Reintroducing Serotonin Back Into the Brain With SSRI
Overview on SSRIs
Selective serotonin reuptake inhibitors (SSRIs), as their name suggests, function by preventing the reuptake (reabsorption) of serotonin by the neurons. This allows serotonin to continue to cycle rather than leave the system.
SSRIs are most commonly prescribed to treat depression, though they have other FDA-approved purposes, which include generalized anxiety disorder, obsessive-compulsive disorder, and panic disorder, to name a few (Chu & Wadhwa, 2023). It is to be taken note of that these treated conditions have root in or involve elements of anxiety and depression.
Three of the most commonly prescribed SSRIS are fluoxetine (Prozac), fluvoxamine (Luvox), and citalopram (Celexa).
Introduction
Medication for anxiety and depression often utilizes a common bioinhibition mechanism. These medications, classified as antidepressants, help tackle the lack of certain biochemicals in the brain, a characteristic often found in patients who have been diagnosed with anxiety and depression. The mechanism which is utilized often involves the blocking of certain receptors at the end of the nerve cell, thus preventing the reuptake of the molecules in question, usually serotonin, but sometimes also norepinephrine.
Fluoxetine
Fluoxetine is safe for children 8 and up (for major depressive disorder) or 7 and up (obsessive-compulsive disorder). For other cases, notably Bipolar I disorder and treatment-resistant depression, it is often used as an adjunct with olanzapine (Zyprexa) (Sohel et al., 2024).
Fluoxetine is not only seen to act as a serotonin reuptake inhibitor but also as a gut microbiome–regulating component, increasing levels of Lactobacillus and decreasing amounts of Oscillibacter and Colidextribacter bacteria in the gut. As the gut microbiome is strongly and bidirectionally linked to the brain, this could be part of fluoxetine’s medicinal effects on treating depression and anxiety, which can cause disruptions and imbalances in the gut. Doxycycline, an antibiotic that has been shown to limit Lactobacillus, was given to mice to test the influence of antibiotics on fluoxetine’s effects. The simultaneous consumption of both doxycycline and fluoxetine showed increased depressive and anxious behaviors, which suggests the gut microbiome effects play a strong role (Lee et al., 2024).
Fluoxetine and norfluoxetine (the active metabolite of fluoxetine) have long half-lives—2 to 4 for fluoxetine and 7 to 9 for norfluoxetine—which is important to consider when discontinuing fluoxetine. These long elimination half-lives mean there needs to be careful consideration when prescribing a medication that may interact with fluoxetine even after discontinuation (Sohel et al., 2024).
Fluvoxamine
Though first developed as an antidepressant, fluvoxamine is used mostly for the treatment of obsessive-compulsive disorder, panic disorder, social anxiety disorder, and other such anxiety-related conditions. It most frequently reports back with nausea as a side effect, without many adverse effects of sedation, on weight, or on the heart. It has also been repurposed to treat COVID-19 in recent years.
It generally has a low affinity for neurotransmitter receptors apart from its binding to σ1 (sigma-1) receptors, which is linked with psychosis and aggression. In fact, fluvoxamine’s affinity for σ1 receptors is higher than seen with other SSRIs.
Fluvoxamine has been seen to increase the efficiency of cognitive behavioral therapy (CBT) (Irons, 2005).
Citalopram
Citalopram hydrobromide’s clinical use is for treating adults with depression, though it can be used off-label for panic disorder, obsessive-compulsive disorder, and other issues and disorders, including coronary and postmenopausal troubles.
Side effects affect up to 10% of patients, some of which include nausea, drowsiness, insomnia, headaches, and more. Some of the less common symptoms included induction of mania and increased suicidal ideation, which is a risk for those affected by those states due to mood disorders or depression. Counterintuitively, the depression that citalopram is meant to combat can worsen due to these side effects.
Additionally, citalopram can interact with a variety of other medications and should be treated with caution when prescribed to patients regularly taking other medications.
If citalopram is to be stopped altogether, it is recommended to slowly decrease the dosage rather than abruptly cutting off intake, as that can lead to antidepressant discontinuation syndrome, which comes with a variety of symptoms such as nausea, vomiting, and headaches (Shoar et al., 2023).
Conclusion
SSRIs—medications that inhibit the reabsorption of serotonin—are used for a variety of purposes, from their typical use as an antidepressant to prescription for conditions such as anxiety, obsessive-compulsive disorder, and bipolar disorder. Despite potential drawbacks in both the psychological and physiological condition of the patient, SSRIs are an effective choice with generally low risk in side effects and continue to be favored in prescription.
Chu, A., & Wadhwa, R. (2023). Selective serotonin reuptake inhibitors. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK554406/
Irons, J. (2005). Fluvoxamine in the treatment of anxiety disorders. Neuropsychiatric Disease and Treatment, 1(4), 289. https://pmc.ncbi.nlm.nih.gov/articles/PMC2424117/
Lee, Y.-B., Cho, Y.-J., & Kim, J.-K. (2024). The unique role of fluoxetine in alleviating depression and anxiety by regulating gut microbiota and the expression of vagus nerve-mediated serotonin and melanocortin-4 receptors. Biomedicine & Pharmacotherapy, 182, 117748. https://doi.org/10.1016/j.biopha.2024.117748
Shoar, N., Fariba, K., & Padhy, R. K. (2023). Citalopram. PubMed; StatPearls Publishing.
https://www.ncbi.nlm.nih.gov/books/NBK482222/
Sohel, A. J., Shutter, M. C., & Molla, M. (2024). Fluoxetine. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK459223/