Antidepressants are a type of medication that has been shown to be highly effective at treating major depressive disorder and other mood disorders. Essentially, antidepressants work by boosting the chemicals in your brain called neurotransmitters. These neurotransmitters, identified as serotonin, dopamine, and norepinephrine, are known for affecting mood and emotions. 

History of Antidepressants 

Major depressive disorder is a very common mood disorder. The National Institute of Mental Health estimates that 17.3 million adults in the US had at least one major depressive episode in 2017. The 1950s actually saw the introduction of the first pharmacological treatments for major depressive disorder, which were iproniazid and imipramine. In 1952, two chemists, Irving Selikoff and Edward Robitzek, were developing a new treatment for tuberculosis and conducted clinical studies on a new drug, iproniazid, which is a monoamine oxidase inhibitor. They noted how patients experienced an improvement in mood, appetite, and sleep. Then, in 1957, the first public report on imipramine was created by Roland Kuhn. Kuhn was originally testing its antipsychotic effects for patients with schizophrenia with no results, and he realized that it instead worked as an antidepressant. So, the first clinically useful tricyclic antidepressant was founded.  

The 1980s brought about the focus on the association between serotonin levels and depression. In response, a new class of drugs called selective serotonin reuptake inhibitors (SSRIs) became established during this decade. Fluoxetine, an SSRI, revolutionized the market and therapy treatments for depression when it was approved by the FDA in 1987 as the brand name Prozac. Fluoxetine and all SSRIs had the advantage over tricyclic antidepressants (TCAs), as they had fewer adverse effects, although TCAs have still been popular over history. Prozac skyrocketed in popularity and became widely prescribed across America.

Types of Antidepressants 

Many people may not know that there are several types of antidepressants and they all function differently by affecting different neurotransmitters. Currently, there are five major classes of antidepressants, with SSRIs and SNRIs being among the most commonly prescribed as the first line of treatment.  

Selective serotonin reuptake inhibitors (SSRIs): SSRIs are a class of antidepressants that work by inhibiting the reuptake of serotonin. This means they block the reabsorption of serotonin into neurons and increase the levels of serotonin available in the brain. SSRIs can also be used to treat other conditions, such as OCD, anxiety, and eating disorders. SSRIs are also known for having fewer side effects than other types of antidepressants.

Common SSRIs are: 

• Celexa (citalopram)
• Lexapro (escitalopram) 
• Luvox (fluvoxamine) 
• Paxil (paroxetine) 
• Prozac (fluoxetine) 
• Viibryd (vilazodone) 
• Zoloft (sertraline) 

Serotonin and norepinephrine reuptake inhibitors (SNRIs): The first FDA-approved SNRI occurred in 1993 and works similarly to SSRIs. SNRIs inhibit the reuptake of both serotonin and norepinephrine, instead of just serotonin like SSRIs do. Some SNRIs can also treat generalized anxiety disorder, post-traumatic stress disorder, social anxiety disorder, panic disorder, and even chronic pain.

Common SNRIs are: 

• Cymbalta (duloxetine) 
• Effexor (venlafaxine) 
• Fetzima (levomilnacipran) 
• Pristiq (desvenlafixine) 
• Savella (milnacipran) 

Tricyclic Antidepressants (TCAs): One of the first antidepressants to be approved by the FDA and hit the market, tricyclic antidepressants get its name from the three rings in its chemical structure. They are similar to reuptake inhibitors, as they block the absorption of serotonin and norepinephrine, but they also block the absorption of the neurotransmitter, acetylcholine. Before SSRIs came along, these were the antidepressants that were used as the first line of treatment. TCAs are still prescribed often, but they can cause more severe side effects than SSRIs.

Common TCAs are: 

• Anafranil (clomipramine) 
• Asendin (amoxapine) 
• Elavil (amitriptyline) 
• Norpramin (desipramine) 
• Pamelor (nortrptyline) 
• Sinequan (doxepin) 
• Surmontil (trimipramine) 
• Tofranil (imipramine) 
• Vivactil (protriptyline)

Monoamine Oxidase Inhibitors (MAOIs): Another of the first antidepressants to become available to people in the mid-1900’s. MAOIs inhibit the action of a brain enzyme known as monoamine oxidase, which helps to break down neurotransmitters like serotonin. MAOIs are no longer commonly used and are generally saved when other antidepressants have not worked. This is due to their ability to interact negatively with other medications and the potential to cause food reactions. Common MAOIs are:   

• Emsam (selegiline) 
• Marplan (isocarboxazid) 
• Nardil (phenelzine) 
• Parnate (tranylcypromine) 
   

Atypical Antidepressants: Atypical antidepressants get their name because these antidepressants do not fit into any of the other major classifications, so they are considered “atypical.” Each medication in this category has a unique function and affects serotonin, norephedrine, and dopamine differently. Along with function, each antidepressant has varying side effects.

Some of the medications classified as atypical are: 

• Oleptro (trazodone) 
• Brintellix (vortioxetine) 
• Remeron (mirtazapine) 
• Symbax 
• Wellbutrin (bupropion) 

How Do I Know If Antidepressants Are Working? 

Antidepressants can do wonders, but unfortunately, they are not an instant cure for depression. These medications can take some time to be effective, and doctors usually expect them to start working in four to six weeks. After this time, if you still do not see any improvements in your mood, then you may wish to contact your doctor. Be sure to take your antidepressant as instructed to maximize the chances of it working. It will most likely be a subtle change over time, and you may not realize it. Your doctor may also want to keep you on your current antidepressant for a couple of months to give the medication more time to start working, and if there continues to be no change, then they might consider switching you to a different one. Medication also works best in combination with psychotherapy, or talk therapy, with cognitive behavioral therapy being the most popular talk therapy for depression. 

Side Effects of Antidepressants 

As with all medications, there are side effects to using antidepressants. If you do have side effects and they are unmanageable, you should speak to your doctor. They may switch your prescription to another type of antidepressant that might work better for you.

Some of the side effects are: 
 

• Headaches 
• Nausea or Vomiting 
• Sleeplessness 
• Agitation, Shakiness, or Anxiety 
• Weight Gain 
• Reduced Sex Drive 
• Dry Mouth 
• Stomach Aches 
• Constipation or Diarrhea 

Please also be aware that you should not suddenly stop using your medication without the guidance of your doctor. These are serious medications that alter the chemicals in your brain. If you suddenly stop taking them without a doctor's supervision, you may start to experience withdrawal symptoms. Your doctor will most likely have you reduce your dosage gradually over several weeks to help lessen your chances of experiencing withdrawal symptoms. These symptoms can include restlessness, trouble sleeping, unsteadiness, stomach problems, sweating, feeling irritable, anxious, or confused. You should also talk with your doctor if you have withdrawal symptoms, as there are some alternative approaches that can be taken to help you manage these symptoms. Withdrawal symptoms will usually start about a week after you stop taking your antidepressant and can last for one to two weeks, sometimes longer. 

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