What antidepressant (and possibly anxiolytic) should be added for a 34‑year‑old woman with major depressive disorder, recent suicide attempt by hydroxyzine (Vistaril) overdose, normal laboratory studies, and current low‑dose quetiapine (Seroquel) therapy?

Antidepressant Selection for Major Depressive Disorder with Recent Suicide Attempt

Add an SSRI—specifically sertraline or escitalopram—starting at a low dose (sertraline 25 mg or escitalopram 5 mg daily) and titrate gradually over 4–6 weeks to therapeutic range (sertraline 100–150 mg or escitalopram 10–20 mg daily), while maintaining the current quetiapine regimen and implementing close weekly monitoring during the first month. 1

Evidence-Based Rationale for SSRI Selection

Second-generation antidepressants show equivalent efficacy for major depressive disorder, so selection should prioritize adverse effect profiles, cost, and patient preferences. 1 Given this patient's recent suicide attempt by overdose, safety in overdose is paramount.

Why SSRIs Over Other Antidepressants

• Bupropion carries lower sexual dysfunction risk (significantly lower than fluoxetine or sertraline) but has weak evidence of increased seizure risk, making it less ideal immediately post-overdose 1
• Paroxetine has higher rates of sexual dysfunction than other SSRIs and should be avoided 1
• Venlafaxine (SNRI) has higher nausea/vomiting rates than SSRIs and may carry cardiovascular risks 1
• Mirtazapine has faster onset than SSRIs but causes significant weight gain and sedation, which may be problematic with quetiapine 1

Critical Safety Consideration: Suicidality Risk

SSRIs are associated with increased risk of nonfatal suicide attempts (odds ratio 1.57–2.25) compared to placebo, particularly in younger patients. 1 However, this must be weighed against the protective effect of treating depression itself. The FDA boxed warning emphasizes that all patients on antidepressants require close monitoring for clinical worsening, suicidality, and unusual behavioral changes, especially during initial months and dose changes. 2

In patients under age 25, antidepressants show 5 additional cases of suicidality per 1,000 patients treated compared to placebo. 2 This 34-year-old woman falls just outside this highest-risk age bracket but still requires intensive monitoring.

Specific Dosing Algorithm

Week 1–2: Initiation Phase

• Start sertraline 25 mg daily OR escitalopram 5 mg daily as a "test dose" to assess tolerability 1
• Schedule follow-up within 1 week to assess for behavioral activation, increased anxiety, agitation, or worsening suicidal ideation 2
• Monitor specifically for: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania 2

Week 2–4: Early Titration

• Increase to sertraline 50 mg daily OR escitalopram 10 mg daily if initial dose tolerated 1
• Continue weekly monitoring for mood destabilization or emergent suicidality 2

Week 4–8: Therapeutic Dosing

• Titrate sertraline by 25–50 mg increments every 1–2 weeks to target 100–150 mg daily 1
• OR titrate escitalopram by 5 mg increments every 2–3 weeks to target 10–20 mg daily 1
• Assess treatment response at 4 weeks and 8 weeks using standardized measures 1

Expected Timeline

• Initial response typically emerges within 2–4 weeks, with maximal benefit by 8–12 weeks 1
• 38% of patients do not achieve treatment response during 6–12 weeks, and 54% do not achieve remission 1

Critical Monitoring Requirements

Immediate Post-Attempt Period (First 4 Weeks)

• Weekly face-to-face visits to assess suicidal ideation, mood symptoms, and medication tolerability 2
• Daily observation by family/caregivers with instructions to report agitation, irritability, unusual behavior changes, or suicidality immediately 2
• Prescribe smallest quantity of tablets consistent with good management to reduce overdose risk 2

Ongoing Monitoring (Months 2–6)

• Biweekly to monthly visits once stable 1
• Continue assessing for: depressive symptoms, suicidal ideation, adverse effects, medication adherence, and environmental stressors 1

Screening for Bipolar Disorder

Before initiating antidepressant therapy, this patient requires screening for bipolar disorder risk, including detailed psychiatric history and family history of suicide, bipolar disorder, and depression. 2 Treating a bipolar depressive episode with an antidepressant alone may precipitate a mixed/manic episode. 2 However, the current quetiapine regimen (50 mg AM, 100 mg PM) provides some mood stabilization, though this is a relatively low dose.

Common Adverse Effects to Anticipate

Most common adverse events with SSRIs include: constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual dysfunction, and somnolence. 1 Nausea and vomiting are the most common reasons for discontinuation in efficacy studies. 1

• Sertraline has higher diarrhea rates than other SSRIs 1
• Sexual dysfunction is common but underreported; bupropion could be considered if this becomes problematic 1

Adjunctive Psychosocial Interventions

Cognitive behavioral therapy (CBT) should be initiated alongside pharmacotherapy, as combination treatment is superior to either alone for depression and anxiety. 1 Psychoeducation about symptoms, treatment options, and medication adherence is essential. 1

Critical Pitfalls to Avoid

• Never use antidepressant monotherapy in undiagnosed bipolar disorder—the quetiapine provides some protection but verify bipolar screening 2
• Avoid rapid titration—increases risk of behavioral activation and anxiety 2
• Do not underdose—ensure adequate trial of 6–8 weeks at therapeutic dose before concluding ineffectiveness 1
• Never discontinue abruptly—taper gradually to avoid discontinuation syndrome 2
• Do not ignore warning signs—agitation, akathisia, or worsening depression may precede emergent suicidality 2

Alternative if SSRI Fails or Not Tolerated

If inadequate response after 8 weeks at therapeutic SSRI dose despite good adherence, consider adding CBT rather than switching medications immediately. 1 If SSRI not tolerated due to side effects, bupropion (150–300 mg daily) represents a reasonable alternative with lower sexual dysfunction risk, though it must be combined with continued mood stabilization. 1