Using SSRI to Target Multiple Monoamines For Reabsorption
SNRIs vs. SSRIs
Direct competition between the SNRI and SSRI is a topic not worth discussing. Because they target very different neurotransmitters, the natural consequence of the medication will differ. Rather it is more beneficial to discuss what causes a patient to choose between an SSRI and a SNRI. SNRI can be thought as an option B, when the general SSRI medication does not work. However, this does not necessarily mean they are less effective at treatment. Additionally, SNRI can be prescribed to patients with severe depression and anxiety, especially those who suffer from lethargy, loss of concentration, or chronic pain (Sansone & Sansone, 2023).
SNRIs have shown to be more effective and fast-paced at treatment, likely due to the dual inhibition nature. They also enhance dopamine levels in some areas of the brain, which may play a role in their course of treatment (Li et al., 2020).
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Javed , 2023
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Introduction
Similarly to the mechanism of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) also work with inhibition, inhibiting the reuptake of serotonin and norepinephrine to different degrees. Depending on the medication, effects may lean to either side or have a more balanced effect overall.
Venlafaxine
Venlafaxine (Effexor) was the first SNRI to be sold in the United States, having first been approved for consumption by the United States Food and Drug Administration (FDA) in 1993 (Sansone & Sansone, 2023). It is prescribed generally to treat depressive, anxiety, and panic disorders, but only for those who are 18 and over. It is recommended to be taken under specific conditions—with food and not in simultaneity with alcohol—as to reduce effects including nausea and sedation. Ironically, in both sudden intake of the medication and sudden cutoff, adverse effects on mood such as anxiety and irritability can take place (Singh & Saadabadi, 2024).
It is to be taken once per day (Sansone & Sansone, 2023).
Duloxetine
Duloxetine (Cymbalta) was first approved by the FDA to be used in the United States in 2004. Despite SNRIs most commonly being used for treating psychological disorders such as major depressive disorder and generalized anxiety disorder (Dhaliwal et al., 2022), it has also shown to be effective in treating physical conditions including diabetic peripheral neuropathy (damage to the nerves as a result of high blood sugar), fibromyalgia (chronic, widespread musculoskeletal pain), and osteoarthritis (cartilage breakdown in joints) (Sansone & Sansone, 2023). It is to be taken once per day.
As conditions of depression are often accompanied by other conditions that involve elements of anxiety and long-term pain, duloxetine can be particularly effective at targeting multiple of these comorbid issues simultaneously. It has been clinically approved to treat chronic musculoskeletal and neuropathic pain conditions after increasing evidence supporting the efficacy of duloxetine for these purposes (Rodrigues-Amorim et al., 2020).
Milnacipran
Milnacipran (Savella) was introduced to the United States in 2009, originally for the treatment of fibromyalgia, a chronic condition causing widespread pain and fatigue.
When abruptly discontinued, milnacipran does not particularly aggravate any severe adverse effects, the effects being much less than the typical of other SNRIs such as paroxetine.
It is to be taken twice per day, unlike most other SNRIs (Sansone & Sansone, 2023).
Its lack of interaction with P-450 isoenzymes (which some other SNRIs engage with) suggest that drug interactions are not a cause for concern with milnacipran. In addition, it is very balanced in its reuptake inhibition of serotonin and norepinephrine, the degree of inhibition in each being nearly equipotent. However, it may have increased inhibition of norepinephrine—up to threefold higher, according to some research. Despite this uncertainty, milnacipran does not seem to have any effect on dopamine, unlike several other SNRIs (Sansone & Sansone, 2023).
Conclusion
SNRIs, which inhibit the reuptake of both serotonin and norepinephrine, are typically prescribed to treat anxiety and depression, similarly to SSRIs, though several of the common SNRIs are also used to treat physiological conditions as well. SNRIs are usually prescribed as a backup to SSRIs, though this does not mean they are less effective. Outside of these two categories of antidepressants, however, there is a third type: atypical antidepressants.