What is/are Fluoxetine?
Fluoxetine (also known by the tradenames Prozac, Sarafem, Fontex, among others) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Fluoxetine was first documented in 1974 by scientists from Eli Lilly and Company. It was presented to the U.S. Food and Drug Administration in February 1977, with Eli Lilly receiving final approval to market the drug in December 1987. Fluoxetine went off-patent in August 2001.
Fluoxetine is approved for the treatment of major depression (including pediatric depression), obsessive-compulsive disorder (in both adult and pediatric populations), bulimia nervosa, panic disorder and premenstrual dysphoric disorder. In addition, fluoxetine is used to treat trichotillomania if cognitive behaviour therapy is unsuccessful. In combination with olanzapine it is known as Symbyax.
Despite the availability of newer agents, fluoxetine remains extremely popular. In 2010, over 24.4 million prescriptions for generic formulations of fluoxetine were filled in the United States alone, making it the third most prescribed antidepressant after sertraline (SSRI; became generic in 2006) and citalopram (SSRI; became generic in 2003). In 2011, 6 million prescriptions for fluoxetine were handed out in the UK.
Fluoxetine is frequently used to treat major depression, obsessive compulsive disorder, post-traumatic stress disorder, bulimia nervosa, panic disorder, body dysmorphic disorder, premenstrual dysphoric disorder, and trichotillomania. Caution should be taken when using any SSRI for bipolar disorder as this can increase the likelihood of mania; however, fluoxetine can be used with an antipsychotic (such as quetiapine) for bipolar. It has also been used for cataplexy, obesity, and alcohol dependence, as well as binge eating disorder.
Sexual dysfunction is a common side effect with SSRIs. Specifically, side effects often include difficulty becoming aroused, erectile dysfunction, lack of interest in sex, and anorgasmia (inability to achieve orgasm). Genital anesthesia, loss of or decreased response to sexual stimuli, and ejaculatory anhedonia are also possible. Although usually reversible, these sexual side effects can last for months, years, or permanently after the drug has been completely withdrawn. This is known as Post SSRI Sexual Dysfunction.
According to the manufacturer of Prozac brand of fluoxetine, Eli Lilly, fluoxetine is contraindicated in individuals taking monoamine oxidase inhibitors, pimozide (Orap) or thioridazine (Mellaril). The prescribing information recommends that the treatment of the patients with liver impairment "must be approached with caution". The elimination of fluoxetine and its metabolite norfluoxetine is about half as fast in these patients, resulting in the proportionate increase of exposure to the drug. Ibuprofen used in combination with fluoxetine can cause significant intestinal bleeding after a period of use.
Among the common adverse effects associated with fluoxetine and listed in the prescribing information, the effects with the greatest difference from placebo are nausea (22% vs 9% for placebo), insomnia (19% vs 10% for placebo), somnolence (12% vs 5% for placebo), anorexia (10% vs 3% for placebo), anxiety (12% vs 6% for placebo), nervousness (13% vs 8% for placebo), asthenia (11% vs 6% for placebo) and tremor (9% vs 2% for placebo). Those that most often resulted in interruption of the treatment were anxiety, insomnia, and nervousness (1–2% each), and in pediatric trials—mania (2%).
Similarly to other SSRIs, sexual side effects are common with fluoxetine; they include anorgasmia and reduced libido.
In addition, rash or urticaria, sometimes serious, was observed in 7% patients in clinical trials; one-third of these cases resulted in discontinuation of the treatment. Postmarketing reports note several cases of complications developed in patients with rash. The symptoms included vasculitis and lupus-like syndrome. Death has been reported to occur in association with these systemic events.
Akathisia, that is inner tension, restlessness, and the inability to stay still, often accompanied by "constant pacing, purposeless movements of the feet and legs, and marked anxiety", is a common side effect of fluoxetine. Akathisia usually begins after the initiation of the treatment or increase of the dose and disappears after fluoxetine is stopped or its dose is decreased, or after treatment with propranolol. There are case reports directly linking akathisia with suicidal attempts, with patients feeling better after the withdrawal of fluoxetine, and again developing severe akathisia on repeated exposure to fluoxetine. These patients described "that the development of the akathisia made them feel suicidal and that it had precipitated their prior suicide attempts". The experts note that because of the link of akathisia with suicide and the distress it causes to the patient, "it is of vital importance to increase awareness amongst staff and patients of the symptoms of this relatively common condition". More rarely, fluoxetine has been associated with related movement disorders acute dystonia and tardive dyskinesia.
Fluoxetine taken during pregnancy also increases rate of poor neonatal adaptation. Because fluoxetine is excreted in human milk, nursing while on fluoxetine is not recommended. A study of fluoxetine administered to newborn mice found that early postnatal exposure of the drug later caused the adult mice to exhibit depressive and anxious behavior similar to those of induced depression, which could be relieved by fluoxetine. The American Association of Pediatrics classifies fluoxetine as a drug for which the effect on the nursing infant is unknown but may be of concern.
Mechanism of action
Fluoxetine's mechanism of action is predominantly that of a serotonin reuptake inhibitor. Fluoxetine delays the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Fluoxetine may also produce some of its effects via its weak 5-HT2C receptor antagonist effects. In addition, fluoxetine has been found to act as an agonist of the σ1-receptor, with a potency greater than that of citalopram but less than that of fluvoxamine. However, the significance of this property is not fully clear.
This article uses material from the Wikipedia article Fluoxetine, which is released under the Creative Commons Attribution-Share-Alike License 3.0.