What is the recommended use and dosage of Sertraline (selective serotonin reuptake inhibitor) for various conditions?

Sertraline: Recommended Use and Dosing

Sertraline is a first-line selective serotonin reuptake inhibitor (SSRI) indicated for major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder, with dosing ranging from 25-200 mg daily depending on the condition and patient population. 1

FDA-Approved Indications and Dosing

Major Depressive Disorder (MDD)

• Start at 50 mg once daily (morning or evening) 1
• Titrate up to maximum 200 mg/day if inadequate response after at least 1 week 1
• Continue treatment for several months or longer beyond acute response for maintenance 1
• Sertraline demonstrates antidepressant efficacy maintained for up to 44 weeks at mean dose of 70 mg/day 1

Obsessive-Compulsive Disorder (OCD)

Adults:

• Start at 50 mg once daily 1
• Maximum dose 200 mg/day 1
• Allow 8-12 weeks to determine full efficacy, though significant improvement may be observed within the first 2 weeks 2
• Maintain treatment for minimum 12-24 months after achieving remission, though longer duration is often necessary due to relapse risk 2

Pediatric (ages 6-17):

• Children 6-12 years: Start at 25 mg once daily 1
• Adolescents 13-17 years: Start at 50 mg once daily 1
• Maximum 200 mg/day for both age groups 1
• Consider lower body weight in children when advancing dose to avoid excess dosing 1

Panic Disorder, PTSD, and Social Anxiety Disorder

• Start at 25 mg once daily 1
• After 1 week, increase to 50 mg once daily 1
• Titrate up to maximum 200 mg/day based on response 1
• Sertraline at 50-175 mg/day has proven effective and well-tolerated for panic disorder 3

Premenstrual Dysphoric Disorder (PMDD)

• Start at 50 mg/day, either continuously throughout menstrual cycle or limited to luteal phase 1
• Continuous dosing: Titrate up to maximum 150 mg/day 1
• Luteal phase dosing: Maximum 100 mg/day with 50 mg/day titration step for 3 days at beginning of each luteal phase 1

Off-Label Uses

Intradialytic Hypotension (IDH)

• Sertraline improves hemodynamic parameters in patients with IDH by counteracting paradoxical withdrawal of central sympathetic outflow 2
• Both retrospective and prospective studies demonstrate benefit, though optimal dosing not specified in guidelines 2

Alzheimer's Disease-Related Depression

• Start at 25-50 mg per day 2
• Maximum 200 mg per day (morning or evening) 2
• Well tolerated with less effect on metabolism of other medications compared to other SSRIs 2

Key Pharmacokinetic Considerations

• Elimination half-life: 22-36 hours, allowing once-daily dosing 4, 5
• Dose changes should not occur at intervals less than 1 week due to 24-hour elimination half-life 1
• Undergoes extensive first-pass metabolism to N-desmethyl-sertraline (weakly active metabolite) 4
• Therapeutic plasma concentration range: 10-50 ng/mL 6
• Steady-state plasma concentrations vary widely (up to 15-fold) at usual doses of 50-150 mg/day 4

Safety and Monitoring

Critical Safety Warnings

• Never combine with MAOIs due to risk of serotonin syndrome 7, 6
• Monitor for suicidal thinking and behavior, especially in first months of treatment and following dosage adjustments 7, 6
• Avoid abrupt discontinuation—taper gradually to prevent withdrawal syndrome characterized by dizziness, fatigue, headaches, nausea, insomnia, sensory disturbances, and anxiety 6

Common Side Effects

• Gastrointestinal: nausea, diarrhea/loose stools (usually mild and transient) 5
• Sexual dysfunction: ejaculatory disturbance, reduced libido, erectile dysfunction (higher doses may increase frequency) 6, 5
• CNS: dizziness, drowsiness, headache, insomnia 6
• Other: dry mouth 6

Drug Interaction Profile

• Sertraline has minimal inhibitory effects on major cytochrome P450 enzymes, resulting in fewer clinically significant drug interactions compared to other SSRIs 2, 6, 4
• Unlike fluoxetine (half-life 1-3 days with active metabolite 7-15 days), sertraline's shorter half-life requires more careful attention to gradual discontinuation 6

Treatment-Resistant OCD Considerations

When sertraline monotherapy fails in OCD:

• Augment with CBT (larger effect sizes than antipsychotic augmentation) 2
• Switch to different SSRI or use higher than maximum recommended dose 2
• Augment with clomipramine: fluoxetine plus clomipramine was superior to fluoxetine plus quetiapine, though risk of seizures, arrhythmia, and serotonin syndrome requires careful monitoring 2
• Augment with antipsychotics (risperidone or aripiprazole): only one-third of SSRI-resistant OCD patients show clinically meaningful response with small effect size; monitor for weight gain and metabolic dysregulation 2

Clinical Pearls

• Sertraline is well tolerated in therapeutic dosages and relatively safe in overdosage 4
• Minimal anticholinergic activity and essentially devoid of cardiovascular effects, making it suitable for elderly patients or those with cardiovascular disorders 5
• When switching from fluoxetine 40 mg, consider washout period due to fluoxetine's long half-life 6
• For OCD, early reduction in severity by 4 weeks predicts treatment response at 12 weeks 2