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A New Wave of Antidepressants

By: Katelyn Six, Section Editor for Bloc[k] Beat (six1@uic.edu)

Imagine this: Having a tough time concentrating at school or at work; constantly falling asleep in meetings or in class; feeling extremely listless and melancholy all the time; suffering from ominous body pains or headaches that cannot be explained by physical health; losing interest in old hobbies or generally ‘fun’ activities. These are just a few of the many symptoms associated with depressive and anxiety disorders.

These disorders broadly range in severity, type, and form. Considered a mood disorder, depression alters the way a person reasons, copes, and conducts oneself in day-to-day activities. Depression exhibits no discrimination regarding who it may affect, as depressive disorders affect people of all races, ethnicities and genders. Due to the prolificness and large amount of the human population suffering from depression, the antidepressants used to treat depressive disorders are of utmost concern and scrutinization.

When exploring the issue of depression, it is imperative to explore antidepressant drugs, which alter brain chemistry and are a common treatment for forms of depression and anxiety disorders. In order to do so, I will discuss two different classes of antidepressants: “new-generation antidepressants” or selective serotonin reuptake inhibitors (SSRIs) and “first-generation antidepressants” or traditional tricyclic antidepressants and monoamine oxidase inhibitors.

New-Generation Antidepressants

First, we will address the effectiveness of SSRIs, how they work in terms of brain biochemistry, and the effects of their anti-inflammatory properties on depression sufferers. According to the 2013 review titled, “A critical review of the mechanism of action for the selective serotonin reuptake inhibitors: Do these drugs possess anti-inflammatory properties and how relevant is this in the treatment of depression?” by Frederick Rohan Walker in Neuropharmacology, the monoamine theory is a crucial element in the examination of SSRIs in proving how inflammation contributes to depression. This journal review asserts that “the term SSRI relates to the fact that these agents bind with very high affinity to the serotonin transporter (5-HTT), inhibiting its reuptake of serotonin (5-HT).”

Essentially, serotonin is a neurotransmitter in the brain that is greatly affected and often afflicted in depressive patients. Serotonin reuptake inhibitors work by attaching, in large quantity, to the serotonin transporter to control how long the serotonin release will last. With respect to Walker’s theory on inflammation, an explanation is given that inflammation is closely connected to depression because cancer patients who were clinically depressed showed improvement in mood and showed less inflammation when treated with pro-inflammatory cytokines.

In the 2011 editorial article by Alessandro Serretti titled, “Antidepressant, Present and Future,” from Progress in Neuro-Phsychopharmacology and Biological Psychiatry, the deep-seated issue lies in the taxing nature of treatment for depression patients with the use of antidepressants. In order to minimize negative side effects and maximize positive responses, Serretti concludes that having the ability to customize antidepressant treatment specifically based on each individual patient’s genetic composition and brain chemistry is critical. The article hastens that scientists must understand that antidepressants are non-linear in the ways they alter brain biochemistry, meaning they are subjective and act uniquely with each individual’s particular genetic brain make-up. Ultimately, the future of depression treatment relies on the capability of these drugs to harmonize with the genetic composition that is exclusive to each patient.

Clinicians and Antidepressant Prescriptions

Another pressing issue revolving around antidepressants is the way clinical personnel dispense medication and treatment, often prescribing antidepressants as the first course of action. The article by Janos Almasi and Zoltan Rihmer titled, “Review of antidepressants from the TCAs to the third generation drugs,” sets out to help psychiatrists make better choices when prescribing antidepressants to patients. As with most medications, antidepressants often come with negative side effects, but this review ascertains that combining antidepressants can be helpful to some depressive individuals, while other patients may experience more intensely negative side effects.

Gender Disparity

What’s more, women are twice as likely as men to encounter depressive symptoms. The research report titled, “Individual differences in novelty-seeking predict differential responses to chronic antidepressant treatment through sex- and phenotype-dependent neurochemical signatures,” in Behavioural Brain Research, investigates the idea that antidepressant agents react differently based on what the patient’s sex is. Male and female rats were used in this study to explore the way reactions to antidepressant treatment with TCA clomipramine differ based on gender. Moreover, the study further broke up the male and female mice into the high novelty-seeker (HR) category and the low novelty-seeker (LR) category.

To test how anxiety and depression may be alleviated in sufferers, rats were given a forced swim test, or FST, to gauge how sluggish or how responsive the animals of both categories and subcategories were when administered tricyclic antidepressants (TCAs). The results were telling, discovering that the high novelty-seeking male rats performed considerably better on the test than the low novelty-seeking female rats. The authors leave us with the conclusion that the results of this study “may be indicative of sex- and region-dependent implication and/or differential responsiveness of neurochemical systems to clomipramine treatment.”

Differences in the rats’ performance suggest that sexual dissimilarities play a salient part in how the brain reacts to TCAs and can correlate to the notion that antidepressant treatment depends in part on the morphology of different male and female brain regions. The bottom line here is that antidepressants need to be specifically suited to individuals based on the unique morphology of their brain regions, and that the brain differences between men and women may also need to be considered when administering treatment of antidepressant agents to patients with depressive disorders and anxiety disorders.

Remission and Long-Term Treatment

Another journal reports that the longer depression goes untreated, the least likely the patient will go into remission or stay in remission from his or her illness. This introduces how well antidepressant treatment works may be contingent on how long treatment is postponed. In this study, the people observed were between the ages of 18-70 years old, which encompasses an enormous amount of the population. All of the people studied had been diagnosed with a depressive disorder of some form and were being treated with antidepressants. These findings hint that those participants who began taking antidepressants shortly or immediately after exhibiting symptoms of a depressive disorder were more prone to stay in remission.

The Bottom Line

In conclusion, issues surrounding how antidepressant drugs alter brain chemistry and how they serve as a common treatment for forms of depression and anxiety disorders, is an important conversation to have. To flesh out this topic, we dove into studies suggesting that inflammation may be a strong contributor to depression and anxiety disorders, and we dipped into the belief that hormones are major factors to consider when understanding the way antidepressants affect patients.

Overall, the future of antidepressants is still in progress, and there is more research that needs to be done to make a considerable breakthrough in the neuropharmocology field. Antidepressant studies often have multiple angles and sometimes contradictory results, leaving many scientists and clinicians to conclude that there is still a laborious amount of work to be done before antidepressants can be understood fully. So, after sinking our teeth into scientific studies, neurophamacological journals, and biological reviews, it is evident that there is still much to be learned about the biochemistry of antidepressants. From traditional tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors to selective serotonin reuptake inhibitors (SSRIs), a new generation of antidepressants is upon us.

Backtracking to the scenario outlined at the start of this post, we can see how important the research of antidepressants is toward alleviating depression and anxiety sufferers. As mentioned earlier, depression does not discriminate based on race, ethnicity, gender or skin color, making this topic one worth examining further. Depression manifests itself in many different ways: through physical symptoms like unexplained exhaustion, weight loss or weight gain, and racing heartbeat; and through psychological symptoms like loss of interest in hobbies, pervasive feelings of worthlessness or hopelessness, and overall debilitating sadness. Perhaps one day, scientific research can successfully pull those suffering from depressive and anxiety disorders out from the dark abyss of their paralyzing disorder.      

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