What is the best treatment approach for a 19-year-old patient with a history of untreated depression and anxiety, presenting with symptoms of low mood, lack of interest in activities, low energy, sleep disturbances, and a family history of bipolar disorder, without any history of hypomanic or manic symptoms, suicidal ideation, or psychiatric hospitalizations?

Treatment Approach for Depression with Family History of Bipolar Disorder

Start with an SSRI (sertraline, fluoxetine, or paroxetine) combined with psychotherapy, but exercise extreme caution given the family history of bipolar disorder—monitor closely for any emergence of hypomanic or manic symptoms, and if any mood destabilization occurs, immediately discontinue the antidepressant and refer to psychiatry for mood stabilizer initiation. 1

Critical Diagnostic Consideration

Before initiating treatment, you must actively screen for any subtle hypomanic symptoms that may have been missed, as antidepressants should be avoided in patients with a history of bipolar depression due to risk of mania 1. The strong family history of bipolar disorder (mother on mood stabilizer and antidepressant, possibly bipolar) significantly elevates this patient's risk 1. Key features suggesting bipolar rather than unipolar depression include:

• Early-onset depression (age 19) 2
• Family history of serious mental illness (bipolar disorder in first-degree relative) 2
• Multiple depressive episodes or treatment resistance if antidepressants are tried 2

First-Line Pharmacotherapy

SSRIs are the recommended first-line agents for depression with comorbid anxiety and sleep disturbances 1. Among SSRIs:

• Sertraline 50-200 mg daily is particularly effective for depression with anxiety and has better efficacy for psychomotor agitation 1, 3
• Paroxetine 10-40 mg daily or fluoxetine 20-40 mg daily are equally effective alternatives 1
• All SSRIs show similar efficacy for treating accompanying anxiety and insomnia in depression 1

Start low and titrate slowly given the patient's treatment-naïve status and monitor for treatment-emergent hypomania/mania, which would indicate bipolar disorder 1, 2.

Essential Psychotherapy Component

Psychotherapy should be initiated concurrently with medication 1. Cognitive-behavioral therapy or interpersonal therapy addressing the work-related burnout and stress management is appropriate 1.

Critical Safety Monitoring

Weekly monitoring for the first 4-6 weeks is essential to detect:

• Treatment-emergent hypomania/mania (decreased need for sleep, increased energy, racing thoughts, impulsivity, increased goal-directed activity) 1, 2
• Suicidal ideation, particularly in patients under age 25 on SSRIs 1
• Response to treatment (improvement in mood, energy, sleep, interest in activities) 1

If Hypomanic/Manic Symptoms Emerge

Immediately discontinue the SSRI as antidepressants can induce switching to mania and are not recommended as monotherapy for bipolar depression 1, 4. This would reclassify the diagnosis as substance-induced mania, suggesting underlying bipolar disorder 1.

Refer urgently to psychiatry for initiation of mood stabilizers (lithium, valproate) or atypical antipsychotics (quetiapine, lurasidone, cariprazine) which are FDA-approved for bipolar depression 1, 2.

If No Response After 6-12 Weeks

Switch to an alternative SSRI (bupropion sustained-release, sertraline, or venlafaxine extended-release) as approximately 38% of patients do not respond to initial SSRI therapy 1. One in four patients becomes symptom-free after switching 1.

Reassess for bipolar disorder as nonresponse to antidepressants is suggestive of bipolar depression rather than unipolar depression 2.

Common Pitfalls to Avoid

• Do not use SSRIs as monotherapy if any hypomanic symptoms are detected, as this can worsen rapid cycling and increase suicidality 1, 4, 2
• Do not abruptly discontinue SSRIs as this may precipitate SSRI withdrawal syndrome; taper gradually if discontinuation is needed 1
• Do not ignore the family history—this patient has significantly elevated risk for bipolar disorder and requires closer monitoring than typical depression cases 1, 2
• Do not delay psychiatric referral if mood destabilization occurs, as untreated bipolar depression is associated with greater suicide risk and functional impairment 4, 2

Expected Adverse Effects

Common SSRI side effects include nausea, headache, diarrhea, insomnia, and sexual dysfunction 5, 3. These are generally well-tolerated and diminish over 2-4 weeks 3. The patient should be counseled about these effects to improve adherence 1.