Prozac (Fluoxetine HCL)

• Generic name: Fluoxetine hydrochloride
• Trade names: Prozac, Prozac Weekly, Sarafem
• Pharmacologic category: Selective serotonin reuptake inhibitor
• 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). Prozac is used to treat depression, obsessive-compulsive disorders, and some eating disorders. It also is occasionally used to treat alcoholism, borderline personality disorders, sleep disorders, headaches, premenstrual syndrome, irregular heartbeat, schizophrenia, Tourette's syndrome, anxiety, and phobias.

The most common early side effects of Prozac 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) [18]. 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.

Prozac may be an appropriate choice in patients with hypersomnia or psychomotor retardation and should probably be avoided in patients with concomitant anxiety, panic, and agitation.

• safe in overdose [15]
• safe in special population groups such as women in pregnancy
• suitable for poorly compliant patients
• relatively low incidence of withdrawal symptoms [4]
• low risk of weight gain [5]
• helps to subside premenstrual mood swings, anger, and unhappiness

• sleep disturbances [9]
• less effective than sertraline, venlafaxine, and mirtazapine in alleviating the acute symptoms of depression
• more likely to interact with other drugs than some of the other SSRI's
• takes longer to achieve an antidepressant response compared with other SSRIs
• longer wash out period may be required when switching to another antidepressant

• fibromyalgia [7]
• irritable bowel syndrome (IBS) [12]
• premature ejaculation [10]
• binge-eating and vomiting behaviors in moderate to severe bulimia nervosa
• prophylaxis of migraines [6]
• chronic daily headache [17]
• decrease alcohol intake in moderately dependent alcoholics [8]
• smoking cessation [11]
• pain relief (in low back pain the efficacy is similar to that of amitriptyline) [13]
• anxiety disorders in children and adolescents [14]

Prozac in 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 [7].

Prozac for smoking cessation

Results of clinical study indicate that fluoxetine improves both positive and negative mood states after quitting smoking [11]. Also, fluoxetine may be a useful drug if weight gain is a major clinical obstacle to smoking cessation.

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 [16].

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 [3].

• User Reviews for Prozac on Drugs.com
• Prozac User Ratings - on WebMD
• User ratings and reviews of Prozac on Revolution Health
• Fluoxetine Reviews on Viewpoints
• Fluoxetine on Psych Central Reviews
• Prozac Reviews, Ratings by Patients on DrugLib.com

• www.Prozac.com - official website
• Fluoxetine (Prozac, Sarafem) on Mental Health
• Prozac (Fluoxetine) on HealthyPlace.com
• 1. Fluoxetine on Merck Manual
• 2. Cipriani A, Brambilla P, Furukawa T, Geddes J, Gregis M, Hotopf M, Malvini L, Barbui C. Fluoxetine versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD004185. PubMed
• 3. Bymaster FP, Zhang W, Carter PA, Shaw J, Chernet E, Phebus L, Wong DT, Perry KW. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl) 2002 Apr;160(4):353-61
• 4. Michelson D, Fava M, Amsterdam J, Apter J, Londborg P, Tamura R, Tepner RG. Interruption of selective serotonin reuptake inhibitor. Br J Psychiatry. 2000 Apr;176:363-8. PubMed
• 5. Michelson D, Amsterdam JD, Quitkin FM, Reimherr FW, Rosenbaum JF, Zajecka J, Sundell KL, Kim Y, Beasley CM Jr. Changes in weight during a one-year trial of fluoxetine. Am J Psychiatry. 1999 Aug;156(8):1170-6. PubMed
• 6. 11. Adly C, Straumanis J, Chesson A. Fluoxetine prophylaxis of migraine. Headache. 1992 Feb;32(2):101-4. PubMed
• 7. Arnold LM, Hess EV, Hudson JI, Welge JA, Berno SE, Keck PE Jr. A randomized, placebo-controlled, double-blind study of fluoxetine in women with fibromyalgia. Am J Med. 2002 Feb 15;112(3):191-7. PubMed
• 8. Naranjo CA, Poulos CX, Bremner KE, Lanctot KL. Fluoxetine attenuates alcohol intake and desire to drink. Int Clin Psychopharmacol. 1994 Sep;9(3):163-72. PubMed
• 9. Armitage R, Emslie G, Rintelmann J. The effect of fluoxetine on sleep EEG in childhood depression: a preliminary report. Neuropsychopharmacology. 1997 Oct;17(4):241-5. PubMed
• 10. Haensel SM, Klem TM, Hop WC, Slob AK. Fluoxetine and premature ejaculation: a double-blind, crossover, placebo-controlled study. J Clin Psychopharmacol. 1998 Feb;18(1):72-7. PubMed
• 11. Cook JW, Spring B, McChargue DE, Borrelli B, Hitsman B, Niaura R, Keuthen NJ, Kristeller J. Influence of fluoxetine on positive and negative affect in a clinic-based smoking cessation trial. Psychopharmacology (Berl). 2004 Apr;173(1-2):153-9. PubMed
• 12. Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R. Fluoxetine for irritable bowel syndrome. Aliment Pharmacol Ther. 2005 Sep 1;22(5):381-5.
• 13. Schreiber S, Vinokur S, Shavelzon V, Pick CG, Zahavi E, Shir Y. Isr J Psychiatry Relat Sci. 2001;38(2):88-94. PubMed
• 14. Clark DB, Birmaher B, Axelson D, Monk K, Kalas C, Ehmann M, Bridge J, Wood DS, Muthen B, Brent D. Fluoxetine for childhood anxiety disorders: open-label, long-term extension to a controlled trial. J Am Acad Child Adolesc Psychiatry. 2005 Dec;44(12):1263-70.
• 15. Borys DJ, Setzer SC, Ling LJ, Reisdorf JJ, Day LC, Krenzelok EP. Acute fluoxetine overdose: a report of 234 cases. Am J Emerg Med. 1992 Mar;10(2):115-20. PubMed
• 16. Nierenberg AA, Farabaugh AH, Alpert JE, Gordon J, Worthington JJ, Rosenbaum JF, Fava M. Timing of onset of antidepressant response to fluoxetine. Am J Psychiatry. 2000 Sep;157(9):1423-8. PubMed
• 17. Gherpelli JL, Esposito SB. A prospective randomized double blind placebo controlled crossover study of fluoxetine efficacy in the prophylaxis of chronic daily headache in children and adolescents. Arq Neuropsiquiatr. 2005 Sep;63(3A):559-63. PubMed
• 18. Stahl SM. Not so selective serotonin reuptake inhibitors. J Clin Psychiatry 1998;59:343-4.

Last modified: August, 2011