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Psychopharmacology book

Fluoxetine (PROZAC)

Fluoxetine (PROZAC)

Fluoxetine (Prozac) was the first available SSRI, released to the US market in 1987. Among antidepressants, Prozac has the best evidence for treatment of depression among children and adolescents. It is the only FDA-approved medication for treatment of depression in children (age 8 and older).


For adults, Lexapro and Zoloft are generally preferred because Prozac interacts with numerous medications. Specifically, Prozac is an inHibitor of several CYP enzymes. If Prozac were a newly introduced drug, it would be unlikely to receive FDA approval due to the magnitude of these interactions. 

Prozac fluoxetine mnemonics

Among SSRIs, Prozac is considered the most activating/energizing (as opposed to calming). As a result, it is more likely to cause anxiety and insomnia than other SSRIs. It is safe for those with sleep apnea because it is a respiratory stimulant. It is not expected to cause weight gain and may result in modest weight loss. As with other SSRIs, the most troublesome side effect is sexual dysfunction.

Fluoxetine Prozac mechanism ballicule
Fluoxetine and nortriptyline interaction.

Prozac has a very long elimination half-life of about 7 days. In other words, Prozac has a Prolonged presence in your body. A mnemonic from Dr. Jonathan Heldt’s book Memorable Psychopharmacology compares the half-life of fluoxetine to the 7 days its takes to recover from the flu (influenza). 


With chronic use, fluoxetine is detectable in the body up to five weeks after discontinuation (elimination half-life x 5). Since Prozac “tapers itself” off over weeks when stopped abruptly, there should be no serotonin withdrawal symptoms. Thanks to long half-life, missed doses are of less consequence (compared to antidepressants with shorter half-lives). If the patient forgets to take a dose on Monday, it is OK to take a double dose on Tuesday. This would not be advisable with most other psychotropics. 


Fluoxetine is safe. Risk of death with single-drug overdose is no more than 1 in 10,000. 


SYMBYAX is a fixed dose combination of fluoxetine with the antipsychotic olanzapine (Zyprexa), approved for acute depressive episodes of bipolar I disorder and for treatment-resistant major depression. Released in 2003, Symbyax (mnemonic Symbiotic Ox) was marketed heavily to primary care physicians, who likely underestimated olanzapine's potential for causing significant weight gain and diabetes. The fixed doses of olanzapine/fluoxetine in Symbyax are 3/25mg, 6/25 mg, 6/50 mg, and 12/50 mg taken in the evening.  


For the sake of trivia, there exists a 90 mg fluoxetine ER capsule intended for once weekly dosing called PROZAC WEEKLY. It runs $50 per capsule. That’s $200 monthly compared to $4–$10 for a month of generic QD fluoxetine. 


When discontinuing fluoxetine 40 mg or less, it may be ok just to stop without tapering, thanks to is long half-life. However, some patients may need a slow taper.  To come off of higher doses, you will want to taper over several months. Switching from fluoxetine to another antidepressant can be tricky due to fluoxetine’s long half-life. When switching to another modern serotonergic antidepressant, consider a washout period before starting the new antidepressant.  The risk of serotonin syndrome is minimal with some overlap of two SSRIs (or an SSRI and an SNRI), so you do not have to wait for fluoxetine to be entirely cleared by the body. However, when switching from fluoxetine to an MAOI, there can be no overlap, because serotonin syndrome is a major risk. You need to wait at least five weeks after stopping fluoxetine to start the MAOI. For the other SSRIs, you only have to wait 2 weeks to start the MAOI.




Fluoxetine, available in 10 mg, 20 mg, and 40 mg capsules, is typically started (for adults) at 20 mg QD. It can be titrated in 20 mg increments to the FDA max dose of 80 mg QD. As a rule of thumb, you would want to wait about 4 weeks between dose increases. If there is a prior effective dose (for a particular patient) you are targeting, you can titrate faster. See above for discontinuation strategies.


For obsessive-compulsive disorder (OCD), you can go as high as 120 mg daily (Stahl, 2016). OCD often requires heroically high doses of SSRIs, and fluoxetine is a safe option. 


For premenstrual dysphoric disorder (PMDD), you can take 20 mg QD starting 14 days prior to the anticipated onset of menses through the first full day of menstruation and repeating with each cycle. The brand SARAFEM (10 mg, 20 mg) is FDA-approved for this indication, but you will want to prescribe generic fluoxetine. For PMDD there is no proven benefit in exceeding 20 mg/day.  


Copyright 2024 CaferMed Publishing.  Intended for prescribers. 

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