Fluoxetine (Prozac, Fontex, Seromex, Seronil, Sarafem, Fluctin)

Fluoxetine was the first SSRI antidepressant approved for use in the US and was introduced by Eli Lilly in 1987. The patent expired in 2001 and fluoxetine is now available as a generic medication.

Fluoxetine was derived from diphenhydramine (Benadryl), an antihistamine that was known to have antidepressant properties. The introduction of SSRI antidepressants dramatically changed the treatment of depression and SSRIs have become the most prescribed medications in the world.

The Bottom Line: What You Really Need to Know

Uses of fluoxetine

Fluoxetine is approved for the treatment of depression and obsessive compulsive disorder in adults and children. It is the only antidepressant approved in the US for use in children. It is also approved to treat bulimia, panic disorder, premenstrual dysphoric disorder (PMDD), hypochondriasis, and body dysmorphic disorder. It is used off label to treat a wide range of other problems such as alcoholism, attention deficit disorder (ADD), borderline personality disorder, obesity, sexual problems and phobias.

Dosage and instructions

Dosage of fluoxetine ranges from 20-80 mg/day in adults and 10-60 mg/day in children and depends on what the medication is being used for. The chart below describes the usual dose for various disorders:

Adult Dose

Pediatric Dose


20-40 mg/day. Initial dose is 20 mg/day with weekly increases up to a maximum of 40 mg/day.

10-20 mg/day

Obsessive-Compulsive Disorder

20-60 mg/day. Initial dose is 20 mg/day with weekly increases as needed. Can use 80 mg/day, but doses over 60 mg/day didn't show any improvement in OCD.

10-60 mg/day


60 mg/day. It may be necessary to begin at a lower dose and titrate up to 60 mg/day.

Panic disorder

20 mg/day. No improvement is seen with higher doses.

The dose of fluoxetine may need to be decreased in elderly people and those with liver problems.

An extended release form of fluoxetine is available from Eli Lilly. Prozac Weekly is available in 90 mg tablets and is taken once a week after therapeutic levels have been established with fluoxetine 20 mg/day. The first weekly tablet is taken 7 days after the last daily tablet. Prozac Weekly doesn't provide adequate antidepressant activity for everybody.

It takes several weeks for people to experience the full therapeutic effect of fluoxetine. The elimination half-life (amount of time it takes to metabolize half of the daily dose) is 4-6 days, and the elimination half-life of the metabolite norfluoxetine is 16 days or more. That means that it takes several weeks or months to completely eliminate fluoxetine from your system.

How fluoxetine works

Although the exact cause or causes of depression is unknown, it is increasingly clear that a biochemical imbalance is involved. Several neurotransmitters-dopamine, norepinephrine and serotonin-seem to play a part in anxiety and mood regulation, with serotonin being the most important. Fluoxetine and other SSRI antidepressants block the reabsorption of serotonin by nerve cells in the brain and throughout the body, allowing serotonin to accumulate and re-establishing biochemical balance.

Fluoxetine was one of the earliest SSRI's and is not as "serotonin specific" as newer ones, so it has some effect on dopamine and norepinephrine, too.

Fluoxetine is metabolized in the liver before it is excreted in the feces. When a substance is metabolized, it is broken down into other compounds. Some of these compounds are biologically inactive and are excreted; some are biologically active, and are called "active metabolites." Fluoxetine has one active metabolite, norfluoxetine, that has the same action as the parent compound. This extends the half-life (the amount of time the drug is active in your body) of fluoxetine significantly.

There is considerable genetically determined variability in how rapidly people metabolize fluoxetine. That is why different people need different doses, and is also why Prozac Weekly is not effective for some people-they metabolize the medication too quickly.

Side effects

Most people who take SSRIs experience mild to moderate side effects initially; those side effects usually get better over time. The most common side effects experienced with fluoxetine are:

For more information about serious side effects, see the section on Warnings and Precautions.


Fluoxetine interacts with many medications, especially those that are metabolized in the liver and those that have an effect on serotonin.

Some of the medications that interact with fluoxetine are:


Abrupt discontinuation of SSRIs can cause unpleasant withdrawal symptoms. Because fluoxetine lasts so long in the body, withdrawal symptoms may not be as severe as with other SSRI's, but they can still occur and the dose should be gradually tapered before stopping the medication. Symptoms of fluoxetine withdrawal include:

Warnings, precautions and contraindications

Increased risk of suicide: Recent studies suggest that there is an increased risk of suicide in the early weeks of therapy. Although this phenomenon was initially observed in children and an FDA warning was mandated related to the use of antidepressants in children, further observations have caused the warning to be extended to adolescents and young adults. All people who start taking fluoxetine, regardless of age, should be monitored closely for the first several weeks. This includes:

There is some concern that a small percentage of individuals are at risk for paranoia and violence rather than suicide. Any alterations in thought processes, mood or anxiety must be reported to the physician immediately.

Serotonin Syndrome: Serotonin syndrome is a toxicity syndrome that occurs in SSRI overdose or when more than one serotonergic medication is taken. Because many, many medications affect serotonin, it is important to make sure your doctor and pharmacist know about all medications, over the counter medications, natural remedies, recreational drugs, herbal teas, nutritional supplements and vitamins you take.

The symptoms of serotonin syndrome begin abruptly and dramatically minutes or hours after the offending medication is taken. The early symptoms are shivering, anxiety, rapid heart rate, tremors and twitches and anxiety. Symptoms may progress to fever, high blood pressure, sweating, muscle contractions and agitation. In severe serotonin syndrome, there may be cardiovascular collapse and shock, fever over 104°F, muscle rigidity, seizures, hallucinations, coma, multiple organ failure and death.

Allergies: Allergic reactions to fluoxetine are rare but do occur. Rashes, hives and anaphylaxis have been observed.

Vasculitis: On rare occasions people have developed a lupus-like vasculitis. This syndrome usually begins with a rash and progresses to involve the lungs, kidneys and liver. It can result in organ failure and death.

Post SSRI Sexual Dysfunction: Transient sexual dysfunction is common in both men and women after starting fluoxetine. Usually it resolves after taking the medication for a few weeks; occasionally it may be necessary to discontinue fluoxetine, and symptoms resolve within a few weeks of discontinuation. Occasionally, however, sexual dysfunction may persist for months or years or may never resolve. The sexual side effects most often seen are decreased libido, female anorgasmia and ejaculatory dysfunction.

Pregnancy: SSRIs, including fluoxetine, are contraindicated in women who are pregnant or who wish to become pregnant. They are associated with cardiac birth defects and pulmonary hypertension of the newborn.

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