What are the indications and contraindications for Selective Serotonin Reuptake Inhibitors (SSRIs)?

SSRI Indications and Contraindications

Primary Indications (Grade A-B Evidence)

SSRIs are first-line pharmacological treatment for major depressive disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, and posttraumatic stress disorder, with demonstrated superiority over placebo and favorable safety profiles. 1

Psychiatric Indications with Strong Evidence:

• Major Depressive Disorder: SSRIs show modest but consistent superiority over placebo (NNT 7-8), particularly effective in severe depression 1
• Obsessive-Compulsive Disorder: First-line pharmacological treatment with NNT of 5, requiring higher doses than depression (8-12 weeks at maximum tolerated dose) 1
• Panic Disorder: Established first-line treatment with demonstrated efficacy 1, 2
• Social Anxiety Disorder: First-line pharmacological option 1, 2
• Posttraumatic Stress Disorder: Recommended first-line treatment 2
• Generalized Anxiety Disorder: Effective treatment option 1, 2
• Bulimia Nervosa: Demonstrated efficacy 2, 3
• Dysthymia: Effective treatment 2, 3
• Premenstrual Dysphoric Disorder: Established indication 3

Off-Label Uses with Evidence:

• Premature Ejaculation: Daily dosing of paroxetine 20mg, sertraline 25-200mg, or fluoxetine 5-20mg increases ejaculatory latency (Grade B evidence) 1

Absolute Contraindications (FDA Label)

Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs is absolutely contraindicated due to risk of serotonin syndrome. 4

• MAOI use: Must allow 14-day washout period before initiating SSRI 4
• Pimozide co-administration: Contraindicated with sertraline due to QT prolongation risk and 40% increase in pimozide levels 4

Relative Contraindications and Cautions

Bipolar Disorder (Critical Warning):

SSRIs should be avoided or used with extreme caution in bipolar disorder due to risk of precipitating manic episodes. 1, 5

• Treatment with SSRIs should be avoided in patients with history of bipolar depression due to mania risk 1, 5
• If antidepressant needed in bipolar disorder, must be combined with mood stabilizer (lithium, valproate) or atypical antipsychotic 5

Age-Related Considerations:

• Children/Adolescents (<18 years): FDA boxed warning for increased suicidal ideation (absolute risk 1% vs 0.2% placebo, NNH 143) 1
• Older Adults: Paroxetine and fluoxetine should generally be avoided; prefer citalopram, escitalopram, sertraline (Grade C) 1

Medical Conditions Requiring Caution:

• Pregnancy: Fluoxetine has demonstrated safety data; other SSRIs require risk-benefit assessment 1, 3
• Seizure disorders: Monitor closely, though risk is low 1
• Bleeding disorders: SSRIs associated with abnormal bleeding risk 1

Drug Interactions Requiring Monitoring

• Lithium: Monitor lithium levels when initiating SSRI 4
• Phenytoin: Monitor phenytoin concentrations 4
• Valproate: Monitor valproate levels 4
• Warfarin: Risk of pharmacokinetic interaction 1
• Tricyclic antidepressants: SSRIs inhibit CYP2D6, increasing TCA levels 4
• Triptans: Risk of serotonin syndrome with co-administration 4

Monitoring Requirements

Suicidality Monitoring (FDA Requirement):

• Close monitoring required especially in first months of treatment and after dose adjustments 1
• Higher vigilance needed in patients <24 years old 1

Behavioral Activation:

• Monitor for motor restlessness, insomnia, impulsiveness, disinhibition (more common in younger children) 1
• Occurs early in treatment or with dose increases 1
• Requires slow up-titration and patient/family education 1

Sexual Dysfunction:

• Common adverse effect across all SSRIs 1
• May require dose adjustment or medication switch 1

Specific SSRI Selection Considerations

For treatment-naive patients, all SSRIs have equal efficacy; selection should be based on adverse effect profile, drug interactions, cost, and dosing frequency. 1

• Fluoxetine/Sertraline: Associated with weight loss short-term, weight neutral long-term 1
• Paroxetine: Highest weight gain risk within SSRI class; avoid in elderly 1
• Citalopram/Escitalopram: Preferred in elderly 1

Treatment Duration

• First episode depression: Minimum 4 months after remission (Grade C) 1
• Recurrent depression: 12-24 months minimum, often longer 1
• OCD: 12-24 months after achieving remission 1

Common Pitfalls to Avoid

• Abrupt discontinuation: Risk of SSRI withdrawal syndrome; requires gradual taper 1
• Inadequate dosing in OCD: Requires higher doses than depression 1
• Premature discontinuation: Maximum benefit may not occur until 12 weeks 1
• Ignoring bipolar screening: Always screen for bipolar history before initiating SSRI 5