What is the best course of treatment for a patient with depression, currently taking sertraline (Selective Serotonin Reuptake Inhibitor - SSRI) 100 mg daily, who has shown some improvement in mood but continues to experience fatigue, poor appetite, and concentration difficulties, and has been experiencing side effects from propranolol (beta blocker), with a history of fleeting suicidal thoughts, and is concerned about possible Attention Deficit Hyperactivity Disorder (ADHD)?

Optimal Treatment Strategy for Partial Response to Sertraline with Residual Symptoms

Continue sertraline 100 mg daily for at least 6-8 weeks from initiation before modifying treatment, as the patient has only been on therapy for two weeks and is already showing some mood improvement. 1

Immediate Management (Weeks 2-8)

Continue Current SSRI Therapy

• Maintain sertraline at 100 mg daily as the patient has been on treatment for only two weeks and is already reporting some improvement in mood 1
• The American College of Physicians recommends assessing therapeutic response within 6-8 weeks before modifying treatment for major depressive disorder 1
• Approximately 38% of patients do not achieve treatment response during 6-12 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 1
• The optimal therapeutic dose of sertraline is typically 50-100 mg daily, with the starting dose of 50 mg being the usually effective therapeutic dose 2

Address Sleep Disturbance

• Discontinue trazodone (as it has lost effectiveness after 2-3 days) and consider hydroxyzine 25 mg as needed for anxiety and sleep, as already planned 1
• Limited evidence suggests some agents may be more effective for insomnia in depression, though sertraline shows similar efficacy to other SSRIs for treating depression with accompanying insomnia 1

Monitor Closely for Safety

• Assess patient status weekly or biweekly during the first 1-2 months of treatment, given the history of fleeting suicidal thoughts 1
• The FDA advises close monitoring for increases in suicidal thoughts and behaviors, particularly during the first 1-2 months when risk for suicide attempts is greatest 1
• Monitor for emergence of agitation, irritability, or unusual behavioral changes that could indicate worsening depression 1

Addressing Concentration Difficulties

Defer ADHD Assessment Initially

• Explain that concentration difficulties, fatigue, and poor appetite are core symptoms of major depression that typically improve with adequate antidepressant treatment 3
• Depression includes symptoms such as slowed thinking or impaired concentration, which overlap significantly with ADHD symptoms 3
• Reassess concentration after 6-8 weeks of adequate sertraline treatment to determine if symptoms persist after depressive symptoms improve 1

If Concentration Problems Persist After 6-8 Weeks

• Consider adding bupropion as augmentation therapy if concentration difficulties and fatigue persist despite improvement in other depressive symptoms 1
• Bupropion is associated with lower rates of sexual adverse events compared to sertraline and may help with focus and concentration 1
• Case series data suggest that combined treatment with SSRIs and psychostimulants can be safe and effective for comorbid depression and ADHD, though this should only be considered after depression is adequately treated 4

Treatment Modification Algorithm (After 6-8 Weeks)

If Inadequate Response at Week 6-8

The STAR*D trial provides the best evidence for next steps 1:

Option 1: Switch to Alternative Antidepressant

• Switch to sustained-release bupropion, or extended-release venlafaxine 1
• Approximately 1 in 4 patients become symptom-free after switching medications 1
• No significant difference exists among these three drugs for treatment-resistant depression 1

Option 2: Augmentation Strategy

• Add bupropion to sertraline to address residual fatigue and concentration difficulties 1
• Bupropion has advantages for sexual dysfunction (lower rates than sertraline) and may improve energy and focus 1

Option 3: Dose Escalation

• Increase sertraline in 50 mg increments at weekly intervals to maximum 200 mg daily 3, 2
• However, recent dose-response meta-analysis suggests therapeutic response increases with dosage, but adverse effects also increase above 150 mg 5

Maintenance Therapy Planning

Duration of Treatment

• Continue treatment for 4-9 months after achieving satisfactory response for a first episode of major depressive disorder 1
• Given the history of fleeting suicidal thoughts, consider longer duration of therapy 1
• Meta-analysis of 31 randomized trials supports continuation of antidepressant therapy to reduce risk of relapse 1

Critical Safety Considerations

Serotonin Syndrome Risk

• Avoid combining sertraline with MAOIs, linezolid, or intravenous methylene blue 3
• Exercise caution if considering augmentation with tramadol, triptans, or other serotonergic agents 3
• Monitor for mental status changes, autonomic instability, neuromuscular symptoms, or gastrointestinal symptoms 3

Bipolar Disorder Screening

• The patient should have been adequately screened for bipolar disorder risk before initiating antidepressant therapy 3
• Treating a depressive episode with an antidepressant alone may increase likelihood of precipitating a mixed/manic episode in patients at risk for bipolar disorder 3

Common Pitfalls to Avoid

• Do not prematurely switch or augment therapy before 6-8 weeks unless there is clinical deterioration or intolerable side effects 1
• Do not attribute all concentration difficulties to ADHD without first adequately treating the depression 3
• Do not discontinue propranolol abruptly if the patient has been on it chronically; taper if needed
• Do not add psychostimulants until depression is adequately treated and ADHD diagnosis is confirmed 4