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MY GLIAL CELLS 1.

My First Science Paper
Submission

While writing in general has always been a passion of mine,
I mostly focused on topics on social factors, and only slightly dabbled in the sciences. For this review paper, I wished to investigate a personal curiosity of mine. What is anxiety and depression? One question I always had was, what are the symptoms that classified anxiety and depression? Are there any parameters? If I am sad, am I depressed? 

 

Thankfully, anxiety and depression, and other Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) classifications, had very distinct parameters that were usually associated with biochemical environment differences.

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ABSTRACT

Anxiety and depression are the result of neurological complications in the human brain. More specifically, both are the result of neurotransmitters and other chemicals working in a detrimental manner. More specifically, serotonin and other neurotransmitters are reabsorbed by presynaptic neurons, which in turn leads to a situation where the brain does not receive the optimal dosage of the chemicals. As such, contemporary medicine focuses on inhibiting the reabsorption of the chemicals by the presynaptic neuron. Such medication is known as antidepressants, and includes selective serotonin reuptake inhibitors(SSRIs) and serotonin-norepinephrine reuptake inhibitors(SNRIs), both of which focus on blocking the reuptake process from happening in the presynaptic neuron. This review manuscript strives to summarize the main drug variants within the two subgroups and thus explain the different characteristics of each variation.

KEYWORDS

Antidepressants, Anxiety Medication, Depression Medication, Serotonin-Norepinephrine Reuptake Inhibitors(SNRIs), Selective Serotonin Reuptake Inhibitors(SSRIs)

INTRODUCTION

Anxiety and depression, although they are classified as two different symptoms, belong to a bigger subset known as internalizing disorders and frequently appear at the same time in the same patient (Gjerde et al., 2011). This phenomenon is known as comorbidity, and stresses the overlap that the patient will have to address if they wish to get rid of their internalizing disorder. A major barrier in identifying anxiety and depression lies in the symptom recognition of the patient, be it by outward means such as friends and family, or by self-reflection and self-recognition.

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Self-reflection is especially difficult, as anxiety has its basis in fear; fear of the future, fear of uncertainty, or a phobia in general(Chand, 2023). Because its root cause lies in such a common emotion, it is hard to gauge the degree to which the patient can label the fear. In essence, anxiety is a complex cognitive and psychological response to an unjustified fear or event. As a result of this self-protection response, the body and neural system are always scanning for uncertain outcomes, and depression might eventually appear in the individual.

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While anxiety is classified as a neuropathological disorder, depression is classified as a mood disorder (Chand & Arif, 2023). Aside from the usual cause of sadness and grief, the loss of motivation for all things in life is often how depression is measured on a spectrum. Additionally, some cognitive changes might occur in individuals who suffer from depression, and if anxiety is also diagnosed in a person who has depression, medication is often recommended to alleviate and deal with the comorbid symptoms.

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From a pathophysiological standpoint, both anxiety and depression are regulated through the central nervous system. Biochemical biofactors of anxiety include serotonin, norepinephrine, dopamine, and gamma-aminobutyric acid, while depression biofactors include serotonin, norepinephrine, dopamine and glutamate. As can be seen, common biochemical factors exist in both symptoms, and as such, medication is often targeted toward serotonin, norepinephrine (NE), and dopamine (DA) and their respective chemical receptors.

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The two main groups of medication are Selective Serotonin Reuptake Inhibitors (SSRIs) and inhibit reuptake of serotonin, and thus help alleviate the symptoms of both anxiety and depression (Stahl, 1998). The other group is Serotonin-Norepinephrine Reuptake Inhibitors (SBRIs) and they work similarly to SSRIs, with norepinephrine binding also increasing in the brain (Feighner, 1999).

 

In this review manuscript, we will explain how anxiety and depression medication, henceforth known as antidepressants, work, take a deeper inspection of their various types and subtle differences, and observe their potential side effects. Additionally, we suggest a guideline on the usage of antidepressants in cases where the negative effects prove to be detrimental to the long-term health of the patient.

METHODS

The search identified 200 records, manuscript and internet page-based libraries, from searching the online libraries of the National Health Institution, PubMed, and Google Scholars. I. Search terminology included but was not limited to “mechanism of SSRI and SNRI, serotonin in anxiety and depression, contemporary SSRI, contemporary SNRI, and side effects of SSRI and SNRI” was uitilized for initial assessment. Follow up search was conducted by specific terminology relating to the names of the antidepressant. The medication terminology or name itself was used as the search term.  Of the 200 records identified, 30 duplicates were removed, 22 records were screened by title, 73 were screened after reading the abstract, and 25 were removed for various reasons related to the suitability regarding the review topic. Additionally, priority was given to scientific reports or data provided by national and governmental bodies.

ANTIDEPRESSANT MECHANISM

Regular serotonin levels are crucial for maintaining a healthy neurological system. Too much or too little often leads to complications in one’s medical health. Low serotonin levels are often associated with anxiety and depression, and additionally, can lead to physical health issues such as digestive complications, hair loss, and low levels of energy (Hartig, 1989; Cowen & Browning, 2015; Zangrossi et al., 2020). On the other hand, higher levels of serotonin lead to a medical situation known as serotonin syndrome, a side effect of antidepressant misdosage. The topic of serotonin will be discussed later on in the manuscript.

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Figure 2 depicts how SSRI and SNRI affect or disrupt serotonin and norepinephrine intake. The low levels of serotonin and norepinephrine associated with anxiety and depression are often a result of these neurotransmitters failing to properly transfer from the presynaptic neuron to the postsynaptic neuron, because of abnormal serotonin and norepinephrine reabsorption by the presynaptic neuron. Although their general mechanism are similar, it is important to look at each different antidepressant in greater detail.

A. Selective Serotonin Reuptake Inhibitors (SSRIs) Medication

The relationship between serotonin and anxiety was first introduced in 1962 (Klein & Flink, 1962) and has undergone significant research on its interaction with neurosystem receptors since then.  At the beginning of its utilization as an antidepressant, serotonin was presented as a possible solution alongside other chemicals, such as buspirone, a chemical that was similar to serotonin, and also ritanserin, another chemical that had similar properties to serotonin. However, while serotonin was efficient in treating multiple anxiety disorders, such as generalized anxiety disorder, panic anxiety disorder, social anxiety disorder, and post-traumatic stress disorder, the other two medications were found to be lacking. Buspirone was woefully inadequate in treating generalized anxiety disorder, panic anxiety disorder, and social anxiety disorder, and ritanserin actually increased panic anxiety disorders (Den Boer & Westenberg, 1990).

 

Contemporary SSRI medications are numerous, but five major subtypes are used in medical environments throughout the world: fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram, in order of general usage.

A.1 Fluoxetine

Fluoxetine is often cited as the first SSRI medication that was widely used by both inpatients and outpatients (Harvey & Preskorn, 1996). It is characterised as having two enantiomor forms, with the S-enantiomer being 50% percent more effective compared to the R-enantiomer form. One characteristic of fluoxetine is its high volume of dosage compared to that of other SSRIs. A single dosage is within the 14-100 L/kg range, and this may have the side effect of accumulating in tissue, which in turn might cause long-term damage. More specifically, accumulation is highest in tissues and organs with high lysosome content, such as the lungs. This is in contrast to its brain accumulation reading, which is lowest when compared to other SSRIs.

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After ingestion, fluoxetine metabolizes to other various metabolites, which include norfluoxetine and fluoxetine glucuronide. Herein lie some potential side effects regarding fluoxetine usage. If the fluoxetine and norfluoxetine do not exit the biological system in an efficient manner, drug buildup may occur. Usually, fluoxetine and norfluoxetine exist within the bloodstream before it is flushed out as urine. However, this process will only occur if the necessary enzymes are within the biological system. Enzyme CYP2D6 is one major enzyme, which is part of the P-450 enzyme reaction, and is associated with the excretion of fluoxetine and norfluoxetine in urine. If a genetic defect exists within the biological system, a gradual buildup will occur in the patient who is unaware of this rare genetic disease. This will eventually be seen in the high concentration of fluoxetine and norfluoxetine in the blood.

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Daily fluoxetine usage ranges from 20-60 mg (Michelson et al., 2001). Initial ingestion should start at 20 mg, but an increase in dosage is recommended if effects are not observed. The patient should see results starting from week two, and stabilization should occur near week four (Sohel, 2024). The drug kinetics of fluoxetine are non-linear (Altmura et al., 1994).

A.2 Fluvoxamine

Fluvoxamine is similar in form to fluoxetine and functions equally as impressively or better than fluoxetine. When comparing the selectivity blockage rate between fluvoxamine and other SNRIs, fluvoxamine shows higher selectivity than the SNRI-based medication, such as norepinephrine-based or dopamine-based medication. When compared to fluoxetine’s absorption rate, fluvoxamine shows a slightly smaller absorption rate. While fluoxetine is almost completely absorbed, fluvoxamine shows an absorption rate of slightly greater than 90%, which is still quite serviceable. The volume dosage is also smaller than that of fluoxetine, and the maximum limit is ~25 L/kg, and thus, is similar to the other three major SSRIs.

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Fluvoxamine was also seen to be flushed out of the biological system in urine, albeit not in its original fluvoxamine form. However, when observing the accumulation in the brain, fluvoxamine was found in higher concentrations in the brain when compared to fluoxetine. Nevertheless, when comparing the fluvoxamine concentration levels between healthy people who did not ingest fluvoxamine and patients who did ingest fluvoxamine, there was no difference in the blood fluvoxamine levels, indicating that fluvoxamine does indeed flush itself out of the biological system.

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Daily fluvoxamine usage ranges from 50-300 mg (Dieckmann et al., 2025). Initial ingestion should start at 50 mg, but an increase in dosage is recommended if effects are not observed. The patient should see results starting from day 5, and stabilization should occur within 5-10 days (van Harten, 1994). The drug kinetics of fluvoxamine are non-linear (Altmura et al., 1994).

A.3 Citalopram

The most appealing characteristic of citalopram-based SSRIs is their high selectivity rate (Lochmann & Richardson, 2018). This biological aspect may be correlated with the 50% recollection rate of citalopram in urine and a small amount of citalopram in feces. To properly understand the relation between citalopram and the biological system, it is important to understand the metabolites that result from citalopram metabolism. The main metabolite is demethylcitalopram, and the other is a citalopram N-oxide; between the two, the citalopram metabolite found in blood is demethylcitalopram and helps indicate where the other 50% of the citalopram went. Additionally, citalopram application on the biological system is linear, which is a major advantage when administering an initial citalopram dosage, as non-linear drug kinetics often result in a trial-and-error period for the patient. Citalopram and sertraline are considered to have linear kinetics, while fluvoxamine, fluoxetine, and paroxetine have nonlinear drug kinetics.

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An interesting characteristic of citalopram medication is its eventual effect on the neurogenesis of a patient. By influencing the brain’s amyloid region, it may be a potential medication for Alzheimer's disease. Indeed, since anxiety, depression, and Alzheimer's all interact with the amyloid of the brain, reducing or regulating the biochemical functions of that portion of the brain is worth looking into.

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Daily citalopram usage ranges from 20-40 mg (Shoar, 2023. Initial ingestion should start at 20 mg, but an increase in dosage is recommended if effects are not observed. A maximum dosage of 40 is not recommended. The patient should see results starting from week one, and stabilization should occur near week 4-6 (Chiarotti et al., 2017). Additionally, 40 mg dosages yielded the best results regarding mood improvement. The drug kinetics of citalopram are linear (Overø, 1982).

A.4 Sertraline

Sertaline is often considered the second most efficient serotonin inhibitor after paroxetine. However, this characteristic may be a result of non-exclusive specificity, as sertraline has a tendency to bind to dopamine receptors instead of exclusively to sertraline receptors.  Nevertheless, because sertraline has a low specificity in regard to general neurotransmitter receptors, it is classified as an SSRI. A pharmacokinetic property of sertraline worth mentioning is its slow uptake in the digestive system. It takes approximately 8 hours for it to achieve its maximum concentration in the blood, and this slow absorption characteristic suggests that sertraline has a linear kinetic drug mechanism, and thus, it is easy to suggest proper dosages. The excretion mechanism of sertraline is in line with other SSRIs, in that it seems to depend on the state of the hepatic cells and tissues; a patient with a faulty liver shows suboptimal sertraline excretion results.

 

Compared to the other four SSRIs, the excretion of sertraline seems to heavily depend on the status of the liver and the enterohepatic system, as 50% of the orally ingested sertraline is found in feces samples and 0.2% is found in urine, which is quite a difference from the urine content of the other SSRIs.

The optimal sertraline dosage is 50 mg (Preskorn & Lane, 1995). For sertraline, there is no range in regards to dosage.. The patient should see results starting from week four, and stabilization should occur near week six (Lewis et al., 2019). The drug kinetics of sertraline are linear (Marqueen et al., 2001).

A.5 Paroxetine

As seen with sertaline, the less selective an SSRI is, the more efficient it may be in regard to serotonin inhibition. However, paroxetine is also known to interact with and block muscarinic acetylcholine receptors in a similar manner to tricyclic antidepressants. However, because the dosage required for detrimental interactions with choline-based side effects is quite high, small amounts of paroxetine are suggested as a source of SSRI.

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 Paroxetine is known to have a chiral structure, a form also seen in sertraline. Like the other four SSRIs, paroxetine is absorbed in the stomach and metabolised in the liver. Like sertaline, paroxetine is found in significant amounts in feces samples, with amounts going up to approximately 36%. Additionally, like sertraline, paroxetine clearance rates depend on the status of the hepatic cells. This is because faulty liver cells result in improper metabolism of paroxetine, which in turn leads to a gradual buildup of paroxetine in the bloodstream.

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Daily paroxetine usage ranges from 10-50 mg (Shrestha, 2023). Initial ingestion should start at 10 mg, but an increase in dosage is recommended if effects are not observed. Weekly dosage increase is suggested at 10 mg per week. The patient should see results starting from week two, and stabilization should occur near week four (Ballenger et al., 1998). The drug kinetics of paroxetine are non-linear (Sindrup et al., 1992).

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B. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) medication

Compared to SSRIs, SNRIs are classified as multiple-reaction medication, due to being less selective than SSRIs. As can be seen in its name, SNRIs mainly target both dopamine and serotonin mechanisms capable of working quicker compared to SSRIs. Additionally, as mentioned before, SNRIs prevent reuptake in the presynaptic receptor by inhibiting the reuptake channels in the presynaptic neuron.

B.1 Venlafaxine

Venlafaxine was the first SNRI approved by the US Food and Drug Administration (FDA), and is utilized as not only an anxiety and depression antidepressant, but also in scenarios where the condition of the patient is not limited to neurological conditions, such as complex pain syndromes. Its chemical structure is characterized by a double-ring structure, and this double-ring structure is different compared to the other four SNRIs. This unique structure might also influence venlafaxine’s different affinity levels toward serotonin and norepinephrine.

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Compared to SSRIs, venlafaxine is subject to complications in both renal tissue and hepatic tissue, as it is metabolized through a liver-centered P-450 isoenzyme system, and thus, may possibly interact with other drugs within the biological system. The metabolite produced through the metabolic process is desvenlafaxine and lingers for half a day inside the blood system.

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Another characteristic of venlafaxine is seen in the unbalanced inhibition effects. Venlafaxine is seen to favor serotonin inhibition more than norepinephrine inhibition, and a sequential inhibition mechanism is observed. This is because the inhibition affinity factor is 30 times greater for serotonin compared to norepinephrine. Consequently, a sequential side effect scenario may occur where the patient may be subject to a tiered inhibition effect. The patient may encounter serotonin-related side effects such as headaches, nausea, and sexual dysfunction, which are then in turn followed by norepinephrine inhibition side effects such as dry mouth and night sweats.

 

Daily venlafaxine usage ranges from 75-300 mg (Cunningham, 1997). Initial ingestion should start at 75 mg, but an increase in dosage is recommended if effects are not observed. Maximum dosage may be suggested to be 300 mg, but it is not recommended as a starting point. High venlafaxine starts from 225 mg, and amounts above 300 mg are prescribed to patients suffering from major depressive disorder (Gainza-Tejedor et al., 2023) The patient should see results starting from week two, and stabilization should occur near weeks four and six (Thase et al., 2006). The drug kinetics of venlafaxine are linear (Jain et al., 2011).

B.2 Duloxetine

Duloxetine is the other well-known SNRI medication alongside venlafaxine. This is because both venlafaxine and duloxetine chemical formulations are available to the public, and thus, easier to access. Similar to venlafaxine, duloxetine has a higher affinity to serotonin inhibition compared to norepinephrine inhibition. However, its imbalance is not as great as Venlafaxine’s, and its affinity is roughly greater by a factor of 10 compared to venlafaxine’s factor of 30. Consequently, duloxetine usage will induce similar sequential side effects in the patient.

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Another characteristic duloxetine shares with venlafaxine is its usage of the P-450 enzyme pathway. Thus, duloxetine is also exposed to possible interactions with other drugs within the biological system. However, although duloxetine uses the same enzyme pathway as venlafaxine, the metabolites produced during this metabolic pathway are of no significance.

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The optimal duloxetine dosage 60 mg (Amann et al., 2024). For duloxetine, there is no dosage suggestion range. The patient should see results starting from week two, and stabilization should occur near week four (Hirschfield, 2005). The drug kinetics of duloxetine are linear (Zhao et al., 2009).

B.3 Milnacipran

Compared to venlafaxine and duloxetine, milnacipran’s general formula has not been released. Milnacipran is classified as a racemic mixture of two enantiomeric forms, d-milnacipran and l-milnacipran. Additionally, it does not interact with the P-450 pathway and, thus, is safer than venlafaxine and duloxetine in regard to other drug interactions.

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Milnacipran has two positive benefits in its usage as a SNRI drug. One benefit is milnacipran’s excretion mechanism, as milnacipran is excreted from the biological system mostly in urine. Another benefit is milnacipran’s balanced affinity in reuptake mechanisms. Milnacipran has similar affinity to both serotonin reuptake inhibition and norepinephrine reuptake inhibition. As such, milnacipran is safe from the sequential side effect process that is characteristic of venlafaxine and duloxetine. However, milnacipran has its own side effects, which include headaches, nausea, vomiting and dry mouth.

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Daily milnacipran usage ranges from 50-150 mg (Keks et al., 2018). Initial ingestion should start at 50 mg, but an increase in dosage is recommended if effects are not observed. Additionally, a dosage above 100 mg is considered high dosage (Hiyashi et al., 2007). The patient should see results starting from week two, and stabilization should occur from week 4-6 (Higuchi & Briley, 2007). The drug kinetics of milnacipran are linear (Delini-Stula, 2000).

B.4 Levomilnacipran

In addition to being the newest SNRI drug on the market, levomilnacipran is characterised as having a sustained-release formula (Young, 2013). In essence, levomilnacipran can be seen as a modified version of milnacipran and can be classified as a different enantiomer of milnacipran. Compared to the other four SNRI, levomilnacipran has a higher affinity for norepinephrine instead of serotonin. This chemical characteristic has researchers and medical personnel suggesting levomilnacipran therapeutic usage as more depression focused-instead of anxiety-focused. However, because levomilnacipran has been utilized only since 2013, its long-term effects have yet to be recorded. Additionally, since both SSRIs and SNRIs are capable of treating both anxiety and depression at the same time, this small advantage of levomilnacipran may not be as appealing as initially suggested.

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In regard to its metabolic process, levomilnacipran utilizes the 3A4 isoenzyme pathway, which is characteristic of SSRIs, but the metabolites produced in this state are similar to those of milnacipran, in that they are not significant. Finally, like milnacipran, approximately more than 50% of levomilnacipran can be seen to leave the biological system as urine.

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Daily levomilnacipran usage ranges from 40-120 mg (Gonmmoll et al., 2014). Initial ingestion should start at 20 mg, but an quick increase to 40 mg is suggested after two days. Because leomilnacipran is a recent addition, extensive research regarding its weekly effects has yet to be conducted properly. Recent research with phase III trials suggests that levomilnacipran is generally effective by week 8 (Asnis et al., 2013; Bakish et al., 2014). The drug kinetics of levomilnacipran are linear (Asnis & Henderson, 2015).

B.5 Desvenlafaxine

As can be seen in its name, desvenlafaxine is related to venlafaxine. More specifically, desvenlafaxine is an active metabolite of venlafaxine. An active metabolite is a metabolite that itself acts as a drug. As such, desvenlafaxine can be seen as a drug that “skipped a step”.  Because it is a metabolite of venlafaxine, it has a similar double-ring structure. Additionally, its affinity toward serotonin and norepinephrine reuptake inhibition is similar to duloxetine, in that the affinity to serotonin reuptake inhibition is 10 times greater than that to norepinephrine reuptake inhibition.

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 Like venlafaxine, desvenlafaxine also interacts with the P-450 enzyme pathway, but only partially. As a result of this partial interaction, approximately 50% of desvenlafaxine is seen leaving the biological system as urine. A biochemical analysis of desvenlafaxine inside urine samples has shown that desvenlafaxine leaves the system without additional biochemical modification, suggesting that desvenlafaxine’s interaction with the P-450 pathway is minimal. Additionally, the metabolite procedure during desvenlafaxine’s limited interaction with the P-450 pathway is not significant.

 

Daily desvenlafaxine usage ranges from 25-50 mg (Michelson et al., 2001). However, optimal dosage seems to be at 50 mg (Roh et al., 2022). The patient should see results starting from week one, and stabilization should occur near week two (Katzman et al., 2017). The drug kinetics of desvenlafaxine are linear (Sproule et al., 2008).

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C.  Serotonin syndrome

The purpose of this review paper was to provide antidepressant medication users with a summary of the biochemical and clinical characteristics of the antidepressant medication they were ingesting. Herein in the discussion, the authors wish to highlight some side effects, both minor and major, that antidepressant users may encounter. This medical knowledge is provided to instil a sense of fear, but to provide medical knowledge so the medication user is not confused.

 

Several minor symptoms were mentioned inside the body of the manuscript. Mild side effects include nausea, lethargy, headaches, and vomiting. Such side effects are not exclusive to antidepressants, but discussing the side effects with the patient’s medical provider is often recommended (Nguyen et al., 2023).

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Serious medication side effects may result in serotonin syndrome. Because the fundamental purpose of antidepressants was to rebalance the serotonin levels,  and in the case of SNRI, the dopamine levels, an overdose scenario will provide the biological system with an unwanted high and unhealthy concentration of serotonin. Depending on the dosage ingested, serotonin syndrome may be limited to excessive sweating and muscle twitching, but higher dosages will bring about extreme symptoms such as seizures or arrhythmia. More importantly, patients should keep track of any other medications they may have also consumed, as other drugs may be negatively affecting the biological system.

DISCUSSION

A side-by-side comparison of SSRI and SNRI reveals the quicker working nature apparent in the SNRI. This is apparent in the roughly 10-12-hour half-life of the SNRI medication. Additionally, compared to the metabolites produced in SSRI, SNRI metabolism yields less active metabolites, suggesting that the liver and kidneys are not subject to the same amount of punishment compared to the SSRI metabolism. That is not to say the SSRI medication is completely liver and kidney pressure-free, but the fact that it puts less stress on the two organs is worth noting.

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However, the quick-working nature of the SNRI is not without its flaws. As stated in the cases for venlafaxine, duloxetine, and desvenlafaxine, an affinity imbalance regarding affinity toward serotonin and norepinephrine reuptake inhibition yields a tiered side effect situation. Additionally, because two different chemicals are being addressed, it may cause a chain reaction. For example, if there was a patient who had slightly low dopamine levels and very low serotonin levels, it is incredibly difficult to find the correct dosage, and the patient will, unfortunately, be subject to trial and error, and thus subject to the side effects mentioned above.

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To summarize, because SSRIs have fewer side effects as they are only concerned with one chemical level, they are suitable in situations where risk is high, such as patients who are pregnant or who have extreme reactions to medication in general. On the other hand, the double treatment nature of SNRI allows for it to tackle anxiety and depression disorders that are higher on the spectrum. Additionally, SNRIs are also suggested as a possible medication for other diseases such as diabetic neuropathy and fibromyalgia.

CONCLUSIONS

Although this review focuses on only the biochemical aspects of the two major antidepressants, it should be noted that the usage of either SSRI or SNRI may have other effects on the brain chemistry and structure. Future steps regarding antidepressants may center on improving the effect and decreasing possible side effects, such as the most recent desvenlafaxine, but another suggestion regarding antidepressant usage may regard the brain’s plasticity or neuropsychological aspect, such as the transmitter system in the brain’s amygdala and cortex.

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Prolonged usage of antidepressants has resulted in a more permanent change in brain chemistry. While the immediate effects of the medication were used to control the serotonin and other monoamine levels, consistent usage through a longer time period has shown that the brain adopted a healthier and more properly controlled environment, a system where the reuptake of serotonin or dopamine did not happen. Consequently, the usage of either SSRI or SNRI is not required as the person can now be considered cured. As such, future research may decide to entertain the idea of bringing about this neuroplastic change quickly. Combination approaches that target both neural plastic changes while addressing the emotional processing change seem to be a possible end goal regarding antidepressant medication.

 

Ketamine is a possible candidate that can facilitate the hybrid changes in both emotional regulation and neuroplasticity (Mandal et al., 2019).  Compared to SSRI and SNRI medications, both of which have a delayed onset, Ketamine has been observed to bring about antidepressant reactions within hours of administration. Ketamine has been known to facilitate synaptic functions in the prefrontal cortex neurons, and reverse the neural damage which was brought about by chronic stress. Additionally, brain-derived neurotrophic factors (BDNF) are also influenced by the presence of ketamine, and ketamine has been observed to work on people who were not responsive to either SSRI or SNRI.

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Ketamine is a promising alternative to either SSRI or SNRI, but major research regarding new types of antidepressants is lacking. While the effects of ketamine on the mood of anxious or depressed people were more immediate than SSRI or SNRI antidepressants, its effects are noticeable for several days before they disappear. Additionally, the long-term effects of consistent ketamine administration have not been recorded. Nevertheless, ketamine has opened new possibilities regarding new types of antidepressants, and other possible antidepressants which focus on the glutamate system are now being looked into.

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