By Naomi Carr

Last updated: 19 March 2024 & medically reviewed by Dr. David Miles

Selective serotonin reuptake inhibitors (SSRIs) are a commonly prescribed class of antidepressant medication. They have a list of possible side effects but are generally considered a safe and effective medication. If SSRI therapy does not produce the desired results, alternative medications and treatments are also available.

Selective Serotonin Reuptake Inhibitors (SSRIs)

What are selective serotonin reuptake inhibitors (SSRIs)?

Selective serotonin reuptake inhibitors (SSRIs) are a type of antidepressant medication. SSRIs are often the first-line treatment for depression, as they are less likely to cause side effects compared to other antidepressants and are generally effective. There are many different SSRIs, and their effectiveness can vary from person to person, depending on the individual condition, symptoms, and dosage. [1]

Each SSRI medication works slightly differently, although they all share a common mechanism of action in the brain. Because of their differences and range of effects, SSRIs can be effective treatments for many physical and mental health conditions. [2]

Most commonly, SSRIs are used to treat major depressive disorder (MDD) and generalized anxiety disorder (GAD), although they can also be used for other FDA-approved and off-label purposes, including in the treatment of: [1][2]

How do SSRIs work?

SSRIs impact the level and activity of serotonin. Serotonin is a neurotransmitter that is involved in the regulation of several functions, including mood, sleep, and appetite. Serotonin is believed to be significantly involved in the development of several mental health conditions, particularly depressive disorders, due to its impact on mood regulation. [3]

SSRIs block the reuptake of serotonin in the brain, thereby creating an increased level of serotonin activity. This is believed to help improve mood and reduce many of the symptoms associated with depression and various other conditions. [2]

List of SSRIs

SSRIs are available in generic and brand-name medications, as tablets, capsules, and liquid solutions. Commonly prescribed SSRIs and their most widely used brand names include: [4]

Possible side effects of SSRIs

Generally, all SSRIs share the same list of side effects. It is common for a new or increased dosage of medication to cause mild side effects that will usually last only a few weeks before being alleviated. However, if side effects persist or become problematic, it is recommended to consult with a doctor as a change of medication or dosage may be required. [1]

Common side effects of SSRI medications include: [1][2][5][6]

  • Nausea

  • Vomiting

  • Constipation

  • Diarrhea

  • Stomach pain

  • Insomnia

  • Agitation

  • Anxiety

  • Restlessness

  • Dizziness

  • Blurred vision

  • Shaking

  • Loss of appetite

  • Weight loss

  • Dry mouth

  • Sweating

  • Headaches

  • Sexual dysfunction

  • Loss of libido

In some cases, severe side effects can occur. The following side effects should be reported to a medical professional as they may require treatment: [1]

  • Hallucinations

  • Extreme changes in mood and behavior

  • Persistent vomiting or diarrhea

  • Urinary retention

  • Severe muscle stiffness or shaking

  • Confusion

  • Unexplained bruising or bleeding

Are SSRIs addictive?

SSRIs are not considered addictive substances. They do not cause euphoric effects and are unlikely to lead to harmful behaviors associated with addiction or drug abuse. However, after taking SSRIs for a prolonged period, some people may experience withdrawal symptoms, also known as discontinuation syndrome, when stopping the medication. [5][6]

Symptoms can include:

  • Insomnia

  • Nausea

  • Low mood

  • Agitation

  • Irritability

  • Unusual sensations, such as ‘electric shocks’ or ‘brain zaps’

  • Headache

  • Fatigue

  • Dizziness

It is advised when stopping an SSRI to gradually taper off the medication to prevent these effects. The prescribing doctor will typically advise on this and monitor for any adverse effects. [7]

Risks associated with SSRIs

Serotonin syndrome

Serotonin syndrome is a rare condition that occurs when the levels of serotonin in the brain become too high. This can occur with SSRIs alone, although it is more likely if SSRIs are used in combination with another serotonergic medication, such as other antidepressants. [8]

Symptoms of serotonin syndrome can include: [1][8]

  • Sweating

  • Shaking 

  • Fever

  • Very high temperature

  • Diarrhea

  • Twitching

  • Confusion 

  • Agitation

  • Irregular heartbeat

  • Seizure

  • Loss of consciousness

If any of these symptoms occur while taking an SSRI, consult with a doctor immediately.

Mania

People with a history of bipolar disorder or manic symptoms may not be able to safely take SSRIs, as they can cause the onset of a manic episode. If SSRIs are used to treat bipolar depression, close monitoring of mood and behavior changes is recommended, and it may be advised only to use SSRIs as an adjunctive treatment. [6]

Health issues

People with a history of glaucoma or heart, lung, or kidney problems may not be able to safely take SSRIs, as the medication may cause or worsen these conditions. If it is necessary to take an SSRI, a doctor will closely monitor symptoms to ensure safety and may prescribe a reduced dosage. [5][6]

Pregnancy and breastfeeding

It is important to discuss with a doctor about taking an SSRI during pregnancy or breastfeeding. Some evidence suggests that there may be a risk to the fetus, particularly during the first trimester, if SSRIs are taken during pregnancy. [1][7]

However, there may be increased risks to the fetus if the mother’s depression is untreated. As such, it is important to discuss the options with a doctor, to make an informed decision and consider if the benefits of treatment outweigh the risks. [7]

Generally, it is safe to take SSRIs while breastfeeding but it may be necessary to monitor the infant for any unusual changes in mental or physical well-being. [1]

Driving

SSRIs might cause drowsiness and dizziness, particularly at the beginning of treatment. As such, it may not be safe to drive or operate heavy machinery until the effects of the medication are known. [6]

Hyponatremia

Some people taking SSRIs, particularly older adults, might be at risk of experiencing a severe drop in sodium levels. This can be dangerous and require treatment. Symptoms include nausea, headaches, confusion, reduced appetite, extreme fatigue, disorientation, psychosis, or seizures. If these symptoms occur, contact a doctor immediately. [6]

Bleeding events

SSRIs might increase the risk of bleeding events, particularly if used alongside blood thinning medications. [5][6]

SSRIs and suicidal ideation

In some cases, the use of SSRIs can cause an increase in suicidal thoughts, particularly at the beginning of treatment. This risk is found to be higher in individuals under the age of 24. People taking these medications, and their family members, should be aware of these risks and monitor for any concerning changes in mood and behavior, and new or worsening thoughts of self-harm or suicide. [1][5]

SSRI contraindications

Some medications can increase the risk of side effects or reduce the effects of the medications if used alongside an SSRI. This includes anticonvulsants, blood thinners, amphetamines, NSAIDs, opioids, diuretics, lithium, migraine medications, tranquilizers and sedatives, other antidepressants, and other mental health medications. [5][6]

MAOIs should not be used alongside an SSRI due to the risk of serotonin syndrome. There should be at least two weeks between doses when changing between these medications. [5]

Always discuss medications with the prescribing doctor before starting a new treatment. 

Alcohol should be avoided or limited while using SSRIs, as it can increase drowsiness and may worsen symptoms of depression.[9]

Alternatives to SSRIs

Antidepressant medications, such as SSRIs, can take several weeks or months to have a full effect, so should be taken consistently to be sure of their effectiveness. Often, if one type of SSRI is not effective, another SSRI will be commenced. [1]

However, if SSRIs are not an appropriate or effective treatment, other antidepressants might be prescribed. This can include: [9]

  • Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and venlafaxine

  • Atypical antidepressants, such as mirtazapine, trazodone, or bupropion

  • Tricyclic antidepressants (TCAs), such as amitriptyline and imipramine

  • Monoamine oxidase inhibitors (MAOIs), such as selegiline and phenelzine (MAOIs are rarely prescribed due to increased risks)

Treatment-resistant depression, a condition that does not respond to typical antidepressant treatment, may require alternative approaches. Treatments that may be effective in these cases can include: [9][10]

  • Ketamine: Esketamine is a nasal spray ketamine enantomer available under the brand name Spravato, that can be used in depression treatment that has not responded to other medications.

  • Psychoactive substances: Psilocybin and MDMA have been shown to be effective for treatment-resistant depression and PTSD. These treatments may be available in some states.

Depression and other mental health conditions are often best treated with a combination of medication and psychotherapy. Evidence-based psychological approaches to depression treatment include: [11]

Other interventions that may be useful include relaxation exercises, holistic approaches, nutritional counseling, and physical exercise. [11]