Fluoxetine (Prozac): Uses, Dosage, and Side Effects

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Fluoxetine (Prozac) is an antidepressant belonging to the group of selective serotonin reuptake inhibitors (SSRIs). Fluoxetine was first marketed in the United States in 1987 for the treatment of depression, and was the first available SSRI in the country. Other SSRIs are fluvoxamine, paroxetine, sertraline, citalopram, escitalopram, vilazodone.

Early clinical experience with fluoxetine showed that the drug sometimes produced dramatic responses without the same type of tolerability problems associated with the tricyclic antidepressants (TCAs). Quickly, first-line treatment of depression quickly shifted from the TCAs to fluoxetine and other SSRIs. Even around the start of the 21st century, the majority of new prescriptions for antidepressant treatments were for SSRIs.

Fluoxetine blister pack 20 mg capsules
Fluoxetine blister pack 20 mg capsules (Source: By Lanfear’s Bane at English Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5222497)

Uses of Fluoxetine or Prozac

The SSRIs were initially indicated for “depression,” then for “anxiety,” and by the time they all finally went off patent, countless were the indications for which this versatile drug class served.

Fluoxetine is indicated in both adult and pediatric populations in the US for major depressive disorder (FDA-approved) and obsessive-compulsive disorder (OCD) (FDA-approved), and in adults for panic disorder (FDA-approved), bulimia nervosa, and premenstrual dysphoric disorder. Other uses for fluoxetine include social anxiety disorder, generalized anxiety disorder, and post-traumatic stress disorder, among others.

  • Major Depressive Disorder: Fluoxetine has FDA approval for acute and maintenance treatment of major depression in adults and children (>8 years old). It may improve your mood, sleep, appetite, and energy level and may help restore your interest in daily living. Fluoxetine is recommended as the first-line medication for preschoolers with major depressive disorder. Fluoxetine has been shown to be helpful in treating depression in children and adolescents with inflammatory bowel disorder. Fluoxetine is equally effective in the acute treatment of late-life depression. The starting daily dosages are 10 to 20 mg for fluoxetine. The dosages should be increased gradually.
  • Treatment-resistant Depression: The combination of 10 to 20 mg/day of olanzapine with fluoxetine (Symbyax) is FDA-approved in the treatment of treatment-resistant depression (i.e., following an inadequate response to at least two different antidepressants). The olanzapine-fluoxetine combination is available in fixed-dose combinations of 3, 6, or 12 mg of olanzapine and 25 or 50 mg of fluoxetine.
  • Bipolar Depression: Fluoxetine given in combination with olanzapine (Symbyax) is FDA-approved to treat bipolar depression. It is initiated at 6 and 25 mg/day (olanzapine 6 mg with fluoxetine 25 mg) but could be increased to 6 and 50 or 12 and 50 mg/day after at least 1 day at each dose.
  • OCD: Large, well-designed, double-blind, placebo-controlled trials have demonstrated that fluoxetine is an effective acute treatment for OCD. It reduces the urge to perform repeated tasks (compulsions such as hand-washing, counting, and checking) that interfere with daily living.Treatment of OCD is also usually at higher doses than those used in major depression, with doses of 20 to 80 mg per day most commonly used.
  • Generalized Anxiety Disorder: In the treatment of generalized anxiety disorder based on the results of several large, placebo-controlled trials, fluoxetine was most effective in response and remission.
  • Social Anxiety Disorder: It has been treated successfully with fluoxetine. Treatment is often started at 10 to 20 mg per day. Dose is adjusted upward as needed.
  • Panic Disorder: It may decrease fear, anxiety, unwanted thoughts, and the number of panic attacks. Treatment of panic disorder is often initiated at less than 5 to 10 mg per day with a gradual upward dose titration. After week 1 it is increased to 20 mg/day until week 6. Patients who had not achieved a CGI-Severity score of 2 or less were increased to 40 mg/day at week 6. Fluoxetine could be further increased to 60 mg/day.
  • Premenstrual dysphoric disorder: Fluoxetine may lessen premenstrual symptoms such as irritability, increased appetite, and depression. Treatment is often started at 10 to 20 mg per day. Dose is adjusted upward as needed.
  • Fluoxetine is the first-choice medication for preschool anxiety disorders in general.
  • Tourette Disorder: Fluoxetine typically is started at 2.5 to 5 mg daily for children and at 5 to 10 mg for adolescents or adults. Dose ranges are not well established for children and adolescents with Tourette disorder. It appears that most children will respond to 10 to 20 mg daily; adults may require 20 to 80 mg daily. Fluoxetine in combination with an antipsychotic can be useful for both tics and obsessive-compulsive symptoms.
  • Post-traumatic Stress Disorder (PTSD): Fluoxetine demonstrated significant improvement compared with placebo treatment.
  • Post-partum Depression (PPD): In small studies, fluoxetine has shown efficacy in treating PPD.
  • Autism Spectrum Disorders (ASD): SSRIs including fluoxetine appear to be modestly effective in improving overall global functioning, including symptoms of repetitive behaviors, anxiety, irritability, and hyperactivity in children with ASD.
  • Bulimia Nervosa: Although several antidepressants appear to significantly reduce binge eating and purging, the SSRI fluoxetine has been studied the most extensively and is viewed as the medication of choice for this illness. Studies have found that higher doses (e.g., 60 mg per day) are more effective in disrupting binge eating and purging. The optimal length of fluoxetine treatment for bulimia nervosa is yet to be determined.
  • Intermittent Explosive Disorder (IED): A study in 2009 on 100 IED patients found that those who took fluoxetine for 12 weeks experienced statistically significant reductions in impulsive-aggressive behavior compared with those who took a placebo.
  • Other uses of fluoxetine include fibromyalgia, neuropathic pain, hypochondriasis, and premature ejaculation.

Dosage of Fluoxetine

Fluoxetine is available as pulvules (10, 20, or 40 mg), tablets (10 mg), an oral concentrate (20 mg/5 mL), and in an enteric-coated, delayed-release, once-weekly form (90 mg).

The initial dose should be started at 10-20 mg and maintained for 1–2 weeks, after which they can be increased in 10 or 20 mg increments to a dose of 40 mg/day if there is no response. Therapeutic dosages will vary, ranging from 10 to 60 mg a day of fluoxetine. A maximum dose of 60 mg/day of fluoxetine is recommended for the treatment of depression, whereas in OCD it can go up to 80 mg/day.

Starting doses of 10 mg per day are often used in treating children, adolescents, or elderly patients. Adjustment upward is based on clinical response and tolerance of side effects.

Starting doses of fluoxetine should be low (10 mg) followed by gradual dosage increases, particularly in those above age 75.

If you miss a dose, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose and do not try to make up the missed dose. If you miss a dose of Prozac Weekly, take the missed dose as soon as you remember and take the next dose 7 days later. Do not take extra medicine to make up the missed dose.

Side Effects of Fluoxetine (Prozac)

Side effects occur more frequently at higher doses.

 The most common side effects are:

  • Headache
  • Sexual dysfunction
  • Nausea
  • Insomnia
  • Anorexia
  • Dry mouth
  • Somnolence
  • Nervousness
  • Tremor
  • Diarrhea

Other side effects that can occur with fluoxetine are:

  • Anxiety
  • Loss of appetite or increase in appetite
  • Weight changes
  • Headaches
  • Blurred vision
  • Gastrointestinal distress
  • Suicidality
  • Allergic reaction – rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing – contact emergency medical services if any of these symptoms occur
  • Excessive sweating
  • Pruritus
  • Hair loss
  • Inflammation
  • Systemic vasculitis
  • The use of SSRIs is not recommended for treating depression in children under 18, in whom efficacy is doubtful and adverse effects, including excitement, insomnia and aggression in the first few weeks of treatment, may occur. The possibility of increased suicidal ideation is a concern in this age group.

Fluoxetine Use during Pregnancy and Lactation

Fluoxetine is one of the most commonly used antidepressants in pregnant women. In large cohort studies, there was no effect of fluoxetine on total malformations. Women who are pregnant or planning a pregnancy and are taking SSRIs should consult with their physician about whether to continue taking their medication.

The clinical need for treatment of the mother—the risk of nontreatment—needs to be weighed. For example, pregnant women with untreated depression have a greater risk of obstetrical complications, premature delivery, and pre-eclampsia. Newborns of these women are at greater risk to be low birth weight, exhibit lower activity and interactive behaviors, have increased irritability, and demonstrate delayed language and behavioral difficulties.

Some neonates exposed to SSRIs late in the third trimester developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. These are listed as precautions in the product information for all SSRIs.

Another possible pregnancy-related side effect in offspring of SSRI-treated mothers is persistent pulmonary hypertension of the newborn (PPHN), a condition associated with substantial infant mortality and morbidity.

There have been isolated case reports of elevated infant levels and toxicity with breastfeeding mothers taking fluoxetine. With fluoxetine, breast-fed infants of fluoxetine-treated mothers gained less weight after birth, although adverse behavioral effects were not observed.

If treatment with an SSRI is started during the postpartum period, fluoxetine should not be the first alternative. Fluoxetine transfers to a greater extent and its active metabolite, norfluoxetine, has a long half-life of 1 to 2 weeks and may accumulate in a breast-fed infant.

Fluoxetine Interactions

Fluoxetine may displace other tightly protein-bound drugs, such as warfarin or digitoxin (Digitaline).

Dosing of 20 mg of fluoxetine raised plasma levels of risperidone by 2.5 times.

Fluoxetine may reduce aripiprazole levels by up to 50 percent.

Serotonin syndrome is associated with concomitant fluoxetine and trazodone use.

Fluoxetine 20 mg/day, on average, raises desipramine levels three- to fourfold in extensive metabolizers.

Adjunctive fluoxetine (Prozac) has been reported to increase serum levels of valproate.

Serotonin Reaction: Fluoxetine’s long half-life is 2–4 days for the parent compound and 4–16 days for its active metabolite. The long half-life can present problems when switching or discontinuing fluoxetine, because 5 weeks or more may be required for the medication to be completely cleared from the body. Hence the added delay, 5 weeks rather than 2 weeks for the other SSRIs, is required when switching from fluoxetine to an MAOI. Otherwise, the dangerous ‘serotonin reaction’ (hyperthermia, muscle rigidity, cardiovascular collapse) can occur if given with MAOIs.

Bibliography

Brunton, L., 2018. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13 ed. New York: McGraw Hill.

Ritter, J. et al., 2020. Rang and Dale’s Pharmacology. 9 ed. Edinburgh: Elsevier.

Sadock, B. J., Sadock, V. A. & Ruiz, P., 2017. Kaplan and Sadock’s Comprehensive Textbook of Psychiatry. 10th ed. Philadelphia: Wolters Kluwer.

Tasman, A. et al. eds., 2015. Psychiatry. 4th ed. Oxford: Wiley Blackwell.

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Fluoxetine (Prozac): Uses, Dosage, and Side Effects
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Fluoxetine (Prozac): Uses, Dosage, and Side Effects
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Fluoxetine (Prozac) is an antidepressant belonging to the group of selective serotonin reuptake inhibitors (SSRIs), first marketed in the US in 1987.
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