BRAND NAMES
 MECHANISM OF ACTION
Fluoxetine, is the prototype of the selective serotonin reuptake inhibitors (SSRIs) antidepressants.
Fluoxetine inhibits the reuptake of serotonin at the serotonin reuptake transporter (SERT), so it blocks the removal of serotonin from the synaptic cleft, thereby enhancing serotonin signals. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.
- Acute and maintenance treatment of Major Depressive Disorder (MDD) in adult and pediatric patients aged 8 to 18 years. A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks; it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation
- Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) in adult and pediatric patients aged 7 to 17 years. Obsessive compulsive disorder is characterized by recurrent and persistent ideas, thoughts, impulses, or images (obsessions) that are ego-dystonic and/or repetitive, purposeful, and intentional behaviors (compulsions) that are recognized by the person as excessive or unreasonable.
- Acute and maintenance treatment of Bulimia Nervosa in adult patients
- Acute treatment of Panic Disorder, with or without agoraphobia, in adult patient. Panic disorder is an unexpected discrete period of intense fear or discomfort, symptoms can include palpitations, sweating, trembling, sensations of shortness of breath, chest pain or discomfort, nausea or abdominal distress, feeling dizzy and fear of dying
- Premenstrual dysphoric disorder: The essential features of PMDD are clear and established cyclicity of symptoms (occurring during the last week of the luteal phase in most menstrual cycles) such as depressed mood, anxiety, affective lability, and physical symptoms such as breast tenderness or swelling, headaches, joint or muscle pain, bloating, and weight gain. PMDD is a severe clinical entity and is distinguished from the broader premenstrual syndrome by the intensity of its symptoms (particularly mood symptoms) and the extent to which it interferes with social and/or occupational function.
- Major Depressive Disorder: 20 mg/day in the morning. The full effect may be delayed until 4 weeks of treatment or longer. Acute episodes of Major Depressive Disorder require several months or longer of sustained pharmacologic therapy
- Obsessive Compulsive Disorder: 20 mg/day in the morning, is recommended as the initial dose. Recommended dosage range: 20-60 mg/day. The full therapeutic effect may be delayed until 5 weeks of treatment or longer. It is reasonable to consider continuation of therapy for a responding patient.
- Panic Disorder: Starting dose is 10 mg/day. After one week, the dose should be increased to 20 mg/day. It is reasonable to consider continuation of therapy for a responding patient.
- Bulimia Nervosa: recommended dose is 60 mg/day (Only the 60 mg dose was statistically significantly superior to placebo in reducing the frequency of binge-eating and vomiting).
- Premenstrual Dysphoric Disorder: 20 mg per day is recommended continuously throughout the menstrual cycle. Initial treatment should be limited to six months, after which patients should be reassessed regarding the benefit of continued therapy.
- Pediatric (children and adolescents):
- Major Depressive Disorder: 10-20 mg/day
- Obsessive Compulsive Disorder: Starting dose is 10 mg/day in the morning. In adolescents and higher weight children, after 2 weeks, the dose should be increased to 20 mg/day. Additional dose increases may be considered after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 60 mg/day is recommended.
Discontinuing Fluoxetine: A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible.
- Known hypersensitivity to Fluoxetine
- It's use within 14 days of stopping an MAOI because of an increased risk of serotonin syndrome
- Do not start Fluoxetine in a patient who is being treated with linezolid or intravenous methylene blue
- Concomitant use with pimozide (Orap®) or Thioridazine (due to risk of drug interaction or QTc prolongation). Do not use thioridazine within 5 weeks of discontinuing Fluoxetine.
 WARNINGS AND PRECAUTIONS
- FDA Black Box Warning for Fluoxetine : Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Fluoxetine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Fluoxetine is approved for use in pediatric patients with Major Depressive Disorder (MDD) and Obsessive Compulsive Disorder (OCD).
- Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including Fluoxetine, both when taken alone, but especially when co-administered with other serotonergic agents (including Triptans, Tricyclic antidepressants, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOI, both those intended to treat psychiatric disorders and also others, such as Linezolid and intravenous Methylene blue). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).If such symptoms occur, discontinue Fluoxetine and initiate supportive treatment. If concomitant use of Fluoxetine with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
- Abnormal Bleeding: May increase the risk of bleeding. Use with NSAIDs, Aspirin, Warfarin, or drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding
- Altered Appetite and Weight: Significant weight loss has occurred
- Anxiety and Insomnia: May occur
- Hyponatremia: Hyponatremia has been reported with Fluoxetine use, either alone or in combination with some diuretics (Hydrochlorothiazide, Furosemide). Hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Signs and symptoms include headache, new or increased seizure frequency, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to fall. Severe Hyponatremia may cause hallucination, syncope, seizure, coma, respiratory arrest, and death.
- Interference with Cognitive and Motor Performance: : Has potential to impair judgment, thinking, and motor skills. Use caution when operating machinery
- Monoamine Oxidase Inhibitors (MAOIs): increased risk for serotonin syndrome (See contraindications)
- Pimozide: Risk of drug interaction or QTc prolongation (Contraindicated)
- Thioridazine: Risk of QTc interval prolongation or potential for elevated thioridazine plasma levels. (Contraindicated)
- Serotonergic agents (Triptans, Tricyclic antidepressants, Fentanyl, Lithium carbonate, Tramadol, Tryptophan, Buspirone and St. John’s Wort): increased risk for serotonin syndrome
- Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway. Tamoxifen indicated for palliative and adjuvant treatment of estrogen-receptor-positive breast cancer is a prodrug, and the formation of the active metabolite is mediated by the CYP2D6 enzyme. Concentrations of the tamoxifen metabolites in patients concomitantly treated with CYP2D6 enzyme inhibitors including Fluoxetine may be reduced.
- CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs
 PREGNANCY AND LACTATION
- Pregnancy Category C (US). Fluoxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Fluoxetine is excreted in human breast milk. Nursing while on Fluoxetine is not recommended
 SIDE EFFECTS
Most common adverse reactions (≥5% and at least twice that for placebo) are: abnormal dreams, abnormal ejaculation, anorexia, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, impotence, insomnia, libido decreased, nausea, nervousness, pharyngitis, rash, sinusitis, somnolence, sweating, tremor, vasodilatation, and yawn.
For more serious adverse effects (see WARNINGS AND PRECAUTIONS)
 RELATED LINKS
|Tricyclic antidepressants||Amitriptyline (Elavil, Laroxyl) • Clomipramine (Anafranil) • Doxepin (Sinequan) • Imipramine (Tofranil) • Nortriptyline (Aventyl, Pamelor) • Trimipramine (Surmontil)|
|Selective serotonin reuptake inhibitors (SSRIs)||Citalopram (Celexa, Seropram) • Escitalopram (Cipralex, Lexapro) • Fluoxetine (Prozac) • Fluvoxamine (Luvox, Maveral) • Paroxetine (Paxil, Seroxat) • Sertraline (Zoloft)|
|Serotonin–norepinephrine reuptake inhibitors (SNRIs)||Desvenlafaxine (Pristiq) • Duloxetine (Cymbalta, Xeristar) • Venlafaxine (Efexor, Effexor)|
|Serotonin antagonists and reuptake inhibitors (SARIs)||Trazodone (Desyrel, Oleptro)|
|Norepinephrine reuptake inhibitors (NRIs)||Maprotiline (Ludiomil) • Reboxetine (Edronax)|
|Norepinephrine-dopamine reuptake inhibitors (NDRIs)||Bupropion (Wellbutrin)|
|Noradrenergic and specific serotonergic antidepressants (NaSSAs)||Mianserin (Lantanon) • Mirtazapine (Remeron)|
|Norepinephrine-dopamine disinhibitors (NDDIs)||Agomelatine (Valdoxan, Thymanax)|
|Monoamine oxidase inhibitors Nonselective||Tranylcypromine (Parnate)|
|Monoamine oxidase inhibitors B-Selective||Selegiline (Transdermal) (Emsam)|
|Others||5-Hydroxytryptophan • S-Adenosyl methionine • Hypericum (St John's wort)|