What are the side effects of Sertraline (Selective Serotonin Reuptake Inhibitor)

Sertraline Side Effects

Sertraline is generally well tolerated, but common side effects include gastrointestinal disturbances (nausea, diarrhea), sexual dysfunction, and sleep changes, while serious risks requiring monitoring include suicidal ideation in patients ≤24 years, serotonin syndrome, bleeding events, and discontinuation syndrome. 1, 2

Common Side Effects

Gastrointestinal Effects

• Nausea, diarrhea/loose stools, dry mouth, heartburn, and constipation are the most frequently reported gastrointestinal adverse events with sertraline use 1, 3
• Sertraline has a notably higher rate of diarrhea compared to other SSRIs including bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, and venlafaxine 1
• These gastrointestinal effects are typically mild and transient, decreasing in frequency with continued treatment 4

Sexual Dysfunction

• Sexual side effects occur commonly and include ejaculatory delay in males, erectile dysfunction, and anorgasmia 3
• Male sexual dysfunction, particularly ejaculatory disturbance, is one of the most characteristic adverse effects of sertraline 4, 5
• Sertraline has higher rates of sexual dysfunction than bupropion but comparable rates to other SSRIs 1

Neuropsychiatric Effects

• Headache, dizziness, insomnia, somnolence, and vivid dreams are common neuropsychiatric side effects 1, 6
• Tremor or shaking may occur during treatment 2
• Feeling tired or fatigued is frequently reported 2

Autonomic Effects

• Increased sweating and diaphoresis are frequently reported autonomic adverse events 3, 6

Weight Changes

• Most patients experience minimal weight changes (1-2 pound loss on average) 2
• Weight loss or gain is possible with long-term use, though significant weight loss requiring discontinuation is rare 3, 2

Serious Side Effects Requiring Monitoring

Suicidal Ideation and Behavior

• All SSRIs including sertraline carry an FDA boxed warning for increased suicidal thinking and behavior in patients aged 24 years or younger 3
• The rate of suicidal ideation/behavior is 1% with antidepressants versus 0.2% with placebo (risk difference 0.7%, number needed to harm = 143) 3
• Close monitoring is essential, particularly during treatment initiation and dose changes 1

Serotonin Syndrome

• Serotonin syndrome is a potentially life-threatening condition characterized by mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis, vomiting, diarrhea) 1
• Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness that can lead to death 1
• Risk is highest when combining sertraline with MAOIs (contraindicated), other serotonergic drugs (SSRIs, SNRIs, TCAs, tramadol, meperidine, methadone, fentanyl, amphetamines, dextromethorphan), or supplements (St. John's wort, L-tryptophan) 1, 2
• Symptoms typically arise within 24-48 hours after combining medications 1

Bleeding Events

• SSRIs including sertraline increase the risk of bleeding events ranging from ecchymoses and epistaxis to life-threatening hemorrhage 1, 2
• Risk is particularly elevated with concomitant use of aspirin, NSAIDs, warfarin, or other anticoagulants 1, 2
• Rare bleeding events include ecchymosis, hematoma, epistaxis, petechiae, and hemorrhage 1

Behavioral Activation/Agitation

• Motor or mental restlessness, insomnia, impulsiveness, disinhibited behavior, and aggression may occur, especially in younger children and those with anxiety disorders 3
• Initial adverse effects can include anxiety or agitation, making it advisable to start with a subtherapeutic "test" dose 1

Mania/Hypomania

• Mania or hypomania occurred in approximately 0.4% of sertraline-treated patients during premarketing trials 2
• This typically appears later in treatment and may persist after discontinuation 3

Seizures

• Four patients out of approximately 1,800 exposed during OCD development trials experienced seizures (0.2% incidence) 2
• Three were adolescents, two with pre-existing seizure disorders 2
• Sertraline should be introduced with care in patients with seizure disorders 2

Other Rare Serious Events

• QT prolongation and cardiac arrhythmias (including Torsade de Pointes) have been reported 2
• Hepatotoxicity with elevated liver enzymes, increased bilirubin, hepatitis, jaundice, and rare cases of liver failure 2
• Hyponatremia, particularly in elderly patients 2
• Severe skin reactions including Stevens-Johnson syndrome 2

Discontinuation Syndrome

Sertraline is associated with discontinuation syndrome, characterized by dizziness, fatigue, lethargy, myalgias, chills, headaches, nausea, vomiting, diarrhea, insomnia, vertigo, sensory disturbances, paresthesias, anxiety, irritability, and agitation 1

• This occurs following missed doses or abrupt discontinuation of sertraline (a shorter-acting SSRI) 1
• Gradual dose tapering is recommended when stopping sertraline to minimize withdrawal symptoms 3, 2
• If intolerable symptoms occur after dose reduction, resume the previous dose and taper more gradually 2

Drug Interactions

Contraindicated Combinations

• Concomitant use with MAOIs is absolutely contraindicated due to serotonin syndrome risk 1, 2

Significant Interactions

• Sertraline may interact with drugs metabolized by CYP2D6 (including propafenone, flecainide, digitoxin) 1
• Interactions possible with drugs that prolong QT interval 1
• Warfarin and other anticoagulants require careful monitoring due to bleeding risk 2

Relative Advantage

• Sertraline has comparatively low potential for drug interactions at the cytochrome P450 enzyme system compared to other SSRIs, particularly fluvoxamine 1, 7, 6

Special Populations

Children and Adolescents

• Additional side effects include abnormal increase in muscle movement, agitation, nose bleeds, urinary frequency, urinary incontinence, aggressive reactions, heavy menstrual periods, and possible slowed growth rate requiring height/weight monitoring 2

Elderly Patients

• No dosage adjustments are warranted based solely on age 6
• Sertraline lacks the marked anticholinergic effects of tricyclic antidepressants, making it better tolerated in elderly patients 6
• Monitor for hyponatremia, which occurs more frequently in this population 2

Clinical Pearls

• Most adverse effects emerge within the first few weeks of treatment 1
• Nausea and vomiting are the most common reasons for discontinuation 1
• The safety margin of sertraline is wider than tricyclic antidepressants 5
• Parental oversight of medication regimens is paramount in children and adolescents 1
• Start with subtherapeutic doses to assess tolerability, particularly given the potential for initial anxiety/agitation 1