Fluoxetine hydrochloride is an antidepressant drug used medically in the treatment of depression, obsessive-compulsive disorder, bulimia nervosa, premenstrual dysphoric disorder and panic disorder. Fluoxetine is also used (off-label) to treat many other conditions, such as ADHD. It is sold under the brand names Prozac�, Symbyax� (compounded with olanzapine), Sarafem�, Fontex� (Sweden), Foxetin� (Argentina), Fluctin� (Austria, Germany), Prodep� (India) and Fludac� (India).
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI), and is marketed in capsules containing 10, 20, 40 or 90 mg of active ingredient, in tablets containing 10 mg, or in a oral solution with concentration of 5 mg/5 ml (?). Dosages in the range of 20-60 mg per day are standard, with 80 mg considered a maximum. Eli Lilly's Prozac was approved by the FDA on December 29, 1987 and introduced in the US at the beginning of 1988. The drug became very popular, with millions around the world having taken the medication. In Fall 2001, Eli Lilly lost a patent dispute with Barr Laboratories and now Fluoxetine HCl is manufactured by many companies.
Fluoxetine has a wide range of published interactions, notably with monoamine oxidase inhibitors. Common side-effects include anxiety, restlessness and insomnia. Weight loss, trembling, weakness, skin rash, anorgasmia, itching, and a decrease in sexual drive, have also been reported.
Compared to other popular selective serotonin reuptake inhibitors fluoxetine has a strong energizing effect. This makes fluoxetine highly effective in treatment of clinical depression cases where symptoms like depressed mood and lack of energy prevail. Although stimulating, it is also approved for a variety of anxiety disorders, including panic disorder and obsessive compulsive disorder
Fluoxetine is eliminated very slowly by the body. The half-life of fluoxetine after a single dose is two days and, after multiple dosing, four days. The liver then metabolizes fluoxetine into norfluoxetine, a desmethyl metabolite, which is also a serotonin reuptake inhibitor; norfluoxetine has an even longer half-life, i.e. 8.6 and 9.3 days for single and repeated dosage respectively. These long half-lives may be helpful in those patients with compliance issues, but fluoxetine is most effective when taken daily. An exception is Prozac Weekly, a long acting formula which delivers 90 mg of sustained release fluoxetine, and may be taken every 7 days. Other SSRIs have, by comparison, a very short half-life. Some professionals feel that it is fluoxetine's long half-life that gives it much of its therapeutic utility, however this has never been proven under rigorous scientific study. Nevertheless, its long half life is also relevant because suddenly discontinuing SSRIs is known to produce both somatic and psychological withdrawal symptoms, a phenomenon known as "SSRI discontinuation syndrome" (Tamam & Ozpoyraz, 2002). It is generally accepted that fluoxetine�s withdrawal symptoms are much smoother than with other SSRIs, as the substance takes several days to completely leave the system. Fluoxetine is a potent CYP2D6 inhibitor, which can decrease metabolism of other medications.
In December 2003 the FDA approved Symbyax to treat bipolar depression. Symbyax is a combination of fluoxetine and olanzapine. (However, the pure form of fluoxetine can cause mania, mixed-states, rapid cycling and psychosis in bipolar patients, particularly if the patient is not also taking a mood stabilizer.)
In the late 1990s, a backlash grew against Prozac�. Prozac�'s manufacturer, Eli Lilly and Company, earned billions from its success, and became the target of numerous accusations (see David Healy affair). Lawsuits amounting to millions were instigated, alleging the drug made users feel suicidal and/or caused other serious side effects. The accusations and lawsuits have been unsuccessful in stemming the prescription and use of the medication, as well as in making the accusers some of Lilly's profits. Recently, the United States FDA considered similar controversial issues regarding Prozac� and its use in children and adolescents; it issued a "black box warning" (its most serious warning) for Prozac� and other antidepressants (SSRI's and antidepressants of related classes) due to findings of increased suicidality in some children and adolescents on the drugs.
A more recent controversy embroiled Lilly, and a class action lawsuit has been filed after several people received in the mail free samples of Prozac�. The suit alleges that the samples' recipients' right to privacy was mishandled.
In August 2004 a report by the Environment Agency found trace amounts of fluoxetine in UK drinking water, although the Drinking Water Inspectorate said that it was unlikely to pose a health risk. However, the effects from ingestion of fluoxetine in drinking water has not been investigated.
Prozac was recently classified as a reproductive and developmental toxin by the Center for the Evaluation of Risks to Human Reproduction (CERHR), an expert panel at the National Institute of Environmental Health Sciences at the National Institutes of Health.
In January, 2005, the British Medical Journal was leaked official Eli Lilly documents from the 1980s suggesting there was a link between fluoxetine and suicide and psychosis. It was originally claimed that the documents had not been previously disclosed, and they were subsequently provided to the FDA for further investigation. However, Eli Lilly later claimed that the documents had been released in earlier litigation.
The resources at the end of this article present a blend of views on this drug, some of which focus on the more controversial and unscientific issues.