How can the medication regimen be optimized for a patient with depression, anxiety, Attention Deficit Hyperactivity Disorder (ADHD), and insomnia, currently taking sertraline (Zoloft) 150mg daily, lurasidone (Latuda) 40mg daily, bupropion (Wellbutrin) HCl 100mg daily, Adderall (dextroamphetamine and amphetamine) 10mg twice a day (BID), and hydroxyzine (Vistaril) 25mg BID as needed (PRN)?

Medication Regimen Optimization for Adolescent with Depression, Anxiety, ADHD, and Insomnia

The bupropion dose is subtherapeutic at 100mg daily and should be increased to at least 150mg daily (the minimum effective dose), with consideration for titration to the target dose of 300mg daily after 4 days, as this patient's depression may be inadequately treated. 1

Critical Dosing Issues

Bupropion Underdosing

• The current bupropion 100mg daily is below the FDA-approved starting dose of 150mg once daily for major depressive disorder 1
• After 4 days at 150mg, the dose should be increased to the target of 300mg once daily in the morning 1
• Bupropion has demonstrated efficacy for ADHD symptoms in controlled trials, though it is less effective than stimulants for attentional symptoms 2
• The subtherapeutic dose may be contributing to inadequate control of both depression and ADHD symptoms 1

Sertraline Dosing Considerations

• The current 150mg daily dose is within the therapeutic range (50-200mg/day) for depression and anxiety 3
• However, sertraline can be activating and may worsen insomnia, particularly at higher doses 4
• Consider whether this dose is contributing to the insomnia problem, as SSRIs are known to cause or exacerbate sleep disturbances 3

Insomnia Management Problems

Hydroxyzine as PRN is Inadequate

• Hydroxyzine 25mg BID PRN is not an evidence-based approach for chronic insomnia in this patient 5
• While hydroxyzine showed some efficacy over placebo for generalized anxiety disorder, the evidence is weak with high risk of bias, and it is not recommended as first-line treatment 5
• For chronic insomnia with comorbid depression, sedating low-dose antidepressants (trazodone, mirtazapine, doxepin) should be considered as scheduled medications, not PRN 6

Stimulant Timing May Worsen Insomnia

• Adderall 10mg BID may be contributing to insomnia if the second dose is taken too late in the day 7
• The FDA label specifically warns that "late evening doses should be avoided because of the resulting insomnia" 7
• Consider changing to once-daily dosing in the morning or ensuring the second dose is given no later than early afternoon 7

Polypharmacy Concerns

Lurasidone 40mg Daily Requires Justification

• Lurasidone is an atypical antipsychotic typically reserved for bipolar depression or treatment-resistant depression 6
• In a 16-year-old with depression, anxiety, and ADHD, the addition of an atypical antipsychotic should be questioned unless there is treatment-resistant depression or psychotic features not mentioned 6
• Atypical antipsychotics like lurasidone carry risks of metabolic side effects, weight gain, and extrapyramidal symptoms that are particularly concerning in adolescents 6

Potential Drug Interactions

• The combination of bupropion with sertraline carries a risk of serotonin syndrome, as bupropion inhibits CYP2D6 and can increase SSRI levels 8
• Monitor for myoclonic jerks, confusion, agitation, or autonomic instability, as these early signs of serotonin syndrome can be misinterpreted as worsening depression 8

Specific Recommendations

Immediate Changes

1. Increase bupropion to 150mg daily immediately, then to 300mg daily after 4 days if tolerated 1
2. Adjust Adderall timing: Give first dose upon awakening and second dose no later than early afternoon (4-6 hours after first dose) 7
3. Discontinue hydroxyzine PRN and replace with a scheduled sedating antidepressant for insomnia 6

Insomnia-Specific Intervention

• Add trazodone 25-50mg at bedtime as it has the least anticholinergic activity and can be used safely with other antidepressants 6
• Alternatively, consider mirtazapine 7.5-15mg at bedtime, though be aware of weight gain risk 6
• These low-dose sedating antidepressants do not constitute adequate treatment of depression alone but are effective adjuncts 6

Re-evaluate Lurasidone

• If there is no clear indication for an atypical antipsychotic (such as psychotic features or documented treatment-resistant depression), consider tapering and discontinuing lurasidone 6
• The guideline specifically warns against off-label use of atypical antipsychotics like quetiapine and olanzapine for insomnia due to weak evidence and significant side effect risks 6

Behavioral Sleep Interventions

• Implement sleep restriction therapy: calculate total sleep time over 1-2 weeks and set bedtime/wake times to achieve >85% sleep efficiency 6
• Ensure proper sleep hygiene: regular schedule, quiet environment, avoiding caffeine and stimulants before bedtime 6
• Consider cognitive behavioral therapy for insomnia (CBT-I) as first-line non-pharmacological treatment 6

Monitoring Requirements

• Weekly follow-up during bupropion dose titration to assess for seizure risk (increased with rapid dose escalation) 1
• Monitor for serotonin syndrome symptoms: tremor, myoclonus, confusion, autonomic instability 8
• Assess sleep efficiency weekly using sleep diary: adjust time in bed by 15-20 minutes based on whether sleep efficiency is >85-90% or <80% 6
• Monitor for activating side effects from increased bupropion: insomnia, agitation, anxiety 1

Common Pitfalls to Avoid

• Do not continue subtherapeutic bupropion dosing as it provides inadequate treatment for depression and ADHD 1, 2
• Do not rely on PRN hydroxyzine for chronic insomnia; scheduled medications are needed 6, 5
• Do not give stimulants late in the day as this directly causes insomnia 7
• Do not misinterpret early serotonin syndrome (myoclonus, confusion) as worsening depression, which could lead to inappropriate medication increases 8
• Do not use atypical antipsychotics for insomnia without clear psychiatric indication due to unfavorable risk-benefit ratio 6