Antidepressant medications are believed to work by modulating the levels of serotonin, norepinephrine, or dopamine in the brain. It is common for a client to take more than one antidepressant medication at a time, particularly those who are experiencing severe, chronic, or atypical depressive symptoms.

There are five main classes of antidepressant medications (Barnhart, 2021):

• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin and norepinephrine reuptake inhibitors (SNRIs)
• Tricyclics
• Monoamine oxidase inhibitors (MAOIs)
• Atypical antidepressants

Conditions Treated

Antidepressant medications, particularly SSRIs, are commonly used for treating depression in primary care settings. However, they can also be used to treat several different mental and physical health conditions. Side effects, major symptoms, and past responses to antidepressants are used to guide the choice of medication.

Mental health conditions treated by antidepressants may include (Thompson, 2016):

• Major depressive disorder
• Anxiety disorder
• Obsessive-compulsive disorder
• Panic disorder
• Phobias
• Post-traumatic stress disorder

Antidepressants are also used off-label for several physical conditions. Chronic pain and nerve pain, including fibromyalgia, can be treated with SNRI antidepressants. Further, insomnia, premenstrual syndrome, and specific urinary and sexual problems may be treated with antidepressants.

FDA Warning and Antidepressants

In 2004, the FDA issued a requirement that all antidepressant prescriptions be labeled with a ‘Black Box’ warning that the medication may increase suicidal ideation for children and adolescents.

That warning was extended to include young adults in 2007 and remains in place. Carefully monitor the person’s symptoms when they are first starting antidepressant medications for signs of worsening symptoms, increased agitation or irritability, or other indicators of suicidality. This is especially important when working with adolescents and young adults.

SSRIs and SNRIs

SSRIs and SNRIs are the two most common types of antidepressants prescribed. This is due to the effectiveness of these medications and due to fewer side effects associated with these drugs (Westphalen, 2020). They are also commonly used to treat anxiety.

Side effects with SSRIs and SNRIs tend to be transient and well tolerated by most clients prescribed these medications. Common side effects may include nausea, headache, dry mouth, insomnia, sexual problems, and restlessness.

SSRIs

SSRIs are the most prescribed type of antidepressant, so you are likely to find that many clients are taking these medications. These medications primarily impact one neurotransmitter, serotonin, and thus are called selective serotonin reuptake inhibitors (SSRIs). These include (Hoffman, 2021):

• Fluoxetine (Prozac^®)
• Sertraline (Zoloft^®)
• Fluvoxamine (Luvox^®)
• Paroxetine (Paxil^®)
• Citalopram (Celexa^®)
• Escitalopram (Lexapro^®)

Serotonin syndrome

Serotonin syndrome is a potentially life-threatening condition. It is associated with medications that enhance serotonin functioning (e.g., SSRIs). Also called serotonin toxicity, this condition can affect the heart negatively and lead to a high fever, requiring immediate medical intervention (Boyer et al., 2022).

SNRIs

Another category of antidepressant that works by increasing both norepinephrine and serotonin in the brain are SNRIs. These medications include:

• Venlafaxine (Effexor^®)
• Desvenlafaxine (Pristiq^®)
• Levomilnacipran (Fetzima^®)
• Duloxetine (Cymbalta^®)

Less Commonly Prescribed Antidepressants

Monoamine oxidase inhibitors, tricyclics, and atypical antidepressants are other classes of medications used to treat depression. Besides perhaps the atypical antidepressants bupropion and mirtazapine, these classes are not as commonly prescribed as SSRIs or SNRIs for the treatment of depressive symptoms.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs are known to influence serotonin, norepinephrine, and dopamine functioning. MAOIs are effective for treatment-resistant depression, panic disorder, and depression associated with bipolar disorder.

Due to their side effect profile and dietary restrictions, MAOIs are now prescribed infrequently. In most instances, MAOIs are only considered when other medications have not been beneficial (i.e., treatment-resistant depression; Laban & Saadabadi, 2021).

Examples of MAOIs include:

• Phenelzine (Nardil^®)
• Tranylcypromine (Parnate^®)
• Isocarboxazid (Marplan^®)

MAOIs: Food Restrictions

Foods containing tyramine must be avoided when prescribed an MAOI. Foods, including aged cheeses and cured, smoked, or processed meats, can result in life-threatening consequences.

The MAOIs block an enzyme that breaks down excess tyramine in the body. This can lead to a sharp increase in blood pressure and an increased risk of stroke (Halverson, 2020). 

Tricyclic Antidepressants

Before the development of newer medications such as SSRIs and SNRIs, tricyclic antidepressants were the first line of treatment for major depressive disorder. These medications act on multiple neurotransmitters, including norepinephrine and serotonin.

Tricyclics are used less commonly today due to their potential for side effects. Their side effects can also be dangerous, such as the risk of fatality if the medication is taken in an overdose.

Therefore, prescribers are more likely to consider tricyclics as a second or third-line treatment. In addition to treating depression, they can help prevent migraine headaches or other types of pain, as well as treat obsessive-compulsive disorder (Moraczewski & Aedma, 2021).

Examples of tricyclics include:

•  Imipramine (Tofranil^®)
• Amitriptyline (Elavil^®)
• Nortriptyline (Pamelor^®)

Atypical Antidepressants

Certain atypical antidepressants have specific uses in helping improve sleep, attention, cognitive symptoms, suicidality, or poor appetite, among other symptoms related to depression.

Common atypical antidepressants include (Hirsch & Birnbaum, 2022):

• Mirtazapine (Remeron^®)
• Trazodone (Desyrel^®)
• Bupropion (Wellbutrin^®)
• Esketamine (Spravato^®)
• Brexanolone (Zulresso^®)

Atypical antidepressants may be combined with other antidepressants to treat individuals with treatment-resistant major depressive disorder. They may also be used when other medications have produced intolerable side effects. Some of these medications offer advantages not found with other antidepressants.

Esketamine

One unique atypical antidepressant is the psychedelic esketamine. Esketamine is a derivative of ketamine, and ketamine has been used as a recreational drug and as an anesthesia medication.

The drug is known to affect glutamate receptors and to facilitate connectivity between major neural networks in the brain. In clinical settings, the medication is administered via nasal spray and under the direct supervision of a trained mental health professional (Brooks, 2022).

Even in low doses, the drug has been associated with psychedelic effects (e.g., hallucinations, altered thinking). Studies indicate that esketamine provides a rapid (i.e., within hours) and long-lasting (e.g., 6 months or longer) reduction in depressive symptoms and suicidal ideation.

Presently, the medication is increasing in availability. However, ongoing research is still being conducted to better understand the implications of this medication for the treatment of depression and other mental health disorders (Canuso et al., 2018; Food and Drug Administration, 2019; Optum Perks, 2021).

Brexanolone

Post-partum depression is thought to have a distinct pathophysiology to major depression. Brexanolone is the first drug to be expressly indicated to treat post-partum depression.

This drug is a derivative of a naturally occurring steroid and targets the effects of neurosteroids on the brain. Like esketamine, the medication has been shown to have positive effects on depressive symptoms within hours after administration. At present, the medication can only be administered in a hospital setting and requires an IV infusion (Azhar & Din, 2021; Sutherby, 2021).