Treatment of Depression and Irritability
For depression with irritability, start with an SSRI—specifically fluoxetine or sertraline—as first-line pharmacotherapy, with close monitoring for treatment response and adverse effects beginning within 1-2 weeks of initiation. 1
Medication Selection
SSRIs are the preferred first-line agents for treating depression, with all second-generation antidepressants showing equal efficacy in treatment-naive patients. 1 Selection should be based on:
- Fluoxetine is the only FDA-approved antidepressant for children and adolescents with depression, and escitalopram is approved for adolescents ≥12 years. 1
- For adults, choose between SSRIs based on adverse effect profiles and cost, as efficacy is equivalent across agents. 1
- Sertraline, fluoxetine, escitalopram, or citalopram are all appropriate first choices. 1
Dosing Guidelines for Adolescents
- Fluoxetine: Start 10 mg daily, increase by 10-20 mg increments, effective dose 20 mg, maximum 60 mg 1
- Sertraline: Start 25 mg daily, increase by 12.5-25 mg increments, effective dose 50 mg, maximum 200 mg 1
- Escitalopram: Start 10 mg daily, increase by 5 mg increments, effective dose 10 mg, maximum 20 mg 1
Understanding Irritability in Depression
Irritability is a common feature of depression (present in ~46% of cases) and is associated with greater depression severity, anxiety, and suicidality—not bipolar disorder. 2 Key points:
- When both depression and anxiety symptoms are present, prioritize treating depressive symptoms first. 1
- Irritability in depression correlates with atypical features (weight gain, rejection sensitivity), higher anxiety, and worse quality of life. 3, 2
- Irritability does NOT indicate bipolar spectrum disorder in most cases of major depression. 2
Monitoring Requirements
Critical monitoring must begin within 1 week of starting treatment:
At every assessment, evaluate: 1
- Ongoing depressive symptoms using standardized instruments
- Suicide risk (irritability is associated with increased suicidality) 2
- Adverse effects, particularly behavioral activation, agitation, hostility, and worsening irritability 4, 5
- Treatment adherence
- New environmental stressors
The FDA black-box warning requires close monitoring for suicidality and unusual behavioral changes, especially during initial months and dose changes. 4, 5 This can be accomplished through telephone contact, which has demonstrated reliability equivalent to in-person visits. 1
Treatment Duration and Response
Assess treatment response at 4 and 8 weeks: 1
- If no improvement after 6-8 weeks at adequate dose, modify the treatment regimen. 1
- An adequate trial requires maximum tolerated dose for 8 weeks before considering the patient a non-responder. 1
- For antidepressants in adolescents, trials may require up to 8 weeks at optimal dose to identify response. 1
After achieving satisfactory response: 1
- Continue treatment for 4-9 months for first episode of major depression
- For patients with ≥2 prior episodes, continue treatment even longer (potentially indefinitely)
- Taper slowly when discontinuing to avoid withdrawal effects 1
Common Pitfalls to Avoid
Do not use antidepressants for mild depression or subsyndromal depressive symptoms without a full depressive episode. 1 The drug-placebo difference is minimal in mild depression. 1
Do not start at high doses, as this increases risk of deliberate self-harm and suicide-related events. 1 Always start at recommended starting doses.
Do not assume irritability indicates bipolar disorder. Screen for bipolar risk factors (family history of bipolar disorder, prior manic episodes), but irritability alone does not warrant bipolar-specific treatment. 5, 2
Do not discontinue abruptly if switching medications or stopping treatment, as this causes withdrawal symptoms. 4, 5
Adjunctive Considerations
If irritability persists despite adequate SSRI trial and depression improves, consider that residual irritability may reflect: 1
- Psychosocial stressors requiring behavioral interventions rather than medication adjustment
- Need for combined psychosocial and pharmacological treatment
For treatment-resistant cases, augmentation strategies or medication switching should be considered after 8 weeks of adequate treatment. 1