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Medically Approved

SSRI medications with the least side effects

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Fewer side effectsMost severe side effectsCommon side effectsSide effect durationAlternative drugsSummary
Selective serotonin reuptake inhibitor (SSRI) medications typically do not lead to severe side effects, although these may be possible. Zoloft, Lexapro, and Celexa may have fewer and milder side effects compared to other SSRIs, although they may lead to insomnia, sexual dysfunction, and bleeding in some people.
Medically reviewed by Ifeanyi Olele, DO, MBA, MS
Written by Rashida Ruwa, RN
Updated on

SSRIs are antidepressant medications that work by reducing the reabsorption of serotonin in the brain, which in turn increases its levels. This may help improve mood and relieve anxiety, among other health benefits.

SSRIs have several uses, both on and off label. On-label uses are those the Food and Drug Administration (FDA) approved, while off-label uses include those the medication may be effective for but have not received FDA approval yet.

The primary on-label uses of SSRIs include:

  • depressive disorders
  • generalized anxiety disorder (GAD)
  • obsessive-compulsive disorder (OCD)
  • social anxiety disorder

While off-label uses of SSRIs may include conditions like:

  • binge eating disorder
  • fibromyalgia
  • body dysphoric disorder

SSRIs may cause side effects including:

  • nausea
  • insomnia
  • diarrhea
  • reduced sexual drive
  • weight changes
  • dry mouth
  • headaches

The severity and frequency of these side effects may vary. Some people taking SSRIs may not experience any side effects, while others may have some occasionally.

What is the most well-tolerated SSRI?

Feet of a person experiencing dizziness as side effects of SSRIs
Chelsea Victoria/Stocksy United

How well a person tolerates a medication depends on many factors, including individual sensitivity and overall health. SSRI medications are no exception. Every person’s body may respond differently to these antidepressants.

In general, SSRIs are first-line treatments because they typically lead to fewer side effects and complications compared to other medications for depression and anxiety. Within the SSRI group, some medications may have fewer reports when it comes to specific side effects.

For example, sertraline (Zoloft) is often considered one of the safer options among SSRIs for use during pregnancy and nursing. It may also be the first option, together with fluoxetine (Prozac), for sexually active individuals because it has fewer reported cases of side effects related to sexual dysfunction.

On the other hand, Zoloft generally seems to have more reports of gastrointestinal side effects and a higher risk of bleeding, compared to other SSRIs.

Citalopram (Celexa) and escitalopram (Lexapro) seem to be well tolerated when it comes to gastrointestinal side effects like nausea and diarrhea but may be more likely to cause or worsen insomnia and headaches.

In sum, it’s difficult to assert that all individuals tolerate one SSRI better than the rest. Consider talking with your healthcare professional to explore which medication may be better suited for your health needs. If you don’t tolerate one SSRI, they can adjust your dose or switch you to a new medication.

If you need help covering the cost of depression medications, the free Optum Perks Discount Card could help you save up to 80% on prescription drugs. Follow the links on drug names for savings on that medication, or search for a specific drug here.

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Which SSRIs have the most severe side effects?

As stated before, every person’s body will respond differently to medications. Severe side effects are rare when using SSRIs, but they’re still possible.

Paroxetine (Paxil) reportedly leads to unintended weight gain, persistent sexual dysfunction, increased risk of suicidal thoughts, and withdrawal symptoms in some people. Everyone may not experience these or any other side effects with this drug.

Fluoxetine (Prozac) may lead to agitation and anxiety in some people, although this isn’t observed in all individuals. 

Fluvoxamine (Luvox) is less commonly prescribed than some other SSRIs. It has been linked to gastrointestinal disturbances and an increased risk of bleeding events when combined with other medications, such as anti-coagulants like warfarin.

Some studies have linked citalopram (Celexa) with a higher risk of QT interval prolongation, a heart rhythm disorder that can be serious in some cases, especially when taken at high doses.

A healthcare professional will conduct a careful assessment of your symptoms, medical history, lifestyle, and potential risks and benefits of the medication when determining the SSRI that’s right for you.

Common side effects of SSRIs

The most common side effects reported during SSRI therapy include

  • insomnia
  • nausea
  • diarrhea 
  • weight gain
  • headache
  • sexual dysfunction 
  • dizziness

The intensity and frequency of these side effects may vary, and if present, they tend to decrease with prolonged use.

How long do SSRI side effects last?

Most common SSRI side effects, like nausea or insomnia, typically last for a few hours to a few weeks after your first few doses. Usually, your body adjusts to the medication, and you may experience fewer and milder effects over time.

However, side effects related to sexual function may persist for the duration of treatment. Weight gain may be slow and gradual over several months, but it can be managed with increased physical activity and a nutrient-dense diet that includes foods like fruits and vegetables. 

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Alternatives to SSRIs

If you are experiencing side effects with your antidepressant, a healthcare professional may prescribe another SSRI or prescribe a medication belonging to an entirely different class of medications.

Alternatives to SSRIs include:

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs): SNRIs work on both serotonin and norepinephrine hormones, providing an alternative for managing symptoms of anxiety and depression.
  • Atypical antidepressants: These drugs have different mechanisms of action from SSRIs, making them options for those whose bodies do not respond well to SSRIs.
  • Tricyclic antidepressants (TCAs): TCAs affect different neurotransmitters and might be considered when other options prove ineffective or are not tolerated well.
  • Monoamine oxidase inhibitors (MAOIs): These drugs are often reserved for use when other treatments have not worked because they have dietary and medication restrictions.

In addition to medications, non-pharmacological approaches may also be effective in managing anxiety and depression. These strategies may include:

  • Cognitive behavioral therapy (CBT): CBT is a widely recognized psychotherapy that may help you identify and manage negative thought patterns and behaviors. It is often used alongside or instead of medication.
  • Transcranial magnetic stimulation (TMS): It’s FDA-approved to manage depression, OCD, and anxiety. TMS stimulates brain cells via repetitive electrical impulses, which seems to relieve symptoms.
  • Exercise: Some studies have shown that regular exercise may improve mood and reduce symptoms of depression. 
  • Mindfulness-based approaches: Techniques like yoga may help manage stress, increase self-awareness, and enhance emotional well-being.
  • Lifestyle changes: A nutrient-dense diet, 7–9 hours of daily sleep, and social support are important for managing anxiety and depression. These lifestyle modifications can complement medical treatments.

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Summary

SSRIs are often the first-line pharmaceutical treatment for depression and anxiety because severe side effects are rare.

However, every person’s body responds differently to SSRIs. You may experience side effects with a medication that other people may not and vice versa.

Therefore, it’s important to consider speaking with a healthcare professional to help determine the most suitable treatment that balances effectiveness and tolerability. 

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