Compared to other popular selective serotonin reuptake inhibitors (SSRIs), 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.

Trade Names

Fluoxetine is sold under the brand names Prozac, Symbyax (compounded with olanzapine), Sarafem, FLUX (Pakistan), Fontex (Sweden, Norway), Foxetin (Argentina), Ladose (Greece), Fluctin (Austria, Germany), Prodep (India), Fludac (India) Oxetin (Bosnalijek,Bosnia and Herzegovina), Seronil (Finland), Lovan (Australia) and Prizma (Israel).

Indications

Approved

FLUOX brand Fluoxetine
Prozac oral capsulesFluoxetine hydrochloride is approved in the United States to treat depression, obsessive-compulsive disorder, bulimia nervosa, premenstrual dysphoric disorder and panic disorder. In the United Kingdom, it is approved to treat depression with or without anxiety, bulimia nervosa, and obsessive-compulsive disorder.

In December 2003 the Food and Drug Administration (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.)

Unapproved/Off-label/Investigational
In 2003, Michel Harper, Fukodome Takayasu, and Andrew G. Engel reported that fluoxetine given over a period of three years at doses of up to 80-120 mg/day to two patients with slow-channel congenital myasthenic syndrome who were allergic to quinidine resulted in substantial subjective and objective improvement in muscle strength.

Fluoxetine is also often prescribed in the therapy of anorexia nervosa, mainly due to comorbidities between this disorder and other psychiatric disorders, such as clinical depression. The efficacy of fluoxetine administration to patients with anorexia nervosa has come into question in a recent publication of a randomized controlled trial.

Mechanism of action

Per the prescribing label, the mechanism of action of fluoxetine is unknown. Recent research indicates that fluoxetine may increase the production of new neurons (brain cells) in adult brain (adult neurogenesis) and that it interacts with the system of "clock genes", the transcription factors involved in drug abuse and possibly obesity .

Atypical SSRI

In a study comparing the effects of fluoxetine, paroxetine, sertraline, citalopram, and fluvoxamine on extracellular concentrations of serotonin, dopamine, and norepinepherine in the prefrontal cortex, only fluoxetine showed robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration, suggesting that fluoxetine is an atypical SSRI.

Interactions

Fluoxetine has a wide range of published interactions, notably with monoamine oxidase inhibitors (serotonin syndrome).

Side effects

Common adverse effects include akathisia, rage, and anxiety, which is possibly associated with an interaction of fluoxetine with the pineal gland, in addition to restlessness and insomnia. Weight loss, trembling, weakness, skin rash, anorgasmia, itching, and a decrease in sexual drive, have also been reported. It has been reported to cause subsequent weight gain .

Like other SSRIs, an overdose of fluoxetine or combining it with other antidepressants can lead to serotonin syndrome.

Metabolism

Fluoxetine is eliminated very slowly by the human 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, ie. 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. 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". 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.

Formulations

Fluoxetine is sold in capsules containing 10, 15, 20, 40, 60 or 90 mg of active ingredient, in tablets containing 10 mg, or 20 mg or in an oral suspension with concentration of 20 mg/5 ml.

Prozac Weekly is 90 mg of regular enteric-coated fluoxetine, taken every 7 days. These capsules resist dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. The enteric coating delays the onset of absorption of fluoxetine 1 to 2 hours relative to the immediate-release formulations.

Prozac for children

On 7th June 2006, the European Medicines Agency had announced that Prozac could be prescribed for children as young as 8 years old. They concluded that the benefits of Prozac outweigh the risks in children with moderate to severe depression who had failed to respond to psychological therapy. However, they have warned that the drug should only be used in combination with on-going therapy and not as a stand alone treament .