Atypical antidepressants refer to a diverse group of medications used to treat depression, anxiety, and other mood disorders. They are "atypical" because they do not fit neatly into the established classes of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). Atypical antidepressants have a variety of mechanisms of action, and their development spans several decades. Here's a concise history and overview of atypical antidepressants, along with some resources to dive deeper into the topic.

1. Early Development of Antidepressants (1950s-1960s):

The history of antidepressants began in the 1950s with the discovery of the first generation of antidepressants, monoamine oxidase inhibitors (MAOIs) , responsive state was first introduced by West and Dally in 1959 and tricyclic antidepressants (TCAs). These were the mainstays of treatment for depression until the 1980s, but they had significant side effects, such as sedation, dry mouth, and orthostatic hypotension.

• MAOIs (e.g., phenelzine, tranylcypromine) inhibit the breakdown of neurotransmitters like serotonin, norepinephrine, and dopamine.

• TCAs (e.g., amitriptyline, imipramine) also work by blocking the reuptake of serotonin and norepinephrine, but they often have a broader range of side effects, including anticholinergic effects (e.g., dry mouth, blurred vision).

2. The Emergence of Atypical Antidepressants (1970s-1990s):

Atypical antidepressants began to emerge in the 1970s and 1980s as researchers sought medications with fewer side effects than the older drugs like TCAs and MAOIs. The goal was to develop drugs that were effective in treating depression but with a more favorable side effect profile. .

Like other mental health medications, they work by restoring the balance of the chemicals in your brain (neurotransmitters). Each medication works on different chemicals and affects them differently

Atypical antidepressants are not typical — they don't fit into other classes of antidepressants. They are each unique medications that work in different ways from one another Like most antidepressants, Atypical antidepressants ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, atypical antidepressants work by ultimately effecting changes in brain chemistry and communication in brain nerve cell circuitry known to regulate mood, to help relieve depression.

Atypical antidepressants change the levels of one or more neurotransmitters, such as dopamine, serotonin or norepinephrine.

🔹 Common Atypical Antidepressants & Their Indications:

1. Bupropion (Wellbutrin, Zyban)

• • Major depressive disorder (MDD)

  • Seasonal affective disorder (SAD)

  • Smoking cessation (as Zyban)

• Bonus: Less risk of sexual side effects, often stimulating (can help with fatigue or hypersomnia)

2. Mirtazapine (Remeron)

• • MDD (especially in patients with insomnia or poor appetite)

• Bonus: Strong sedative effect (good for sleep issues), increases appetite (often used in elderly or underweight patients)

3. Trazodone

• • MDD (rarely used at full antidepressant doses due to sedation)

  • Insomnia (common off-label use at low doses)

• Bonus: Very sedating — often prescribed as a sleep aid

4. Vilazodone (Viibryd)

• • MDD

• Bonus: May cause fewer sexual side effects than SSR

5. Vortioxetine (Trintellix)

• • MDD

• Bonus: May improve cognitive symptoms of depression, generally well-tolerated

🧠 Antidepressants can also be used to help treat other mental health conditions, including:

• anxiety disorder.

• obsessive compulsive disorder (OCD)

• panic disorder.

• serious phobias, such as agoraphobia and social anxiety (social phobia)

• bulimia.

• post-traumatic stress disorder (PTSD)

Bupropion (brand names: Wellbutrin, Zyban)

Many antidepressants can decrease a person’s sex drive and lead to drowsiness and weight gain. Bupropion is unlikely to do any of these things—in fact, it is often prescribed alongside another antidepressant to counteract these side effects .

However, bupropion can have its own side effects. Common ones include:

Dry mouth

• Dry mouth

• Trouble sleeping

• Headache and nausea

• Weight loss

More rarely:

• Restlessness or anxiety

• Constipation

• Congestion

• Dizziness and fatigue

Trazodone

Trazodone is an antidepressant, but it is commonly prescribed for sleep problems, such as trouble sleeping or nightmares due to PTSD.

Common side effects include:

• Headaches and fatigue

• Drowsiness and sleepiness

• Dry mouth

• Dizziness or fainting

• Rarely, hallucinations or irregular heartbeat

Some of these side effects go away after the first week or so of taking trazodone.

Mirtazapine (brand name: Remeron)

Mirtazapine is unlikely to have any negative sexual side effects. Possible side effects include:

• Increased appetite and weight gain (this may be a positive thing, if you are already underweight or have an eating disorder)

• Dry mouth

• Sleepiness and fatigue

Vortioxetine (brand names: Trintellix, Brintellix)

Common side effects include nausea, constipation, and vomiting. More serious side effects are rare, but may include:

• Serotonin syndrome

• Increased bleeding or bruising when injured

• Hypomania

• Changes in vision, or swelling or pain near the eyes

• Low sodium levels

SHOW

contraindications:

should not be taken by:

• Pregnant and breastfeeding women.

• People with a seizure disorder.

• People with liver or kidney problems.

• People with heart problems.

• People on certain medications, such as other antidepressants.

• Children.

• Alcohol. 

• Illegal drugs. 

• St John's wort

preacautions:

Atypical antidepressants are safe for most people. However, in some circumstances they can cause problems. For example: Bupropion should not be used by people who have a seizure disorder or an eating disorder such as bulimia or anorexia.

https://screening.mhanational.org/content/atypical-antidepressants/

https://www.psychiatrist.com/pcc/history-concept-atypical-depression/#:~:text=The%20term%20atypical%20depression%20as,for%20the%20next%2030%20years.

https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/antidepressants/uses/

https://addictionresource.com/drugs/antidepressants/side-effects/

https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/antidepressants/uses/

https://www.mayoclinic.org/diseases-conditions/depression/in-depth/atypical-antidepressants/art-20048208#:~:text=Atypical%20antidepressants%20approved%20by%20the%20FDA&text=Bupropion%20(Wellbutrin%20SR%2C%20Wellbutrin%20XL,Trazodone