What is the recommended initial treatment approach for a patient with Major Depressive Disorder (MDD) and insomnia?

Treatment Approach for Major Depressive Disorder with Insomnia

For patients with Major Depressive Disorder (MDD) and insomnia, the recommended initial treatment approach is cognitive behavioral therapy for insomnia (CBT-I) combined with a second-generation antidepressant that has favorable sleep effects, such as mirtazapine.

Initial Assessment and Treatment Selection

First-line Treatment Options:

1. Psychotherapy + Pharmacotherapy Combination:

   • CBT-I + Second-generation antidepressant is the most effective approach for addressing both MDD and insomnia 1, 2
   • Studies show that combining CBT-I with antidepressants results in higher remission rates for both depression (61.5% vs 33.3%) and insomnia (50% vs 7.7%) compared to antidepressant alone 2

2. Antidepressant Selection:

   • Mirtazapine (7.5-15mg at bedtime) is preferred for patients with MDD and insomnia due to:
     • Sedative properties that help with sleep
     • Faster onset of action compared to SSRIs 1, 3
     • Additional benefit of appetite stimulation in depressed patients with poor appetite

3. Alternative Antidepressant Options:

   • Trazodone (25-100mg at bedtime) - effective for sleep maintenance issues
   • Bupropion (150mg in morning, can increase to 300mg) - less sedating option if daytime fatigue is a concern 4

Implementation of CBT-I

CBT-I components should include:

• Sleep restriction
• Stimulus control
• Cognitive restructuring
• Sleep hygiene education
• Relaxation techniques 3

CBT-I can be delivered through:

• In-person individual or group therapy
• Telephone or web-based modules
• Self-help books 3

Monitoring and Follow-up

1. Initial follow-up: Schedule within 7-10 days of starting treatment 3
2. Assessment tools:
   • Use Insomnia Severity Index (ISI) to track sleep improvements
   • Use PHQ-9 or HAM-D to track depression symptoms 1, 3
3. Medication adjustments:
   • If starting with mirtazapine 7.5mg, can increase to 15mg if needed for sleep
   • For bupropion, increase from 150mg to 300mg after 4 days if tolerated 4

Special Considerations

Insomnia Subtypes in MDD

• Mid-nocturnal insomnia is the most common subtype in MDD patients 5
• Sleep disturbances should be recognized as a core symptom of MDD, not just a comorbidity 6

Cautions and Contraindications

• Benzodiazepines: Avoid as first-line agents due to risks of tolerance, dependence, withdrawal seizures, and cognitive impairment 3
• Z-drugs: Use with caution due to risks of cognitive impairment and falls 3
• Elderly patients: Use lower doses of medications; avoid benzodiazepines 3
• Cardiac conditions: Use trazodone with caution due to potential for QT prolongation 3

Treatment Resistance

If initial treatment is ineffective after 4-6 weeks:

1. For persistent insomnia despite improved depression:

   • Consider low-dose doxepin (3-6mg) for sleep maintenance issues 3
   • Consider eszopiclone (1-3mg) for short-term use 3

2. For persistent depression with improved sleep:

   • Consider switching antidepressants or augmentation strategies 1
   • The STAR*D trial showed that 1 in 4 patients became symptom-free after switching medications 1

3. For persistent depression and insomnia:

   • Consider referral to a sleep specialist for further evaluation 3
   • Rule out other sleep disorders like sleep apnea with polysomnography if indicated 3

Remember that insomnia is often a residual symptom even after depression remits, and untreated insomnia increases the risk of depression relapse 5, 6. Addressing both conditions simultaneously provides the best outcomes for long-term recovery.