The history of antidepressants began by accident. In the 1950s, chemists were tasked to find a cure for tuberculosis and took to experimenting with excess rocket fuel left over from World War II stockpiles. Two chemicals, iproniazid, and isoniazid appeared promising due to their ability to destroy bacteria. While the treatment ultimately failed to cure patients of TB, researchers noticed the beneficial effects the drugs had on patients’ mental states. These compounds boosted monoamines, neurotransmitters that are known to influence mood, and thus, became essential components in the first antidepressants.
Merriam Webster defines an antidepressant as “a drug that is used to relieve or prevent depression in a person.” The development of antidepressants has allowed millions of people to take back their lives from darkness and find ways to cope with conditions that are impossible to avoid. These drugs are staples in many people’s lives, so it can be difficult to imagine a world without access to this kind of healthcare. Antidepressants have been officially prescribed for only 70 years, and the science behind them is still developing every day. To get a better understanding of the state of mental healthcare today, it’s essential to look back on the history of antidepressants and understand how these medications developed.
The History of Antidepressants
The first generation of antidepressants were tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), which were introduced in the 1950s. While these medications were a major development in the field of Psychiatry by finally providing a pharmacological treatment modality for depression, they were also problematic due to their pharmacological properties and side effects (Hillhouse & Porter, 2015). For example, the TCAs have a narrow therapeutic index and therefore can easily cause fatal toxicity. TCA’s also block the effects of the neurotransmitter acetylcholine, which leads to dry mouth and eyes, constipation, and urinary hesitancy or retention.
MAOIs can also precipitate a hypertensive crisis in combination with dietary tyramine (which is also referred to as the “cheese effect”) and consumption of cured meats and fermented products with concurrent MAOI usage (Yamada & Yasuhara, 2004). While these first-generation antidepressants are no longer doctors’ first treatment choice, they are still prescribed today and approved for use worldwide by the World Health Organization.
The second generation of antidepressants was developed to more specifically target certain neurotransmitters and include medication classes such as the selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). The first SSRI introduced was fluoxetine (Prozac) in the late 1980s.
One major benefit to SSRIs as compared to the older antidepressants was that SSRIs are much safer, including in overdose. However, while SSRIs are considered as effective as the older antidepressants in mild or moderate depression, they were perceived to not be as effective as the older antidepressants in treating severe depression. That perception led to the development of other antidepressants, such as SNRIs, as focus shifted from solely boosting one neurotransmitter (serotonin) to also boosting other neurotransmitters (i.e. norepinephrine and dopamine) involved in mood regulation.
The first SNRI to be approved was venlafaxine, also known by the brand name Effexor, in 1993 for MDD. The immediate-release (IR) form that was dosed twice a day was approved for MDD in 1993. In 1997, the extended-release (XR) form, dosed only once a day, was also approved for MDD.
Other indications that have since been added include generalized anxiety disorder, social anxiety disorder (social phobia), and panic disorder. Venlafaxine has also shown efficacy in treating various pain conditions such as diabetic peripheral neuropathy and vasomotor symptoms associated with perimenopause, although it is not FDA-approved for such use. Duloxetine, also known as Cymbalta, was approved in 2004 for MDD and was the first drug in the U.S. to be approved for diabetic peripheral neuropathy. Duloxetine was later approved for generalized anxiety disorder (GAD), fibromyalgia, and chronic musculoskeletal pain. Because of this, it holds the most FDA-approved indications out of all the SNRIs (Eli Lilly and Company, 2004).
Desvenlafaxine, or Pristiq, a metabolite of venlafaxine, was approved in 2008 for the treatment of MDD (Liebowitz et al., 2008). Milnacipran (brand name, Savella) was approved in 2009 for fibromyalgia in the US; however, it has not been approved in the U.S. for MDD even though it is approved for MDD in many other countries. Levomilnacipran (brand name, Fetzima), the levo-enantiomer of milnacipran, is the most recent addition to the SNRIs and was approved in 2013 for MDD (Wagner et al., 2018).
The second generation in the history of antidepressants is complex, and research is still ongoing. While many second-generation medications have fewer side effects than their TCA counterparts, they have amine blocking and sedative properties that should be kept in mind. Doctors must be aware of the patient’s other conditions to prescribe medications safely. For example, the drug bupropion is considered a safe option, but can occasionally increase risks of seizures, and therefore should not be prescribed to a patient with a history of this condition.
The Process of Medication
A human mind is a complex machine that doctors and scientists have only just begun to understand. Just as MDD and other disorders manifest differently in each individual, so too will the effects of antidepressants. It is important to remain vigilant of your symptoms or the mental state of your loved ones if a new treatment plan is introduced. Be aware of changes in mood, isolation, or suicidal thoughts and actions, since certain medications may increase these symptoms. Medication is not always effective, and the trial and error of finding the ideal antidepressant can take an emotional toll, but this process is essential to achieve remission.
Taking Antidepressants and Need Extra Support? Call Mid City TMS
While many find depression relief through medication alone, antidepressants are not always effective. Some patients with MDD cannot find symptom improvement through medication alone, and that is where Mid City TMS can help. Mid City TMS is a New York-based treatment center specializing in transcranial magnetic stimulation for depression and anxiety. TMS is an FDA-approved, non-invasive, treatment that uses electromagnetic pulses to stimulate areas of the brain affected by depression. Our patient’s experience reduced anxiety, increased motivation, normalized sleep, and better overall mood. TMS is can be used in coordination with your current antidepressant regimen. Contact us today to learn how MidCity TMS can help improve your quality of life.