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The 5 Major Classes of Antidepressants

By Olivia Guy-Evans, published June 16, 2021

by Saul Mcleod, PhD

antidepressants tablets

What are antidepressants?

Antidepressants are a type of medication which is primarily used as a treatment of depression, although they can be used to treat other conditions such as anxiety disorders.

As depression is a condition which is strongly believed to be associated with chemical imbalances within the brain, antidepressants are used to help alter these imbalances to improve the symptoms of this condition.

There are 5 main classifications of antidepressants that are commonly prescribed to treat depression (SSRIs, SNRIs, TCAs, MAOIs, and atypical antidepressants).

These were all developed at different times and differ in their benefits, risks, and what conditions they are best at treating.

The medication chosen will depend upon the severity of symptoms, other prescribed medications taken in conjunction, the symptoms experienced, and if there are any comorbid mental health conditions.

How antidepressants work

Antidepressants work by acting on some part of neurotransmission within the brain. Neurotransmission is when neurotransmitters (chemical messengers) which have travelled through neurons, reach the presynaptic terminals, and are released into the synaptic cleft, to be taken up by the corresponding receptors of the postsynaptic neuron.

This is how chemicals travel around the brain and have an influence on mood and behavior. There are three main neurotransmitters which are influenced by antidepressants and are believed to be involved in the regulation of mood:

  • Serotonin – this is believed to play a role in mood, feelings of happiness, rewards, appetite, and sleep.
  • Dopamine – this plays a role in how we feel pleasure, motivation, arousal, and decision-making.
  • Norepinephrine – this plays a role in regulating cognition, motivation, alertness, and regulating heart rate and blood pressure during stressful periods.

Types of antidepressants

Selective serotonin re-uptake inhibitors (SSRIs)

Selective serotonin re-uptake inhibitors (SSRIs) are antidepressants that were developed in the 1980s and 1990s and work on effecting the use of the neurotransmitter serotonin in the brain.

SSRIs are called selective because they mainly affect serotonin, rather than any of neurotransmitters. These antidepressants do not cause more serotonin to be produced in the brain, but instead help the brain to use the serotonin levels it has more effectively.

During neurotransmission, when the serotonin is released into the synaptic cleft, the serotonin can either be transported to receptors on the postsynaptic neuron, being destroyed by enzymes, or being reabsorbed back into the presynaptic neuron which released the chemical. This latter process is called re-uptake.

SSRIs work by blocking the re-uptake of serotonin into the presynaptic neuron

SSRIs work by blocking the re-uptake of serotonin into the presynaptic neuron. Because of this, more serotonin will be circulating around the synaptic cleft, making it more likely that serotonin will reach the receptors of the postsynaptic neuron.

If this happens, it means that more serotonin will be working in the brain, resulting in increases in mood and feelings of happiness.

SSRIs have been shown to be effective in treating depression, but also have proven to be effective in a treatment of other conditions such as obsessive-compulsive disorder, posttraumatic stress disorder, anxiety disorders, and panic disorder.

There are several types of SSRIs, which are though to all act in a similar way and have similar side effects. Below are examples of some of the SSRIs that can be prescribed:
  • Fluoxetine (Prozac) – this was the first major SSRI created in 1987
  • Citalopram (Celexa)
  • Paroxetine (Paxil, Pexera)
  • Sertraline (Zoloft)
  • Vilazodone (Viibryd)

SSRIs are typically the most prescribed antidepressant due to most people being more tolerant of them compared to other antidepressants and they have fewer side effects.

Some side effects that could be experienced as a result of SSRIs are as follows:

  • Headaches
  • Nausea
  • Dizziness
  • Weight loss or weight gain
  • Drowsiness
  • Sexual dysfunction, e.g. reduced sex drive
  • Agitation or restlessness
  • Problems with sleep
  • Increased sweating

Some SSRIs can also interfere with other medications and their effectiveness, sometimes causing dangerous reactions.

Serotonin syndrome is a condition which can occur if there is too much serotonin present in the brain. This could come as a result of beginning to take SSRIs or an increase in dosage. This can have mild side effects to begin with but may become life-threatening in rare cases so therefore it still needs to be considered if someone is taking SSRIs.

Also, it is reported that occasionally people can feel suicidal in the first few weeks of beginning to take SSRIs, especially in children and adolescents.

Once they have got used to the medication, the risk of suicide is typically reduced, and feelings of depression should begin to decrease.

Despite this risk, SSRIs are more likely to reduce the risk of suicide in the long term, but other therapeutic options could be considered first before young people begin taking this antidepressant.

Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) was one of the first classes of antidepressants, developed in the 1950s. MAOIs work by blocking the function of the enzymes called monoamine oxidase.

This enzyme is present within the synapses at neurotransmission and function in breaking down the neurotransmitters within the synapse that do not get taken up by receptors on the postsynaptic neuron reabsorbed back into the presynaptic neuron.

If the enzymes are blocked by the MAOIs, this means there will be more neurotransmitters (serotonin, dopamine, and norepinephrine) circulating around the synaptic cleft.

This makes it more likely that these neurotransmitters will reach the receptors of the next neuron, leading in an increase in mood.

MAOIs are primarily used as a cure for depression but are also good at helping relieve other conditions such as agoraphobia, social phobia, posttraumatic stress disorder, borderline personality disorder, and bulimia.

These days, this class of antidepressants are not typically used as the first option for people with depression as they are particularly strong and have several side effects:

  • Nausea
  • Dizziness
  • Restlessness
  • Insomnia
  • Drowsiness

There are dietary restrictions which must be followed if taking MAOIs as these can cause reactions to food which contain tyramine (e.g. strong cheeses, cured and processed meats, alcohol, and soybeans).

If food containing tyramine is eaten, this can trigger critical increases in blood pressure.

MAOIs could also have adverse reactions when mixed with other types of medication, and in rare cases, can cause dangerously high levels of serotonin, known as serotonin syndrome.

Likewise, MAOIs can also cause irreversible high blood pressure, all of which are reasons why MAOIs are usually only used as a ‘last resort’ if other treatments are not working.

Tricyclics (TCAs)

ricyclic antidepressants (TCAs) are known as the second generation of antidepressant drugs, invented after MAOIs.

TCAs were originally tested on people who had schizophrenia and became a popular antidepressant treatment in the 1960s. this is an older classification of antidepressants but work in a similar way to SSRIS in the sense that they also work to block the reuptake of serotonin from returning to the presynaptic neuron which produced it.

However, TCAs also work by blocking the reuptake of another neurotransmitter called norepinephrine which also affects mood.

TCAs are most used to help treat depression, but can also have an effect on a variety of other conditions:

  • Obsessive compulsive disorder
  • Panic disorder
  • Insomnia
  • Migraines
  • Chronic pain
  • Chronic bedwetting
  • Irritable bowel syndrome
  • Neuropathic pain

In the past, TCAs were used to help with the symptoms of attention deficit hyperactivity disorder (ADHD) in children but have since been replaced with a medication with less side effects.

Like MAOIs, TCAs are also very strong and are not often used as a first treatment due to its unpleasant side effects.

Below are some of the side effects that could occur as a result of taking this antidepressant:

  • Weight gain
  • Dizziness
  • Fatigue
  • Headaches
  • Disorientation
  • Nausea
  • Sexual dysfunction
  • Irregular heart rate
  • Increased appetite

Drinking alcohol alongside taking TCAs is often not recommended as alcohol can lessen the action of the antidepressant. Similarly, certain medications can react badly with TCAs.

For instance, Epi-pens, which are made of epinephrine (also known as adrenaline), used to cure allergic reactions, can result in heart rhythm problems and high blood pressure when taking TCAs at the same time of use.

Also, TCAs can elevate blood sugar levels, meaning that those with diabetes would be at higher risk if they were to take TCAs.

Finally, as TCAs can have an effect on the heart and thyroid, if someone has existing heart or thyroid problems, they would probably not be prescribed this antidepressant.

Serotonin norepinephrine reuptake inhibitors

Serotonin norepinephrine reuptake inhibitors (SNRIs) were first introduced as a class of antidepressants in the mid-1990s.

This medication works in a similar way to SSRIs, in the sense that they block the reuptake of serotonin from being reabsorbed back into the presynaptic neuron.

However, they also block the reuptake of the neurotransmitter norepinephrine, a chemical which plays a role in alertness, motivation, heart rate, and blood pressure during stressful situations.

AS SNRIs block the reuptake of both serotonin and norepinephrine, this means more of these chemicals will be circulating around the synaptic cleft during neurotransmission, making it more likely that these will reach the appropriate receptors on the postsynaptic neuron and relieve the symptoms associated with depression.

As SNRIs affect two neurotransmitters, serotonin and norepinephrine, these are sometimes called dual reuptake inhibitors or dual-acting antidepressants.

SNRIs are mostly used to treat depression but can also be useful in treating other mental health conditions such as bipolar depression, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), attention deficit hyperactivity disorder (ADHD), chronic nerve pain, and fibromyalgia.

Below are some of the types of SNRIs that can be prescribed, and their main uses:

  • Desvenlafaxine (Pristiq) – used mostly for depression and panic disorder
  • Levomilnacipran (Fetzima) – used as a treatment for depression
  • Duloxetine (Cymbalta) – used to treat depression and chronic pain
  • Milnacipran (Savella) – used to treat fibromyalgia

Like all antidepressants, there are several side effects that have been associated with them.

Below are some of the possible side effects that could be experienced:

  • Dizziness
  • Headaches
  • Insomnia
  • Nausea
  • Excessive sweating
  • Change in appetite
  • Muscle weakness
  • Increased blood pressure
  • Increased heart rate or heart palpitations
  • Agitation or restlessness

The side effects for SNRIs are similar to those of SSRIs, however SNRIs are typically prescribed for short-term use because prolonged use has shown cases of people experiencing manic or hypomanic episodes.

Moreover, as SNRIs can increase blood pressure, they are usually not recommended for people who already have high blood pressure levels.

Atypical antidepressants

Atypical antidepressants are primarily newer types of medication which cannot be characterized under the branches of the other types of antidepressants.

These are known as atypical since they do not function in the way that SSRIs, SNRIs, MAOIs, and TCAs work in the brain.

Depending on the type of atypical antidepressant, they work on changing the levels of the neurotransmitters serotonin, norepinephrine, and dopamine in different ways.

A type of atypical antidepressant, Bupropion, works by blocking the reuptake of dopamine and norepinephrine at the synaptic cleft, making it more likely that these chemicals will reach the receptors of the postsynaptic neuron.

Another atypical antidepressant called agomelatine, encourages the release of dopamine and norepinephrine through agonizing melatonin receptors (a hormone related to sleep and wake) and antagonizing serotonergic receptors (serotonin receptors).

Another example of an atypical antidepressant is mirtazapine, which is a noradrenergic antagonist which is used to block the receptors of the hormone epinephrine (also known as adrenaline, a stress hormone).

As each of the atypical antidepressants have different functions and structure, the side effects can vary depending on which is being taken. Some possible side effects could include:

  • Dizziness or light-headedness
  • Sleep changes – either sleeping too much or insomnia
  • Weight gain
  • Nausea
  • Sexual dysfunction
  • Dry mouth


Depending on which antidepressant is prescribed will depend on the condition and severity of symptoms being experienced. It can take approximately four to six weeks after beginning to take the medication until improvements in mood are noticed.

For SSRIs for instance, people usually report having more energy, feeling less anxious, and feeling less hopeless about the future after taking this antidepressant for a few weeks.

If, however, individuals report not experiencing any improvements after approximately six weeks, it is likely that a different antidepressant, or a high dosage, will be recommended. Occasionally, antidepressants can be used in combination with other drug therapies to treat various symptoms which may be higher in severity.

A consideration that must be considered when taking high dosages of antidepressant is that a condition called serotonin syndrome could occur. This is when there is too much serotonin in the body and can cause symptoms such as confusion, rapid heart rate, high blood pressure, and headaches.

This can be treated by a doctor through stopping or decreasing the dosage of the medication but can become severe and life threatening if left untreated.

If stopping the antidepressant treatment, this could result in withdrawal symptoms such as nausea, dizziness, tremors, and feeling depressed. It is therefore important to not stop taking the antidepressant without doctor’s advice.

Antidepressants will usually stop through a gradual reduction in the dosage, so the body adjusts to lower doses and it is not a shock when stopped completely.

Related Article

Long-Term Use of Antidepressants

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About the Author

Olivia Guy-Evans obtained her undergraduate degree in Educational Psychology at Edge Hill University in 2015. She then received her master’s degree in Psychology of Education from the University of Bristol in 2019. Olivia has been working as a support worker for adults with learning disabilities in Bristol for the last four years.

How to reference this article:

Guy-Evans, O. (2021, June 16). The 5 major classes of antidepressants. Simply Psychology.

APA Style References

Fookes, C. (2018, May 30). Tricyclic antidepressants. Drugs.

Institute for Quality and Efficiency in Health Care. (2015). Depression: How effective are antidepressants.

Krans, B. (2018, September 29). What Are MAO Inhibitors. Healthline.

Mayo Clinic (2019, September 17). Selective serotonin reuptake inhibitors (SSRIs).

Schimelpfening, N. (2020, November 15). The 5 Major Classes of Antidepressants. Very Well Mind.

Sheffler, Z. M., & Abdijadid, S. (2020). Antidepressants. StatPearls [Internet].

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