Fluoxetine

Chemical structure of fluoxetine hydrochloride. Source: EPA.

Other Names

• Prozac is the original marketed form of fluoxetine hydrochloride.
• Prozac Weekly is an extended-release formulation.
• Sarafem also contains fluoxetine hydrochloride as the active ingredient.
• Symbyax contains a combination of fluoxetine and olanzapine.

Uses

• Depression
• Obsessive-Compulsive Disorder (OCD), characterized by bothersome and persistent thoughts and the need to perform certain activities repeatedly.
• Some eating disorders with a psychiatric component, such as bulimia, which is characterized by abnormal regard for food.
• Panic attacks, characterized by sudden, unexpected attacks of extreme fear and worry about having these attacks.
• Premenstrual dysphoric disorder characterized by mood swings, irritability, bloating, and breast tenderness in the premenstrual phase of the ovulatory cycle.

How Fluoxetine is Taken

Fluoxetine is taken by mouth, with or without food.

How Fluoxetine Works

Fluoxetine works by helping to restore the balance of a certain neurotransmitter called serotonin, which is a natural substance in the brain that acts as a chemical messenger between nerve cells. Fluoxetine elevates the circulating levels of serotonin by preventing it from being taken back up into the cells.

Increased levels of serotonin result in improvements in mood, sleep, appetite, and energy level and may help restore interest in daily living. It may decrease anxiety/unreasonable fears, persistent/troubling thoughts (obsessions), and unwanted urges that keep returning (compulsions). It may decrease the number and severity of panic attacks. Fluoxetine may lessen premenstrual symptoms such as irritability, increased appetite, and depression. It may decrease bingeing and purging behaviors in bulimia.

Benefits

In clinical trials of antidepressants, the placebo effect can be quite high (in the range of 30% for subjects diagnosed with major depression^[1]), meaning that many patients who take placebos (which contain no active ingredient) experience significant mood improvements despite not having taken any medication. The most dramatic benefits from fluoxetine tend to occur in people who have moderately severe illness,^[2] and the data that support clinical benefits are convincing.^[3]

Side Effects

Potential side effects of fluoxetine therapy include:

• Possible life-threatening serotonin syndrome when used with triptan medicines
• Infant persistent pulmonary hypertension
• Suicidal thoughts or actions, most often noted on dose initiation or increase
• Rash and possible allergic reactions
• Mania, characterized by unusual hyperactivity, elation, or excitability
• Seizures
• Weight loss
• Sexual problems, including decreased sexual desire, erectile dysfunction, or difficulty achieving orgasm
• Other side effects include nausea, difficulty sleeping, anxiety, nervousness, and sleepiness

Risks and Precautions

An FDA Alert was issued in July 2006 concerning serotonin syndrome that can happen when medicines in the SSRI class of drugs (fluoxetine included) are used together with triptan medicines used to treat migraine headaches. Signs and symptoms of serotonin syndrome include: restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, fast changes in blood pressure, overactive reflexes, diarrhea, nausea, and vomiting. Untreated serotonin syndrome can result in coma. Serotonin syndrome is more likely to occur when starting or increasing the dose of an SSRI or a triptan.

An FDA alert was issued in July 2006 concerning infant persistent pulmonary hypertension. A study investigating the use of antidepressant medicines during pregnancy in mothers of babies born with a serious condition called persistent pulmonary hypertension of the newborn (PPHN) were recently published in a medical journal. Babies born with PPHN have abnormal blood flow through the heart and lungs and do not get enough oxygen to their bodies. This condition can be fatal.

History

Scientists at Eli Lilly began searching for molecules that were active in blocking the reuptake of neurotransmitters in the 1970s. Bryan Molloy (1939-2004) co-invented a class of drugs that includes fluoxetine, which was found to be a highly specific reuptake inhibitor—that is, it only inhibited the reuptake of serotonin, and not the reuptake of other neurotransmitters.^[4] After its introduction in 1988, fluoxetine quickly became popular and by 1990 was the most-prescribed antidepressant in the US. To date, it has been prescribed for over 35 million people.

Controversy

Lawsuits

Suggestions that fluoxetine caused an increased risk of suicide^[5] led to litigation between Lilly and the British Medical Journal (BMJ), in which the article was published. The litigation eventually led BMJ to retract the article.^[6]

Key legislation

In 2002, after a six-year fight to maintain its patent on Prozac, Eli Lilly & Company's efforts ended when the Supreme Court refused to consider reinstating its exclusive rights to market the drug. This cleared the way to competition from generic versions of fluoxetine.^[7]

Alternatives

Motivated in part by the success of fluoxetine, other pharmaceutical companies have sought to discover and develop their own reuptake inhibitors. Other drugs designed with high specificity for serotonin reuptake inhibition include citalopram (Celexa), fluvoxamine (Luvox), sertraline (Zoloft, Lustral), and paroxetine (Paxil).^[8]

Clinical Trials

Several actively-recruiting clinical trials are investigating the potential utility of fluoxetine in a wide variety of conditions, including autism,^[9] pediatric body dysmorphic disorder,^[10] and rehabilitation to improve movement function after ischemic strokes.^[11]

References

1. ↑ Healy D. The Antidepressant Era. Harvard University Press, Cambridge, MA. 1997
2. ↑ Peselow ED, Sanfilipo MP, Difiglia C, Fieve RR. Melancholic/endogenous depression and response to somatic treatment and placebo. Am J Psychiatry. 1992 Oct;149(10):1324-34. Abstract
3. ↑ Burke MJ, Preskorn SH. Short-term treatment of mood disorders with standard antidepressants. In Psychopharmacology: The Fourth Generation of Progress. Bloom FE, Kupfer DL, eds. Raven Press, New York, 1995.
4. ↑ Wong DT, Perry KW, Bymaster FP. Case history: the discovery of fluoxetine hydrochloride (Prozac). Nat Rev Drug Discov. 2005 Sep;4(9):764-74. Abstract
5. ↑ Beasley CM Jr, Dornseif BE, Bosomworth JC, et al. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. BMJ. 1991 Sep 21;303(6804):685-92. Erratum in: BMJ 1991 Oct 19;303(6808):968. Abstract
6. ↑ Jick SS, Dean AD, Jick H. Antidepressants and suicide. BMJ. 1995 Jan 28;310(6974):215-8. Abstract
7. ↑ New York Times: Lilly Loses Fight Over Prozac Patent. January 15, 2002. Full Text
8. ↑ Pirraglia PA, Stafford RS, Singer DE. Trends in Prescribing of Selective Serotonin Reuptake Inhibitors and Other Newer Antidepressant Agents in Adult Primary Care. Prim Care Companion J Clin Psychiatry. 2003 Aug;5(4):153-157. Abstract Full Text PDF
9. ↑ Clinicaltrials.gov: Study of Fluoxetine in Autism
10. ↑ Clinicaltrials.gov: Fluoxetine in Pediatric Body Dysmorphic Disorder
11. ↑ Clinicaltrials.gov: Fluoxetine on Motor Rehabilitation After Ischemic Stroke