What Was First Prescribed For Major Depressive Disorder?

In the early days of treating major depressive disorder, doctors often resorted to a rather surprising remedy – cocaine. Yes, you read that right. Believe it or not, cocaine was once used as a prescription for depression. However, this unconventional method was soon replaced with more effective and less harmful treatments. As we explore the history of depression treatment, it’s fascinating to discover the surprising remedies that were once considered cutting-edge. So, let’s take a trip back in time and uncover the origins of depression medication.

Early Treatments for Major Depressive Disorder

Major Depressive Disorder (MDD) is a serious mental health condition affecting millions of people worldwide. Throughout history, various treatments have been explored to alleviate the symptoms of MDD and improve the quality of life for those suffering from it. In this article, we will explore the early treatments for MDD, including bloodletting and herbal remedies, and how they paved the way for the development of modern therapies.


Centuries ago, bloodletting was widely believed to be an effective treatment for a range of illnesses, including mental disorders like MDD. The theory behind this practice was to remove “excess” or “impure” blood from the body, thus restoring balance and promoting healing. However, this approach was based on the now-discredited theory of humorism, which believed that imbalances in bodily fluids were the cause of illnesses.

While bloodletting may have provided temporary relief for some individuals due to the placebo effect, its inefficacy as a long-term treatment for MDD became apparent over time. Thankfully, advancements in medical knowledge and understanding led to the abandonment of bloodletting as a mainstream treatment for MDD.

Herbal Remedies

Herbal remedies have been used for centuries as a natural approach to treating various ailments, including mental health conditions. Early societies often turned to plants and herbs with purported mood-enhancing properties to alleviate symptoms of depression.

One such herbal remedy historically used for MDD is St. John’s Wort. This yellow-flowered plant contains active compounds that are believed to have antidepressant effects. While St. John’s Wort continues to be a popular herbal remedy for some individuals, its effectiveness in treating MDD is still a topic of debate within the medical community. It is important to note that herbal remedies should always be approached with caution and under the guidance of a healthcare professional.

Electroconvulsive Therapy (ECT)

Development and Early Use

Electroconvulsive Therapy (ECT) emerged as a treatment option for severe depression in the 1930s. At that time, it was known as electroshock therapy and was initially met with skepticism and fear. However, as more research and understanding of its mechanism grew, ECT became a valuable treatment option for individuals with MDD who did not respond well to other forms of treatment.

Modern Use

Over the years, ECT has evolved significantly. The procedure now involves the administration of an electric current to the brain, inducing a controlled seizure under general anesthesia. Despite the stigma that still surrounds ECT, it remains a safe and effective treatment for severe depression, especially in cases where other interventions have been unsuccessful.

While ECT is generally well-tolerated, it may have some side effects, including temporary memory loss and confusion immediately after the procedure. However, these effects are usually short-lived, and most individuals do not experience long-term cognitive impairments.

Tricyclic Antidepressants (TCAs)

Discovery and Development

Tricyclic Antidepressants (TCAs) were one of the first classes of drugs developed specifically to treat depression. They were discovered in the 1950s and quickly gained popularity as a means of alleviating the symptoms of MDD.

Mechanism of Action

TCAs work by increasing the levels of certain neurotransmitters, such as serotonin and norepinephrine, in the brain. By doing so, they help regulate mood and improve the overall well-being of individuals with MDD.

Side Effects

Although TCAs were effective in treating depression, they often came with a range of side effects that could be unpleasant for patients. These side effects include dry mouth, blurry vision, constipation, dizziness, and sedation. Additionally, TCAs have a higher risk of overdose compared to other antidepressant medications, making careful monitoring imperative during treatment.

Monoamine Oxidase Inhibitors (MAOIs)

Discovery and Development

Monoamine Oxidase Inhibitors (MAOIs) were discovered in the 1950s and provided another significant breakthrough in the treatment of depression. These medications function by blocking the enzyme monoamine oxidase, which is responsible for breaking down neurotransmitters like serotonin, norepinephrine, and dopamine.

Mechanism of Action

By inhibiting the breakdown of these neurotransmitters, MAOIs increase their availability in the brain, ultimately helping to alleviate depressive symptoms.

Side Effects

Although MAOIs were effective in treating depression, they posed certain risks and side effects. One of the most concerning side effects of MAOIs is their potentially dangerous interactions with certain foods and medications. These interactions can lead to a sudden increase in blood pressure and pose a significant health risk. Due to these risks, MAOIs are generally considered a treatment option of last resort and are prescribed with great caution.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Discovery and Development

Selective Serotonin Reuptake Inhibitors (SSRIs), such as Prozac and Zoloft, represented a significant advancement in the treatment of depression. They were first developed in the 1980s and introduced a more targeted approach to increasing serotonin levels in the brain.

Mechanism of Action

SSRIs work by blocking the reuptake of serotonin, allowing it to remain in the synaptic space between nerve cells for a longer period. This leads to increased serotonin levels, which can positively impact mood and alleviate symptoms of depression in many individuals.

Side Effects

While generally well-tolerated, SSRIs can have side effects that vary from person to person. These can include nausea, headache, sexual dysfunction, and changes in sleep patterns. It is important for individuals starting SSRI therapy to communicate openly with their healthcare providers about any concerns or side effects they may experience.

Atypical Antidepressants

Atypical antidepressants represent a diverse group of medications that are often prescribed when other treatments have been ineffective or not well-tolerated. Here, we will explore three common atypical antidepressants: Bupropion, Mirtazapine, and Trazodone.


Bupropion is an atypical antidepressant that works by increasing the levels of dopamine and norepinephrine in the brain. It is often prescribed as an alternative to SSRIs when individuals experience side effects such as sexual dysfunction. Bupropion is also approved for use in smoking cessation programs.


Mirtazapine functions by blocking specific receptors in the brain, leading to increased levels of norepinephrine and serotonin. It is often prescribed to individuals with depression who also struggle with insomnia or a lack of appetite.


Trazodone is commonly used as an antidepressant and sleep aid. It acts by increasing serotonin levels in the brain while also blocking specific receptors. Trazodone is often prescribed at lower doses for sleep disorders and at higher doses for depression.

Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Discovery and Development

Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are a class of antidepressant medications that emerged in the late 1980s. These medications, such as Effexor and Cymbalta, target both serotonin and norepinephrine reuptake, providing a dual mechanism of action.

Mechanism of Action

By inhibiting the reuptake of both serotonin and norepinephrine, SNRIs increase the availability of these neurotransmitters in the brain, leading to improvements in mood and overall well-being.

Side Effects

Like other antidepressants, SNRIs can cause side effects such as nausea, dizziness, and changes in appetite. In some cases, individuals may also experience elevated blood pressure. It is important for individuals to discuss any concerns or side effects with their healthcare provider.

Novel Treatments and Approaches

While the aforementioned treatments have played a significant role in managing MDD, ongoing research and scientific advancements have led to the exploration of novel treatments and approaches for this debilitating disorder. Three noteworthy examples include ketamine, transcranial magnetic stimulation (TMS), and psychotherapy.


Ketamine, traditionally used as an anesthetic, has shown promising results in treating severe depression. It works by targeting the glutamate system in the brain, resulting in rapid relief of depressive symptoms. However, ketamine treatments typically require careful consideration and monitoring due to potential side effects and risks.

Transcranial Magnetic Stimulation (TMS)

Transcranial Magnetic Stimulation (TMS) is a non-invasive procedure that uses magnetic fields to stimulate specific regions of the brain associated with depression. This treatment option has shown efficacy in individuals who have not responded well to other forms of therapy. TMS is generally well-tolerated, although some individuals may experience mild discomfort or headache during or after the procedure.


In addition to medication-based approaches, various forms of psychotherapy have proven effective in treating MDD. Cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), and mindfulness-based therapy are examples of psychotherapeutic interventions that aim to address the underlying causes of depression and provide individuals with coping strategies and support.

In conclusion, the early treatments for Major Depressive Disorder, such as bloodletting and herbal remedies, may have paved the way for advancements in modern therapies. From Electroconvulsive Therapy (ECT) to the development of Tricyclic Antidepressants (TCAs), Monoamine Oxidase Inhibitors (MAOIs), Selective Serotonin Reuptake Inhibitors (SSRIs), and beyond, scientists and healthcare professionals continue to explore innovative approaches to ensure individuals living with MDD receive the most effective and personalized treatments available. With ongoing research and a comprehensive understanding of the complex mechanisms underlying depression, hope remains for even more effective interventions in the future.