What conditions does SSRIs make worse?: Understanding the Risks and Adverse Effects

October 10, 2025 •

3 min read

While selective serotonin reuptake inhibitors (SSRIs) are generally well-tolerated and effective for treating conditions like depression and anxiety, approximately 80% of patients will experience at least one side effect. Some of these side effects can mimic or worsen existing conditions, highlighting the importance of understanding what conditions does SSRIs make worse and under what circumstances this can happen.

Quick Summary

SSRIs can exacerbate certain conditions, notably triggering mania or hypomania in undiagnosed bipolar disorder, and worsening anxiety or agitation during initial treatment. Rare but serious risks include serotonin syndrome, heightened suicidal ideation in young adults, increased bleeding risk, and complications with pre-existing heart or seizure conditions. These effects highlight the need for careful patient screening and monitoring.

Key Points

Bipolar Disorder Diagnosis: Unidentified bipolar disorder is a major risk, as SSRIs can trigger a manic or hypomanic episode.
Initial Anxiety and Agitation: Anxiety can temporarily worsen during the first few weeks.
Suicidal Ideation in Youth: Young adults under 25 have a heightened risk, warranting close observation.
Serotonin Syndrome: Combining SSRIs with other serotonin-affecting drugs can lead to this condition.
Increased Bleeding Risk: SSRIs can impair blood clotting, especially when used with NSAIDs.
Cardiac Concerns: Individuals with heart conditions must be carefully monitored, especially with medications like citalopram.
Early OCD Treatment: For pediatric OCD patients, the initial activating side effects can hinder treatment.

SSRIs function by increasing serotonin levels in the brain, but this action is not confined to one area and can have broader physiological and psychological impacts. For individuals with specific underlying health issues, this can lead to a worsening of symptoms rather than an improvement. A comprehensive understanding of these risks is crucial for both patients and healthcare providers to ensure safe and effective treatment.

Bipolar Disorder and Mood Switches

One of the most significant risks associated with SSRI use is the potential to induce a manic or hypomanic episode in individuals with undiagnosed bipolar disorder. SSRIs can trigger a manic switch in those with underlying bipolar disorder. Even with a mood stabilizer, mood destabilization, including mixed features, is possible. Mixed states are more severe and increase suicide risk. Subtle mood changes can occur, necessitating careful screening for bipolar symptoms before prescribing antidepressants.

Worsening of Anxiety and Agitation

SSRIs can initially increase anxiety and agitation, especially during the first couple of weeks of treatment. This is thought to be an "activating" effect as the body adjusts. Patients with high pre-existing anxiety may experience a worsening of depressive symptoms. It is important to inform a doctor about increased nervousness or jitteriness.

Increased Suicidal Ideation in Young Adults

A black box warning on antidepressants, including SSRIs, highlights the risk of suicidal thoughts and behaviors in pediatric and young adult patients up to age 25. This risk is highest early in treatment or after dose changes. The risk must be weighed against the danger of untreated depression, a known suicide risk factor. Close monitoring is vital for this population during initial treatment.

The Danger of Serotonin Syndrome

Serotonin syndrome is a rare but life-threatening condition caused by excessive serotonin. It often occurs when SSRIs are combined with other serotonin-affecting substances, including:

Other antidepressants (e.g., SNRIs, MAOIs)
St. John's Wort
Certain pain or headache medications

Symptoms can include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, sweating, and muscle rigidity. Suspected serotonin syndrome requires immediate medical attention.

Other Physical Conditions Worsened by SSRIs

Seizure Disorders

While modern SSRIs pose a lower seizure risk than older antidepressants, they can still reduce the seizure threshold. Individuals with a history of epilepsy or other risk factors need close monitoring. Some SSRIs have been associated with seizures in vulnerable patients.

Bleeding Risk

SSRIs can impact platelet function, increasing the risk of bleeding. This risk is higher with concurrent use of medications that also increase bleeding, such as NSAIDs. Patients should report any unusual bruising or bleeding.

Cardiac Abnormalities

Some SSRIs, notably citalopram and escitalopram, can prolong the QT interval on an ECG. This can increase the risk of dangerous heart rhythms in individuals with pre-existing heart conditions. Lower maximum doses and ECG monitoring may be needed for at-risk patients.

Hyponatremia

SSRIs can cause low sodium levels (hyponatremia), particularly in older adults. This can be due to SIADH. Symptoms range from headache and confusion to seizures. At-risk patients require regular monitoring.

Gastrointestinal Issues

Initial GI side effects like nausea, diarrhea, and constipation are common. These are often temporary but can be bothersome. Specific SSRIs are linked to certain GI issues.

What to Discuss with Your Doctor

Open communication with a healthcare provider is crucial. Discuss any family history of bipolar disorder, epilepsy, or other medical conditions.


Risk Factor	Conditions Impacted	Important Consideration
Underlying Bipolar Disorder	Bipolar I or II Depression	Risk of triggering a manic or hypomanic switch. Should ideally be co-prescribed with a mood stabilizer.
Early Treatment Phase	Anxiety, Agitation	Initial worsening of anxiety or restlessness can occur.
Age Under 25	Depression, Suicidal Ideation	FDA black box warning for increased risk of suicidal thoughts/behaviors; requires close monitoring.
Co-administration with Other Drugs	Serotonin Syndrome	Combining SSRIs with other serotonergic drugs can lead to this dangerous condition. Always disclose all medications.
Specific Health Conditions	Epilepsy, Heart Disease, Kidney Disease	Can lower seizure threshold; risk of QT prolongation; risk of hyponatremia.
Drug Interactions (NSAIDs)	Bleeding Risk	Increased risk of bleeding, especially with concurrent use of blood-thinning agents.

Conclusion

SSRIs are valuable but carry risks. Conditions that SSRIs can make worse include triggering mania in undiagnosed bipolar disorder and causing initial anxiety or GI issues. Careful patient evaluation and open communication are key to mitigating risks. A personalized risk-benefit analysis is essential for safe and effective SSRI use.

Important Resources

{Link: National Institutes of Health https://pmc.ncbi.nlm.nih.gov/articles/PMC8395812/}

Frequently Asked Questions

Yes, if a person has an undiagnosed bipolar disorder, an SSRI can trigger a manic or hypomanic episode. Screening for bipolar symptoms and family history is crucial.

During the first one to two weeks, SSRIs can cause an 'activating' effect that temporarily increases anxiety. This often subsides, but report these symptoms to your doctor.

Serotonin syndrome is a rare but serious condition. Symptoms can include agitation, confusion, rapid heart rate, high fever, sweating, and muscle rigidity. It typically occurs from a drug interaction and requires immediate medical help.

There is a black box warning for an increased risk in young adults (under 25) when starting or changing the dose of an SSRI. Close monitoring is essential.

Some SSRIs, particularly citalopram, can cause a prolonged QT interval, which is a heart rhythm abnormality. This is a risk for individuals with existing cardiac conditions.

Yes, SSRIs can interfere with platelet function, increasing the risk of bleeding. This risk is higher if you also take NSAIDs or other blood thinners.

Older adults have a higher risk of developing hyponatremia (low sodium levels) from SSRI use. Symptoms include confusion, weakness, and fatigue.