither active treatment was more effective than the placebo, because Lexapro (escitalopram) was significantly more effective than Prozac (fluoxetine) in reducing depressive symptoms – this trial supports the idea that Lexapro (escitalopram) is superior over Prozac (fluoxetine) in antidepressant efficacy.

2005: Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder.

Hansen et al. performed a meta-analysis to determine the head-to-head efficacies of second-generation antidepressants, including Lexapro (escitalopram) and Prozac (fluoxetine), in the treatment of major depressive disorder.  For the meta-analysis, data were analyzed from 46 head-to-head randomized, controlled trials (published between 1980 and 2005) encompassing 11,553 patients.

Results of this meta-analysis indicated that there were minimal disparities in the efficacies of second-generation antidepressants.  In 88% of head-to-head trials, no significant differences were discovered between antidepressants at trial endpoints on any measures of efficacy.

While it was reported that sertraline and venlafaxine appeared modestly more effective than fluoxetine, no differences in efficacy were reported between Lexapro (escitalopram) and Prozac (fluoxetine).  This meta-analysis does not support the idea that Lexapro (escitalopram) is more effective than Prozac (fluoxetine).

Verdict: Lexapro (escitalopram) might be more effective than Prozac (fluoxetine) in the treatment of major depressive disorder

Considering all studies in which the efficacies of escitalopram (Lexapro) and fluoxetine (Prozac) were examined and compared (directly or indirectly) in the treatment of depression, it seems as though escitalopram (Lexapro) might be modestly more effective (on average) than fluoxetine (Prozac) [as an antidepressant].  In the comprehensive meta-analysis by Cipriani et al. (2018), escitalopram exhibited higher odds (1.68) than fluoxetine (1.52) of facilitating a therapeutically-relevant antidepressant effect.

Furthermore, in the meta-analysis by Ramsberg et al. (2010), escitalopram was associated with a higher probability of depression remission (0.456 vs. 0.371) and quality-of-life score (0.6978 vs. 0.6847) than fluoxetine.  In an earlier meta-analysis by Cipriani et al. (2009), the cumulative respective probabilities of escitalopram and fluoxetine of being within the top 4 most effective antidepressant options (of 12 antidepressants) were: 23.7% for escitalopram – and 0% for fluoxetine.

A different review by Cipriani et al. (2009), escitalopram appeared significantly more effective than fluoxetine in “reducing depressive symptoms.  In a direct comparison trial by Kasper et al. (2005) involving 517 elderly participants, fixed-dose escitalopram (10 mg/day) was significantly more effective than fixed-dose fluoxetine (20 mg/day) as a treatment for depression over an 8-week period.

In a review by Hansen et al. (2005), no difference was reported between escitalopram and fluoxetine in antidepressant efficacy, however, fluoxetine appeared significantly less effective than sertraline and venlafaxine in the treatment of depression.  Because there’s no evidence to suggest that sertraline or venlafaxine is more effective than escitalopram, one might interpret the finding of superior antidepressant efficacy with sertraline and venlafaxine relative to fluoxetine – as support for the preexisting trend of superior antidepressant efficacy with escitalopram relative to fluoxetine.

To recap: Three large-scale meta-analysis and/or reviews have documented trends of escitalopram (Lexapro) exhibiting superior antidepressant efficacy relative to fluoxetine (Prozac).  Additionally, one large-scale study reported that escitalopram (Lexapro) was significantly more effective than fluoxetine (Prozac) as a treatment for major depressive disorder.

However, in the one study that reported a significantly superior antidepressant response with escitalopram (Lexapro) relative to fluoxetine (Prozac), the placebo was equally as effective as escitalopram (Lexapro).  Moreover, two serious limitations associated with this study included: fixed dosing and an age-homogenous sample of elderly adults.

In conclusion, there are data from several large-scale studies supporting the idea that escitalopram (Lexapro) might be more effective than fluoxetine (Prozac) in the treatment of major depressive disorder – but zero data supporting the idea that fluoxetine (Prozac) might be more effective than escitalopram (Lexapro).  Because escitalopram (Lexapro) might be more effective than fluoxetine (Prozac) – but not the opposite, it makes logical sense to try escitalopram (Lexapro) as a treatment for major depressive disorder prior to fluoxetine (Prozac).

Comparing the efficacy of Lexapro & Prozac for other medical conditions

If comparing escitalopram (Lexapro) and fluoxetine (Prozac): (1) only escitalopram is approved by the FDA for the treatment of generalized anxiety disorder; and (2) only fluoxetine is approved by the FDA for the treatment of obsessive-compulsive disorder; bulimia nervosa; and panic disorder.  Considering the disparities in FDA approvals for escitalopram and fluoxetine, it makes sense to regard escitalopram as a medically-superior “treatment choice” relative to fluoxetine for generalized anxiety disorder (on the basis of its FDA approval).

Similarly, it makes sense to regard fluoxetine as a medically-superior “treatment choice” over escitalopram for obsessive-compulsive disorder, bulimia nervosa, and panic disorder (on the basis of its FDA approval).  The reason each medication should be regarded as a medically-superior “treatment choice” (relative to the other) for conditions in which the other lacks FDA approval – is because the efficacy of an agent with FDA approval is generally supported by strong evidence and its odds of facilitating a therapeutic effect are high.

The efficacy of an agent in treating a medical condition for which it has not received FDA-approval is often unclear – such that its odds of facilitating a therapeutic effect are unknown.  That said, it’s important to avoid assuming that one medication is more effective than another on the basis of FDA approval.

Just because one agent has received FDA approval for the treatment of a medical condition and another has not – does not automatically mean that the agent with FDA approval is more effective than the agent without FDA approval.  Below are brief discussions of the respective efficacies and/or strength of evidence associated with escitalopram and fluoxetine in the treatment of medical conditions for which only the other agent has received FDA-approval.

Generalized anxiety disorder (GAD)

Lexapro (escitalopram) is medically-approved for the treatment of generalized anxiety disorder in the U.S. but Prozac (fluoxetine) is not.  That said, numerous studies have been performed to elucidate whether Prozac (fluoxetine) might be efficacious in the management of generalized anxiety disorder.

For example, a literature review by Zou et al. (2013) assessed the clinical efficacy of fluoxetine as a treatment for generalized anxiety disorder.  Results of the review indicated that fluoxetine rapidly alleviated symptoms of generalized anxiety (within 1-2 weeks) and was efficacious as a maintenance therapy.

However, the studies from which data were extracted for the review had serious limitations, including: (1) small sample sizes; (2) zero placebo controls; and (3) high risk of bias.  Due to these limitations, Zhou et al. stated “it is not possible to recommend fluoxetine as a reliable first-line treatment” in generalized anxiety disorder.

Moreover, a different 6-week, open-label trial by Simon et al. (2006) reported that fluoxetine was a poor treatment choice for women with generalized anxiety disorder – especially if the disorder had a late age of onset.  Though this study also has notable limitations such as: lack of randomization; zero placebo control; and small sample size – the results indicate that fluoxetine may be a suboptimal intervention for a subset of the populace with generalized anxiety disorder.

In a 12-week, placebo-controlled trial by Birmaher et al. (2003) involving 74 pediatrics (7 to 17 years of age) with anxiety disorders (generalized anxiety disorder, social phobia, separation anxiety disorder), 61% of fluoxetine users (37 persons) experienced significant reductions in anxious symptoms – relative to just 35% of placebo users (37 persons).  Analysis of responders indicated that pediatrics with social phobia and generalized anxiety disorder responded better to fluoxetine than the placebo, however, only pediatrics with social phobia exhibited significant clinical and functional improvement.

While the aforementioned trial by Birmaher et al. suggested that fluoxetine may attenuate symptoms of generalized anxiety disorder in pediatrics, the magnitude of attenuation was not statistically significant.  Furthermore, though this trial has numerous limitations, it failed to showcase the efficacy of fluoxetine in the treatment of generalized anxiety disorder.

As of current, there are zero quality data from large-scale, randomized controlled trials to substantiate the recommendation of fluoxetine (Prozac) for generalized anxiety disorder.  Additionally, there are some data suggesting that fluoxetine (Prozac) may be an ineffective intervention for generalized anxiety disorder – particularly among women who developed the disorder in late age.

Because there are: (1) no quality data to support the usefulness of fluoxetine in generalized anxiety disorder; and (2) data suggesting that fluoxetine may be ineffective for generalized anxiety disorderthere’s no reason to recommend fluoxetine (Prozac) as a treatment for this condition.  Though we cannot definitively know whether escitalopram (Lexapro) is significantly more effective than fluoxetine (Prozac) as a treatment for generalized anxiety disorder (due to lack of high-quality studies involving fluoxetine), escitalopram (Lexapro) remains a significantly better treatment choice based upon the fact that it has proven effective in large-scale, randomized controlled trials for this condition.

Obsessive-compulsive disorder (OCD)

Prozac (fluoxetine) is medically-approved for the treatment of obsessive-compulsive disorder in the U.S. but Lexapro (escitalopram) is not.  That said, there are mounting data supporting the idea that escitalopram (Lexapro) is effective in the treatment of obsessive-compulsive disorder.

For example, a naturalistic, open-label study by Shim et al. (2011) reported significant improvement in CGI-S (Clinical Global Impressions-Scale) scores among 246 patients with obsessive-compulsive disorder following escitalopram (Lexapro) treatment.  It was further noted that doses of escitalopram at 40 mg/day or below were generally effective in reducing obsessive-compulsive disorder symptoms.

A 16-week study by Rabinowitz et al. (2008) assessed the efficacy of high-dose escitalopram (10 mg/day for 1 week, then 20 mg/day for 3 weeks, and 20 mg/day to 50 mg/day thereafter – if symptom relief wasn’t significant) in 67 patients with obsessive-compulsive disorder.  Results of this study indicated that high-dose escitalopram significantly reduced symptoms of obsessive-compulsive disorder (as evidenced by substantial Y-BOCS score reductions from pre-treatment baseline).

A 24-week, fixed-dose, placebo-controlled, paroxetine-referenced trial conducted by Stein et al. (2007) examined the efficacy of escitalopram in the treatment of obsessive-compulsive disorder.  The trial included 466 adults diagnosed with OCD and assigned them at random to receive either: 10 mg/day escitalopram (116 persons); 20 mg/day escitalopram (116 persons); 40 mg/day paroxetine (119 persons); or a placebo (115 persons) – for a 24-week duration.

Results of the trial indicated that escitalopram at 20 mg/day was significantly more effective than the placebo in treating obsessive-compulsive disorder – as evidenced by superior improvement on all primary and secondary outcome measures.  Escitalopram at 10 mg/day and paroxetine at 40 mg/day were also more efficacious than the placebo in treating obsessive-compulsive disorder – as evidenced by significant improvement on primary outcome measures and a subset of secondary outcome measures.

Moreover, escitalopram at 20 mg/day was associated with a faster onset of therapeutic effect, higher response rates, higher remission rates, and better functioning than the placebo and paroxetine-reference (a medication that’s FDA-approved to treat OCD).  Based on the findings in this large-scale, well-designed study, authors concluded that escitalopram should be regarded as a first-line intervention for the long-term management of obsessive-compulsive disorder.

A series of 3 case reports authored by Zutshi et al. (2007) provides additional evidence to support the idea that escitalopram can be effective in the treatment of obsessive-compulsive disorder.  In summary, all studies evaluating escitalopram in the treatment of OCD are unanimous in suggesting that it is an effective intervention.

Based on the fact that: (1) escitalopram appears effective in all studies for which it has been evaluated as a treatment for OCD; (2) escitalopram was effective in a large-scale, long-term, placebo-controlled, paroxetine-referenced study for the treatment of OCD; (3) escitalopram was more effective than paroxetine (an FDA-approved intervention for OCD) in one study; and (4) escitalopram is approved to treat OCD in European countries – it’s reasonable to suspect that escitalopram is useful in the management of obsessive-compulsive disorder.

Although there are stronger data to substantiate the use of fluoxetine in the treatment of obsessive-compulsive disorder (relative to escitalopram), it is unclear as to whether fluoxetine and escitalopram significantly differ in efficacy for this condition.

Bulimia nervosa

Prozac (fluoxetine) is medically-approved for the treatment of bulimia nervosa in the U.S. – but Lexapro (escitalopram) is not.  As of current (2018) zero trials have evaluated the efficacy of escitalopram for the treatment of bulimia nervosa.  For this reason, it remains unknown as to whether escitalopram is effective for this condition.

Nevertheless, one randomized controlled trial by Leombruni et al. (2006) directly compared the efficacy of citalopram (a medication that’s nearly identical to escitalopram in chemical structure and pharmacodynamics) to that of fluoxetine in the treatment of bulimia nervosa.  The trial involved 37 bulimic patients who were randomly assigned to receive fluoxetine (18 patients) or citalopram (19 patients).

Results of the trial indicated that both citalopram and fluoxetine significantly reduced: eating psychopathology, angry feelings, and CGI (Clinical Global Impressions) scores.  Fluoxetine recipients exhibited greater reductions in introjected anger – whereas citalopram recipients exhibited greater reductions in depressive feelings.

Authors of the trial concluded that citalopram may be useful in depressed patients with bulimia – and that fluoxetine is useful in patients with introjected anger and bulimia.  Based on the results of the aforementioned small-scale study, it’s reasonable to extrapolate the findings to suggest that escitalopram (an extremely-similar medication to citalopram) might also be effective for bulimia nervosa.

Because there are no strong data to directly support the use of escitalopram (Lexapro) in the treatment of bulimia nervosa, fluoxetine (Prozac) remains a superior treatment choice for this condition.  That said, unless escitalopram (Lexapro) is evaluated in large-scale trials for the management of bulimia nervosa, we cannot know whether it differs in efficacy from fluoxetine (Prozac) for this condition.

Panic disorder

Prozac (fluoxetine) is medically-approved to treat panic disorder – but Lexapro (escitalopram) is not.  That said, there are data to suggest that escitalopram might be efficacious in the treatment of panic disorder.

A 24-week open-label trial by Choi et al. (2012) involving 119 Korean adults with panic disorder reported that escitalopram treatment led to: (1) significant reduction of panic disorder symptoms in 96 patients (80.7%); and (2) remission of panic disorder in 87 patients (73.1%).  This open-label trial supports the idea that escitalopram might be effective in the treatment of panic disorder.

A review by Townsend and Conrad (2007) provides additional support for the idea that escitalopram is efficacious in the treatment of panic disorder.  In the review, Townsend and Conrad reflected upon trials by Stahl et al. (2003); Sayer and Cetin (2004); and Rampello et al. (2006) – in which escitalopram was directly evaluated as a treatment for panic disorder.

Though the trial by Sayer and Cetin (2004) was limited by a small-sample size and open-label design, its result supported the idea that escitalopram is useful in the treatment of panic disorder.  The trial by Stahl et al. (2003) implemented a randomized, double-blind, placebo-controlled design in which 366 adults with panic disorder were assigned at random to receive either: 10-20 mg/day escitalopram; 20-40 mg/day citalopram; or a placebo – for 10 weeks.

Results of this larger-scale trial by Stahl et al. indicated that escitalopram was significantly more effective than a placebo in reducing anticipatory anxiety, frequency of panic attacks, and intensity of panic attacks – among adults with panic disorder.  Additionally, the onset of therapeutic effect associated with escitalopram was quicker than that associated with citalopram.

In the trial by Rampello et al. (2006), 40 elderly adults (over 65 years of age) were assigned to receive either 10 mg/day escitalopram or 20 mg/day citalopram for 8 weeks.  Though this trial was limited by its small sample size, age-homogenous sample, and open-label design – its result indicated that escitalopram significantly reduces the frequency of panic attacks.

Similar to the trial by Stahl et al., the trial by Rampello et al. discovered that escitalopram exhibited a faster onset of therapeutic action than citalopram.  The review by Townsend and Conrad also highlighted the fact that, citalopram (a medication that contains escitalopram and exhibits similar pharmacodynamics to escitalopram) has showcased its efficacy as a treatment for panic disorder in several controlled trials by Wade et al. (1997); Lepola et al. (1998); and Perna et al. (2001).

Considering that: (1) all trials evaluating escitalopram for panic disorder are unanimous in suggesting its effectiveness; (2) a large-scale randomized, controlled trial (involving 366 adults) found escitalopram more effective than a placebo for panic disorder; and (3) several controlled trials have found citalopram (an extremely similar medication to escitalopram) effective for panic disorder – it’s reasonable to surmise that escitalopram is useful as a treatment for panic disorder.

As of current, because there are stronger data supporting the use of fluoxetine (Prozac) for panic disorder – relative to escitalopram (Lexapro) – it’s reasonable to regard fluoxetine as a better treatment choice than escitalopram for this condition.  Still, it remains unknown as to whether fluoxetine (Prozac) and escitalopram (Lexapro) significantly differ in efficacy in the treatment of panic disorder.

Social anxiety disorder

A meta-analysis by Baldwin et al. (2016) states that Lexapro (escitalopram) is effective for the treatment of social anxiety disorder.  This meta-analysis included data from 3 randomized controlled trials with a total of 1,598 patients (1,061 escitalopram users vs. 537 placebo users).

In comparison, several studies that’ve examined Prozac (fluoxetine) for the treatment of social anxiety disorder report that it’s ineffective for this condition.  For example, a 60-patient study by Clark et al. (2003) compared the efficacy of: cognitive therapy (CT); fluoxetine plus self-exposure; and placebo plus self-exposure – for social phobia.

Results of this study indicated that cognitive therapy significantly reduced symptoms of social phobia – whereas fluoxetine did not.  Another 60-patient study by Kobak et al. (2002) compared the efficacy of therapy; fluoxetine; and a placebo – for social anxiety disorder.

In the study by Kobak et al., no difference in efficacy was found between fluoxetine and the placebo – over a 14-week period.  Although fluoxetine might be more effective for social anxiety disorder than existing data suggest, it remains inferior to escitalopram as a treatment selection for this condition.

Post-traumatic stress disorder (PTSD)

Preliminary evidence suggests that Lexapro and Prozac may be effective in the treatment of PTSD.  A study by Qi et al. (2017) involving 45 patients with PTSD reported that Lexapro at doses up to 40 mg/day significantly attenuated the severity of PTSD symptoms – over a 12-week period relative to baseline (as evidenced by score reductions on the CAPS (Clinician-Administered PTSD Scale).

A different 12-week, open-label study by Robert et al. (2006) reported that Lexapro (10 mg/day for 4 weeks, then 20 mg/day for 8 weeks) substantially reduced PTSD symptoms in 24 persons with the condition.  The reductions in PTSD symptoms among Lexapro users were evidenced by significant score reductions on the CAPS (Clinician-Administered PTSD Scale) after 12 weeks – relative to baseline.

A meta-analysis by Xu et al. (2011) encompassing 7 randomized controlled trials (published between 2008 to 2010) reported that fluoxetine appears effective in the treatment of PTSD.  A double-blind, randomized, placebo-controlled trial by Martenyi et al. (2002) examined the efficacy of fluoxetine (226 recipients) relative to a placebo (75 recipients).

Results of this trial indicated that fluoxetine was significantly more effective than the placebo in reducing symptoms of PTSD – as evidenced by greater improvement in a variety of measures (TOP-8 scores; CAPS total score; CGI-S; CGI-I; HAM-A; MADRS).  A 12-week, randomized, double-blind study by Connor et al. (1999) involving 53 patients with PTSD also discovered that fluoxetine was more effective than the placebo in reducing symptoms of PTSD (severity, disability, stress vulnerability, high end-state function).

As of current, there is stronger evidence to support the use of fluoxetine (Prozac) than to support the use of escitalopram (Lexapro) in the treatment of PTSD.  That said, it remains unknown as to whether one medication (fluoxetine or escitalopram) is significantly more effective than the other for PTSD.

Mechanism of action

The primary mechanism of action for both Lexapro (escitalopram) and Prozac (fluoxetine) is identical – each medication functions chiefly as a selective-serotonin reuptake inhibitor (SSRI).  As selective-serotonin reuptake inhibitors, Lexapro and Prozac bind to serotonin transporters (SERTs) and prevent these transporters from effectively shuttling serotonin from the extracellular space – back into presynaptic serotonergic neurons.

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The inhibition of presynaptic serotonin reuptake [via modulation of serotonin transport] yields significant increases in serotonin concentrations (relative to homeostasis) within extracellular spaces (i.e. positions between presynaptic and postsynaptic receptors).  Significantly increasing extracellular serotonin levels [as a result of diminished serotonin transporter-mediated reuptake] amplifies the activation of postsynaptic serotonin receptors.

Amplification of postsynaptic serotonin receptor activation is observed within just hours of Lexapro and Prozac administration – and is accompanied by changes in neural connectivity (i.e. neural remodeling).  The combination of increased postsynaptic serotonin receptor activation and changes in neural connectivity are potential reasons as to why a subset of Lexapro and Prozac users observe improvement in neuropsychiatric symptoms on Day 1 of treatment.

With continued administration of Lexapro or Prozac over a longer-term (4 to 8 weeks), additional neurochemical changes manifest, including: (1) somatodendritic 5-HT1A receptor activity downregulation (which disinhibits serotonergic neurons and increases firing rates); and (2) upregulation of BDNF concentrations (which facilitates hippocampal neurogenesis).  These additional neurochemical changes (5-HT1A downregulation and BDNF upregulation) may be reasons as to why most Lexapro and Prozac users won’t observe improvement in neuropsychiatric symptoms for 4 to 12 weeks after treatment induction.

Though the primary mechanism of action for Lexapro and Prozac is identical, Lexapro is a slightly more potent selective-serotonin reuptake (SSRI) inhibitor than Prozac.  In addition to Lexapro exerting a slightly greater degree of serotonin reuptake inhibition than Prozac, Lexapro is significantly more selective in its serotonergic action than Prozac – and is understood to be the most selective SSRI developed.

As the most selective SSRI, Lexapro does not substantially interact with many neurochemical sites beyond the serotonin transporter (SERT).  Radioligand binding assays by Owens et al. (2002) suggest that Lexapro exhibits virtually zero binding affinity for more than 100 binding sites – including histamine, alpha-adrenergic, and muscarinic receptors.

The only relevant non-primary (i.e. secondary) neurochemical action of Lexapro involves agonizing sigma-1 and sigma-2 receptors.  Since agonism of sigma-1 and sigma-2 receptors generates antidepressant and anxiolytic effects in animal models, it’s reasonable to speculate that this secondary action contributes [in some degree] to the overall therapeutic effect of Lexapro.

The most significant non-primary (i.e. secondary) neurochemical actions of Prozac involve: upregulating allopregnanolone concentrations (yielding positive allosteric modulation of GABAA receptors) and antagonizing 5-HT2C receptors.  If administered at a high dose, Prozac interacts with 5-HT2A receptors (to a lesser extent than 5-HT2C receptors) and functions as an inhibitor of the norepinephrine transporter (NET) to increase extracellular norepinephrine concentrations.

High-dose Prozac might also negligibly inhibit M1 receptors and (to a lesser degree) M3 receptors.  Furthermore, at high doses, the major metabolite of Prozac known as “norfluoxetine” functions as a dopamine transporter (DAT) inhibitor (which increases dopamine signaling) and, to a negligible extent, inhibits M3 muscarinic acetylcholine receptors (mAChRs).

Research also suggests that Prozac: agonizes sigma-1 receptors; blocks anoctamin-1 channels; inhibits acid sphingomyelinase; interacts with 5-HT3 receptors; modulates nicotinic acetylcholine receptors (nAChRs); and modulates various ion channels.  The extent to which the aforementioned actions contribute to the therapeutic properties of Prozac (in the treatment of neuropsychiatric disorders) remains unknown.

Other neurochemical sites (listed in order of highest to lowest binding affinity) with which Prozac negligibly binds include: M3, M5, M2, M4 muscarinic acetylcholine receptors (mAChRs); alpha-1 adrenergic receptors; H1 histamine receptors; the dopamine transporter (DAT); and 5-HT2B receptors.  Because the binding of Prozac at these neurochemical sites is negligible, it is unlikely that these targets contribute to its overall therapeutic effect in attenuating neuropsychiatric symptoms.

In summary, both Lexapro and Prozac function primarily as inhibitors of serotonin transport and presynaptic serotonin reuptakeLexapro is significantly more selective than Prozac in its neurochemical action such that the only notable non-primary neurochemical action facilitated by Lexapro involves agonism of sigma-1 and sigma-2 receptors.

Prozac is significantly less selective than Lexapro in its neurochemical actions such that it exerts a variety of notable secondary neurochemical actions including: allopregnanolone upregulation; 5-HT2C receptor antagonism; 5-HT2A receptor modulation; norepinephrine transporter (NET) inhibition; dopamine transporter (DAT) inhibition; and M1 muscarinic acetylcholine receptor (mAChR) inhibition.

Disparities in the respective non-primary neurochemical actions of Lexapro and Prozac might be reason as to why Lexapro appears modestly more effective than Prozac as an: (1) antidepressant in meta-analyses and (2) anxiolytic in the management of generalized anxiety disorder.  Moreover, pharmacodynamic differences between these agents might be reason as to why certain individuals exhibit markedly greater neuropsychiatric symptom attenuation when treated with one agent (e.g. Lexapro) relative to the other (e.g. Prozac).

Metabolism & Half-Life

Lexapro and Prozac are both subject to hepatic metabolism via CYP450 (cytochrome P450) enzymes, however, there are notable differences between Lexapro and Prozac in the specifics of their respective hepatic metabolisms.  Lexapro (escitalopram) is metabolized in a relatively even manner by three enzymes, including: CYP2C19 (36%); CYP3A4 (34%); and CYP2D6 (30%) and has an oral bioavailability of ~80%.

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Prozac (fluoxetine) is metabolized primarily by the enzyme CYP2D6 and, to a lesser extent, by enzymes such as CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP3A4, and CYP3A5 – and has an oral bioavailability of ~72%.  Pharmacokinetic research indicates that enzymes implicated in fluoxetine metabolism exhibit similar affinities for fluoxetine enantiomers (R-fluoxetine and S-fluoxetine); the only exception to this is the CYP2C9 enzyme which stereo-selectively metabolizes R-fluoxetine over S-fluoxetine.

The biotransformation of Lexapro (initiated by CYP2C19, CYP3A4, and CYP2D6) yields a variety of metabolites, including: S-demethylcitalopram (S-DCT), S-didemethylcitalopram (S-DDCT), escitalopram-N-oxide, and escitalopram propionic acid.  The biotransformation of Prozac (initiated primarily by CYP2D6) yields one highly-bioactive metabolite known as “norfluoxetine” (via demethylation) – plus fluoxetine glucuronide (via glucuronidation).

The average elimination half-life of Lexapro (escitalopram) ranging from 27 to 33 hours is also significantly shorter than the average elimination half-life of Prozac (fluoxetine) ranging from 96 to 144 hours.  Knowing the average elimination half-lives of Lexapro and Prozac, we can estimate that it’ll take: (1) between 6.18 and 7.56 days to eliminate Lexapro from the body, and (2) between 11 and 22 days to eliminate Prozac from the body – after treatment cessation.

The average elimination half-lives of Lexapro metabolites S-demethylcitalopram and S-didemethylcitalopram are estimated to be ~60 hours and ~100 hours, respectively – whereas the average elimination half-life of Prozac metabolite norfluoxetine is estimated to range from ~168 to ~216 hours.  This means that it could take: (1) up to ~23 days to eliminate Lexapro metabolites from the body, and (2) up to ~50 days to eliminate Prozac metabolites from the body – after treatment cessation.

The longer elimination half-lives of Prozac and its principal “norfluoxetine” metabolite (relative to Lexapro and its metabolites) is suspected to yield a lower-difficulty withdrawal syndrome for Prozac users when compared to Lexapro users.  However, because Prozac is metabolized primarily by CYP2D6 enzymes, Prozac users may be at higher risk of experiencing pharmacokinetically-mediated adverse reactions than Lexapro users (as Lexapro is metabolized evenly by several hepatic enzymes).

Research suggests that genetically-mediated abnormalities in CYP2D6 expression (and possibly CYP2C19 expression), might yield atypical plasma concentrations of both Lexapro and Prozac (relative to the general population) whereby magnitude of therapeutic effects and risk of adverse reactions can significantly decrease and increase, respectively.  Because CYP2D6 enzymes might be implicated in Prozac metabolism to a greater extent than Lexapro metabolism – suboptimal treatment responses and/or risk of adverse reactions might be higher among Prozac users than among Lexapro users.

Popularity

In the United States, Lexapro was initially released as a pharmaceutical medication in August 2002 – whereas Prozac was initially released as a pharmaceutical medication in December 1987.  If comparing the respective historical popularities of Lexapro and Prozac, the latter (Prozac) has been significantly more popular than the former (Lexapro).

Not only is Prozac arguably the most popular antidepressant medication of all time, Prozac might be among the most popular prescription medications of all time.  As the first SSRI medication to hit the market, Prozac has been used in book/movie titles (e.g. “Prozac Nation”), song lyrics, comedy routines, and many laypersons use the term “Prozac” as a loose, nonspecific reference to all antidepressants (similar to using the term “Coke” to refer to all sodas) – but the same cannot be said for Lexapro.

Since Prozac was available for pharmaceutical use over 14 years prior to Lexapro, it’s logical to assume that the cumulative medical use of the Prozac, throughout history, is astronomically greater than that of the Lexapro.  Furthermore, even in recent years, it appears as though the number of annual Prozac prescriptions have exceeded the number of annual Lexapro prescriptions.

According to IMS Health, during 2013, 28.258 million prescriptions were filled for generic Prozac (fluoxetine) and 24.92 million prescriptions were filled for generic Lexapro (escitalopram) – making Prozac (fluoxetine) more popular than Lexapro (escitalopram).  In years 2005, 2009, 2011, and 2013: Prozac (fluoxetine) was the 4th (2005), 5th (2009), 5th (2011), and 4th (2013) most-prescribed psychiatric medication – whereas Lexapro (escitalopram) was the 3rd (2005), 2nd (2009), 6th (2011), and 7th (2013) most-prescribed psychiatric medication.

In other words, the popularity of Lexapro only exceeded the popularity of Prozac in 2005 and 2009.  According to ClinCalc DrugStats Database, during 2015, approximately 28.3 million prescriptions were filled for generic Prozac (fluoxetine) and approximately 24 million prescriptions were filled for generic Lexapro (escitalopram).

Reasons that Prozac remains more popular than Lexapro might include: (1) its FDA-approval to treat more medical conditions than Lexapro; (2) its release ~14 years before Lexapro (potentially leading it to accumulate a larger user-base over time); (3) its milder withdrawals (due to its longer half-life); (4) its strategic use in withdrawal (to attenuate discontinuation symptoms of other SSRIs); (5) its generic availability (prior to Lexapro); (6) its availability in more formats than Lexapro; (7) the use of Celexa (a chemically-similar agent to Lexapro) instead of Lexapro (thereby reducing Lexapro prescriptions).

Reasons that Lexapro might eventually surpass Prozac in future popularity include: (1) its availability as a low-cost generic; (2) its superior efficacy relative to Prozac in the treatment of neuropsychiatric conditions (e.g. depression, generalized anxiety disorder, etc.); (3) its hypothesized ability to treat most medical conditions equally as well as, or better than, Prozac; (4) its more selective pharmacodynamics; (5) its metabolism (facilitated proportionately by three hepatic enzymes – rather than disproportionately by one hepatic enzyme); and (6) its potentially-superior tolerability relative to Prozac.

Side effects

The most common Lexapro side effects (documented by FDA reports) include: insomnia, ejaculation disorder, nausea, sweating, fatigue, somnolence, reduced libido, and anorgasmiaThe most common Prozac side effects (documented by FDA reports) include: abnormal dreams, abnormal ejaculation, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, impotence, insomnia, libido reduction, nausea, nervousness, rash, somnolence, sweating, tremor, vasodilation, and yawning.

Reflecting upon the most common side effects (documented by FDA reports) for Lexapro and Prozac, there appears to be some overlap in the most common side effects of these agents.  Common side effects associated with both Lexapro and Prozac include: insomnia, ejaculation dysfunction, libido reduction, sweating, nausea, somnolence, and anorgasmia.

Assuming the most common side effects documented by the FDA for Lexapro and Prozac are accurate, it seems as though the most common side effects of Lexapro are also common side effects of Prozac.  However, it seems as though Prozac is more likely than Lexapro to cause side effects such as: abnormal dreams, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, nervousness, rash, tremor, vasodilation, and yawning.

Since Lexapro and Prozac exhibit similar primary mechanisms of action (as selective-serotonin reuptake inhibitors), it isn’t surprising that these agents share common side effects.  However, it could be hypothesized that Prozac might cause a greater number of side effects and/or side effects that aren’t associated with Lexapro as a result of its: (1) less selective neurochemical action (i.e. interactions with a variety of secondary targets); (2) greater reliance on CYP2D6 in hepatic metabolism; (3) highly-bioactive norfluoxetine metabolite.

In terms of tolerability, it seems as though both Lexapro and Prozac are among the most-tolerable antidepressants available.  In the largest meta-analysis to date by Cipriani et al. (2018), the odds ratio for acceptability (“dropout rate”) of Lexapro [relative to a placebo] was “0.90” – and the odds ratio for acceptability (“dropout rate”) of Prozac [relative to a placebo] was “0.88.

The aforementioned odds ratios indicate that, on average, fewer users of Lexapro and Prozac discontinue treatment than users of placebo interventions in the management of major depressive disorder.  Although Prozac had a clinically-superior acceptability rate than the placebo and Lexapro did not, there were no statistically-significant differences in acceptability between Lexapro and Prozac.

Cipriani et al. (2018) reported that Lexapro and Prozac appear to be among the most acceptable antidepressants along with agomelatine, citalopram, sertraline, and vortioxetine.  Agents that were significantly less tolerable than Lexapro and Prozac (as evidenced by high dropout rates) included: amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine.

In an earlier meta-analysis by Cipriani et al. (2009), Lexapro was reported as exhibiting the highest acceptability of all antidepressant medications along with Zoloft.  Although Lexapro exhibited superior acceptability relative to Prozac in the meta-analysis by Cipriani et al. (2009), there were no statistically-significant differences in acceptability rates between these agents.

This further supports the idea that Lexapro and Prozac exhibit similar tolerability in the management of major depressive disorder.  In sum, evidence suggests that Lexapro and Prozac are extremely well-tolerated antidepressants – and that there are no clinically-significant differences between these agents in tolerability.

Withdrawal

In the event that an individual discontinues Lexapro or Prozac after regular use, he/she will be at risk of developing physical and/or psychological withdrawal symptoms.  Though all former users of Lexapro and Prozac are at risk of developing withdrawal symptoms, symptoms tend to be most prevalent and debilitating among persons who: (1) used these agents for a long-term; (2) used high doses; and (3) abruptly stopped treatment without tapering (i.e. “cold turkey”).

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For some individuals, withdrawal symptoms from Lexapro or Prozac will linger for months (or longer) after the date of complete discontinuation – such that these persons experience a “post-acute withdrawal syndrome” (PAWS).  Throughout Lexapro or Prozac withdrawal, former users might experience severe deficits in academic, occupational, familial, and/or social abilities.

Examples of common withdrawal symptoms associated with Lexapro and Prozac cessation include: rebound neuropsychiatric symptoms (anxiety, depression, obsessive-compulsive disorder, etc.); dizziness and balance problems; frequent headaches; sleepiness; muscle tension; nausea; insomnia; fatigue and sleepiness; lightheadedness; flu-like symptoms; and brain zaps.

Withdrawal symptoms associated with Lexapro and Prozac are hypothesized to emerge as a result of neurochemical imbalances throughout the brain while it transitions from a medication-adapted state – to “drug free” homeostasis.  Anytime an individual administers Lexapro or Prozac regularly (i.e. daily) for a reasonable duration (e.g. months, years, etc.), his/her neurophysiology will adapt to the constant presence of the medication.

Neurophysiologic adaptations to the presence of Lexapro and Prozac may include: (1) decreased production of endogenous serotonin; (2) presynaptic 5-HT1A receptor desensitization; (3) altered expression of various genes implicated in neurotransmitter production; (4) modified activation of secondary chemical messengers (e.g. cyclic-AMP); and (5) downregulation of 5-HT1A autoreceptors.  Once a person exhibits significant neurophysiologic adaptations in response to a medication, that medication becomes required to maintain preexisting neurophysiologic balance.

In the aftermath of medication cessation, all medication-induced neurophysiologic adaptations will remain – and neurophysiology will become grossly imbalanced without the medication from which the adaptations were induced.  Neurophysiologic imbalances in Lexapro or Prozac discontinuation are what give rise to disconcerting physical and/or psychological withdrawal reactions that former users report.

With adequate time removed from Lexapro or Prozac treatment, neurophysiologic processes will gradually readjust (re-adapt) to functioning without the presence of medication.  Though this readjustment period can take longer than expected (e.g. weeks, months, years, etc.), once complete, withdrawal symptoms will abate.

Since Lexapro and Prozac exhibit the same primary mechanism of action (as SSRIs), there are likely commonalities between these agents in the specific withdrawal symptoms and/or severities of withdrawal symptoms that they cause.  However, because Lexapro and Prozac exhibit differences in elimination half-life and secondary neurochemical actions, there could be disparities between these agents in: (1) severity of withdrawal; (2) onset of withdrawal symptoms; and (3) specific withdrawal symptoms.

Elimination half-life is understood to significantly influence both the severity of withdrawal – and onset of withdrawal symptoms.  In general, antidepressants with long elimination half-lives like Prozac are associated with delayed-onset withdrawal and lower-severity withdrawal symptoms – relative to antidepressants with short elimination half-lives.

The elimination half-life of Prozac ranges from 96 to 144 hours, and the elimination half-life of its primary bioactive metabolite norfluoxetine ranges from 168 to 360 hours – whereas the elimination half-life of Lexapro ranges from 27 to 33 hours, and the elimination half-life of its longest-acting metabolite is estimated to be ~100 hours.  Based on the aforementioned half-lives, one would expect Prozac withdrawal be of lower severity and later onset – than Lexapro withdrawal.

This is because the longer elimination half-life of Prozac enables neurophysiology to slowly recalibrate towards functioning with lower concentrations of the medication (to which it has adapted) over a lengthier duration – prior to complete systemic elimination.  With Prozac, neurophysiology recalibrates itself over a lengthier duration [relative to Lexapro] prior to complete elimination, such that, by the time the medication is eliminated from the body, neurophysiology will be closer to homeostasis – making for a shorter-term and smoother homeostatic transition.

Because it takes 11 to 22 days to eliminate Prozac (and up to ~50 days to eliminate its bioactive metabolite) from the body – versus 6.18 to 7.56 days to eliminate Lexapro (and up to ~23 days to eliminate one of its metabolites), withdrawal symptoms may be “delayed onset” with Prozac relative to Lexapro.  A delay in onset of withdrawal symptoms for Prozac users (relative to Lexapro users) is attributable to the fact that fluoxetine remains in systemic circulation for a longer duration than escitalopram – and withdrawal symptoms tend to emerge and/or peak only once the medication has been fully eliminated from the body.

Differences between Lexapro and Prozac in specific withdrawal symptoms could be attributable to disparities in the non-primary neurochemical actions of each medication.  Lexapro interacts with sigma receptors as a non-primary action – whereas Prozac interacts with: 5-HT2C receptors; 5-HT2A receptors; anoctamin-1 channels; acid sphingomyelinase; the norepinephrine transporter (NET); muscarinic acetylcholine receptors; the dopamine transporter (DAT); sigma-1 receptors; 5-HT3 receptors; and nicotinic acetylcholine receptors.

In other words, Lexapro users might experience withdrawal symptoms that are attributable to adaptations stemming from interactions with the serotonin transporter (SERT) and sigma receptors.  In comparison, Prozac users might experience withdrawal symptoms that are attributable to adaptations stemming from interactions with the serotonin transporter (SERT), 5-HT2C; 5-HT2A; anoctamin-1; acid sphingomyelinase; norepinephrine transporters; dopamine transporters; 5-HT3; sigma-1 receptors; and acetylcholine receptors.

Knowing that Prozac interacts with a greater number of neurochemical targets than Lexapro at high doses, it’s reasonable to hypothesize that high-dose Prozac users might experience a greater number of unique withdrawal symptoms – relative to high-dose Lexapro users.  Nevertheless, it is unknown as to whether Lexapro and Prozac differ in duration of withdrawal in the aftermath of systemic elimination.

In conclusion, withdrawal from Lexapro will likely be more difficult (on average) than withdrawal from Prozac (at an equipotent-dose) due to its shorter elimination half-life.  Moreover, Lexapro withdrawal will begin sooner than Prozac withdrawal (as a result of its shorter elimination half-life) and may cause fewer total symptoms than Prozac withdrawal (as a result of its more selective action).

Similarities (Synopsis): Lexapro vs. Prozac

Included below is a brief recap of general similarities of Lexapro (escitalopram) and Prozac (fluoxetine).  Lexapro and Prozac are similar in regards to: cost; drug classification; duration of action; efficacy in the treatment of major depressive disorder; legal status; medical uses; onset of action; primary mechanism of action; and tolerability.

  • Cost: Both standard Lexapro and standard Prozac are sold as low-cost generics. A total of 30 generic Lexapro tablets costs between $8 and $49 – whereas a total of 30 generic Prozac capsules costs between $4 and $26.  Though Prozac might be slightly cheaper (on average) than Lexapro, most consumers won’t consider the cost difference of these agents as being significant.
  • Drug classification: Lexapro and Prozac share the same drug classification as “selective-serotonin reuptake inhibitors” (SSRIs). This classification is based upon the fact that each functions primarily by preventing the presynaptic reuptake of serotonin to increase extracellular serotonin concentrations and bolster postsynaptic serotonergic signaling.
  • Duration of action: The approximate duration of action associated with standard Lexapro and Prozac formats is ~24 hours. Based on the ~24-hour duration of action, both Lexapro and Prozac are generally recommended to be administered once daily (at the same time each day).  (It should be noted that there is a delayed-release version of Prozac that remains active for 1-week).
  • Efficacy (?): Though there are some data suggesting that Lexapro might be slightly more effective than Prozac for major depressive disorder, the difference in efficacy is not clinically-relevant. In other words, Lexapro and Prozac are equally efficacious for major depressive disorder.  Moreover, while Lexapro might be more effective than Prozac for certain medical conditions, and Prozac more effective than Lexapro for other medical conditions, no difference in efficacy between these agents for any condition has been substantiated.
  • Generic availability: Both Lexapro and Prozac are available as generics in the United States. (Lexapro became available as a generic in 2012 – and Prozac became available as a generic in 2001). Generic Lexapro is sold under the chemical name “escitalopram oxalate” and generic Prozac is sold under the chemical name “fluoxetine hydrochloride.”
  • Legal status: Lexapro and Prozac are legally-classified as prescription-only (Rx-only) medications. With this classification, Lexapro and Prozac can only be acquired and administered with an authentic prescription from a licensed medical doctor.
  • Medical uses: There aren’t significant differences in the medical uses of Lexapro and Prozac. Both medications are commonly prescribed to treat neuropsychiatric conditions such as: major depressive disorder; obsessive compulsive disorder (OCD); panic disorder; post-traumatic stress disorder (PTSD); premature ejaculation; premenstrual dysphoric disorder (PMDD); body dysmorphic disorder; and social anxiety disorder.
  • Onset of action: Although certain studies suggest that Lexapro might provide a faster onset of antidepressant action than other medications (including Prozac), most evidence indicates onset of therapeutic action is similar for Lexapro and Prozac. Both Lexapro and Prozac enhance serotonin signaling and modulate connections throughout the brain on the first day of treatment, but most users won’t experience therapeutic effects for 4 to 8 weeks of treatment.
  • Primary mechanism of action: The primary mechanism of action for both Lexapro and Prozac involves interacting with the serotonin transporter (SERT) to prevent it from facilitating the presynaptic reuptake of serotonin. This action increases extracellular serotonin concentrations and strengthens postsynaptic serotonin signaling to alleviate neuropsychiatric symptoms.
  • Side effects: Because Lexapro and Prozac exhibit the same primary mechanism of action, common side effects associated with these agents tend to be similar. All of the most common side effects for Lexapro are also listed as common side effects for Prozac, including:  insomnia, ejaculation dysfunction, impaired libido, sweating, nausea, somnolence, and anorgasmia.
  • Tolerability: As of 2018, Lexapro and Prozac are considered two of the most-tolerable antidepressants on the market. Evidence from a comprehensive meta-analysis by Cipriani et al. (2018) reveals that Lexapro and Prozac are associated with lower dropout rates than placebos.  There are no data to substantiate the idea that one agent (Lexapro or Prozac) is notably more tolerable than the other.

Note: If you know of additional similarities between Lexapro and Prozac that weren’t noted in the above list – mention them in the comments.

Differences (Synopsis): Lexapro vs. Prozac

Included below is a brief recap of general differences between Lexapro (escitalopram) and Prozac (fluoxetine).  Lexapro and Prozac differ in: elimination half-life; FDA-approved uses; formatting options; ingredients; metabolism; popularity; secondary neurochemical actions; and withdrawal severity.

  • Bioavailability: The bioavailability of Lexapro is ~80% – and the bioavailability of Prozac is ~72%. In other words, a slightly greater percentage (~8%) of ingested Lexapro is bioactive (modulates physiology) than ingested Prozac.
  • Developers: Lexapro was developed as a collaboration between the pharmaceutical companies Lundbeck and Forest Laboratories. Prozac was developed by chemists Bryan Molloy and Robert Rathburn at the pharmaceutical company Eli Lilly.
  • Elimination half-life: The elimination half-life of Lexapro ranges from 27 to 33 hours, whereas the elimination half-life of Prozac ranges from 96 to 144 hours. Moreover, the longest-acting metabolite of Lexapro has an elimination half-life of ~100 hours, whereas the primary bioactive metabolite of Prozac known as “norfluoxetine” has an elimination half-life ranging from 168 to 360 hours.  This means that Prozac [and its metabolites] require more time to eliminate from the body than Lexapro [and its metabolites] following discontinuation.
  • FDA approved uses: Although Lexapro and Prozac are both approved by the U.S. FDA for the treatment of major depressive disorder (MDD), the medications differ in additional U.S. FDA-authorized uses. Lexapro is FDA-approved to treat generalized anxiety disorder (Prozac is not) – and Prozac is FDA-approved to treat obsessive-compulsive disorder (OCD), bulimia nervosa, and panic disorder (Lexapro is not).
  • Formatting: There are notable differences in the available formats for Lexapro and Prozac, respectively. Lexapro is manufactured in 2 standard-release formats: tablet and oral solution (both of which remain active for ~24 hours).  Prozac is manufactured in 3 standard-release formats: capsule, tablet, and oral solution (all of which remain active for ~24 hours) and 1 delayed-release tablet (which remains active for ~1 week).
  • Ingredients: The active ingredient in the medication Lexapro is the chemical “escitalopram oxalate.” The active ingredient in the medication Prozac is the chemical “fluoxetine hydrochloride.”
  • Metabolism: Lexapro and Prozac both undergo hepatic metabolism via CYP450 (cytochrome P450) isoenzymes, however, there are differences in the specific enzymes implicated in their respective metabolisms – and the magnitudes of contribution from each enzyme involved. Lexapro is metabolized in a near-even manner by 3 enzymes: CYP2C19 (36%), CYP3A4 (34%), and CYP2D6 (30%).  Prozac is metabolized mostly by CYP2D, but other enzymes modestly contribute to its metabolism, including: CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP3A4, and CYP3A5.
  • Popularity: The respective popularities of Lexapro and Prozac in the United States differ in present day – and historically. In 2015, ~24 million prescriptions were filled for generic Lexapro (escitalopram) and ~28.3 million prescriptions were filled for generic Prozac (fluoxetine) – making the latter (Prozac) more popular than the former (Lexapro).  Moreover, as the first SSRI approved in the U.S. in 1987, Prozac has historically been significantly more popular than Lexapro (and other SSRIs).
  • Secondary neurochemical actions: Though Lexapro and Prozac share the same primary mechanism of action, these agents differ in their non-primary (i.e. secondary) neurochemical effects. Lexapro is highly-selective in that its only relevant non-primary neurochemical action is modest agonism of sigma-1 and sigma-2 receptors.  Non-primary neurochemical actions of Prozac include modulation of: 5-HT2C receptors, 5-HT2A receptors, anoctamin-1 channels, acetylcholine receptors (muscarinic and nicotinic), norepinephrine transporters, dopamine transporters, acid sphingomyelinase, allopregnanolone, and ion channels.
  • Side effects: Although Lexapro and Prozac cause many similar side effects (likely due to their identical primary mechanisms of action), it seems as though a greater number of “common side effects” have been reported for Prozac – relative to Lexapro. Assuming these reports accurately reflect side effect differences between Lexapro and Prozac, it’s reasonable to surmise that Prozac users may experience more side effects (on average) than Lexapro users.  Common side effects of Prozac (but not Lexapro) include: abnormal dreams, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, nervousness, rash, tremor, vasodilation, and yawning.
  • Withdrawal: Lexapro and Prozac might differ in aspects of withdrawal, including: withdrawal onset, severity of withdrawal symptoms, and/or specific symptoms (i.e. presentation). Because Prozac has a significantly longer elimination half-life than Lexapro, the onset of Prozac withdrawal (following its discontinuation) is much later than the onset of Lexapro withdrawal (following its discontinuation).  The severity of Prozac withdrawal is also hypothesized as being lesser than that of Lexapro as a result of its longer elimination half-life enabling a smoother physiologic transition from medication-adapted to homeostasis.  There might also be differences in specific withdrawal symptoms associated with each agent due to disparities in non-primary neurochemical actions (and corresponding physiologic adaptations).

Note: If you know of additional differences between Lexapro and Prozac that weren’t noted in the above list – mention them in the comments.

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

To assess whether Lexapro or Prozac might be “better” (on average) than the other in the management of a specific medical condition, it’s important to reflect upon variables that prospective users and/or medical doctors care about.  The most important variables would be: efficacy (in the management of a specific medical condition) and tolerability – followed by things like: average cost, formatting/dosages, onset and duration of action, FDA-authorized uses, side effects, and discontinuation difficulty.

In a majority of the aforementioned variables (including efficacy and tolerability) there don’t appear to be clinically-significant differences between Lexapro and Prozac.  As a result, most psychiatrists and general medical doctors won’t regard one medication (Lexapro or Prozac) as being “superior” relative to the other in the management of major depressive disorder (MDD) and other neuropsychiatric conditions.

Why Lexapro over Prozac? (Possible reasons)

Lexapro might be regarded as modestly or potentially-advantageous over Prozac based on its: (1) efficacy (major depressive disorder); (2) tolerability and side effects; (3) onset of therapeutic action; (4) metabolism; and/or (5) FDA-approval for generalized anxiety disorder.

1. Efficacy (MDD): In a comprehensive meta-analysis of antidepressant efficacy by Cipriani et al. (2018), Lexapro appeared slightly more effective (on average) than Prozac in the treatment of major depressive disorder. Specifically, the odds ratio of Lexapro facilitating a therapeutically-relevant antidepressant effect (relative to a placebo) based on existing clinical trial data was “1.68” whereas the reported odds ratio of Prozac facilitating a therapeutically-relevant antidepressant effect (relative to a placebo) based on existing clinical trial data was “1.52.”

Though the difference between respective odds ratios for Lexapro and Prozac was not clinically-significant, the numbers indicate that Lexapro might be slightly more effective than Prozac as a treatment for major depressive disorder.  A different meta-analysis by Ramsberg et al. (2010) revealed that Lexapro treatment was associated with a higher probability of depression remission (0.456 vs. 0.371) and quality-of-life score (0.6978 vs. 0.6847) – when compared to Prozac treatment.

Moreover, a meta-analysis by Cipriani et al. (2009) noted that the probability of Lexapro being among the top 4 most effective antidepressants (of 12 medications) was 23.7% – whereas the probability of Prozac being among the top 4 most effective antidepressants (of 12 medications) was 0%.  Reflecting upon the respective efficacies of Lexapro and Prozac for the treatment of major depressive disorder, it seems as though there are data to support the idea that Lexapro could be [modestly] effective than Prozac – but zero data to suggest the opposite.

Knowing that Lexapro could be [modestly] more effective than Prozac for major depressive disorder (in terms of response rates, remission rates, and quality-of-life), it’s reasonable for some to consider it a slightly “better” treatment option.

2. Tolerability & side effects: In addition to its potentially-superior efficacy, Lexapro might be [modestly] more tolerable and/or cause fewer total side effects (on average) than Prozac. A meta-analysis by Cipriani et al. (2009) reported that Lexapro was associated with higher acceptability (fewer patients discontinued treatment) than Prozac and many other antidepressants (the only exception being Zoloft) – supporting the idea that Lexapro might be [modestly] more tolerable than Prozac.

Moreover, according to respective FDA reports of adverse effects associated with Lexapro and Prozac, the former (Lexapro) causes fewer common adverse effects than the latter (Prozac).  All of the most common Lexapro side effects (as reported by the FDA): insomnia, ejaculation disorder, nausea, sweating, fatigue, somnolence, reduced libido, and anorgasmia – are also documented (by the FDA) as common Prozac side effects.

That said, other common Prozac side effects (as reported by the FDA): abnormal dreams, abnormal ejaculation, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, impotence, insomnia, libido reduction, nausea, nervousness, rash, somnolence, sweating, tremor, vasodilation, and yawning – are not documented (by the FDA) as common Lexapro side effects.

Assuming the respective FDA reports of common side effects for Lexapro and Prozac are fully comprehensive and accurate, it would seem as though Lexapro causes fewer total side effects than Prozac – potentially making the former (Lexapro) more tolerable, on average, than the latter (Prozac).

3. Onset of therapeutic action: It’s also reasonable to surmise that Lexapro might have a slightly faster onset of action than Prozac in the management of neuropsychiatric conditions. Some studies have reported that Lexapro is associated with a quicker onset of therapeutic action than medications like citalopram (Celexa) paroxetine (Paxil) in the treatment of major depressive disorder and obsessive-compulsive disorder.

Considering that: (1) citalopram and paroxetine are associated with similar onset rates of therapeutic action as Prozac; and (2) Lexapro might exhibit a faster onset of therapeutic action than citalopram and paroxetine – it’s reasonable to surmise that Lexapro might also exhibit a [modestly] faster onset of therapeutic action than Prozac.

4. Metabolism: Lexapro users might be at lower risk of experiencing pharmacokinetically-mediated adverse effects than Prozac users due to the fact that Lexapro is metabolized in near-parallel by three hepatic enzymes: CYP2C19 (36%); CYP3A4 (34%), and CYP2D6 (30%). In comparison, Prozac is metabolized primarily by the CYP2D6 enzyme (rather than in parallel and similar magnitude by other enzymes).

Due to heavy reliance on CYP2D6 enzymes in Prozac metabolism, Prozac users with abnormal CYP2D6 function as a result of gene expression and/or concurrent substance use – might be at higher risk of experiencing pharmacokinetically-mediated adverse effects than Lexapro users.

5. FDA-approval for generalized anxiety disorder: Some might regard Lexapro as a superior treatment choice (over Prozac) for generalized anxiety disorder (GAD) – and/or other anxiety disorders – based on the fact that: (1) Lexapro is FDA-approved to treat generalized anxiety disorder (Prozac is not); and (2) preliminary data suggest that Prozac might be ineffective for anxiety reduction.

Though there’s no definitive proof that Lexapro is significantly more effective than Prozac for anxiety disorders, Lexapro remains the better treatment choice (relative to Prozac) for anxiety disorders.  Strong evidence supports the idea that Lexapro alleviates anxious symptoms, whereas preliminary evidence indicates that Prozac might be incapable of significantly alleviating anxious symptoms.

Why Prozac over Lexapro? (Possible reasons)

Prozac might be regarded as modestly or potentially-advantageous over Lexapro in aspects such as: (1) withdrawal; (2) tolerability; (3) formatting; (4) FDA-approval to treat OCD, bulimia nervosa, and panic disorder; and/or (5) cost.

1. Withdrawal: Withdrawal symptoms that emerge following Prozac discontinuation are hypothesized to be significantly less severe than withdrawal symptoms that emerge following Lexapro discontinuation. The hypothesized lower-severity withdrawal associated with Prozac cessation (relative to Lexapro cessation) is believed to be related to the longer elimination half-life of Prozac.

The elimination half-life of Prozac ranges from 96 to 144 hours – meaning it takes between 11 and 22 days (on average) to exit the body after discontinuation.  Moreover, the elimination half-life of “norfluoxetine” (the bioactive metabolite of Prozac) ranges from 168 to 216 hours – meaning it could take up to ~50 days to fully eliminate active Prozac metabolites from the body after discontinuation.

Since Prozac and its metabolites are gradually eliminated from the body over an extended period (up to 50 days), the neurophysiology of a former Prozac user will slowly readjust over a longer period, such that, by the time Prozac is fully cleared from the body, neurophysiology will be closer to homeostasis.  This allows for a smoother and more efficient transition back to homeostatic neurophysiology from a medication-adapted state, and likely, lower-magnitude withdrawal symptoms (on average) relative to Lexapro.

2. Tolerability: A meta-analysis by Cipriani et al. (2018) indicates that Prozac may be negligibly more tolerable than Lexapro (on average). In the meta-analysis by Cipriani et al. (2018), the odds ratio for the acceptability of Prozac was “0.88” and the odds ratio for the acceptability of Lexapro was “0.90.”

Although the difference in acceptability odds ratios for Prozac and Lexapro were not “statistically significant” – the odds ratio of “0.88” for Prozac suggests that it might be negligibly more tolerable than Lexapro with an odds ratio of “0.90.”  In other words, “0.02” fewer people discontinued Prozac treatment than Lexapro treatment in well-designed trials.

Moreover, Prozac exhibited significantly greater average acceptability than a placebo – whereas Lexapro did not.  Based upon the aforementioned respective odds ratios of acceptability associated with Prozac and Lexapro, some persons might regard Prozac as being more tolerable than Lexapro – and thus, prefer its usage instead of Lexapro.

3. Formatting: Although both Prozac and Lexapro are manufactured in standard tablet and oral solution formats, only Prozac is also available in standard capsule and delayed-release capsule formats. Certain individuals might perceive the total number of and/or specific formatting options associated with Prozac as being advantageous over the limited formatting options associated with Lexapro.

Perhaps the most significant formatting advantage associated with Prozac (relative to Lexapro) is its availability in delayed-release capsules.  Delayed-release Prozac capsules may be more convenient for certain patients in that they provide a ~1-week duration of action and thus only require once-per-week dosing.

Medical professionals might also perceive delayed-release Prozac capsules as advantageous in that they might increase treatment compliance for certain patients (particularly those who frequently forget to administer daily doses of standard-release formats).  Because Prozac is offered in standard-release and longer-acting (delayed-release) formats – it’s reasonable to regard its formatting options as an advantage for Prozac over Lexapro.

4. FDA-approvals: Some might regard Prozac as a superior treatment choice (over Lexapro) for the treatment of obsessive-compulsive-disorder (OCD), bulimia nervosa, and panic disorder – based on the fact that Prozac is FDA-approved to treat these conditions (Lexapro is not). Though there’s preliminary evidence suggesting that Lexapro may be efficacious for these conditions, Prozac remains the better treatment choice (relative to Lexapro) in OCD, bulimia nervosa, and panic disorder based on the fact that there’s stronger evidence to support its efficacy (when compared to Lexapro).

5. Lower average cost (?): Though the cost of standard generic Prozac (fluoxetine) isn’t much different than the cost of standard generic Lexapro (escitalopram), it seems as though standard generic Prozac (fluoxetine) is marginally less expensive (on average) than standard generic Lexapro (escitalopram). A total of 30 standard fluoxetine capsules retail for $4 to $26 (on average) – whereas a total of 30 standard escitalopram tablets retail for $8 to $49 (on average).

Taking the averages of the aforementioned price ranges for each medication, it would seem as though a “30 count” of fluoxetine retails for ~$15 and a “30 count” of fluoxetine retails for ~$28.50.  Based upon these price averages, it would seem as though generic Prozac (fluoxetine) costs ~$13.50 less per month than generic Lexapro (escitalopram).

Over a 1-year period, someone paying $13.50 per month less for his/her prescriptions would save ~$162.  Though not everyone considers $162 per year in prescription savings to be of financial significance, certain persons might use Prozac (fluoxetine) over Lexapro (escitalopram) if they were able to save this amount.

Deciding whether to try Lexapro or Prozac…

It may be difficult for patients and/or medical doctors considering an SSRI (selective-serotonin reuptake inhibitor) to choose between Lexapro and Prozac.  In the treatment of major depressive disorder (MDD), there are no substantial data to suggest that Lexapro and Prozac differ significantly in measures of efficacy and tolerability – the most important variables to consider when comparing medications.

Moreover, there don’t appear to be significant differences between Lexapro and Prozac in cost – both are available as low-cost generics (usually retailing at less than $10 for a 30-day supply).  That said, there are data from multiple meta-analyses and trials to suggest that Lexapro might be modestly superior to Prozac in terms of: response rates, remission rates, and quality-of-life during treatment – in the treatment of major depressive disorder.

Additionally, some evidence suggests that Lexapro exhibits a faster onset of therapeutic action than other SSRIs like citalopram and paroxetine.  Since there are no reports of a faster onset of therapeutic action associated with Prozac relative to other SSRIs – it’s reasonable to surmise that Lexapro might be a faster-acting medication than Prozac.

It’s also reasonable to hypothesize that Lexapro might be less likely than Prozac (on average) to provoke pharmacokinetic-related adverse reactions due to its seemingly parallel metabolism by three enzymes (CYP2C19, CYP3A4, CYP2D6) – versus metabolism primarily by one enzyme (CYP2D6) for Prozac.  Lexapro is also advantageous over Prozac in the management of generalized anxiety disorder (GAD) based upon its FDA-approval for this condition and lack thereof for Prozac (accompanied by evidence suggesting that Prozac may be ineffective for generalized anxiety).

Okay, but might there be some advantages associated with using Prozac over Lexapro?  Some might argue that Prozac is a better medication to use than Lexapro based upon its perceived easier withdrawal in the aftermath of discontinuation, however, it is unknown as to whether Prozac withdrawal is legitimately less severe than Lexapro withdrawal – particularly if Lexapro withdrawal involves a gradual taper of dosing over an extended duration.

Prozac may have a delayed onset of withdrawal (due to its longer half-life) wherein patients do not notice withdrawal symptoms until the medication has been completely eliminated from systemic circulation (this can take nearly 2 months).  This might lead patients to mistakenly assume that they experienced no withdrawal after stopping and/or that symptoms they experience ~2 months after stopping Prozac are a worsening of preexisting medical conditions – rather than Prozac withdrawal symptoms.

Furthermore, since high-dose Prozac modulates a greater number of neurochemical targets than Lexapro (which mostly affects the serotonin transporter and negligibly interacts with sigma receptors), Prozac users might experience a greater number of withdrawal symptoms than Lexapro users.  That said, assuming Prozac withdrawal is legitimately less severe than Lexapro withdrawal due to the longer elimination half-life of Prozac, Lexapro users can simply use a “Prozac bridge” (i.e. transition to Prozac) upon Lexapro cessation to attenuate Lexapro withdrawal symptoms.

It is known that Prozac is offered in a greater number of formats than Lexapro, including a delayed-release capsule that exerts a long-lasting effect of ~1-week.  Because delayed-release Prozac (also referred to as “Prozac weekly”) is more convenient for some patients and/or may improve treatment compliance in a subset of patients, this format option could be a reason to choose Prozac over Lexapro in the management of major depressive disorder.

Prozac may also be advantageous over Lexapro in the treatment of bulimia nervosa, obsessive-compulsive disorder, and panic disorder – based on the fact that it has received FDA-approval to treat these conditions and Lexapro has not.  Moreover, while some evidence from a 2018 meta-analysis suggests that Prozac might be negligibly more tolerable than Lexapro (on average), both medications are classified as being among the most-tolerable agents on the market.

Additionally, older meta-analyses and head-to-head studies suggest that Lexapro is more tolerable than Prozac.  Assuming patients have no issue with treatment compliance (and wouldn’t benefit from delayed-release Prozac), and that Lexapro and Prozac are being considered as treatments for major depressive disorder (the only condition for which both are FDA-approved) – there’s no reason to favor Prozac over Lexapro.

However, because Lexapro is associated with: (1) potentially-superior efficacy; (2) potentially-faster onset of action; (3) potentially-lower rates of pharmacokinetically-mediated adverse reactions; and (4) fewer total side effects (according to FDA reports) – it makes logical sense to regard Lexapro as a potentially “better” medication (on average) than Prozac in the management of major depressive disorder.

Still, it’s important to underscore that responses to Lexapro and Prozac for the management of major depressive disorder (and other neuropsychiatric conditions) generally vary significantly among users.  Certain individuals might claim that “Lexapro worked way better than Prozac,” others might claim that “Prozac worked way better than Lexapro,” and additional persons might note that both medications were equally efficacious (or ineffective).

Individual variables such as genetic or epigenetic expression; pre-treatment neurochemistry and physiology; neural connectivity; brain morphology; autonomic nervous system activation; medical conditions; etc. – could explain why certain persons exhibit markedly different reactions to treatment with Lexapro and Prozac.

To accurately gauge whether one medication (Lexapro or Prozac) is “better” than the other for a particular condition, patients will need to test each medication, separately, for adequate duration (usually 4 to 8 weeks) under medical guidance.

Which medication do you prefer to use? (Lexapro or Prozac)

If you’ve personally experienced treatment with Lexapro and Prozac (separately), feel free to leave a comment discussing your respective experiences with each agent.  In your comment, mention whether you: prefer one medication over the other OR have zero preference for one medication over the other.

To help others best understand your respective treatments with Lexapro and Prozac, provide specific details in your comment such as: dosages administered; treatment durations; concurrent substance use during each treatment; and/or the medical condition(s) for which each agent was prescribed.

Assuming you were asked to provide ratings for Lexapro and Prozac on a scale ranging from 1 to 10 (with “1” being ineffective/intolerable and “10” being maximally effective/zero tolerability issues) – what ratings would you provide for the “efficacy” (1-10) and “tolerability” (1-10) of these agents?  In the event that you prefer one medication over the other, document reasons for your preference.

Examples of reasons for preferring one medication over the other might be: superior efficacy in managing symptoms; easier to tolerate (causes fewer unwanted side effects and/or less severe side effects); lower cost; formatting options (e.g. delayed-release Prozac).

If you’ve noticed that one agent (Lexapro or Prozac) was more effective or tolerable than the other – might differences in efficacy or tolerability be attributable to disparities in: potencies of dosing; concurrent substance use throughout treatment; and/or pre-treatment neurophysiology?