Fluoxetine
Fluoxetine, sold under the brand name Prozac, among others, is an antidepressant medication of the selective serotonin reuptake inhibitor class used for the treatment of major depressive disorder, anxiety, obsessive–compulsive disorder, panic disorder, premenstrual dysphoric disorder, and bulimia nervosa. It is also approved for treatment of major depressive disorder in adolescents and children 8 years of age and over. It has also been used to treat premature ejaculation. Fluoxetine is taken by mouth.
Common side effects include loss of appetite, nausea, diarrhea, headache, trouble sleeping, dry mouth, and sexual dysfunction. Serious side effects include serotonin syndrome, mania, seizures, an increased risk of suicidal behavior, and an increased risk of bleeding. Antidepressant discontinuation syndrome is less likely to occur with fluoxetine than with other antidepressants. Fluoxetine taken during pregnancy is associated with a significant increase in congenital heart defects in newborns. It has been suggested that fluoxetine therapy may be continued during breastfeeding if it was used during pregnancy or if other antidepressants were ineffective.
Fluoxetine was invented by Eli Lilly and Company in 1972 and entered medical use in 1986. It is on the World Health Organization's List of Essential Medicines and is available as a generic medication. In 2023, it was the eighteenth most commonly prescribed medication in the United States and the fourth most common antidepressant, with more than 27million prescriptions.
Eli Lilly also markets fluoxetine in a fixed-dose combination with olanzapine as olanzapine/fluoxetine, which was approved by the US Food and Drug Administration for the treatment of depressive episodes of bipolar I disorder in 2003 and for treatment-resistant depression in 2009.
Medical uses
Fluoxetine is frequently used to treat major depressive disorder, obsessive–compulsive disorder, post-traumatic stress disorder, bulimia nervosa, panic disorder, premenstrual dysphoric disorder, and trichotillomania. It has also been used for cataplexy, obesity, alcohol dependence, social anxiety disorder, as well as binge eating disorder. Studies do not support a benefit in children with autism, though there is weak evidence for benefit in adult autism. Fluoxetine and the related fluvoxamine have shown some initial promise as a potential treatment for reducing COVID-19 severity if given early.Depression
Fluoxetine is approved for the treatment of major depression in children and adults. A meta-analysis of trials in adults concluded that fluoxetine modestly outperforms placebo. Fluoxetine may be less effective than other antidepressants, but has high acceptability.For children and adolescents with moderate-to-severe depressive disorder, fluoxetine seems to be the best treatment but more research is needed to be certain, as effect sizes are small and the existing evidence is of dubious quality. A 2022 systematic review and trial restoration of the two original blinded-control trials used to approve the use of fluoxetine in children and adolescents with depression found that both of the trials were severely flawed, and therefore did not demonstrate the safety or efficacy of the medication. In 2025, a trial restoration of the influential TADS study found that fluoxetine had not been superior to placebo in the treatment of depressed adolescents, contradicting previously reported results used in meta-analyses and guidelines.
Obsessive–compulsive disorder
Fluoxetine is effective in the treatment of obsessive–compulsive disorder for adults. It is also effective for treating OCD in children and adolescents. The American Academy of Child and Adolescent Psychiatry state that SSRIs, including fluoxetine, should be used as first-line therapy in children, along with cognitive behavioral therapy, for the treatment of moderate to severe OCD.Panic disorder
The efficacy of fluoxetine in the treatment of panic disorder was demonstrated in two 12-week randomized multicenter phase III clinical trials that enrolled patients diagnosed with panic disorder, with or without agoraphobia. In the first trial, 42% of subjects in the fluoxetine-treated arm were free of panic attacks at the end of the study, vs. 28% in the placebo arm. In the second trial, 62% of fluoxetine-treated patients were free of panic attacks at the end of the study, vs. 44% in the placebo arm.Bulimia nervosa
A 2011 systematic review discussed seven trials that compared fluoxetine to a placebo in the treatment of bulimia nervosa, six of which found a statistically significant reduction in symptoms such as vomiting and binge eating. However, no difference was observed between treatment arms when fluoxetine and psychotherapy were compared to psychotherapy alone.Premenstrual dysphoric disorder
Fluoxetine is used to treat premenstrual dysphoric disorder, a condition where individuals have affective and somatic symptoms monthly during the luteal phase of menstruation. Taking fluoxetine 20 mg/d can be effective in treating PMDD, though doses of 10 mg/d have also been prescribed effectively.Impulsive aggression
Fluoxetine is considered a first-line medication for the treatment of impulsive aggression of low intensity. Fluoxetine reduced low-intensity aggressive behavior in patients in intermittent explosive disorder and borderline personality disorder. Fluoxetine also reduced acts of domestic violence in alcoholics with a history of such behavior.Obesity and overweight adults
In 2019 a systematic review compared the effects on weight of various doses of fluoxetine in obese and overweight adults. When compared to placebo, all dosages of fluoxetine appeared to contribute to weight loss but lead to increased risk of experiencing side effects, such as dizziness, drowsiness, fatigue, insomnia, and nausea, during the period of treatment. However, these conclusions were from low-certainty evidence. When comparing, in the same review, the effects of fluoxetine on the weight of obese and overweight adults, to other anti-obesity agents, omega-3 gel capsule and not receiving treatment, the authors could not reach conclusive results due to poor quality of evidence.Special populations
In children and adolescents, fluoxetine is the antidepressant of choice due to tentative evidence favoring its efficacy and tolerability. Evidence supporting an increased risk of major fetal malformations resulting from fluoxetine exposure is limited, although the Medicines and Healthcare products Regulatory Agency of the United Kingdom has warned prescribers and patients of the potential for fluoxetine exposure in the first trimester to cause a slight increase in the risk of congenital cardiac malformations in the newborn. Furthermore, an association between fluoxetine use during the first trimester and an increased risk of minor fetal malformations was observed in one study.However, a systematic review and meta-analysis of 21 studies—published in the Journal of Obstetrics and Gynaecology Canada—concluded, "the apparent increased risk of fetal cardiac malformations associated with maternal use of fluoxetine has recently been shown also in depressed women who deferred SSRI therapy in pregnancy, and therefore most probably reflects an ascertainment bias. Overall, women who are treated with fluoxetine during the first trimester of pregnancy do not appear to have an increased risk of major fetal malformations."
Per the US Food and Drug Administration, infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn. Limited data support this risk, but the FDA recommends physicians consider tapering SSRIs such as fluoxetine during the third trimester. A 2009 review recommended against fluoxetine as a first-line SSRI during lactation, stating, "Fluoxetine should be viewed as a less-preferred SSRI for breastfeeding mothers, particularly with newborn infants, and in those mothers who consumed fluoxetine during gestation." Sertraline is often the preferred SSRI during pregnancy due to the relatively minimal fetal exposure observed and its safety profile while breastfeeding.
Adverse effects
Side effects observed in fluoxetine-treated persons in clinical trials with an incidence >5% and at least twice as common in fluoxetine-treated persons compared to those who received a placebo pill include abnormal dreams, abnormal ejaculation, anorexia, anxiety, asthenia, diarrhea, dizziness, dry mouth, dyspepsia, fatigue, flu syndrome, impotence, insomnia, decreased libido, nausea, nervousness, pharyngitis, rash, sinusitis, somnolence, sweating, tremor, vasodilation, and yawning. Fluoxetine is considered the most stimulating of the SSRIs. It also appears to be the most prone of the SSRIs for producing dermatologic reactions.Sexual dysfunction
Sexual dysfunction, including loss of libido, erectile dysfunction, lack of vaginal lubrication, and anorgasmia, are some of the most commonly encountered adverse effects of treatment with fluoxetine and other SSRIs. While early clinical trials suggested a relatively low rate of sexual dysfunction, more recent studies in which the investigator actively inquires about sexual problems suggest that the incidence is >70%.In 2019, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency recommended that packaging leaflets of selected SSRIs and SNRIs should be amended to include information regarding a possible risk of persistent sexual dysfunction. Following on the European assessment, a safety review by Health Canada "could neither confirm nor rule out a causal link... which was long lasting in rare cases", but recommended that "healthcare professionals inform patients about the potential risk of long-lasting sexual dysfunction despite discontinuation of treatment".