Prozac (Fluoxetine HCL)
- Generic name: Fluoxetine hydrochloride
- Trade names: Prozac, Prozac Weekly, Sarafem
- Pharmacologic category: Selective serotonin
- FDA approved: December 29, 1987
- Manufacturer: Eli Lilly and Company
- Habit forming? No
- Pregnancy risk factor: C
Prozac (Fluoxetine) is in the class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). Fluoxetine hcl is indicated for the treatment of depression, obsessive-compulsive disorder, panic attacks, premenstrual dysphoric disorder, and some eating disorders. It also is occasionally used to treat alcoholism, borderline personality disorders, sleep disorders, headaches, premenstrual syndrome, schizophrenia, Tourette's syndrome, anxiety, and phobias.
The most common early side effects of fluoxetine are agitation, insomnia, and neuromuscular restlessness resembling akathisia. This may be caused by fluoxetine's relative lack of selectivity over norepinephrine and serotonin-2C receptors (5-HT2C) . These side effects are short-lived and may improve with a dose reduction or temporary co-administration of a beta-adrenergic blocker or long-acting benzodiazepine.
- Absorption: Well-absorbed with a small first-pass effect. Food does not affect the extent of absorption, although the rate may be slightly decreased.
- Metabolism: Metabolized by demethylation in the liver to the active metabolite, norfluoxetine, and other unidentified metabolites. In vivo studies indicate that cytochrome P450 2D6 (CYP2D6) is involved in fluoxetine metabolism. An in vitro study indicates that CYP2C9 and, to a lesser extent, CYP3A may also be involved in fluoxetine metabolism. The active metabolite of fluoxetine, norfluoxetine, exists as a racemic mixture. The selective serotonin reuptake inhibition activity of S-norfluoxetine is comparable to that of fluoxetine. R-norfluoxetine is significantly less potent than the parent compound.
- Elimination half-life:
Fluoxetine: 1 to 3 days after a single dose, and 4 to 6 days with long-term administration.
Norfluoxetine: 4 to 16 days.
- Excretion: 80% excreted in the urine (11.6% fluoxetine, 7.4% fluoxetine glucuronide, 6.8% norfluoxetine, 8.2% norfluoxetine glucuronide, > 20% hippuric acid, 46% other). Renal function impairment does not alter fluoxetine or norfluoxetine pharmacokinetics; however, effects on other metabolites are unknown. Approximately 15% in the feces.
Fluoxetine is a suitable choice for patients with hypersomnia or psychomotor retardation. This antidepressant should probably be avoided in patients with concomitant anxiety, panic, and agitation.
- Safe in overdose 
- Relatively safe for use during pregnancy 21
- Suitable for poorly compliant patients prone to miss doses
- Relatively low incidence of withdrawal symptoms upon discontinuation 
- Low risk of weight gain 
- Helps to subside premenstrual mood swings, anger, and unhappiness
- There is evidence that the use of fluoxetine can reduce periodontal disease severity 19.
- Fluoxetine has mild psychostimulant-like propertirs
- Best evidence for suitability in children and adolescents. Fluoxetine (Prozac) is the only SSRI antidepressant approved by the FDA for the treatment of depression in children aged 8 and older.
- Sleep disturbances 
- Less effective than sertraline, venlafaxine, and mirtazapine in alleviating the acute symptoms of depression
- Drug interactions via CYP isoenzyme inhibition
- Takes longer to achieve an antidepressant response compared with other SSRIs
- Long wash out period may be required when switching from fluoxetine to another antidepressant
- fibromyalgia 
- irritable bowel syndrome (IBS) 
- premature ejaculation 
- binge-eating and vomiting behaviors in moderate to severe bulimia nervosa
- prophylaxis of migraines 
- chronic daily headache 
- decrease alcohol intake in moderately dependent alcoholics 
- smoking cessation 
- pain relief (in low back pain the efficacy is similar to that of amitriptyline) 
- anxiety disorders in children and adolescents 
Prozac for Fibromyalgia
In the randomized, placebo-controlled, double-blind study women with fibromyalgia who received fluoxetine had significant improvement in pain, fatigue and depression compared with those who received placebo. Fluoxetine was generally well tolerated .
Prozac for Smoking cessation
Results of clinical study indicate that fluoxetine improves both positive and negative mood states after quitting smoking . Also, fluoxetine may be a useful drug if weight gain is a major clinical obstacle to smoking cessation.
In smokers with depressive symptoms starting fluoxetine 8 weeks before quit date and continuing for 8 weeks following quit date ensures significantly lower levels of depressive symptoms throughout smoking cessation treatment and significantly lower nicotine withdrawal-related negative feeling20.
How long Prozac takes to work?
The results of the study demonstrated that at weeks 2, 4, and 6, the probabilities of having an onset of response (for responders to fluoxetine) were 55.5%, 24.7%, and 9.3%, respectively. The cumulative probabilities of onset of response at each time point were 55.5%, 80.2%, and 89.5%. Neither demographics nor clinical characteristics of depression predicted time until initial response. These data suggest that more than half of eventual responders to fluoxetine treatment at 8 weeks start to respond by week 2; over 75% start to respond by week 4. So, if fluoxetine does not start to work at 4-6 weeks there is 73%-88% chance that it would not work by 8 weeks .
Mechanism of action
The antidepressant, antiobsessive-compulsive, and antibulimic actions of fluoxetine are supposed to be linked to its inhibition of CNS neuronal uptake of serotonin. Studies in man have demonstrated that fluoxetine blocks the uptake of serotonin into human platelets. Studies in animals also suggest that fluoxetine is a much more potent uptake inhibitor of serotonin than of norepinephrine. Antagonism of muscarinic, histaminergic, and a1-adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects of classical tricyclic antidepressants (TCA). Fluoxetine binds to these and other membrane receptors from brain tissue much less potently in vitro than do the TCA.
Fluoxetine is an atypical SSRI. Animal studies have shown that amongst the SSRIs, only fluoxetine acutely increases extracellular concentrations of norepinephrine and dopamine as well as serotonin in prefrontal cortex .
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Interesting Prozac facts
- Prozac was the first FDA approved Selective serotonin reuptake inhibitor (SSRI), which hit the United States market in 1987.
- Prozac is unique antidepressant because of its long half-life and the long half-life of its active metabolite norfluoxetine.
- The long half-life of Prozac may blunt the effects of missed doses or treatment discontinuation and makes it easier to discontinue than any of the other SSRIs.
- In January 2003, Prozac was approved by the FDA for the treatment of depression and OCD in children and adolescents who are 7 to 17 years of age.
- Prozac (Fluoxetine) is the only SSRI that is FDA-approved specifically for depression in patients who are 65 years of age or older.