Antidepressants

An antidepressant is the name given to a medicine that can help relieve the symptoms of depression, such as low mood, anxiety, and worthlessness.

Antidepressants are classified into different types depending on their structure and the way that they work. There are at least seven types of antidepressant:

• Monoamine oxidase inhibitors (MAOIs)
• Norepinephrine and dopamine reuptake inhibitors (NDRIs)
• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin and norepinephrine reuptake inhibitors (SNRIs)
• Serotonin antagonist and reuptake inhibitors (SARIs)
• Tricyclic antidepressants (TCAs) and tetracyclic antidepressants (TeCAs)
• And miscellaneous antidepressants.

MAOIs and TCAs were among the first antidepressants developed. They have largely been superseded by newer antidepressants (such as the SSRIs) that have fewer side effects, although these older antidepressants may still suit certain people or be effective when other antidepressants have been ineffective.

Experts are not sure exactly how antidepressants work, but historically they were thought to work by increasing levels of certain neurotransmitters, such as dopamine, serotonin, and/or norepinephrine, in the brain. This does not appear to be the way they work for depression, although, they are still effective at treating depression.

What are antidepressants used for?

Antidepressants help to relieve the symptoms of depression such as low mood, irritability, feelings of worthlessness, restlessness, anxiety, and difficulty in sleeping.

In addition to depression, certain antidepressants may also be used to treat a range of other conditions, for example:

• Anxiety
• Bed-wetting
• Bulimia nervosa
• Chronic nerve-related pain
• Fibromyalgia
• Hot flashes
• Migraine prevention
• Obsessive-compulsive disorder
• Panic disorder
• Post-Traumatic Stress Disorder (PTSD)
• Premenstrual dysphoric disorder.

It is important to note that not all antidepressants are used to treat the conditions mentioned above.

Antidepressants generally provide some relief of symptoms within one to two weeks; however, it may take six to eight weeks of treatment before the full effects are seen.

What are the differences between antidepressants?

There are distinct differences between the different classes of antidepressants available because they all work in a different way. In addition, within each class, there are differences between individual antidepressants with regards to how long they remain in the body, how they are metabolized, and how much they interact with other medications.

Monoamine oxidase inhibitors (MAOIs)

MAOIs block the effects of monoamine oxidase enzymes, and increases levels of dopamine, norepinephrine, and serotonin in the brain.

Norepinephrine and dopamine reuptake inhibitors (NDRIs)

NDRIs block the reuptake of norepinephrine and dopamine, increasing levels of norepinephrine and dopamine in the nerve synapse.

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs increase levels of serotonin in the brain by preventing the reuptake of serotonin by nerves.

Serotonin and norepinephrine reuptake inhibitors (SNRIs)

SNRIs block the reuptake of both serotonin and norepinephrine, increasing levels of serotonin and norepinephrine in the nerve synapse.

Serotonin antagonist and reuptake inhibitors (SARIs)

SARIs prevent the reuptake of serotonin and affects the binding of serotonin to certain receptors.

Tricyclic antidepressants (TCA) and tetracyclic antidepressants (TeCAs)

TCAs and TeCAs work by increasing levels of norepinephrine and serotonin. They may also block the actions of other neurotransmitters, such as acetylcholine and histamine.

Tricyclics

Tetracyclics

Miscellaneous antidepressants

Increase levels of neurotransmitters by an unknown mechanism of action that is different from other pre-existing classes of antidepressant.

Are antidepressants safe?

When taken at the recommended dosage, antidepressants are considered safe. However, some have been associated with severe side effects, some potentially fatal, such as:

• An increase in suicidal thoughts and behaviors, particularly in children and young adults under the age of 25 years. This is most likely to occur when starting therapy
• An increased risk of seizures in people with a history of seizures
• Serotonin syndrome – this is caused by excessive levels of serotonin in the body and is more likely to occur with higher dosages of SSRIs or when SSRIs are administered with other medications that also release serotonin. Symptoms include agitation, confusion, sweating, tremors, and a rapid heart rate
• The precipitation of a manic episode in people with undiagnosed bipolar disorder
• Duloxetine: A severe discontinuation syndrome
• MAOIs: Very severe drug interactions, very severe food interactions, and rarely, rapid but transient increases in blood pressure within 30 minutes to two hours of MAOI ingestion
• Nefazodone: Life-threatening liver failure, more common two weeks to six months after starting therapy
• SSRIs and vortioxetine: An increase in the risk of bleeding, especially if used with other medications that also increase bleeding risk
• TCAs: An increased risk of arrhythmias, heart attacks, stroke, and other cardiovascular effects, particularly in people with pre-existing heart disease; and the triggering of an angle closure attack in people with angle-closure glaucoma.

For a complete list of severe side effects, please refer to the individual drug monographs.

What are the common side effects of antidepressants?

Not everybody experiences significant side effects with antidepressants, and some antidepressants are more likely to cause side effects than others. Some of the more commonly reported side effects include:

• Blurred vision
• Disorientation or confusion
• Dizziness
• Drowsiness, sometimes insomnia
• Dry mouth
• Excessive sweating
• Gastrointestinal upset (such as constipation, diarrhea, or nausea)
• A headache
• Increased or irregular heartbeat
• Low blood pressure when going from a standing to a sitting position (called orthostatic hypotension). In most people, this can be managed by slowly increasing the dosage of the medication, giving split doses, and increasing fluid intake
• Sexual dysfunction (such as reduced desire or erectile dysfunction)
• Tremor
• Urinary retention
• Weight loss or weight gain.

Some antidepressants have been associated with a discontinuation syndrome when they have been stopped suddenly. For this reason, it is best to withdraw all antidepressants slowly.

For a complete list of side effects, please refer to the individual drug monographs.