Antidepressants are a cornerstone of treatment for major depressive disorder and other conditions like anxiety disorders, chronic pain, and obsessive-compulsive disorder (OCD) [1.9.5]. They function by altering the levels of brain chemicals called neurotransmitters, which are involved in regulating mood [1.3.2]. The different classes of antidepressants target these neurotransmitters in unique ways, leading to varied effectiveness and side effect profiles. The choice of medication is a personalized decision made between a patient and their healthcare provider, taking into account symptoms, potential side effects, and other health conditions [1.2.5].
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are the most widely prescribed class of antidepressants, often serving as the first-line treatment for depression [1.2.2, 1.2.5]. They are popular because they generally cause fewer side effects than older medications [1.2.5].
How They Work
SSRIs work by blocking the reabsorption, or reuptake, of the neurotransmitter serotonin in the brain. This action leaves more serotonin available in the synaptic space between neurons, enhancing neurotransmission and improving mood [1.3.2, 1.3.3].
Examples of SSRIs
- Fluoxetine (Prozac) [1.2.1, 1.2.5]
- Sertraline (Zoloft) [1.2.1, 1.2.5]
- Citalopram (Celexa) [1.2.1, 1.2.5]
- Escitalopram (Lexapro) [1.2.1, 1.2.5]
- Paroxetine (Paxil, Pexeva) [1.2.1, 1.2.5]
Common Side Effects
Common side effects include nausea, headache, insomnia or drowsiness, and sexual dysfunction, such as low libido or difficulty achieving orgasm [1.4.2, 1.4.3]. SSRIs are more likely to cause sexual side effects compared to some other classes [1.4.6].
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
SNRIs are similar to SSRIs but have a broader mechanism of action. They are effective for depression and are also used to treat anxiety disorders and chronic nerve pain [1.4.4].
How They Work
SNRIs increase the levels of two neurotransmitters: serotonin and norepinephrine. They achieve this by inhibiting the reuptake of both chemicals in the brain, which helps regulate mood and alertness [1.3.1, 1.3.2].
Examples of SNRIs
- Venlafaxine (Effexor XR) [1.2.2, 1.2.5]
- Duloxetine (Cymbalta) [1.2.2, 1.2.5]
- Desvenlafaxine (Pristiq) [1.2.5]
Common Side Effects
Side effects are similar to SSRIs and can include nausea, dry mouth, dizziness, and excessive sweating [1.4.4, 1.4.5]. SNRIs can also lead to an increase in blood pressure [1.4.4].
Tricyclic Antidepressants (TCAs)
TCAs are an older class of antidepressants, developed in the 1950s [1.4.4]. Due to a higher incidence of side effects, they are generally not prescribed as a first-line treatment but may be used when newer medications are ineffective [1.2.5, 1.4.4].
How They Work
Like SNRIs, TCAs block the reuptake of serotonin and norepinephrine. However, they are less selective and also affect other receptors in the brain, which contributes to their broader range of side effects [1.3.2, 1.3.5].
Examples of TCAs
- Amitriptyline [1.2.1, 1.2.5]
- Nortriptyline (Pamelor) [1.2.1, 1.2.5]
- Imipramine [1.2.1, 1.2.5]
- Doxepin [1.2.1, 1.2.5]
Common Side Effects
TCAs tend to cause more side effects, including dry mouth, blurred vision, constipation, drowsiness, weight gain, and difficulty urinating [1.4.3, 1.4.6]. An overdose of TCAs can be more dangerous than with newer antidepressants [1.4.4].
Monoamine Oxidase Inhibitors (MAOIs)
MAOIs are another older class of antidepressants. They are highly effective but are used less frequently today due to the risk of serious side effects and the need for strict dietary restrictions [1.2.5, 1.4.4]. They are typically prescribed only when other treatments have failed [1.2.5].
How They Work
MAOIs work by inhibiting monoamine oxidase, an enzyme that breaks down neurotransmitters like serotonin, norepinephrine, and dopamine. This leads to higher levels of these chemicals in the brain, which can stabilize mood [1.3.2, 1.4.5].
Examples of MAOIs
- Phenelzine (Nardil) [1.2.1, 1.2.5]
- Tranylcypromine (Parnate) [1.2.1, 1.2.5]
- Isocarboxazid (Marplan) [1.2.1, 1.2.5]
- Selegiline (Emsam), which is available as a skin patch and may have fewer side effects [1.2.5].
Critical Safety Information
Using an MAOI requires a strict diet to avoid foods high in tyramine, such as aged cheeses, cured meats, and certain wines [1.2.5]. Consuming tyramine while on an MAOI can cause dangerously high blood pressure, increasing the risk of a stroke [1.4.4]. They also have significant interactions with other medications, including SSRIs [1.2.5].
Atypical Antidepressants
This is a broad category for medications that don't fit into the other classes. Each has a unique mechanism of action and may be chosen to target specific symptoms or avoid certain side effects [1.2.2, 1.2.5].
Examples of Atypical Antidepressants
- Bupropion (Wellbutrin): Works primarily on norepinephrine and dopamine [1.3.6, 1.5.1]. It is one of the few antidepressants not frequently associated with sexual side effects and is also used to help people quit smoking [1.2.5, 1.4.6].
- Mirtazapine (Remeron): Enhances serotonin and norepinephrine neurotransmission [1.5.2]. It is often prescribed for people experiencing insomnia or loss of appetite due to its sedative effects and tendency to increase appetite [1.2.2, 1.4.6].
- Trazodone: Acts as a serotonin antagonist and reuptake inhibitor (SARI) [1.5.3]. It is commonly used off-label at lower doses to treat insomnia due to its sedative properties [1.2.2, 1.5.4].
Comparison of Antidepressant Classes
| Class | Mechanism of Action | Common Examples | Key Distinguishing Feature | Typical Side Effects |
|---|---|---|---|---|
| SSRIs | Selectively blocks serotonin reuptake [1.3.2] | Fluoxetine, Sertraline, Citalopram [1.2.3] | Most common first-line treatment with fewer side effects than older drugs [1.2.5] | Nausea, insomnia, sexual dysfunction [1.4.3] |
| SNRIs | Blocks reuptake of serotonin and norepinephrine [1.3.2] | Venlafaxine, Duloxetine [1.2.3] | Also effective for nerve pain; can increase blood pressure [1.4.4] | Dry mouth, dizziness, sweating, constipation [1.4.5] |
| TCAs | Blocks reuptake of serotonin and norepinephrine (less selective) [1.3.5] | Amitriptyline, Nortriptyline [1.2.3] | Older class with more side effects; overdose is more dangerous [1.2.5, 1.4.4] | Dry mouth, blurred vision, constipation, weight gain [1.4.6] |
| MAOIs | Inhibits the monoamine oxidase enzyme, increasing serotonin, norepinephrine, and dopamine [1.4.5] | Phenelzine, Tranylcypromine [1.2.1] | Requires strict dietary restrictions to avoid a hypertensive crisis [1.2.5] | Dizziness, insomnia, low blood pressure, muscle aches [1.4.4] |
| Atypicals | Various unique mechanisms [1.5.1] | Bupropion, Mirtazapine, Trazodone [1.2.5] | Bupropion has low risk of sexual side effects; Mirtazapine is sedating and increases appetite [1.2.5, 1.4.6] | Varies by drug; Bupropion may cause insomnia/anxiety, Mirtazapine causes drowsiness/weight gain [1.4.6] |
Conclusion
Multiple classes of antidepressants are available, each with a distinct mechanism of action, efficacy profile, and set of potential side effects. The most commonly prescribed are SSRIs and SNRIs due to their better tolerability [1.2.5]. Older medications like TCAs and MAOIs are reserved for cases where newer drugs are not effective, often due to their increased side effect burden and safety concerns [1.2.5]. Atypical antidepressants provide alternative options that can be tailored to an individual's specific symptoms and needs. The selection and management of an antidepressant is a critical medical decision that should always be guided by a qualified healthcare professional who can weigh the benefits and risks for each individual.
For more detailed information, consult authoritative sources such as the National Institute of Mental Health (NIMH).
