brands

Class

• Neuroscience-based Nomenclature: serotonin reuptake inhibitor (S-RI)
• SSRI (selective serotonin reuptake inhibitor); often classified as an antidepressant, but it is not just an antidepressant

FLUOXETINE commonly prescribed for

(Bold for FDA approved)

How FLUOXETINE works

• Boosts neurotransmitter serotonin

• Blocks serotonin reuptake pump (serotonin transporter)

• Desensitizes serotonin receptors, especially serotonin 1A receptors

• Presumably increases serotonergic neurotransmission

• Fluoxetine also has antagonist properties at serotonin 2C receptors, which could increase norepinephrine and dopamine neurotransmission

How long until FLUOXETINE works

• Some patients may experience increased energy or activation early after initiation of treatment

• Onset of therapeutic actions usually not immediate, but often delayed 2–4 weekS

• If it is not working within 6–8 weeks, it may require a dosage increase or it may not work at all

• May continue to work for many years to prevent relapse of symptoms

Notable Side Effects

• Sexual dysfunction (men: delayed ejaculation, erectile dysfunction; men and women: decreased sexual desire, anorgasmia)

• Gastrointestinal (decreased appetite, nausea, diarrhea, constipation, dry mouth)

• Mostly CNS (insomnia but also sedation, agitation, tremors, headache, dizziness)

• Note: patients with diagnosed or undiagnosed bipolar or psychotic disorders may be more vulnerable to CNS-activating actions of SSRIs

• Autonomic (sweating)

• Bruising and rare bleeding

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Life Threatening Side Effects

• Rare seizures

• Rare induction of mania

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

weight gain

unusual

sedation

unusual

What to do about FLUOXETINE side effects

• Wait

• Wait

• Wait

• If fluoxetine is activating, take in the morning to help reduce insomnia

• Reduce dose to 10 mg, and either stay at this dose if tolerated and effective, or consider increasing again to 20 mg or more if tolerated but not effective at 10 mg

• In a few weeks, switch or add other drugs

usual dosage range

• 20–80 mg for depression and anxiety disorders

• 60–80 mg for bulimia

Dosage Forms

• Capsule 10 mg, 20 mg, 40 mg

• Tablet 10 mg, 15 mg, 20 mg, 60 mg

• Liquid 20 mg/5 mL–120 mL bottles

• Weekly capsule 90 mg

• Olanzapine–fluoxetine combination capsule (mg equivalent olanzapine/ mg equivalent fluoxetine) 3 mg/25 mg, 6 mg/25 mg, 6 mg/50 mg, 12 mg/25 mg, 12 mg/50 mg

long term use

• Safe

habit forming

• No

Renal Impairment

• No dose adjustment

• Not removed by hemodialysis

Hepatic Impairment

• Lower dose or give less frequently, perhaps by half

Cardiac Impairment

• Preliminary research suggests that fluoxetine is safe in these patients

• Treating depression with SSRIs in patients with acute angina or following myocardial infarction may reduce cardiac events and improve survival as well as mood

Elderly

• Some patients may tolerate lower doses better

• Risk of SIADH with SSRIs is higher in the elderly

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Use with caution, observing for activation of known or unknown bipolar disorder and/ or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• Approved for OCD and depression

• Adolescents often receive adult dose, but doses slightly lower for children

• Children taking fluoxetine may have slower growth; long-term effects are unknown

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• Not generally recommended for use during pregnancy, especially during first trimester

• Nonetheless, continuous treatment during pregnancy may be necessary and has not been proven to be harmful to the fetus

• Current patient registries of children whose mothers took fluoxetine during pregnancy do not show adverse consequences

• At delivery there may be more bleeding in the mother and transient irritability or sedation in the newborn

• Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child

• For many patients this may mean continuing treatment during pregnancy

• Exposure to SSRIs early in pregnancy may be associated with increased risk of septal heart defects (absolute risk is small)

• SSRI use beyond the 20th week of pregnancy may be associated with increased risk of pulmonary hypertension in newborns, although this is not proven

• Exposure to SSRIs late in pregnancy may be associated with increased risk of gestational hypertension and preeclampsia

• Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying

Breast Feeding

• Some drug is found in mother’s breast milk

• Trace amounts may be present in nursing children whose mothers are on fluoxetine

• If child becomes irritable or sedated, breast feeding or drug may need to be discontinued

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Must weigh benefits of breast feeding with risks and benefits of antidepressant treatment versus nontreatment to both the infant and the mother

• For many patients this may mean continuing treatment during breast feeding