FDA Approved Uses
There are various drugs used for the treatment of depression, and they are made up of 7 classes depending on the mode of action. The seven classes include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, atypical antidepressants, serotonin modulators, and N-methyl-D-aspartate receptor antagonists. Fluoxetine is approved by the Food and Drug Administration (FDA) as an antidepressant with the generic name Prozac and the brand name fluoxetine (Marshall, 2023). The FDA-approved indications for fluoxetine include treating depressive disorders, including major depressive disorder, bipolar depression, and premenstrual dysphoric disorder (Sheffler et al., 2023). It is also used for the management of obsessive-compulsive disorder, eating disorders (bulimia nervosa and binge eating disorder), and panic disorder. Fluoxetine is FDA-approved to be used in combination with olanzapine for the management of treatment-resistant depression.
Off Label Uses
Fluoxetine is the most popular selective serotonin reuptake inhibitor compared to sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram. Due to its popularity, it has a variety of FDA-approved indications and has been noted to be prescribed for the management of other illnesses. The non-FDA-approved uses include the management of general anxiety disorder, social anxiety disorder, Raynaud’s syndrome, repetitive tendencies in autism spectrum disorder, selective mutism, and borderline personality disorder (Sheffler et al., 2023). The use of fluoxetine for post-traumatic stress disorder is restricted to adult patients. Physicians are expected to be transparent with the patient that there is limited research on using fluoxetine for these conditions to increase vigilance that will inform treatment plan adjustments for the best treatment outcomes.
Contraindications
The use of fluoxetine is contraindicated in patients with a known hypersensitivity to fluoxetine or any other selective serotonin reuptake inhibitors. A combination of fluoxetine with other selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants is contraindicated. These combinations increase the patient’s risk of developing serotonin syndrome, which is potentially life-threatening due to autonomic symptoms and severe neuromuscular symptoms. The use of fluoxetine for the management of depressive disorder is contraindicated in patients who are younger than seven years. The use of fluoxetine during lactation and breastfeeding is contraindicated as large amounts of the medication pass into the milk (Marshall, 2023). The use of fluoxetine during the third trimester is controversial as neonates are predisposed to complications, but the lack of treatment or abrupt discontinuation of treatment results in the reoccurrence of the illness for the mother in a severe form. Fluoxetine is metabolized in the liver, and hepatic illnesses affect the metabolism and clearance of fluoxetine and its metabolite norfluoxetine. In these cases, fluoxetine is tapered to a lower dose and taken at a decreased frequency.
Mechanism of Action
Fluoxetine belongs to a class of antidepressants known as selective serotonin reuptake inhibitors because of its mode of action. This class of antidepressants exerts therapeutic effects by binding to the serotonin reuptake transporter in the presynaptic neuron and, by doing this, prevents the reuptake of serotonin from the synaptic cleft (Sheffler et al., 2023). Serotonin is a neurotransmitter that modulates mood, appetite, aggression, sexuality, and reward. Under normal physiological function to stop serotonin from binding to the postsynaptic neuron and the consequent neurotransmission, it undergoes enzyme degradation, diffusion, or reuptake. Therefore, inhibiting reuptake prolongs the availability of serotonin to bind to the receptors. Administration of fluoxetine over a long period results in modifications, including increased cyclic adenine monophosphate (Camp) signaling and nuclear transcription factors, which are phosphorylated more, and the trophic factors are expressed more. Fluoxetine is classified as selective due to its low affinity for norepinephrine reuptake transporters and the lack of affinity for dopamine reuptake transporters.
Potential Side Effects
The side effects of fluoxetine result from the physiological impact of increased availability of serotonin. The common side effects include headache, sexual dysfunction, anorexia, insomnia, QT prolongation, seizures, agitation, anxiety, angle closure, glaucoma, teeth grinding, and bleeding events (Sheffler et al., 2023). The clinician has the responsibility to educate the patient on what to expect. Since most of the side effects disappear after a short while, alteration of the regimen should factor in time for the side effects to subside and adjust the dose appropriately. When switching from fluoxetine to another antidepressant, its long half-life should be considered. Fluoxetine has a half-life between 1-3 days for acute administration and 4-6 days for chronic administration. Patients who were on long-term use of fluoxetine would be advised to wait between 4-7 days before starting the next antidepressant at a low dose. The long half-life is advantageous since the patient is less likely to experience withdrawal symptoms compared to those taking medication with low half-lives. The treatment guidelines advise that switching to another antidepressant is prioritized before considering augmentation.
Lab Monitoring
Therapeutic drug monitoring is a more reliable index for establishing the effectiveness of antidepressants. TDM is more effective as it acknowledges that metabolism varies across individuals and uses the plasma concentration of fluoxetine to explain its effectiveness, side effects, and the need to switch regimens (Sohel et al., 2022). Despite its high cost, TDM offers the physician insight regarding compliance or misuse of fluoxetine. Because of its ability to cause QT prolongation, it is necessary to carry out ECG assessment for patients at a higher risk of cardiac arrhythmias. Hepatic function tests are necessary as fluoxetine is metabolized in the liver. Finally, blood glucose tests are recommended for patients on fluoxetine and at risk of developing diabetes mellitus.
Role of Practitioners
The psychiatric mental health nurse practitioner plays the role of diagnosing the patient first, noting whether the patient is presenting with pessimism, change in appetite, insomnia or sleeping for too long, lack of self-worth, irritability, low energy, and thoughts about dying. If the patient reports having experienced five of the above symptoms every day for two weeks, they will undergo a psychiatric assessment using a depression diagnostic tool (DSM-5 NIMH., 2021). Considering all factors, the practitioner will counsel the patient and educate them on the proper use of fluoxetine and what to expect. The nurse should advise the patient to avoid taking alcohol while on medication, clarify that the medication can be taken concomitantly with food, and encourage them to report persistent side effects. The importance of compliance should be emphasized, and the dose should be adjusted accordingly. In the case that the patient experiences adverse effects and requests a change in regimen, consider another single drug before moving to a drug combination. Fluoxetine’s long half-life should be considered when switching the regimen, and the patient should take a 4-7 day break before starting the new regimen. The nurse is required to monitor the patient for misuse and dependence and ensure gradual cessation of treatment to avoid experiencing withdrawal symptoms.
References
Marshall, H. (2023). Prozac: Side effects, doses, generic version, and more. Medical and health information. https://www.medicalnewstoday.com/articles/drugs-prozac#_noHeaderPrefixedContent
NIMH. (2021). Depression. National Institute of Mental Health (NIMH). https://www.nimh.nih.gov/health/publications/depression#:~
Sheffler, Z., Patel, P., & Abdijadid, S. (2023, May 26). Antidepressants – StatPearls – NCBI bookshelf. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK538182/
Sohel, A., Shutter, M., & Molla, M. (2022, July 4). Fluoxetine – StatPearls – NCBI bookshelf. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK459223/#:~
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