What is the best course of treatment for a adult trans woman on Gender Affirming Hormone Therapy (GAHT) with sleep-maintenance insomnia, hyperarousal, and a history of substance use, currently taking mirtazapine 7.5 mg nightly and oral micronized progesterone 200 mg nightly?

Treatment Approach for Sleep-Maintenance Insomnia in a Trans Woman on GAHT

Continue mirtazapine 7.5 mg nightly and implement structured Cognitive Behavioral Therapy for Insomnia (CBT-I) immediately, as this combination addresses both the hyperarousal and sleep fragmentation while the medication provides short-term relief during nervous system recalibration. 1, 2

Why Continue Current Mirtazapine Dose

Your current 7.5 mg dose is working—you're sleeping 7-8.5 hours with multiple 6-hour uninterrupted blocks over 2.5 weeks, which represents significant improvement from baseline. 3, 4 The frequent awakenings with rapid return to sleep indicate improving sleep maintenance, not treatment failure. 3

• Low-dose mirtazapine (7.5 mg) demonstrates statistically significant and clinically relevant reduction in insomnia severity at 6 weeks in placebo-controlled trials, with particular efficacy for sleep maintenance problems. 3
• In older adults with chronic insomnia, mirtazapine 7.5 mg significantly reduced Insomnia Severity Index scores by 6.5 points versus 2.9 points for placebo after 28 days, with improvements in wake after sleep onset, total sleep time, and sleep efficiency. 4
• The vivid dreams and morning grogginess you're experiencing are common initial side effects that typically resolve over the first 1-2 weeks; you're at week 3, so further improvement is expected. 5

Do not increase to 15 mg. Higher doses provide more noradrenergic activation rather than additional sedation, which could worsen your hyperarousal and anxiety. 5, 6 The 7.5 mg dose maximizes histamine H1 blockade (sedation) while minimizing noradrenergic effects. 6

Critical CBT-I Implementation (Non-Negotiable)

Pharmacotherapy must be supplemented with behavioral interventions—medication alone provides inferior long-term outcomes. 1, 7, 2 Your therapist's framework is correct; now implement these specific techniques:

Stimulus Control Therapy (Highest Priority)

• Get out of bed after 15-20 minutes of wakefulness during nighttime awakenings—your current practice of "staying in bed resting" reinforces the bed-wakefulness association and perpetuates sleep fragmentation. 1, 2
• Use your bed only for sleep and sex; no phone scrolling, no "soft engagement" activities in bed. 1, 2
• Maintain consistent wake time (you're already doing this correctly). 1
• Return to bed only when sleepy, not just tired. 1

Sleep Restriction Therapy

• Calculate your average total sleep time from the past week (appears to be ~7.5 hours). 1
• Set time-in-bed window to match this (e.g., 11:30 PM to 7:00 AM), achieving >85% sleep efficiency. 1
• Do not allow time-in-bed to drop below 5 hours. 1
• Increase time-in-bed by 15 minutes weekly only when sleep efficiency exceeds 85-90% for 7 consecutive days. 1

Cognitive Restructuring (You're Already Doing This Well)

• Continue challenging catastrophic beliefs: "waking is normal," "I am safe," "rest is enough." 1
• Add: "Brief awakenings don't prevent restorative sleep," "My body knows how to sleep." 1
• Stop checking the clock—this creates performance anxiety. 1

Progesterone Timing Optimization

Take your 200 mg oral micronized progesterone at the exact same time nightly (ideally 30-60 minutes before target sleep time) with consistent food conditions. 1 Progesterone's conversion to allopregnanolone (a neurosteroid with GABA-A activity) is highly variable based on timing and food intake, which may explain your "surreal between awake and dreaming" experiences. 1

• Avoid taking progesterone with high-fat meals or intentional "boosters," as this increases erratic absorption and may worsen dream intensity. 1
• Consider taking progesterone 30 minutes before mirtazapine to stagger peak sedative effects. 1
• Do not discontinue progesterone—GAHT improves mental health outcomes in trans women, including anxiety and depression. 1

Addressing Hyperarousal and Anxiety

Your rapid heart rate upon waking and nighttime anxiety represent persistent sympathetic nervous system activation, not medication failure. 1, 8 This requires behavioral intervention:

• Resume exercise (swimming, cycling, walking) immediately when medically cleared—physical activity reduces hyperarousal and improves sleep consolidation. 1, 8
• Continue avoiding alcohol completely—you correctly identified it worsens next-day anxiety and sleep fragmentation. 1
• Maintain Reddit/social media blocks—doom scrolling about trans safety and health anxiety directly perpetuates hyperarousal. 1

Progressive Muscle Relaxation (Add This)

• Practice 10-15 minutes before bed: systematically tense and relax muscle groups from toes to head. 1
• Use during nighttime awakenings instead of staying in bed awake. 1

What NOT to Do

Do not add or switch to other medications at this point. 9, 7, 2

• Do not add trazodone—the American Academy of Sleep Medicine explicitly recommends against it for insomnia, as harms outweigh benefits. 9, 7
• Do not add ramelteon—it addresses sleep onset, not your primary problem of sleep maintenance. 9, 7
• Do not add benzodiazepines—your substance use history (cannabis, MDMA, ketamine) makes these inappropriate due to dependence risk. 7, 2
• Do not add doxepin 3-6 mg—you're already on an effective sedating antidepressant; combining them increases anticholinergic burden and QTc prolongation risk without additional benefit. 9, 7

Timeline for Recovery

Realistic expectation: 6-12 weeks for full consolidation of sleep architecture with combined mirtazapine + CBT-I. 3, 4

• Weeks 1-4 (current): Medication reduces sleep latency and increases total sleep time; frequent awakenings persist but with easier return to sleep. 3, 4
• Weeks 4-8: CBT-I effects emerge—sleep efficiency improves, awakenings decrease in frequency. 1, 2
• Weeks 8-12: Sleep consolidates into longer uninterrupted blocks; morning grogginess resolves. 3, 4
• After 12 weeks: Consider gradual mirtazapine taper if sleep remains stable, as CBT-I provides more durable long-term effects than medication alone. 1, 7, 2

Monitoring and Red Flags

Follow up with your prescriber at weeks 4,8, and 12 to assess:

• Insomnia Severity Index score (should decrease by ≥7 points for clinically meaningful improvement). 3, 4
• Adverse effects: weight gain (common with mirtazapine), daytime sedation, or worsening depression. 5
• Sleep efficiency calculation from sleep logs. 1

Discontinue mirtazapine immediately and contact your provider if you develop:

• Sore throat, fever, or signs of infection (agranulocytosis risk, though rare). 5
• Agitation, confusion, rapid heart rate with sweating (serotonin syndrome, especially if combining with other serotonergics). 5
• Rash with fever and lymph node swelling (DRESS syndrome). 5

Common Pitfalls to Avoid

• Assuming frequent awakenings = treatment failure—brief awakenings are normal; the problem is difficulty returning to sleep, which you've already improved. 1, 3
• Staying in bed during prolonged awakenings—this is the single most important behavioral change you need to make. 1, 2
• Expecting linear improvement—recovery is nonlinear; you'll have setbacks, especially around stressors like job interviews. 1
• Attributing all sleep problems to medication—your 6+ month history of cannabis use, multiple surgeries, MDMA use, and health anxiety created the hyperarousal; medication is helping, not causing, your current state. 10, 8
• Seeking reassurance about sleep quality—this perpetuates anxiety; trust the objective data (7-8.5 hours total sleep time). 1