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Fluoxetine vs Sertraline
Introduction
For those dealing with major depressive disorder (MDD) or different forms of depression, drugs known as antidepressants can assist in managing symptoms and stabilizing depressive lows. Antidepressants generally work by modifying the levels of chemical messengers known as neurotransmitters that are involved in mood and many other processes. Fluoxetine and sertraline are two such drugs frequently prescribed for treating depression. Both primarily influence the neurotransmitter serotonin within the brain, working to stabilize mood in patients experiencing depression. Fluoxetine, commonly marketed under the brand name Prozac, belongs to a class of drugs called selective serotonin reuptake inhibitors (SSRIs), which primarily influence serotonin levels. Sertraline, often known by the brand name Zoloft, is also an SSRI antidepressant that primarily affects levels of serotonin. While these antidepressant medications have many similarities, they may be prescribed under different circumstances and they have tolerability and side effect profiles. Read on to find out more about how fluoxetine (Prozac) compares to sertraline (Zoloft).
Fluoxetine vs Sertraline Side By Side
| Attribute | Prozac | Zoloft |
|---|---|---|
| Brand Name | Prozac | Zoloft |
| Contraindications | Should not be taken by those currently taking–or who have recently taken–monoamine oxidase inhibitors (MAOIs) | Should not be taken by those currently taking–or who have recently taken–monoamine oxidase inhibitors (MAOIs) |
| Cost | Approximately $0.05 to $0.90 per day for generic versions | Approximately $0.28 to $1.00 per day for generic versions |
| Generic Name | Fluoxetine | Sertraline |
| Most Serious Side Effects | Worsening of depression symptoms or suicidal thoughts, allergic reaction, vision changes, accelerated or irregular heart rate, low sodium levels in the blood, severe nervous system reaction, serotonin syndrome | Signs of an allergic reaction, severe skin reaction, unusual changes in mood or behavior, changes in vision, accelerated or irregular heartbeat, serotonin syndrome, low sodium levels in the blood |
| Severe Drug Interactions | Monoamine oxidase inhibitors (MAOIs) | Monoamine oxidase inhibitors (MAOIs) |
| Typical Dose | 20 mg/day, up to a maximum of 80 mg/day | 50 mg/day, up to a maximum of 200 mg/day |
What is Fluoxetine?
Fluoxetine (commonly known by the brand name Prozac) is one of the most commonly prescribed drugs in the SSRI class of antidepressants (selective serotonin reuptake inhibitors). It was approved by the FDA in 1987. Fluoxetine, like other SSRIs, functions by increasing levels of free serotonin within the brain by inhibiting (blocking) its reuptake (reabsorption into neurons), essentially allowing it to remain active for longer periods of time. Fluoxetine is frequently used for treating various forms of depressive disorders, along with other mental health conditions like obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), bulimia nervosa, and anxiety disorders. Fluoxetine/Prozac has a selective impact on serotonin receptors, with minimal influence on dopamine and norepinephrine (other neurotransmitters which are targeted by some other types of psychiatric medications). Fluoxetine can be highly effective in treating the symptoms of both depressive and anxiety disorders, and its side effect profile is similar to that of many SSRIs. Common side effects can include sexual dysfunction, indigestion, insomnia, decreased appetite, gastrointestinal upset (nausea, diarrhea, etc.), dry mouth, and skin rash.
What conditions is Fluoxetine approved to treat?
Fluoxetine is approved for the treatment of various psychiatric disorders, including:
- Major depressive disorder (MDD), also known as unipolar depression or simply "depression"
- Obsessive-compulsive disorder (OCD)
- Panic disorder, with or without agoraphobia
- Bulimia nervosa
- Premenstrual dysphoric disorder (PMDD)
- Post-traumatic stress disorder (PTSD)
How does Fluoxetine help with these illnesses?
Fluoxetine (Prozac) is a selective serotonin reuptake inhibitor (SSRI) that works to alleviate symptoms of depression by increasing the amount of serotonin available in the brain's synapses (the spaces between neurons). It achieves this by preventing serotonin from being reabsorbed by neurons, allowing it to remain active for longer periods of time. Serotonin is a neurotransmitter that plays a vital role in regulating mood, memory function, sleep patterns, appetite, and body temperature, among other things. By boosting serotonin levels in the brain, fluoxetine can help mitigate depressive symptoms and stabilize mood. Over the long-term, this can lead to downregulation (decreased availability) of 5-HT1A receptors, which has been linked to improved passive stress tolerance and decreased negativity bias–the tendency to overemphasize or focus on things perceived as 'negative,' which is a characteristic of depressive and anxiety disorders. The same mechanism of action results in effects that can also alleviate anxiety and help manage symptoms of other psychiatric disorders such as PTSD and OCD. An ideal strategy for treating depression will leverage antidepressants to support patients in making positive changes to their lifestyle and habits, in tandem with therapy. Over the long-term, the patient could be taken off of antidepressant medications but continue to be supported by the positive effects of healthy lifestyle habits and the changes to thought patterns and behaviors brought about through therapy.
What is Sertraline?
Sertraline, marketed under the brand name Zoloft among others, is a selective serotonin reuptake inhibitor (SSRI). It works similarly to fluoxetine, increasing levels of available serotonin in the synapses of the brain by limiting its reabsorption. Sertraline also inhibits the dopamine transporter (DAT), affecting dopamine as well, although to a lesser extent than its effect on serotonin levels.
Sertraline was first approved by the FDA in 1991. It is approved for treating individuals suffering from major depressive disorder (MDD) as well as other psychiatric disorders such as obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder. Sertraline can be highly effective in treating the symptoms of these disorders, and its side effect profile is similar to that of many SSRIs, although with a relatively higher incidence of diarrhea (particularly in higher doses). Common side effects can include nausea, insomnia, sexual dysfunction such as failure to ejaculate or decreased libido, diarrhea, dry mouth, drowsiness, fatigue, dizziness, tremor, headache, excessive sweating, and restless legs syndrome.
What conditions is Sertraline approved to treat?
Sertraline is approved for treating a range of conditions, namely:
- Major depressive disorder (MDD)
- Obsessive-compulsive disorder (OCD)
- Panic disorder
- Social anxiety disorder
- Post-traumatic stress disorder (PTSD)
- Premenstrual dysphoric disorder
How does Sertraline help with these illnesses?
Sertraline works by increasing the levels of serotonin available in the brain, thereby helping to stabilize mood and alleviate symptoms of depression and anxiety. Serotonin is a neurotransmitter that plays a key role in regulating mood, sleep, and appetite, among other processes. The specificity of sertraline for serotonin receptors defines it as an SSRI (selective serotonin reuptake inhibitor). Drugs in this class work by preventing serotonin from being reabsorbed by neurons, making it available for longer periods of time. Over the long-term, this can lead to downregulation (decreased availability) of 5-HT1A receptors, which has been linked to enhanced stress tolerance and decreased negativity bias, which describes the tendency to overemphasize or focus on things perceived as 'negative' (a common characteristic of depressive and anxiety disorders). Sertraline has higher affinity than fluoxetine for the dopamine transporter, but the clinical significance of this is not fully understood. It's likely that it affects dopamine to a greater extent than fluoxetine does, but this effect is secondary to its effect on serotonin levels. As with other antidepressant medications, the treatment strategy may involve tempoprary (short- to medium-term) use of antidepressants alongside therapy to support patients in being able to make positive, long-term changes to their lifestyle and habits. The patient could then be slowly taken off of antidepressant medications, in hopes that the positive changes made continue to support their mental health over the long run. However, this will not be possible in all cases and some patients may need to remain on antidepressants for longer periods of time. Sertraline is used both over the short-term as well as for longer-term treatment.
How effective are fluoxetine and sertraline?
Both fluoxetine (Prozac) and sertraline (Zoloft) are selective serotonin reuptake inhibitors (SSRIs), exerting their effects by increasing the levels of serotonin in the brain. Both drugs have a proven track record in treating depression and anxiety disorders and have been in use since 1987 (fluoxetine) and 1991 (sertraline). Direct comparisons have been made between sertraline and fluoxetine in scientific studies, with results suggesting that they have similar efficacy in alleviating symptoms of depression as well as comparable safety profiles. For example, a double-blind study published in 1999 reported significant improvements in a major depressive episode in patients taking fluoxetine and patients taking sertraline, although fewer people stopped taking sertraline during the study, indicating potentially better tolerability relative to fluoxetine. A 2003 analysis of five double-blind comparative studies also demonstrated the efficacy of both drugs in major depression, but suggested that sertraline might have an advantage over fluoxetine in more severe cases. A 1993 study found slightly higher rates of agitation, anxiety, and insomnia in those taking fluoxetine, thus also favoring sertraline, although only to a minor extent. Both of these medications are considered first-line treatments in major depressive disorder and certain anxiety disorders. They would not be prescribed together since they have nearly identical mechanisms of action, and the combination would increase the risk of side effects.
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At what dose is fluoxetine typically prescribed?
Oral dosages of fluoxetine (Prozac) typically start at 20 mg per day, usually taken in the morning to reduce the risk of insomnia (trouble sleeping). Data from routine clinical practice has shown this to be an effective dosage for treating major depressive disorder in the majority of adults. For children and adolescents starting on this medication, the recommended dose is usually lower, at 10 mg per day. If there's no response after a few weeks, the dosage can be increased, but this should only be done under guidance by a healthcare professional. However, the maximum dosage, which should not be exceeded in any case, is limited to 80 mg per day. Fluoxetine should ideally be taken at the same time every day. If you forget or miss a dose, do not double-dose, simply resume the following day with your regular schedule.
At what dose is sertraline typically prescribed?
Treatment with sertraline is typically initiated at a dose of 50 mg per day, taken in a single dose either in the morning or in the evening. The dosage can be increased depending on patient response and tolerability, but the maximum dosage of sertraline that should not be exceeded is 200 mg per day. Dosages should be increased slowly, in intervals of at least one week, since the full effects of sertraline (like other SSRIs) are not seen until after a few weeks of treatment. If there is no significant improvement in symptoms after several weeks at higher dosages, a different SSRI medication or another class of antidepressant medication may be tried instead. Sertraline should ideally be taken at the same time every day. If you forget or miss a dose, do not double-dose to make up for the missed dose. SImply resume the following day with your regular schedule.
What are the most common side effects of fluoxetine?
Common side effects of fluoxetine can include:
- Indigestion
- Insomnia (trouble sleeping) or somnolence (drowsiness)
- Tremors (unintentional trembling or shaking)
- Decreased appetite
- Nausea and dyspepsia (burning sensation, discomfort, or pain in the upper abdomen)
- Diarrhea
- Dry mouth
- Sweating more than usual
- Decreased libido (sex drive) and other sexual problems such as delayed ejaculation and inability to reach orgasm
- Rash
- Feeling tired or fatigued
- Abnormal dreams
If you experience these symptoms for a prolonged period of time or they interfere with your wellbeing, speak with your doctor about adjusting your dosage or trying a different medication.
Are there any potential serious side effects for Fluoxetine?
Rare but potentially severe side effects can occur with fluoxetine. If you experience any of the following symptoms, please seek immediate medical attention as they could be a sign of a severe adverse reaction:
- Worsening of depression or suicidal thoughts
- Signs of an allergic reaction: hives; difficult breathing; swelling in your face, lips, tongue, or throat
- Vision changes, such as seeing rainbows around lights at night
- Fast or irregular heart rate, or feeling faint/light-headed
- Symptoms associated with low sodium levels: headache, confusion, severe weakness, vomiting, loss of coordination
- Severe nervous system reaction: rigid muscles, high fever, sweating, confusion, rapid heartbeat
- Symptoms related to serotonin syndrome: restlessness, hallucinations, fever, fast heartbeat, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea
If you experience any of these symptoms while taking fluoxtine, seek immediate medical attention.
What are the most common side effects of sertraline?
Common mild side effects of sertraline can include:
- Dry mouth or increased salivation
- Upset stomach, diarrhea, and/or mild nausea
- Problems sleeping (insomnia) or drowsiness
- Sweating
- A feeling of nervousness or restlessness
- Weight changes
- Mild tremors
- Sexual dysfunction such as delayed ejaculation or decreased libido
- Headache, dizziness
- Muscle pain
If you experience these symptoms for a prolonged period of time or they interfere with your wellbeing, speak with your doctor about adjusting your dosage or trying a different medication.
Are there any potential serious side effects for Sertraline?
While sertraline is generally well-tolerated and its common side effects tend to be mild, in rare instances it can cause more serious side effects. If you notice any of the following symptoms while taking sertraline, please seek immediate medical attention as they could indicate a severe adverse reaction:
- Signs of an allergic reaction, such as: hives, difficulty breathing, swelling of your face, lips, tongue or throat
- Signs indicative of a severe skin reaction, such as: fever, sore throat, burning eyes, skin pain, or a red/purple rash that spreads and causes blistering/peeling
- Sudden and/or unusual changes in mood or behavior, including increased suicidal ideation
- Changes to your vision, such as blurred vision or seeing halos around lights
- Accelerated heart rate or irregular heartbeat
- Symptoms suggestive of serotonin syndrome, which can include: agitation, hallucinations, problems with coordination or overactive reflexes, rapid heart rate, or increased body temperature
- Signs indicating low levels of sodium in the blood, which can include: headache, confusion, memory issues, weakness, or instability, potentially leading to falls
If you experience any of the symptoms listed above, it's important to stop taking sertraline and seek urgent medical assistance to ensure your safety.
Contraindications for fluoxetine and sertraline
Both fluoxetine and sertraline, like most other selective serotonin reuptake inhibitor (SSRI) medications, may exacerbate symptoms of depression in some individuals. If you observe an intensification of your depression symptoms, or an increase in suicidal thoughts or behaviors, it is crucial to seek immediate medical attention.
Neither fluoxetine nor sertraline should be taken if you are currently using (or if you have recently used) monoamine oxidase inhibitors (MAOIs), such as phenelzine (Nargil), tranylcypromine (Parnate), or selegiline (Eldepryl, Emsam). It's imporant to always keep your doctor fully informed about any and all medications you're taking, including over-the-counter drugs, vitamins, and herbal supplements. MAOIs in particular will require a washout period of approximately 5 weeks to be fully cleaned out from the system before starting treatment with either fluoxetine or sertraline, in order to avoid a potentially dangerous condition called serotonin syndrome.
Both sertraline and fluoxetine have been associated with an increase in congenital heart defects in newborns when taking during pregnancy, particularly during the third trimester. The extent of this risk is not entirely clear, but pregnant mothers and those trying to convceive should speak with their doctor about tapering off the medication during the third trimester and during the first months of lactation. If SSRI use is necessary during pregnancy, sertraline seems to be the preferred option (over fluoxetine) as it results in relatively little exposure to the fetus and thus poses a lower risk.
How much do Fluoxetine and Sertraline cost?
For the brand-name versions of these drugs:
- The price for 30 tablets of Zoloft (50 mg), the most comon brand name for sertraline, averages around $320. This works out to approximately $10–$20/day, depending on your dose.
- A pack of 30 capsules of Prozac (20 mg), brand-name fluoxetine, is priced at about $570, working out to roughly $19/day.
Zoloft and Prozac are thus comparable in cost on a per-day treatment basis, but this will also depend on the dosage that you've been prescribed. However, cost should not be the main factor when deciding between these two medications.
Both medications have generic versions available, which can offer significant cost savings:
- Sertraline can be purchased in packs starting from 30 tablets, with costs ranging from $0.28–$1 per day, depending on dosage.
- Fluoxetine is available in packages starting as small as 15 capsules, all the way up to packs of 1000 capsules (20 mg). Depending on the quantity you purchase, daily cost can be as low as just $0.05, ranging up to about $0.90.
Thus, the generic versions of sertraline and fluoxetine are also comparably priced. For either drug, the generic versions can cost you just 5–10% (or less) of the price of the brand-name medications, representing significant savings for those paying out-of-pocket. Generic medications are functionally equivalent to their brand-name counterparts, with the same ingredients, clinical benefits, and side effect profiles.
Popularity of Fluoxetine and Sertraline
Sertraline, commonly recognized by the brand name Zoloft, was estimated to have been prescribed to nearly 40 million people in the US in 2021. This makes sertraline the most frequently prescribed selective serotonin reuptake inhibitor (SSRI), and the most common antidepressant overall. It received FDA approval in 1991, and has since shown promise as a first-line treatment for major depression and anxiety disorders. It is thought to be safer than other SSRIs when pregnant mothers need to continue antidepressant therapy during pregnancy and lactation. It is about the same as other SSRI antidepressants in terms of effectiveness, but some studies have suggested it may be more tolerable (with fewer side effects or a lower incidence thereof).
Fluoxetine, commonly known by the brand name Prozac, was prescribed to roughly 22 million individuals in the US in 2021, ranking #4 among the most-common antidepressants. Fluoxetine was approved by the FDA in 1987 and has a proven track record of effectiveness in treating symptoms of depressive and anxiety disorders. Its efficacy is comparable to that of most other commonly precribed SSRIs, and its side effect profile is also similar. An interesting feature is that fluoxetine is thought to be less likely to lead to antidepressant discontinuation syndrome upon stopping treatment.
Conclusion
Both fluoxetine (Prozac) and sertraline (Zoloft) are SSRIs that are widely used in managing depression and other psychiatric disorders such as anxiety disorders, PTSD, and OCD. Both drugs have been in use since the 1990s, and numerous clinical studies have demonstrated their superiority over placebo for treating these conditions. The mechanisms of action of sertraline and fluoxetine are similar – they both inhibit the reuptake of serotonin into presynaptic cells, increasing the amount of serotonin available to bind to the postsynaptic receptor. Sertraline has greater affinity for the dopamine transporter (DAT) than fluoxetine, although the clinical significance of this is not entirely clear.
Both sertraline and fluoxetine may be considered as first-line treatment options for major depression due to their long history of successful use and generally good tolerability. Both medications are available in generic form, which offers significant savings for patients paying out-of-pocket. The generic forms of both drugs can cost less than $1.00 per day of treatment. Both are taken in single doses, once per day, ideally at the same time. Patients may change the timing of this dosage to see if certain side effects such as insomnia may become less troublesome. If a dosage is missed, treatment should be resumed on the following day as normal (neither medication should be double-dosed to make up for a missed dose).
The side effect profiles of the two drugs are similar due to their shared mechanism of action as SSRIs. Common mild side effects include nausea, diarrhea, dry mouth, insomnia, and sexual dysfunction. Sertraline may be less likely than fluoxetine to cause trouble sleeping, and some studies have suggested that sertraline may be better tolerated in general, although it carries a slightly higher likelihood of causing diarrhea. There is an adjustment period to be aware of when starting these medications; as with other SSRIs, clinical benefits may not appear until a few weeks into treatment.
Patients should closely monitor their oerall health as well as their mood while taking either of these medications. Especially when just starting therapy, it's important to watch for signs of worsening depression or an increase in suicidal thoughts. Patients should speak to their doctor immediately if any strange or sudden changes are noted, including the side effects listed above. If side effects are severe, emergency medical assistance should be sought. Neither fluoxetine nor sertraline should be used by people taking MAOIs, and all medications and supplements should be checked by a doctor to ensure they won't interact dangerously with either drug.