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

SSRIs are called selective because they mainly affect serotonin rather than any other neurotransmitter. These antidepressants do not cause more serotonin to be produced in the brain but instead help the brain to use the serotonin in a more effective way.

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

SSRIs work by blocking the reuptake of serotonin into the presynaptic neuron. Because of this, more serotonin will be circulating through 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 they also have proven to be effective in the treatment of other anxiety disorders such as obsessive-compulsive disorder, posttraumatic stress disorder, and panic disorder.

There are several types of SSRIs, which 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 because most people are more tolerant of them than other antidepressants, and they typically have fewer side effects.

It is important to note that side effects vary and depend on the individual.

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.

Therefore it is always useful to seek professional support from a doctor or psychiatrist to discuss these potential reactions further.

Serotonin syndrome is a condition that can occur if there is too much serotonin present in the brain. This could result from the beginning of taking 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.

Usually, once they have gotten used to the medication, the risk of suicide is typically reduced, and feelings of depression should begin to decrease. However, this is not the case for everyone since people react to medication in different ways.

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

Monoamine oxidase inhibitors (MAOIs) were developed in the 1950s and were one of the earliest classifications of antidepressants.

MAOIs work by affecting the neurotransmitters in the brain. Depression is believed to be caused by low levels of the neurotransmitters dopamine, serotonin, and norepinephrine.

Together, these neurotransmitters are called monoamines. Monoamines are naturally found in the body.

Monoamine oxidase is an enzyme that removes these neurotransmitters, meaning there are fewer of these monoamines circulating around the brain.

Thus, the antidepressant MAOIs inhibit the monoamine oxidase, meaning that more neurotransmitters can circulate in the brain, which helps to elevate mood through improved brain cell communication.

MAOIs are primarily used for depression but also help relieve other conditions associated with depression or anxiety, such as agoraphobia, social phobia, and posttraumatic stress disorder.

These days, this class of antidepressants is not typically used as the first option for people with depression as they are particularly strong and can have severe side effects mentioned previously.

There are dietary restrictions that must be followed if taking MAOIs, as these can cause reactions to food that 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.

Tricyclic antidepressants (TCAs) are known as a first 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 works 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 mostly used to help treat depression, but can also affect 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 fewer side effects.

Like MAOIs, TCAs are also very strong and are not often used as a first treatment due to their 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 affect the heart and thyroid, if someone has existing heart or thyroid problems, they would probably not be prescribed this antidepressant.

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

This medication works similarly 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 that 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 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 of 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 with high blood pressure levels.

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

These are atypical since they do not function like 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, 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