The purpose of this report is to raise awareness on why fluoxetine can be used to treat certain mental disorders such as depression. The main focus of this report is how the individual’s mental health is affected by fluoxetine. The mental health of any individual in some way will affect everyone, therefore it is important to society. The mental health of a person affects how they perceive the world, how they behave and how they feel.  It also affects how they communicate, how they react to stressful situations and how they relate to those around them. Mental health is extremely important at every stage of life; if a person’s mental health is affected by a disorder it could impact their home life, their work, their friendships and their physical health. Many factors can cause mental disorders, such as traumatic experiences or biological factors such as genetics and brain chemistry. This means that society needs to have both mental and physical treatments to effectively manage mental disorders. To gain a thorough understanding of why fluoxetine is prescribed for certain mental disorders, this report includes its basic molecular structure, the synthesis of fluoxetine and basic chemical properties, how the body absorbs fluoxetine and the brain’s response to the chemical. It then goes on to discuss the effect of fluoxetine on mental health.

Background

Fluoxetine is part of a group of antidepressants called selective serotonin-reuptake inhibitors. Fluoxetine is used to treat major depressive disorder (MDD), bulimia nervosa, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), panic disorder and if combined with olanzapine can treat treatment-resistant bipolar or depression.

 The synthesis of fluoxetine is complicated process that can be summarised into 4 stages. Firstly, a substituted propyl carbamate (IX) is acquired by reacting 3-dimethylamino-1-phenyl-1-propanol (III) with haloformate (VIII) to produce 4-methyl-3-[(4-trifluormethyl)phenoxy]-3-phenyl propylamine (I). This compound is then hydrolysed (broken down with water) to produce methylamino-1-phenyl-1-propanol (X). The methylamino-1-phenyl-1-propanol is then converted to fluoxetine (I) due to being reacted with 4-halobenzotrifluoride (XI).

Fluoxetine is combination of R- and S- enantiomers (pair of molecules that are mirror images of each other) and are of equal pharmacological activity. Its molecular structure is 17 carbon, 18 hydrogen, 3 fluorine, 1 nitrogen and 1 oxygen. Fluoxetine’s melting point is from 179 to 182 ℃, it is soluble in Water and in Dichloromethane (DCM). It is freely soluble in Ethanol and in methanol but is insoluble in ether. Fluoxetine has a molecular mass of 309.33 g/mol (grams per mole).

Figure 1: Molecular structure of fluoxetine Retrieved from: https://commons.wikimedia.org/wiki/File:Fluoxetine_structure.svg

Fluoxetine can only be administered orally; through immediate-release capsules or tablets in dosages of 10, 20 or 40 mg (milligrams) or a delayed-release capsule in enteric-coated pellets (called Prozac weekly) which is a 90 mg dosage. It can also be administered in the form of a liquid with a solution containing 20 mg of fluoxetine/ 5ml.  After being administered, sixty to eighty percent of the fluoxetine is then absorbed by the gastrointestinal tract, the rest is filtered out of the body without being utilised. First-pass metabolism occurs in the liver, which greatly reduces the concentration of the fluoxetine before it can reach the systemic circulation. It is then thoroughly metabolised in the liver; this produces norfluoxetine, which is formed via demethylation of fluoxetine, and other active metabolites. Norfluoxetine has similar pharmacologic potency as fluoxetine. Both fluoxetine and norfluoxetine undergo phase II glucuronidation reactions in the liver. It is believed that they also undergo   O-dealkylation to form p-trifluoromethylphenol, which is then metabolized to hippuric acid.

Several weeks of treatment may be required before any clinical effect occurs. Side effects generally happen during the first two weeks; these include, dry mouth, dizziness, drowsiness, nausea, headaches and sexual dysfunction. 

Fluoxetine affects the serotonin levels in the brain to achieve its purpose (treat certain mental disorders).  Serotonin is produced from the amino acid L-TRYPTOPHAN. It is found in the central nervous system, blood platelets and gastrointestinal tract. Serotonin is used for multiple physiological functions such as neurotransmissions, homeostasis and gastrointestinal motility. It is also associated with mood, sleep, appetite and sex drive.  

When used as a neurotransmitter, serotonin is released from the axon into the synapse as a ‘message.’ Once it is in the synapse, the serotonin finds a matching receptor on the dendrite and ‘sends the message’. After the ‘message’ is received, the serotonin is reabsorbed back into the neuron by a monoamine transporter protein called the sodium-dependant serotonin transporter (SERT protein). Fluoxetine changes the serotonin levels of the brain by blocking and reducing the production of the SERT protein. Fluoxetine achieves this by reducing the amount of genes that design and produce the SERT protein, therefore reduce the amount produced. Because of this, the leftover serotonin is also absorbed by the receptors. Fluoxetine also inhibits the sensor on the axon that determines how much serotonin is needed and this makes the axon release more serotonin than is needed.  This means that there is essentially a ‘constant’ supply of serotonin being absorbed by the matching receptors on the dendrite.  After approximately two weeks, the receiving cells become more sensitive to the serotonin which causes the clinical effects.  

If overdosed, fluoxetine can potentially have some adverse effects, even lead to a condition called serotonin syndrome. The syndrome can cause changes in mental health such as confusion, agitation, anxiety and even lead to a coma. It also affects cardiovascular function, cause gastrointestinal issues such as nausea and diarrhoea and movement issues such as loss of coordination, muscle contractions and seizures.

Discussion

Fluoxetine is normally prescribed if other treatments (such as psychological) are ineffective or have no effect on the particular disorder. Using fluoxetine to increase the amount of serotonin in an individual who has a disorder that disturbs mood balance (depression, panic disorder, obsessive compulsive disorder or a combination of these) benefits from Fluoxetine. It to some extent improves their mood balance and therefore their mental health. The effectiveness of fluoxetine is different for every individual. It is often combined with other treatments for the best results.  Although it generally improves mental health, it can potentially deteriorate mental health. Adolescents and young children who have been prescribed to fluoxetine will often display suicidal tendencies.

Fluoxetine is used to treat premenstrual dysphoric disorder (PMDD) because approximately five percent of women who are of childbearing age experience premenstrual symptoms that can cause mental distress. Approximately fifteen percent of women with PMDD who are not given proper treatment commit suicide. By increasing and maintaining the amount of serotonin in the brain, it is preventing or diminishing symptoms such as depression, anxiety, sudden mood swings and difficulty concentrating. 

Bulimia nervosa is a disorder where the individual has an almost compulsive need to lose weight because they have uncontrollable bouts of binge eating. The individual attempts to compensate for the overeating by self-induced vomiting, fasting, misusing laxatives or diuretics and excessive exercise. The development of bulimia is different for everyone, it can be caused by genetic predisposition and social factors. Bulimia nervosa typically leads to anorexia. Some individuals who suffer from bulimia nervosa, also suffer from other disorders like depression. Fluoxetine can be used to treat the additional disorders, therefore improving the overall mental health of the individual. 

Conclusion

In conclusion, this report provides an understanding of how fluoxetine affects the brain and therefore mental health. This report has outlined the synthesis of fluoxetine, molecular structure and basic chemical properties, how the body absorbs fluoxetine, the brains response to the chemical then discusses what effect fluoxetine has on mental health. 

Fluoxetine is prescribed to individuals who have certain mental disorders that affect mood balance. Fluoxetine reduces the amount of SERT proteins in the brain, this increases the amount of serotonin in the brain. This change improves mood balance and therefore mental health. 

Public Education Piece

My public education piece is a pamphlet to advise the general public of the information learned during this research assignment.

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