Antidepressant Side Effects Vary Widely by Drug, Large Study Finds

• A large new study found that the side effects of antidepressants vary significantly by drug.
• Some medications resulted in weight loss, while others resulted in weight gain.
• Heart rate and blood pressure also differed notably among medications.
• Those experiencing persistent, severe, or concerning side effects should speak with a healthcare professional.

New research has found that antidepressant side effects may be more varied than previously thought.

The large-scale study, published on October 21 in The Lancet, examined the impact of antidepressant medications on more than 58,000 participants within the first eight weeks of starting treatment.

The researchers analyzed 151 studies of 30 drugs commonly used to treat depression. While not everyone develops side effects, some of the most common noted in the research were changes in weight, blood pressure, and metabolic markers.

There were striking differences between antidepressant medications. For example, an eight-week course of agomelatine was associated with an average weight loss of around 2.4 kilograms (about 5.3 pounds), while maprotiline users gained nearly 2 kg in the same timeframe.

There were also notable changes in heart function: fluvoxamine tended to slow heart rate, whereas nortriptyline increased it, creating a gap of about 21 beats per minute between the two drugs. Blood pressure varied too, with an 11 mmHg difference seen between nortriptyline and doxepin.

Here’s what you need to know about the different types of antidepressants and their side effects.

Sharon Batista, MD, assistant clinical professor of psychiatry at Mount Sinai Hospital, said the study’s findings aren’t new or surprising to psychiatrists.

“We’ve long known that different antidepressants vary in their effects on weight, blood pressure, and other metabolic measures,” Batista, who wasn’t involved in the study, told Healthline.

“However, what is notable about this study is the rigorous, comparative quantification of these differences across a wide range of physiological parameters using data from over 58,000 participants,” she said.

Batista explained that the study provides robust evidence of the magnitude of side effects, some of which are more common than others. Common antidepressant side effects may include:

• gastrointestinal symptoms (nausea, diarrhea, constipation)
• sexual dysfunction (decreased libido, anorgasmia)
• weight changes (gain or loss, depending on the agent)
• sleep disturbances (insomnia or sedation)
• dry mouth, sweating, headache

Meanwhile, less common but clinically significant side effects may include:

• increases in blood pressure or heart rate (notably with SNRIs and some tricyclics)
• hyponatremia (especially in older adults, with SSRIs and SNRIs)
• liver enzyme elevations
• QTc prolongation (risk of arrhythmia, especially with citalopram and some tricyclics)
• emotional blunting or apathy

“One thing to note here is that there are multiple different classes of antidepressants, which contribute to the different adverse medication side effects,” Whitley Lassen, PsyD, MBA, clinical psychologist and head of operations at Willow Behavioral Health, told Healthline. Lassen wasn’t involved in the study.

“Additionally, antidepressant medications can affect each person differently, and adverse side effects can vary depending on the specific drug, dosage, and individual factors like metabolism or co-occurring conditions.”

While some side effects, such as changes in sleep, appetite, or energy levels, are fairly common and often improve over time, Lassen said others may be less typical or more persistent.

Antidepressant side effects may range in severity, which could warrant a change in your medication.

“A change in antidepressant may be warranted if the patient experiences persistent or intolerable side effects that do not improve with time or supportive measures,” Batista said.

“Additionally, if there is an emergence of new medical issues that may be exacerbated by the current medication, for example, hypertension, arrhythmia, or significant weight gain.”

You may also consider talking with your doctor about any lack of meaningful improvement in depressive or anxiety symptoms after an adequate trial period. Batista said an adequate trial period is typically 4–8 weeks at a therapeutic dose.

Patient preference is also important. Batista said that some people may want to avoid certain side effects, such as sexual dysfunction or weight gain.

Sometimes there will be red flag side effects that suggest changing medication is necessary. These may include:

• new or worsening suicidal thoughts, especially in the first weeks of treatment or after dose changes
• signs of serotonin syndrome (confusion, agitation, fever, muscle rigidity)
• significant, unexplained weight gain or loss
• marked increases in blood pressure or heart rate
• severe allergic reactions (rash, swelling, difficulty breathing)
• jaundice or dark urine (possible liver injury)
• hyponatremia symptoms (confusion, seizures, severe headache)

In some cases, you should reach out to your healthcare provider straight away.

“Thoughts of wishing you were dead, feeling like you don’t want to be here, thinking about harming yourself or others, or experiencing serious suicidal thoughts are major warning signs that require immediate attention,” Lassen warned.

Side effects are an expected outcome of taking any kind of medication. If you’re experiencing side effects from your antidepressants that are disruptive, there are some strategies that can help make them more manageable.

Batista said adjusting the timing of your doses may be helpful. “Taking sedating antidepressants at night or activating ones in the morning can help manage sleep-related side effects,” she said.

Supporting your physical health can also be beneficial. Batista advised regularly monitoring your weight, blood pressure, and metabolic parameters, and adhering to a balanced diet and regular exercise to mitigate weight gain and metabolic changes.

Hydration, nutrition, and good sleep hygiene are also key. “Ensuring adequate fluid intake and a diet rich in fiber can help with constipation and other gastrointestinal side effects,” Batista said.

“Meanwhile, establishing a consistent sleep routine and minimizing caffeine or screen time before bed can help with insomnia.”

If you’re experiencing psychological side effects, collaborative care may be the most effective tool in your mental health toolbox.

Batista recommended working with a therapist or counselor to address emotional blunting, apathy, or other psychological side effects, and to support adherence and coping strategies.

Ultimately, antidepressant side effects vary greatly, but if you’re experiencing anything severe, persistent, or worrying, it should be discussed with your healthcare team right away.

The decision to switch antidepressants is an important one that should be made in collaboration with your doctor.

“Together, you can weigh the potential benefits of treatment against possible side effects to determine what approach best supports your mental health recovery,” Lassen said.

“When choosing a medication, health care professionals typically consider several key factors, including the specific mental health symptoms being treated, any co-occurring medical conditions, family history of medication response, medication interactions, and the side effect profiles of different options,” she continued.

These elements help guide a more tailored and effective treatment plan.

Lassen said that your voice as the patient matters, too.

“While your healthcare professional who prescribes medications, such as a psychiatrist or psychiatric nurse practitioner, brings medical expertise to the process, your voice and preferences are equally important,” she said.

“Sharing your goals, past experiences with medications, and concerns about side effects helps ensure the decision is truly collaborative, leading to a treatment plan that feels both safe and empowering for you.”