Fluoxetine (Prozac)

Class

SSRI (Selective Serotonin Reuptake Inhibitor)

Mechanism

Selective serotonin reuptake inhibitor (SERT) with additional 5-HT2C receptor antagonism, enhancing serotonergic neurotransmission and modulating anxiety and mood.

FDA-Approved Use

Major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bulimia nervosa, panic disorder, premenstrual dysphoric disorder (PMDD)

Off-Label Use

Binge eating disorder, posttraumatic stress disorder (PTSD), social anxiety disorder (SoAD), generalized anxiety disorder (GAD), post-stroke affective lability, post-stroke depression (PSD), depression in Parkinson’s disease (PD), depression in dementia, agitation and aggression in neurodevelopmental disabilities

Formulation

Oral capsules, tablets, liquid solution (10 mg, 20 mg, 40 mg)

Titration

10–20 mg p.o. daily, titrating gradually based on clinical response and tolerability

Dose Range

20–80 mg/day

Kinetics

Long half-life (~2–4 days) with active metabolite norfluoxetine (half-life ~7–15 days); steady state reached in several weeks; metabolized primarily via CYP2D6

Common AEs

Insomnia, nausea, headache, sexual dysfunction, weight loss

Serious/Rare AEs

Serotonin syndrome (especially with other serotonergic agents), increased risk of bleeding, hyponatremia, QTc prolongation (lower risk compared to other SSRIs)

Monitoring

Monitor for serotonin syndrome symptoms, suicidality, and adverse effects; ECG monitoring if combined with QT-prolonging drugs or cardiac risk factors

Black Box Warning

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders

Considerations

Fluoxetine is generally considered safe in patients with seizure disorders but may lower the seizure threshold; monitoring is recommended. It can effectively treat depressive symptoms in neurodegenerative disorders such as Parkinson’s disease (PD) and dementia, but should be used cautiously in dementia due to potential exacerbation of agitation or cognitive decline. In elderly patients, fluoxetine is typically well tolerated; however, dose reductions may be necessary in those with severe hepatic impairment. Its long half-life and active metabolite can reduce withdrawal symptoms but complicate cross-tapering when switching antidepressants.