SSRI Side Effects: Serotonin Syndrome and Discontinuation

SSRI side effects appear in almost every psychiatry and pharmacology exam. Selective serotonin reuptake inhibitors are first-line for depression and anxiety disorders, and most patients tolerate them well. Questions usually test the dangerous effects, the interactions and what to do when a patient stops the drug.

Common side effects

• Nausea, diarrhea and other gastrointestinal upset, often early and temporary
• Sexual dysfunction, including reduced libido and delayed orgasm
• Headache, insomnia or drowsiness
• Initial anxiety or jitteriness in the first weeks
• Weight changes with long-term use

Patients should know that benefits usually take two to four weeks to appear.

Important adverse effects

Hyponatremia: SSRIs can cause the syndrome of inappropriate antidiuretic hormone secretion, especially in older adults.

Bleeding risk: SSRIs affect platelet function, and the risk rises with non-steroidal anti-inflammatory drugs and anticoagulants.

QT prolongation: citalopram and escitalopram are associated with dose-related QT effects.

Suicidality: monitor young adults closely when treatment starts or doses change.

Serotonin syndrome

This is a toxic state caused by excess serotonergic activity. It is typically triggered by combining serotonergic agents, such as an SSRI with a monoamine oxidase inhibitor, linezolid, tramadol, triptans or certain herbal products. Features include agitation, tremor, clonus, hyperreflexia, sweating, diarrhea, fever and autonomic instability. Treatment involves stopping the offending drugs, supportive care, cooling and benzodiazepines. Cyproheptadine can be used in selected cases.

Discontinuation syndrome

Abrupt cessation can cause dizziness, nausea, flu-like symptoms, sensory disturbances and irritability. It is more common with short half-life drugs such as paroxetine. Fluoxetine has a long half-life and a lower risk. Taper gradually.

Interactions and pregnancy

Fluoxetine and paroxetine inhibit CYP2D6 and can raise the levels of other drugs. Paroxetine is generally avoided in early pregnancy because of concerns about malformations, and late pregnancy exposure can cause neonatal adaptation symptoms.

A classic exam pattern

A patient on an SSRI is given tramadol after surgery and develops agitation, tremor, hyperreflexia and fever. The diagnosis is serotonin syndrome, and the first step is to stop the offending drugs and provide supportive care.

Study tips

• Memorize the combinations that cause serotonin syndrome
• Compare serotonin syndrome with neuroleptic malignant syndrome
• Review each wrong answer for the missing clue

This article is for exam revision and does not replace current clinical guidelines. Practice psychiatry cases in the Namazj free trial.