106 Advancements in Antidepressants

Introduction

Major depressive disorder has long been a heavy burden for millions of individuals, affecting their daily lives and well-being. Effective treatments for this condition were not discovered until the 1950s, with the first antidepressant introduced in 1958. Since then, advancements in medication have significantly transformed the treatment options available for individuals diagnosed with depression. Over the years, these drugs have demonstrated significant benefits, though they have also sparked important discussions and concerns regarding their long-term effects, overuse, and placebo effects. As ongoing research into depression and its treatments progresses, concerns and risks may be alleviated, paving the way for the ultimate goal of societal advancement.

Connection to Science, Technology, and society

The advancement in depression medication is connected to the various fields of science, technology, and society. The development of new antidepressants is grounded in scientific research on the brain. As neuroscience and pharmacology have advanced, an increasing amount of research has enabled scientists to gain a deeper understanding of depression and, in turn, develop more effective treatments. Technology has been crucial in the development of these medications. Innovations in drug delivery systems, like the intranasal esketamine treatment, have improved the range, as well as effectiveness, of treatment options. As the availability of more effective antidepressants has increased, it has had a profound effect on society, improving the lives of millions of people. As antidepressants become increasingly accessible and effective, they will play a pivotal role in advancing societal well-being and progress.

Discovery of the First Antidepressant

In the 1950s, a significant breakthrough in depression treatment emerged with the development of the monoamine hypothesis. The monoamine hypothesis proposed that patients with depression have depleted concentrations of three monoamines: serotonin, norepinephrine, and dopamine. Through this hypothesis, the discovery of the mechanism of monoamine oxidase (MAO) inhibitors proved to be the first progress towards treating depression. The first antidepressant was discovered through an attempt to treat tuberculosis. Chemists developed isonicotinyl hydrazide, also known as isoniazid, as a treatment option for tuberculosis. In 1953, while developing more antitubercular compounds, Herbert Fox and John T. Gibas synthesized isopropyl-isonicotinyl hydrazide, also known as iproniazid,

as a derivative of isoniazid. The tuberculosis patients who were being treated with iproniazid were showing side effects that included euphoria, increased appetite, and improved sleep. In 1958, a clinical study was conducted on patients with depression. The patients were given iproniazid for several weeks and monitored closely. The findings reported significant improvements in 70% of these patients, leading to iproniazid, classified as a MAO, becoming the first successful pharmacological treatment for depression. (Hillhouse & Porter, 2015)

The BEnefits of Antidepressants

Antidepressants have revolutionized the treatment of depression, offering hope and relief to millions of individuals. During 2015-2018, the Center for Disease Control and Prevention found that 13.2% of adults aged 18 and over had used an antidepressant in the past 30 days. (Brody & Gu, 2020) This data alone highlights the significant role antidepressants play in the lives of Americans.

It is difficult to measure the exact effects of antidepressants, as their benefits are dependent on the severity of the depression. The more severe the depression, the greater the benefit will be. Studies involving individuals who have been diagnosed with moderate or severe depression have lead to them noticing an improvement in their symptoms within six to eight weeks of taking the antidepressant. Antidepressants can alleviate the reoccurring symptoms of chronic depressive disorder and chronic depression, and may even help eliminate them entirely (Informedhealth.org, 2006).

Antidepressants can help individuals regain a sense of normalcy and functionality. By boosting neurotransmitters that are deficient in the brains of depression patients, antidepressants help restore the chemicals that have been depleted. Antidepressants have profoundly transformed the lives of those diagnosed with depression, significantly improving their quality of life.

The Risks of Antidepressants

While some people claim that antidepressants have only benefited society, others argue that they have only had a worsening effect on individuals. Each year, an annual rise in antidepressant prescribing has been reported. Antidepressants have almost doubled in a single decade, numbers soaring to 61 million prescriptions in 2015. (Spencer, 2015) The news continuously informs society that antidepressants are not being overused, however, some people find this hard to believe. Most patients who are prescribed antidepressants fall under the mild to moderate depression symptoms. Plenty of studies have found antidepressants to be ineffective in this category and have found other non-drug alternatives to be more effective, yet patients are still prescribed the medication.

One issue with the overuse of antidepressants is the lack of information society has on the long-term effects of taking such medications. With these medications being fairly new, not much information is known or available to the public on risk factors associated with taking antidepressants for such an extended period of time. Yet, patients are prescribed antidepressants for decades. Even when patients try to stop their medications, they can experience withdrawal symptoms such as agitation, insomnia, and mood swings, which may explain the return of their depressive symptoms shortly after stopping medication. (Spencer, 2015) Some analyses of both published and unpublished data hidden by drug companies suggest that the majority of antidepressant benefits may be attributed to the placebo effect. While some antidepressants raise serotonin levels, others lower them, and some have no impact on serotonin at all. However, they all seem to have the same therapeutic benefit. (Kirsch, 2014) The overuse of antidepressants is further complicated by concerns that certain popular medications might create a biological vulnerability, potentially increasing the risk of future depression.

While the development of newer medications for Major Depressive Disorder appears to have positively impacted society, much remains to be uncovered through ongoing clinical trials and long-term studies. It’s important to approach these medications with caution, as potential risks may not yet be fully understood.

Recent Advancements

As the years have passed, new discoveries and developments in various types of antidepressants continue to show promising results. For the first time in decades, on March 5, 2019, the Food and Drug Administration (FDA) approved the first new medication for depression. This new drug is used as a nasal spray called esketamine, which is derived from ketamine. In a single clinical study, 70% of patients with treatment-resistant depression experienced improvement after starting a combination of oral antidepressants and intranasal esketamine.

This new drug works differently than antidepressants in the past. With older antidepressants, the antidepressant effect only lasts while the drug is in your system. When the medication is discontinued, rebound effects may occur, a concern associated with antidepressants for many years. In contrast, ketamine triggers reactions in the cortex of the brain that allow brain connections to regrow. The effect is not caused by the presence of ketamine in the body, but rather by the brain’s initial reaction to ketamine. (Chen, 2022) With groundbreaking advancements like these, the realm of antidepressants continues to evolve, offering new treatment options to millions battling depression.

Conclusion

The journey of antidepressants from their discovery in the 1950s to present day has profoundly impacted the treatment of depression, offering help to millions of individuals who suffer daily. While the development of these drugs have brought significant benefits to society, it has also raised important questions regarding their long-term effects, overuse, and placebo effect. As science and technology continue to advance, the future of antidepressants promises the development of even more effective and safer treatments. These advancements will only contribute to the progression of society, enhancing mental health care and improving the quality of life for individuals affected by depression.

References

Brody, D. J., & Gu, Q. (2020). Antidepressant use among adults: United States, 2015–2018. (NCHS Data Brief No. 377). Hyattsville, MD: National Center for Health Statistics.

Chen, J. (2022, March 9). How ketamine drug helps with depression. Yale Medicine. https://www.yalemedicine.org/news/ketamine-depression

Hillhouse, T. M., & Porter, J. H. (2015). A brief history of the development of antidepressant drugs: from monoamines to glutamate. Experimental and clinical psychopharmacology, 23(1), 1–21. https://doi.org/10.1037/a0038550

InformedHealth.org. (2006–). Depression: Learn more – How effective are antidepressants? (Updated 2024, April 15). Institute for Quality and Efficiency in Health Care (IQWiG). Cologne, Germany. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK361016/

Kirsch, I. (2014). Antidepressants and the Placebo Effect. Zeitschrift Für Psychologie, 222(3), 128–134. https://doi.org/10.1027/2151-2604/a000176

Spence D. (2016). Bad Medicine: The rise and rise of antidepressants. The British journal of general practice : the journal of the Royal College of General Practitioners, 66(652), 573. https://doi.org/10.3399/bjgp16X687793

Images

“Iproniazid Chemical Structure” by Edgar181, Wikimedia Commons is in the Public Domain, CC0

AI Acknowledgment

I used Microsoft Co-Pilot to generate images used in this chapter. Images are meant to clarify topics explained in this chapter and amplify connections drawn throughout the chapter. (2024). Co-Pilot [Large Language Model]. https://copilot.microsoft.com