When SSRIs and SNRIs do not work.
Atypical antidepressants
Atypical antidepressants often do not target the origin of the problem, but rather they try to fill in the deficiencies caused by the problem itself. For example, bupropion increases the levels of dopamine and norepinephrine in the body, while ignoring the reapportion mechanic that occurs in the brain (Stahl et al., 2004). However because they do not specialize in targeting the specific biomarkers, they are often suggested as a third option.
Conclusion
The atypical medications mentioned above, can be concisely summarized by the following sentence: in case of emergency, break glass. SSRIs and SNRIs are the mainstream medication because they tend to have less health complications and side-effects compared to the three categories of this blog post. In the case the general medication proves inefficient, doctors may have to target biochemicals and portions of the body that were passed over during the initial assessment, and this may cause the biochemical concentration inside the body to become less than optimal.
Tricyclic antidepressants (TCAs)
TCAs are often considered a second-line treatment for major depressive disorder after SSRIs; though they have a similar level of efficacy to SSRIs, they have a greater number of adverse effects upon consumption.
TCAs, similarly to SNRIs, typically target neurotransmitters such as serotonin and norepinephrine. However, rather than keeping that narrow focus, they can sometimes affect systems outside of those two substrates that lead to the wider array of side effects (Moraczewski et al., 2023).
Adverse effects can also stem from the medication’s anticholinergic properties (inhibiting the physiological action of acetylcholine), which becomes increasingly significant with age. Age-related physiological changes and the taking of more drugs at once, makes this particularly dangerous for the elderly. Some studies link the intake of TCAs with increased falls and fractures (Santandreu et al., 2024).
In addition, due to their narrow therapeutic index (range within which a medication can be taken without unacceptable adverse effects), TCAs are prone to toxicity by overdose.
The name “tricyclic” comes from the three rings in TCAs’ chemical structure, not necessarily due to any temporal cycles (Moraczewski et al., 2023).
MAOIs can be used to treat depression as well as other nervous system disorders including panic disorder and depression with atypical features. They are also used to treat Parkinson’s disease and a neurodegenerative disease called multiple system atrophy (Laban & Saadabadi, 2023).
MAOIs have a variety of side effects including hypotension, weight gain, insomnia, and more, though there are management systems to negate those effects. In addition, the consumption of a MAOI requires a careful restriction of diet, some of which are cheese, wine, and aged meat (Remick & Froese, 1990).
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A detailed description of how dopamine is affected by MAOA and MAOB (Youdim et al., 2006)
Monoamine oxidase inhibitors (MAOIs)
Despite being the first antidepressants to be introduced (introduced in the 1950s), MAOIs are typically used as the last option when other medications are not effective because of side effects and other health concerns.
This categorizes MAOIs into two main categories sorted by the substrates they act on; these categories are referred to as monoamine A (MAOA) and monoamine B (MAOB). Monoamine A acts upon serotonin, epinephrine, norepinephrine, normetanephrine, octopamine, tyramine, and dopamine in the gut, and liver. Monoamine B acts upon benzylamines, phenelethylamine, N-methylhistamine, tyramine, and dopamine in the brain, liver, and platelets. As tyramine and dopamine are in both MAOA and MAOB, it is important to understand how they interact with their respective regions. Originally, MAOIs sold were non-specific, but later there began to be growing research specifically regarding A or B substrates (Remick & Froese, 1990).
Introduction
Other than the most commonly prescribed SSRIs and backup option SNRIs, there are three main types of antidepressant medication used: monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and atypical antidepressants. Though they are less common due to their tendency to incite more intense side effects or affect unnecessary hormones, they are still to be kept in mind when considering medications.
Laban, T. S., & Saadabadi, A. (2023, July 17). Monoamine Oxidase Inhibitors (MAOI). Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK539848/
Moraczewski, J., Aedma, K. K., & Awosika, A. O. (2023, August 17). Tricyclic Antidepressants. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK557791/
Remick, R. A., & Froese, C. (1990). Monoamine Oxidase Inhibitors: Clinical Review. Canadian Family Physician, 36, 1151. https://pmc.ncbi.nlm.nih.gov/articles/PMC2280482/#supplementary-material1
Santandreu, J., Francisco Félix Caballero, M Pilar Gómez-Serranillos, & González-Burgos, E. (2024). Association between tricyclic antidepressants and health outcomes among older people: A systematic review and meta-analysis. Maturitas, 188, 108083–108083. https://doi.org/10.1016/j.maturitas.2024.108083
Stahl, S. M., Pradko, J. F., Haight, B. R., Modell, J. G., Rockett, C. B., & Learned-Coughlin, S. (2004). A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor. Primary care companion to the Journal of clinical psychiatry, 6(4), 159–166.
https://doi.org/10.4088/pcc.v06n0403
Youdim, M. B. H., Edmondson, D., & Tipton, K. F. (2006). The therapeutic potential of monoamine oxidase inhibitors. Nature Reviews. Neuroscience, 7(4), 295–309.
https://doi.org/10.1038/nrn1883
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