First generation antidepressants (11+)

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In this blog we will discuss what the first generation antidepressants are.

We will briefly touch upon how they work to treat depression, what antidepressants are, other types of antidepressants, their uses, and side effects. 

What are the first generation antidepressants?

According to a systematic review on Antidepressants used for the primary care for adult patients, the first generation antidepressants include:

  • Tricyclic antidepressants (TCAs) 
  • Monoamine oxidase inhibitors (MAOIs)

Tricyclic antidepressants (TCAs) 

Tricyclic antidepressants are drugs that block the reabsorption of Serotonin and norepinephrine in the brain and they were the first approved drugs for depression; it is part of the first generation antidepressants that were developed and used during the 1950s. 

According to Jennifer Fink, a writer for Healthline, TCAs that are still being used and are currently available include:

  • amitriptyline
  • amoxapine
  • desipramine (Norpramin)
  • doxepin
  • imipramine (Tofranil)
  • maprotiline
  • nortriptyline (Pamelor)
  • protriptyline (Vivactil)
  • trimipramine (Surmontil)

With the advent of other more effective antidepressants with lesser or milder side effects, medical providers and clinicians prescribe tricyclic antidepressants as a last resort treatment after other drugs have failed to relieve depression. 

This particular class of antidepressant helps to improve symptoms of depression by retaining higher levels of serotonin and norepinephrine in the  brain thus, helping elevate your mood.

It is not only used for depression but also has many off-label uses for treatment of conditions such as obsessive compulsive disorder (OCD) and lower doses can be used for the treatment of migraines and to treat chronic pain. 

One of the major reasons why Tricyclic Antidepressants are no longer considered prianmcy treatments is because of the high number of adverse effects it has on the body. Because it is not selective, it can impact several neurotransmitters in the brain leading to many side effects.

It can impact the muscles of the body, secretions, as well as the digestive system of the body. It can also lead to various side effects because of its impact on histamines- a biological chemical in the body when blocked can lead to side effects such as drowsiness, blurred vision, dry mouth, constipation, and glaucoma. (Healthline)

Possible side effects of tricyclic antidepressants include (Healthline):

  • dry mouth
  • dry eyes
  • blurred vision
  • dizziness
  • fatigue
  • headache
  • disorientation
  • seizure (especially with maprotiline)
  • drowsiness
  • constipation
  • urinary retention
  • sexual dysfunction
  • low blood pressure
  • weight gain (especially with amitriptyline, imipramine, and doxepin)
  • Nausea 

Monoamine oxidase inhibitors (MAOIs) 

MAOIs is another first generation class of antidepressants which were introduced around the same time as tricylic drugs- during the 1950s. 

Monoamine oxidase inhibitors are drugs that work by blocking or inhibiting the activity of monoamine oxidase which is crucial in the breakdown of norepinephrine, serotonin, and dopamine in the brain and other parts of the body. 

To understand how this particular drug works is to understand what Monoamine oxidase is. 

Monoamine oxidase is a type of enzyme that helps the functioning of neurons- is what regulates the firing of the neurons throughout one’s body (Healthline).

This enzyme is formed in your liver and cleans up exhausted neurotransmitters as well as a chemical called tyramine that regulates one’s blood pressure. 

The enzyme is what clears aware these neurotransmitters in the brain however the Monoamine oxidase inhibits inhibits the role and function of the Monoamine oxidase and thus, delays the removal of neurotransmitters such as dopamine, serotonin, and norepinephrine- increasing and sustaining their levels in the brain. 

As a result of more neurotransmitters to remain in the brain,there are higher levels of feel-good chemicals elevating mood and relieving depression symptoms. 

Because of the high amount of drug and food interactions and servois side effects of MAOIs, it is not a first choice drug intervention. However, according to Brian Kerns for Healthline, there are some approved MAOIs:

  • Isocarboxazid (Marplan)
  • Phenelzine (Nardil)
  • Tranylcypromine (Parnate)
  • Selegiline (Emsam, Atapryl, Carbex, Eldepryl, Zelapar), which is a newer type of MAOI.

This drug is not a primary option that many physicians prescribe because it has many drug and food interactions and also causes significant side effects. As a result, this class of drug has been replaced by newer antidepressants that are safer and cause fewer side effects.

Common side effects of this class of drugs include postural hypotension, weight gain, and sexual side effects as well as various food and drug reactions.

MAOIs with tyramine-containing foods or beverages may cause dangerous elevations in blood pressure as it inhibits the enzyme that cleans out tyramine, a chemical that helps regulate blood pressure.

Foods such as wine, aged cheese, sauerkraut, cured meats, draft beer, soy products should also be avoided and this particular drig also elevates the risks of Suicidal thoughts or behavior in children, adolescents, and young adults (18 to 24 years of age).

What are Antidepressants?

Antidepressants are medications that were first developed in the 1950s that are used to help treat symptoms of depression, social anxiety disorder, anxiety disorders, seasonal affective disorder, and dysthymia, or mild chronic depression, as well as other conditions.

Antidepressants work to correct chemical imbalances in the brain- chemicals known as neurotransmitters that are responsible for changes in mood, behaviour, and emotions. 

By correcting and balancing the levels of these chemicals in the brain in various ways, these medicines can help improve your mood, bring positive changes related to various symptoms such as focus and concentration, sleep, appetite etc.

What are the other types of Antidepressants?

Antidepressants are of different classes or different types depending on their target and the process by which they help balance neurochemical levels in the brain. 

The different classes of antidepressants are as follows:

Selective serotonin reuptake inhibitors (SSRIs) 

These are the most commonly prescribed antidepressants because of their high levels of efficacy and low number of side effects. 

These drugs help to increase levels of serotonin in the brain by inhibiting reuptake of these chemicals by blocking the receptors. 

As SSRIs affect the levels of serotonin and not other neurotransmitters, they are referred to as “selective.”

The use of this class of antidepressants commonly involve a few side effects such as nausea, vomiting, diarrhea, sexual dysfunction, headache, weight gain, anxiety, dizziness, dry mouth, and trouble sleeping.

One might also experience abnormal bleeding if it is used with painkillers and blood thinners. Some might also be affected by Serotonin syndrome which is a serious medical condition with symptoms such as anxiety, restlessness, sweating, muscle spasms, shaking, fever, rapid heartbeat, vomiting, and diarrhoea that occur when SSRIs are used with other medication. 

It is also obersevered that antidepressants such as SSRIs may also increase the risk of suicidal thoughts or behavior in children, adolescents, and young adults (18 to 24 years of age).

Serotonin norepinephrine reuptake inhibitors (SNRIs) 

This particular medication works by blocking the reabsorption of the neurotransmitters serotonin and norepinephrine in the brain so as to increase the levels of these neurotransmitters. 

The difference between SSRIs and SNRIs is that SNRI is not selective and may influence the levels of other neurotransmitters. 

The common side effects of SSRIs include nausea, dizziness, and sweating as well as sexual dysfunction. Other less serious side effects include tiredness, constipation, insomnia, anxiety, headache, and loss of appetite.

Significant and serious side effects also include abnormal bleeding when used wiht other drugs and blood thinners as well as increase in the rates and the risk of suicidal thoughts or behavior in children, adolescents, and young adults (18 to 24 years of age).

Some SNRIs should also not be used by people who are affected with uncontrolled narrow angle or angle-closure glaucoma.

Atypical antidepressants

This type of drugs do not fit into any of the other classes of antidepressants and each drug under this category has unique mechanism with which it affects  the body. 

However, atypical antidepressants also affect the levels of dopamine, serotonin, and norepinephrine in the brain. 

Since medications in this class are all unique in their effect on the body, their side effects also vary. Some common side effects include dry mouth, constipation, dizziness, and lightheadedness.

Some of these drugs can cause abnormal heart rhythms that can be life threatening as well as cause a rare sexual disorder that involves painful and prolonged erection in males.

Some of these drugs are also not recommended in patients with active liver disease and it can increase the likelyhood of Suicidal thoughts or behavior. 

What are the uses of Antidepressants?

Antidepressants are primarily used to treat depression and depression realted symotoms however, these medications are used not only to treat depression but for other conditions too.

Some of the conditions that these drugs have been approved for include:

  • agitation
  • obsessive-compulsive disorders (OCD)
  • childhood enuresis, or bedwetting
  • depression and major depressive disorder
  • generalised anxiety disorder
  • bipolar disorder
  • posttraumatic stress disorder (PTSD)
  • social anxiety disorder

Other “Off-Label” uses where the drug has not been approved for certain uses and conditions but tend to be effective include:

  • insomnia
  • pain
  • migraine

What are the side effects of Antidepressants?

Common side effects of Antidepressants include:

  • Gastrointestinal symptoms such as indigestion, diarrhoea, constipation, loss of appetite
  • Headache, dizziness, dry mouth, sweating
  • Agitation, shakiness, nervous feeling
  • Palpitations, fast heartbeat
  • Blurry vision
  • Unexpected weight loss or weight gain
  • Sexual dysfunction and low libido
  • Insomnia


In this blog we have discussed what the first generation antidepressants are.

We have also briefly touched upon how they work to treat depression, what antidepressants are, other types of antidepressants, their uses, and side effects. 

FAQ related to What are first generation antidepressants?

Which is a second generation antidepressant drug?

Second-generation antidepressants are drugs that were developed and used widely during the late half of the 20th Century and include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other drugs that selectively targeted neurotransmitters.

What are the 3rd generations of antidepressants?

Third-generation antidepressants are a group of antidepressants that are not only restricted to serotonin reuptake. Some of the examples for third generation antidepressants include:

venlafaxine, reboxetine, nefazodone and mirtazapine.

What are the top 5 antidepressants?

According to Sunrise House, the most commonly prescribed antidepressants include:

  • Celexa (citalopram)
  • Wellbutrin (bupropion)
  • Paxil (paroxetine)
  • Savella (milnacipran)
  • Prozac (fluoxetine)
  • Cymbalta (duloxetine)
  • Luvox (fluvoxamine)

Is Zoloft first generation?

Zoloft is a “third generation antidepressant” and it is considerably a newer antidepressants, from the 1990s and 2000s, and it is a selective serotonin reuptake inhibitor.


O’Connor EA, Whitlock EP, Gaynes B, et al. Screening for Depression in Adults and Older Adults in Primary Care: An Updated Systematic Review [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Dec. (Evidence Syntheses, No. 75.) Table 2, List of antidepressants and their categorizations. Available from:

Cherney.L.What Medications Help Treat Depression?. Healthline. Retrieved on 6th January 2022.

Nordqvist.C. All about antidepressants. Medicalnewstoday. Retrieved on 6th January 2022.

Fink.J.Tricyclic Antidepressants. Healthline. Retrieved on 7th march 2022.

Krans.B. What Are MAO Inhibitors? Healthline.  Retrieved on 7th march 2022.

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