How Prozac "Fluoxetine" has changed the treatment of depression

How Prozac "Fluoxetine" has changed the treatment of depression


     Prozac®, the flagship drug of the 1990s, was nicknamed the "happy pill". 

     Indeed, this antidepressant therapy is now one of the most widely prescribed in the world. As the leader of a new class of antidepressants, Prozac® has been a great success with general practitioners. 

     However, it now faces competition from other more recent molecules.

     Until the early 1990s, effective antidepressants were available to people with depression, but they were relatively difficult to handle and sometimes caused side effects.

     As a result, general practitioners were reluctant to treat the depressed and readily turned to psychiatrists. This all changed with the advent of Prozac®. 

     Well tolerated, supported by a very active marketing policy, this drug was quickly widely prescribed, a success which explains why its consumption was considered excessive by certain experts such as Prof. Edouard Zarifian.

Prozac: the arrival of a safe antidepressant

     Like other antidepressants, Prozac® can reduce the feelings of sadness and depression that characterize depressed people, provided that the treatment is delayed for a few weeks and continued for a sufficient period of time, usually 6 months. 


     But more than its efficacy, which actually seems somewhat less than that of previous generations of antidepressants, it is its safety of use that is of interest. 

     Because Prozac® has little or no effect on other brain mediators such as acetylcholine, it does not cause dry mouth, prostate problems or lower blood pressure.

     Prozac® is composed of fluoxetine, a substance that almost exclusively inhibits the reuptake of serotonin, a brain neurotransmitter. 

     It thus increases the concentration of serotonin in the neurons. It has been shown that depressed patients have a lower concentration of serotonin degradation products in the cerebrospinal fluid (surrounding the brain). 

     Numerous medical studies have shown that fluoxetine reduces depressive symptoms and also reduces the severity of other mental disorders, obsessive-compulsive disorder, and bulimia.

     In addition, it has low toxicity, especially to the heart, making it suitable for cardiac patients, the elderly or those taking any medications. In the depressed, in whom the risk of suicide is always present, this is also a reassuring element.

A few precautions to be taken however

     Nevertheless, apart from its effectiveness, which is sometimes insufficient in severe depressions, Prozac® has a few drawbacks. 

     For example, its administration may cause nervousness or insomnia in patients or even an episode of overexcitement. 

     Conversely, it may cause drowsiness, an effect that should be warned to motor vehicle drivers. Minor digestive disturbances (nausea, constipation) and skin rashes have also been reported. 

     Finally, Prozac® requires some precautions for use in people with epilepsy, diabetes, liver disease, or those receiving oral anticoagulants.

     Serotoninogens are the first antidepressants prescribed in the city

     The success of Prozac® could not go unnoticed by other pharmaceutical companies and many other fluoxetine-like molecules acting by the same mechanism soon appeared on the market. 

    Within a few years, serotoninergic, i.e. substances that increase the amount of serotonin in the central nervous system, became the first class of antidepressants delivered by doctors practicing in cities, and the prescription of antidepressants doubled in 5 years (from 1992 to 1997) in France.

     Other serotonergic drugs available include sertraline (Zoloft®), paroxetine (Deroxat®), fluvoxamine (Floxyfral®) and citalopram (Seropram®). 

     These antidepressants differ in their pharmacological characteristics and some have other indications such as anorexia, social phobia...

 The advent of dual-action antidepressants

     More recently, other antidepressants have been developed that act on two neurotransmitters: serotonin, such as Prozac, and norepinephrine. 

     This is the case with milnacipran (Ixel®) and venlafaxine (Effexor®). 

     This dual-action could allow these drugs to be more effective than Prozac® and comparable to tricyclics (which are considered the reference antidepressants) while maintaining the good tolerance of serotonergic antidepressants. However, their side effects are also greater.

     Prozac is currently available in capsule form or as a drinkable solution and most depressants respond to the 20 mg daily dose, which is one capsule only, to be taken with or without meals. 

     Others require 2 or even 3 capsules depending on the indication. Reimbursed at 65% by Social Security, the price of Prozac is 9.17 euros for 14 capsules.

Which antidepressants should I take?

     In the absence of a demonstrated difference in efficacy between the different types of antidepressants, the choice is made according to the patient's efficacy, tolerance, and preferences. The French National Authority for Health (HAS) recommends

     In 1st intention, because of their better tolerance:

  • Selective serotonin reuptake inhibitors (SSRIs);
  • Serotonin and norepinephrine reuptake inhibitors (SNRIs);
  • Three "other antidepressants" (of different pharmacological mechanisms): mianserin, mirtazapine, and vortioxetine;
     The second line, because they risked cardiovascular toxicity, the imipramine (tricyclic) antidepressants;

     In the third line, agomelatine because of its hepatic toxicity and tianeptine which carries a risk of abuse and dependence.

     As a last resort, because of their numerous adverse effects and drug interactions, monoamine oxidase inhibitors (MAOIs), only after failure of other alternatives.

Samir Sali

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