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Fluoxetine hydrochloride is the first agent of the class of antidepressants known as selective serotonin-reuptake inhibitors (SSRIs). Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity. As with other antidepressant agents, several weeks of therapy may be required before a clinical effect is seen. SSRIs are potent inhibitors of neuronal serotonin reuptake. They have little to no effect on norepinephrine or dopamine reuptake and do not antagonize & alpha; – or & beta; -adrenergic, dopamine D< sub> 2< /sub> or histamine H< sub> 1< /sub> receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT< sub> 1A< /sub> and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT< sub> 1A< /sub> and terminal autoreceptors. The overall clinical effect of increased mood and decreased anxiety is thought to be due to adaptive changes in neuronal function that leads to enhanced serotonergic neurotransmission. Side effects include dry mouth, nausea, dizziness, drowsiness, sexual dysfunction and pain in the head or upper neck. সহজ বাংলা: মাথাব্যথা।" data-rx-term="headache" data-rx-definition="Headache means pain in the head or upper neck. সহজ বাংলা: মাথাব্যথা।">headache. Side effects generally occur within the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Fluoxetine may be used to treat major depressive disorder (MDD), moderate to severe bulimia nervosa, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), panic disorder with or without agoraphobia, and in combination with olanzapine for treatment-resistant or bipolar I depression. Fluoxetine is the most anorexic and stimulating SSRI.
Fluoxetine is the first agent of the class of antidepressants known as selective serotonin-reuptake inhibitors (SSRIs & an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of the major depressive disorder, obsessive-compulsive disorder (OCD), bulimia nervosa, panic disorder, and premenstrual dysphoric disorder.
Mechanism of action of Fluoxetine
Metabolized to norfluoxetine, fluoxetine is a selective serotonin-reuptake inhibitor (SSRI), it blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs. According to the amines hypothesis, a functional decrease in the activity of amines, such as serotonin and norepinephrine, would result in depression; a functional increase of the activity of these amines would result in mood elevation. Fluoxetine’s effects are thought to be associated with the inhibition of 5HT receptor, which leads to an increase of serotonin level. Antagonism of muscarinic, histaminergic, and α1–adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects of classical tricyclic antidepressant (TCA) drugs. Fluoxetine binds to these and other membrane receptors from brain tissue much less potently in vitro than do the tricyclic drugs.
Indications of Fluoxetine
- Anxiety and stress
- Borderline personality disorder
- Body dysmorphic disorder
- Depression
- Premenstrual dysphoric disorder
- Major depressive disorder
- Bulimia nervosa (BN)
- Depression, bipolar
- Depressive disorders
- Obsessive-compulsive disorder
- Panic disorders
- Premature ejaculation
- Fibromyalgia
- Intermittent explosive disorder
- Obsessive-compulsive disorder
- Persistent depressive disorder
- Postpartum depression
- Schizoaffective disorder
- Somatoform pain disorder
- Trichotillomania
or
Labeled indication include: major depressive disorder (MDD), moderate to severe bulimia nervosa, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), panic disorder with or without agoraphobia, and combination treatment with olanzapine for treatment-resistant or bipolar I depression. Unlabeled indications include selective mutism, mild dementia-associated agitation in nonpsychotic patients, post-traumatic stress disorder (PTSD), social anxiety disorder, chronic neuropathic pain, fibromyalgia, and Raynaud’s phenomenon.
Contra Indications of Fluoxetine
- Diabetes
- Syndrome of Inappropriate Antidiuretic Hormone Secretion
- low amount of magnesium in the blood
- low amount of sodium in the blood
- low amount of potassium in the blood
- increased risk of bleeding
- Behaving with Excessive Cheerfulness and Activity
- Mild Degree of Mania
- Manic-Depression
- Having Thoughts of Suicide
- Serotonin syndrome – adverse drug interaction
- Closed-angle glaucoma
- heart attack within the last 30 days
- Very Rapid Heartbeat – Torsades de Pointes
- Slow Heartbeat
- prolonged QT interval on EKG
- Suddenly serious symptoms of heart failure
- Abnormal EKG with QT changes from Birth
- Hardening of the Liver
- Liver problems
- Bleeding from Stomach
- Esophagus or Duodenum
- seizures
Dosages of Fluoxetine
Strengths: 90 mg; 10 mg; 20 mg; 40 mg; 20 mg/5 mL; 15 mg; 60 mg
Depression
Immediate-release oral formulations
Initial dose: 20 mg orally once a day in the morning, increased after several weeks if sufficient clinical improvement is not observed
- Maintenance dose: 20 to 60 mg orally per day
- Maximum dose: 80 mg orally per day
Delayed release oral capsules
- Initial dose: 90 mg orally once a week, commenced 7 days after the last daily dose of immediate-release fluoxetine 20 mg formulations.
Obsessive Compulsive Disorder
Immediate-release oral formulations
- Initial dose: 20 mg orally once a day in the morning, increased after several weeks if sufficient clinical improvement is not observed.
- Maintenance dose: 20 to 60 mg orally per day
- Maximum dose: 80 mg orally per day
Panic Disorder
Immediate-release oral formulations
- Initial dose: 10 mg orally once a day, increased after one week to 20 mg orally once a day
- Maintenance dose: 20 to 60 mg orally per day
- Maximum dose: 60 mg orally per day
Premenstrual Dysphoric Disorder
Immediate-release oral formulations
Initial dose
- Continuous regimen: 20 mg orally once a day on every day of the menstrual cycle
- Cyclic regimen: 20 mg orally once a day starting 14 days prior to the anticipated start of menstruation through to the first full day of menses, and repeated with each new cycle
- Maintenance dose: 20 to 60 mg per day for either the continuous or intermittent regimens
- Maximum dose: 80 mg orally per day
Pediatric Dose for Depression
Immediate-release oral formulations
8 to 18 years
- Initial dose: 10 to 20 mg orally once a day; the 10 mg daily dose may be increased after one week to 20 mg orally once a day
Pediatric Dose for Obsessive Compulsive Disorder
Immediate-release oral formulations
7 to 17 years
- Adolescents and higher weight children
- Initial dose: 10 mg orally once a day, increased to 20 mg orally once a day after 2 weeks
- Maintenance dose: 20 to 60 mg orally per day
- Maximum dose: 60 mg orally per day
Side Effects of Fluoxetine
The most common
- clumsiness or unsteadiness
- dizziness
- drowsiness
- dry mouth
- false sense of well-being
- increased watering of mouth
- lightheadedness
- constipation;
- vision changes;
- breast swelling (in men or women); or
- decreased sex drive, impotence, or difficulty having an orgasm.
- blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- restless muscle movements in your eyes, tongue, jaw, or neck;
- a light-headed feeling, like you, might pass out;
Common
- Drowsiness and lightheadedness the day after taking the medicine.
- Confusion.
- Numbed emotions.
- Visual disturbances such as blurred vision or double vision.
- Shaky movements and unsteady walk (ataxia).
- Loss of memory (amnesia).
- Muscle weakness.
- Dizziness.
- A headache.
- Skin rashes.
- Disturbances of the gut such as diarrhea, constipation, nausea, vomiting or abdominal pain.
- Difficulty in passing urine (urinary retention).
- Changes in sex drive.
- Low blood pressure (hypotension).
- Blood disorders.
- Jaundice.
- Unexpected aggression, restlessness or irritability (tell your doctor if you experience this).
- Nightmares or hallucinations (tell your doctor if you experience this).
Serious
- agitation
- anxiety
- behavioral changes, including aggressiveness, angry outbursts, bizarre behavior, or decreased inhibitions
- confusion
- increased trouble sleeping
- memory problems
- muscle spasms
- shortness of breath
- signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
- sleepwalking
Drug Interactions of Fluoxetine
Fluoxetine may interact with following drugs, supplements & may change the efficacy of drugs
- amlodipine
- general anesthetics
- antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- aripiprazole
- baclofen
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- bupropion
- celecoxib
- cilostazol
- clopidogrel
- cyclosporine
- diabetes medications (e.g., chlorpropamide, metformin, nateglinide, rosiglitazone)
- diltiazem
- estrogens (e.g., conjugated estrogen, )
- glucosamine
- heparin
- low molecular weight heparins
- mirtazapine
- monoamine oxidase inhibitors (MAOIs; e.g. rasagiline, selegiline, )
- multivitamins
- muscle relaxants
- nifedipine
- non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, naproxen)
- omega-3 fatty acids
- pentoxifylline
- propranolol
- quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
- rasagiline
- seizure medications ( phenobarbital, phenytoin, valproic acid, )
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- tapentadol
- theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
- thiazide diuretics (water pills; e.g., hydrochlorothiazide, )
- thyroid replacements (e.g., desiccated thyroid, levothyroxine)
- tizanidine
- tramadol
- tricyclic antidepressants (e.g., desipramine, nortriptyline)
- triptans (e.g., sumatriptan, rizatriptan)
Pregnancy & Lactation of Fluoxetine
FDA Pregnancy Category C
Pregnancy
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist or nurse for advice before taking this medicine. When taken during pregnancy, particularly in the last 3 months of pregnancy, medicines like Fluoxetine may increase the risk of a serious condition in babies, called persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and appear bluish. These symptoms usually begin during the first 24 hours after the baby is born.
Lactation
Breastfeeding is not recommended whilst taking fluoxetine. Fluoxetine has been shown to reduce the quality of sperm in animal studies. Theoretically, this could affect fertility, but the impact on human fertility has not been observed as yet.
References
