Millions of people around the world take antidepressants to help manage depression, anxiety, and other mental health conditions.
These medicines can make a major difference in people’s lives by improving mood, reducing anxiety, and helping them return to normal daily activities.
However, many people worry about side effects before starting treatment. In some cases, people stop taking their medication not because it is ineffective, but because the unwanted effects are difficult to tolerate.
Antidepressants have been used for decades, and scientists have developed several different types. The most commonly prescribed medicines today include selective serotonin reuptake inhibitors, often called SSRIs, serotonin-norepinephrine reuptake inhibitors, known as SNRIs, and several newer antidepressants that work in different ways.
Older medicines such as tricyclic antidepressants and monoamine oxidase inhibitors are still available, but they are used less often because they can cause more side effects and require additional precautions.
Each antidepressant affects chemicals in the brain that help regulate mood, emotions, sleep, and motivation. Because these medicines work differently, they can also produce different side effects.
Common side effects may include nausea, headaches, sleep problems, tiredness, dry mouth, weight changes, or sexual difficulties. The type and severity of these effects can vary greatly from one person to another.
One of the largest and most influential studies comparing antidepressants was published in The Lancet in 2018. In this major review, researchers examined information from more than 500 clinical trials involving over 100,000 participants.
The goal was to compare how well different antidepressants worked and how likely people were to continue taking them. Researchers used treatment dropout rates as one measure of tolerability because people who experience severe side effects are often more likely to stop their medication.
The study found that several antidepressants stood out for their balance of effectiveness and tolerability. Among the medicines that people were generally more likely to continue taking were escitalopram, sold under the brand name Lexapro, sertraline, known as Zoloft, and agomelatine.
Escitalopram and sertraline belong to the SSRI group. These medicines increase the amount of serotonin available in the brain, which can help improve mood and reduce symptoms of depression and anxiety.
They are often chosen as first-line treatments because they usually cause fewer side effects than many older antidepressants. Some people may experience nausea, headaches, stomach upset, or changes in sleep when they first begin treatment. However, these effects are often mild and may improve after a few weeks as the body adjusts.
Another reason these medicines are widely prescribed is that they are generally less likely to cause severe tiredness or significant weight gain compared with some older antidepressants.
Even so, some people may experience sexual side effects, including reduced sexual desire or difficulty reaching orgasm. For certain individuals, this can become an important factor when deciding whether to continue treatment.
Agomelatine works differently from SSRIs. Instead of mainly targeting serotonin, it affects melatonin and norepinephrine systems in the brain. Melatonin plays an important role in regulating the body’s internal clock and sleep patterns. Because of this, many people who take agomelatine report improvements in sleep quality.
Unlike some antidepressants, it is less likely to cause weight gain or sexual side effects. However, doctors may recommend regular liver function tests while a person is taking this medicine because it can affect liver health in some cases. Availability also varies between countries.
Another antidepressant that is often considered well tolerated is bupropion, commonly known by the brand name Wellbutrin. This medicine works mainly through dopamine and norepinephrine, two brain chemicals involved in motivation, energy, and concentration.
Bupropion is often used when people do not respond well to SSRIs or when they want to avoid sexual side effects. Some people find that it improves energy levels and focus. It is also used to help people stop smoking. However, it may increase anxiety or cause sleep difficulties in some individuals, especially at higher doses.
In contrast, older antidepressants such as amitriptyline and other tricyclic medicines are generally associated with more side effects. People taking these drugs may experience dizziness, dry mouth, constipation, weight gain, or drowsiness.
Monoamine oxidase inhibitors can also interact with certain foods and medications, making them more difficult to use safely. As a result, these older treatments are usually reserved for situations where newer medicines have not been successful.
Although research can identify medicines that are generally easier for most people to tolerate, no antidepressant works perfectly for everyone.
Factors such as age, overall health, genetics, other medications, and personal sensitivity can all influence how a person responds. A medicine that works extremely well for one person may cause troublesome side effects in another.
Doctors often recommend starting with a low dose and increasing it gradually when needed. This approach can help reduce side effects and allow the body time to adapt. Regular communication with a healthcare professional is also important because treatment can be adjusted if problems occur.
Overall, current evidence suggests that escitalopram, sertraline, agomelatine, and bupropion are among the antidepressants that many people find easiest to tolerate. Research published in The Lancet supports their reputation for having relatively manageable side effects and higher treatment continuation rates.
However, finding the right antidepressant remains a highly personal process. The most suitable medication is the one that provides meaningful improvement while causing the fewest unwanted effects for the individual taking it.
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