Fluoxetine (Prozac)

Trade name Prozac

Oral agent with bioavailability of 72%.

Protein binding 94-95%.

Metabolism is hepatic and mostly CYP2D6-mediated.

Half-life 1–3 days for acute exposure and 4–6 days for chronic use.

Excretion is by urine in 80%, and fecal in 15%.

An antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.

Used for the treatment of major depressive disorder, obsessive-compulsive disorder, bulimia nervosa, panic disorder and premenstrual dysphoric disorder.

Can be used to treat trichotillomania.

Used in combination with the atypical antipsychotic olanzapine it is used

for the treatment of depressive episodes as part of bipolar I disorder and in the treatment of treatment-resistant depression.

Frequently used to treat post-traumatic stress disorder, cataplexy, obesity, and alcohol dependence, bulemia, as well as binge eating disorder.

Used as a treatment for autism spectrum disorders with moderate success in adults.

The effectiveness of fluoxetine with mild or moderate symptoms, along with other SSRIs is clinically insignificant in many studies, but a 2012 meta analysis from 18 randomized controlled clinical trials concluded that statistically and clinically significant benefit was seen irrespective of baseline depression severity.

In children and adolescents it is the antidepressant of choice.

In pregnancy, fluoxetine is considered a category C drug.

Evidence supports an increased risk of major fetal malformations from exposure in the first trimester, although reviews and a meta-analysis of 21studies suggest women who are treated with fluoxetine during the first trimester of pregnancy do not appear to have an increased risk of major fetal malformations.

Tapering SSRIs such as fluoxetine during the third trimester should be considered.

The Journal of Human Lactation recommends against fluoxetine as a first-line SSRI during lactation.

Sertraline is considered the pref2242ed SSRI during pregnancy due to the relatively minimal fetal exposure observed and its safety profile while breastfeeding.

Adverse reactions include: headache, nausea, insomnia, anorexia, anxiety, weakness, diarrhea, nervousness, somnolence, dizziness, dry mouth, dyspepsia, tremor, impaired libido, abnormal taste, agitation, chest pain, chills, confusion, prolonged QTc interval, restlessness, abnormal dreams, sleep disorders, vomiting, sexual dysfunction, and weight gain or loss,

Fluoxetine 20 mg capsules.

Withdrawal or discontinuation symptoms may occur following int2242uption of treatment, but side effects of discontinuation are uncommon and mild.

One of the recommended strategies for the management of discontinuation syndrome with other SSRIs is to substitute fluoxetine for the original agent, in cases where tapering off the dose of the original SSRI is ineffective.

Fluoxetine has the lowest incidence of discontinuation syndrome among several antidepressants including paroxetine and venlafaxine.

May increase the risk of suicide in people younger than 25 with a a 2-fold increase of the suicidal ideation and behavior in children and adolescents, and 1.5-fold increase of suicidality in the 18–24 age group.

Reent comparison of aggression and hostility occurring during treatment with fluoxetine to placebo in children and adolescents found that no significant difference between the fluoxetine group and a placebo group.

Fluoxetine use in children increased the odds of suicidality by 50%, and in adults decreases the odds of suicidality by approximately 30%.

Fluoxetine and other SSRIs may reduce the propensity for violence.

Reduces acts of domestic violence in alcoholics, and reduces aggressive behavior in patients with borderline personality disorder.

Increases in antidepressant drug prescriptions has been associated with reductions in violent crime.

Contraindications include prior treatment with MAOIs due to the potential for serotonin syndrome.

Fluoxetine can inhibit many isozymes of the cytochrome P450 system involved in drug metabolism.

Potent inhibitor of CYP2D6 and mild to moderate inhibitors of CYP1A2, CYP2B6, CYP2C9/2C19, and CYP3A4.

Initially metabolized through cytochrome P450 (CYP) 2D6 which is subject to genetic variation and inhibition.

Also inhibits the activity of P-glycoprotein, a type of membrane transport protein that plays an important role in drug transport and metabolism.

Use should also be avoided in those receiving other serotonergic drugs such as monoamine oxidase inhibitors, tricyclic antidepressants, methamphetamine, MDMA, triptans, buspirone, serotonin-norepinephrine reuptake inhibitors and other SSRIs due to the potential for serotonin syndrome to develop.

The cytochrome P450 isoenzyme is responsible for converting fluoxetine to its only active metabolite, norfluoxetine.and drugs are also potent inhibitors of CYP2D6.

Norfluoxetine is the chief metabolite, and is the only one that is biologically active.

Peak plasma concentrations are reached in 6 to 8 hours.

Highly bound to plasma proteins, mostly albumin and α1-glycoprotein.

Metabolized in the liver by isoenzymes of the cytochrome P450 system, including CYP2D6.

Fluoxetine and its active metabolite norfluoxetine have extremely slow elimination from the body and distinguishes it from other antidepressants.

With time, fluoxetine and norfluoxetine inhibit their own metabolism.

The drug’s elimination half-life changes from 1 to 3 days, after a single dose, to 4 to 6 days, after long-term use.

The half-life of norfluoxetine is 16 days after long-term use.

The concentration of the drug and its active metabolite grows through the first few weeks of treatment, until their steady concentration in the blood is reached after four weeks.

The brain concentration of fluoxetine and its metabolites increases through at least the first five weeks of treatment, so that the full benefits of the the drug are not realized for at least a month after initiation.

The median time to achieving a consistent response is 29 days.

The complete excretion of the drug may take several weeks and during the first week after the treatment discontinuation, the brain concentration of fluoxetine decreases only by 50%,

Fluoxetine and norfluoxetine may be quantitated in blood, plasma or serum to monitor therapy.

Therapeutic blood or plasma fluoxetine concentrations are usually in a range of 50–500 μg/L..

A selective serotonin reuptake inhibitor and does not appreciably inhibit norepinephrine and dopamine reuptake.

The least selective of all the SSRIs, with a 10-fold difference in binding affinity between its first and second neural targets.

Delays the reuptake of serotonin, resulting in serotonin persisting longer when it is released.

Affects chemicals in the brain that cause depression, panic, anxiety, or obsessive-compulsive symptoms.

Used to treat major depressive disorder, bulimia nervosa, obsessive-compulsive disorder, and panic disorder.

Sometimes used with olanzapine (Zyprexa). to treat depression caused by bipolar disorder, and depression that has failed at least 2 other medications.

Should not be used with pimozide, thioridazine, methylene blue injection, MAO inhibitors.

MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine.

Can pass into breast milk and may harm a nursing baby.

Drinking alcohol can increase side effects.

Common side effects may include: insomnia, strange dreams, headache, dizziness, vision changes, tremors or shaking, anxiety, pain, weakness, yawning, tired feeling, loss of appetite, nausea, vomiting, diarrhea, dry mouth, sweating, hot flashes, changes in weight or appetite,stuffy nose, sinus pain, sore throat, flu-like symptoms, decreased sex drive, impotence, and difficulty having an orgasm.

Associated with weight gain.

Warnings for treatment emergent suicidality, particularly in adolescents and young adults.

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