The 5 Types of Antidepressants

Different types of antidepressants may be used to treat mental health conditions. There are five major types of antidepressants and several others that are less commonly used. The major types are:

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

While some may be considered preferred options, the drug selection can vary based on your symptoms, treatment history, and co-existing psychological disorders. Keep reading to learn about each type of antidepressant, including how they work, their benefits and uses, and their potential side effects and risks.

How Antidepressants Work

There are three basic molecules, known chemically as monoamines, believed to be involved in mood regulation. These primarily serve as neurotransmitters, which transmit nerve signals to their corresponding receptors in the brain.

Antidepressants work by influencing neurotransmitters such as:

• Dopamine: Plays a central role in decision-making, motivation, arousal, and the signaling of pleasure and reward
• Norepinephrine: Influences alertness and motor function, and helps regulate blood pressure and heart rate in response to stress
• Serotonin: Regulates mood, appetite, sleep, memory, social behavior, and sexual desire

In people with depression, the availability of these neurotransmitters in the brain is characteristically low. Antidepressants increase the availability of one or several of these neurotransmitters in different, distinctive ways.

How Antidepressants are Categorized

As the name implies, an antidepressant is a drug primarily used to treat depression. Depression is a common disorder that affects brain chemistry and function. Antidepressants can help correct the dysfunction by altering the circuits and chemicals that pass signals along nerve routes to the brain.

Antidepressants are grouped into classes based on how they affect the chemistry of the brain. While the antidepressants in a class will tend to have similar side effects and mechanisms of action, there are differences in their molecular structures, which can influence how well the drug is absorbed, disseminated, or tolerated in different people.

Selective Serotonin Reuptake Inhibitors (SSRIs)

There are a number of antidepressants that work by preventing the reabsorption (reuptake) of neurotransmitters into the body. Collectively known as reuptake inhibitors, they prevent the reuptake of one or more neurotransmitters so more are available and active in the brain.

Selective serotonin reuptake inhibitors (SSRIs) work by specifically inhibiting the reuptake of serotonin. SSRIs are a newer class of antidepressants first developed during the 1970s. Examples include:

• Celexa (citalopram)
• Lexapro (escitalopram)
• Luvox (fluvoxamine)
• Paxil (paroxetine)
• Prozac (fluoxetine)
• Viibryd (vilazodone)
• Zoloft (sertraline)

In addition to treating depression, SSRIs are also sometimes used to treat anxiety disorders, eating disorders, autism spectrum disorders, and premenstrual dysmorphic disorder. They have also proved helpful during stroke recovery.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Serotonin and norepinephrine reuptake inhibitors (SNRIs) work in a similar way to SSRIs except that they inhibit the reuptake of both norepinephrine and serotonin. The first SNRI was FDA-approved in December of 1993.

Increasing norepinephrine levels in tandem with serotonin levels can be particularly useful for people with psychomotor retardation (the slowing of physical movement and thought). Examples of SNRIs include:

• Cymbalta (duloxetine)
• Effexor (venlafaxine)
• Fetzima (levomilnacipran)
• Pristiq (desvenlafaxine)
• Savella (milnacipran)

Some SNRIs, like Cymbalta, can also be used to treat chronic pain, a condition closely linked to the development of depression. They have also proven useful in treating generalized anxiety, post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), panic disorder, and nerve pain associated with fibromyalgia.

Tricyclic Antidepressants (TCAs)

Tricyclic antidepressants (TCAs) are an older class of drugs first designed in the 1950s. They were named after their chemical structure, which is composed of three interconnected rings of atoms.

TCAs work similarly to reuptake inhibitors in that they block the absorption of serotonin and norepinephrine into nerve cells, as well as another neurotransmitter known as acetylcholine (which helps regulate the movement of skeletal muscles). Examples of TCAs include:

• Anafranil (clomipramine)
• Asendin (amoxapine)
• Elavil (amitriptyline)
• Norpramin (desipramine)
• Pamelor (nortriptyline)
• Sinequan (doxepin)
• Surmontil (trimipramine)
• Tofranil (imipramine)
• Vivactil (protriptyline)

Ludiomil (maprotiline) belongs to the same class of drugs. However, it is more appropriately described as a tetracyclic antidepressant (TeCA) due to its fourth atomic ring.

In addition to their use in depression, tricyclic antidepressants can help treat chronic pain. They were also once commonly used in children with attention deficit hyperactivity disorder (ADHD) but have since been replaced with more effective drug agents with fewer side effects.

Monoamine Oxidase Inhibitors (MAOIs)

One of the first types of antidepressants developed was monoamine oxidase inhibitors (MAOIs). This antidepressant class, first discovered in the 1950s, inhibits the action of an enzyme called monoamine oxidase, whose role is to break down monoamines. By blocking this effect, more neurotransmitters are available for mood regulation.

Examples of MAOIs include:

• Emsam (selegiline)
• Marplan (isocarboxazid)
• Nardil (phenelzine)
• Parnate (tranylcypromine)

Despite the risks, MAOIs have proven useful in treating agoraphobia, social phobia, bulimia, PTSD, borderline personality disorder, and bipolar depression. Even so, its use is usually reserved for when other antidepressant options have failed.

Atypical Antidepressants

There are also other fairly new types of antidepressants that do not fit into any of the above-listed categories. Broadly described as atypical antidepressants, they affect serotonin, norepinephrine, and dopamine levels in unique ways.  

Examples include:

• Oleptro (trazodone) and Brintellix (vortioxetine): Serotonin antagonist and reuptake inhibitors (SARIs) used for major depression that both inhibits serotonin reuptake and block adrenergic receptors
• Remeron (mirtazapine): A noradrenergic antagonist used for major depression, that blocks receptors of the stress hormone epinephrine (adrenaline) on the brain
• Symbax: Combines the SSRI fluoxetine with the antipsychotic drug olanzapine to treat bipolar depression or treatment-resistant depression
• Wellbutrin (bupropion): Classified as a dopamine reuptake inhibitor, used to treat depression and seasonal affective disorder as well as a smoking cessation aid

Antidepressant Effectiveness

Antidepressants are effective in treating depression, although individual responses may vary. One 2018 review of 21 different types of antidepressants found that all of these medications were more effective at treating depression than placebo. However, a 2020 meta-analysis concluded that for many people, the treatment effects of antidepressants were relatively small.

So which type of antidepressant is the most effective? According to the 2018 review, the five most effective antidepressants that people were least likely to stop taking were:

• Lexapro (escitalopram)
• Paxil (paroxetine)
• Zoloft (sertraline)
• Valdoxan/Thymanax (agomelatine)
• Remeron (mirtazapine)

In general, SSRIs are the most commonly prescribed, primarily because they are effective, well-tolerated, and produce relatively few side effects. Wellbutrin and SNRIs also typically have fewer side effects and good efficacy.

All types of antidepressants take a few weeks to begin working. For many people, this means it may take up to eight weeks to feel the full effects of an antidepressant medication.

Choosing the Right Antidepressant

There are several factors that go into choosing the right antidepressant. Chief among them is tolerability. Because many different types of antidepressants are equally effective in treating depression, a greater emphasis is placed on prescribing the drugs with the fewest short- and long-term side effects.

This is especially true with nausea and weight gain. Both of these effects can impact a person's quality of life and lead to the premature discontinuation of treatment.

Antidepressants are most effective when used in conjunction with psychotherapy, self-help strategies, social support, and the treatment of co-existing conditions (such as chronic pain, anxiety, bipolar disorder, and personality disorders).

Natural Antidepressants

In addition to the different types of prescription antidepressants, some people opt to try natural antidepressant options. Options include herbs and supplements that may have a beneficial effect on mood, such as St. John's wort. Some people may find that alternative therapies such as brain stimulation therapy and acupuncture can be helpful.

Even natural options can have side effects, may come with risks, and can interact with other medications you are taking. Always talk to your healthcare provider before trying a natural antidepressant.

Lifestyle modifications can also play an important role in depression treatment and augment medication and therapy. Exercise, nutrition, social support, and spending time in nature are just a few things you can do to feel better.

Antidepressant Risks and Considerations

Antidepressants are sometimes used in combination with other drugs to treat a variety of conditions. In some cases, the combined use of drugs that both exert serotonergic action can lead to serotonin syndrome. This is the toxic accumulation of serotonin that can trigger a cascade of potentially dangerous physical and psychiatric symptoms.

Antidepressants should only be used as prescribed and may take up to eight weeks before the benefits are fully felt. It is important never to stop, interrupt, decrease, or increase doses without first speaking with your physician.

Stopping abruptly can lead to disruptive and often debilitating withdrawal symptoms, including nausea, vomiting, tremors, nightmares, dizziness, depression, and electrical shock sensations. This can be avoided by gradually tapering the dose, preferably under the direction of a medical professional.

Antidepressants should be used with extreme caution in children, teens, and younger adults. In 2007, the FDA issued a black box warning about the increased risk of suicidal thoughts and actions in people under 24 on antidepressants of any type.

Antidepressants should only be used in children, teens, and younger adults when absolutely needed and only after weighing the potential benefits of treatment against the potential risks.