Antidepressants - The Accidental Revolutionary Drug, By- Ahana

In the 1950s the discovery of two new drugs sparked what would become a multibillion dollar market for antidepressants. Funnily enough, neither drug was intended to treat depression at all - in fact at the time psychotherapy was viewed as the most effective method for curbing depression. The decades-long journey of discovery that followed, revolutionized our understanding of depression and introduced variables that we had never considered before.

One of those first two antidepressant drugs was iproniazid, which was intended to treat tuberculosis. In a 1952 trial, it not only treated tuberculosis, but it also improved the moods of patients who had been previously diagnosed with depression. In 1956, a Swiss clinician observed a similar effect when running a trial for imipramine, a drug for allergic reactions. Both drugs affected a class of neurotransmitters called monoamines.

The discovery of these antidepressant drugs gave rise to the ‘chemical imbalance’ theory - the idea that depression is caused by having insufficient monoamines in the brain's synapses. Iproniazid, imipramine and other drugs like them were thought to restore that balance by increasing the availability of monoamines in the brain. These drugs targeted several different monoamines, each of which acted on a wide range of receptors in the brain. This often meant a lot of side effects including headaches and cognitive impairments. In order to reduce these undesirable side effects, scientists began studying existing antidepressants to find out which specific monoamines were most associated with improvements in depression. Several researchers then converged on an answer - the most effective antidepressants all seemed to act on one monoamine called serotonin, better known as the ‘happy chemical’.

This discovery led to the production of Prozac (or fluoxetine) in 1988. It was the first of a new class of drugs called Selective Serotonin Reuptake Inhibitors or SSRIs, which block the reabsorption of serotonin, leaving more available in the brain. This makes it easier for the brain cells to receive and send messages, resulting in better and more stable moods. Prozac worked very well and had fewer side effects than its predecessors. Other SSRIs since released include paroxetine, sertraline, citalopram, escitalopram, and fluvoxamine.

Soon other types of antidepressants were developed including SNRIs (Serotonin and Noradrenaline Reuptake Inhibitors). SNRIs raise levels of serotonin and norepinephrine, two neurotransmitters in the brain that play a key role in stabilizing mood.

So how exactly do neurotransmitters work?

The human brain has about 10 billion brain cells. Each brain cell can have over 25,000 connections with other cells. Messages which direct many functions throughout our body, travel through the brain from cell to cell through these connections. For these signals to move from a sending cell to a receiving cell, they must cross a small gap called the synapse. Chemicals called neurotransmitters, located at the ends of the sending cells, help the signal cross this gap. Serotonin is one such neurotransmitter that helps regulate mood, emotions and other body functions. After the serotonin has done its job, it is reabsorbed by the sending cells and is sonn back in position to help with the next nerve signal. People with depression may have low levels of serotonin, and some of it may be reabsorbed too soon, as a result communication between the brain cells is impaired. SSRIs thus help block this reabsorption of serotonin. As serotonin builds up, normal communication between cells can resume and the symptoms of depression may improve.

As more and more antidepressants became marketable, awareness of the dangers of depression was spread to the public. More people have come to see depression as a disease caused by mechanisms beyond their control, which has reduced the culture of blame and stigmatization surrounding depression. In the 1990s, the number of people being treated for depression skyrocketed. Psychotherapy and other treatments fell by the wayside and most people were treated solely with antidepressant drugs. Since then, we’ve developed a more nuanced view of how to treat depression and what causes it. Not everyone with depression responds to SSRIs like Prozac - some respond better to drugs that act on other neurotransmitters, or don’t respond to medication at all. For many, a combination of psychotherapy and antidepressant drugs is more effective than either alone

The working of antidepressant drugs is still quite a mystery. Despite causing immediate chemical changes in the brain once taken, patients usually don’t feel the benefit until weeks later. And after stopping their medication some people never experience depression again, while others relapse. Scientists are still unsure of the root cause of depression - serotonin deficiency is just one explanation of it. We still have a long way to go in terms of understanding this disease, but fortunately in the meantime we have a multitude of tools to treat and manage it.