Medication Adjustments for Increased Anxiety and Poor Sleep
Increase mirtazapine from 7.5 mg to 15-30 mg at bedtime to address both insomnia and anxiety, as this dose is subtherapeutic and the patient is already on a mood stabilizer (lamotrigine) which reduces the risk of manic switching. 1, 2
Rationale for Mirtazapine Dose Optimization
The current 7.5 mg dose is below the FDA-recommended starting dose of 15 mg and well below the therapeutic range of 15-45 mg daily. 1 At this subtherapeutic dose, the patient is experiencing primarily antihistaminic effects without adequate antidepressant or anxiolytic benefit.
Mirtazapine demonstrates important anxiolytic and sleep-improving effects related to its unique pharmacodynamic properties, including alpha-2 antagonism that enhances noradrenergic and serotonergic neurotransmission, plus 5-HT2 and 5-HT3 receptor blockade. 3, 4
The risk of switching to mania with mirtazapine is minimal when combined with a mood stabilizer like lamotrigine. Studies show that low-to-moderate doses of mirtazapine administered with mood stabilizers are safe in bipolar disorder, with switching primarily occurring at antidepressant doses without mood stabilizer co-therapy. 2
Titration should occur in 1-2 week intervals, starting at 15 mg at bedtime, with potential increase to 30 mg if needed based on response. 1 The sedating effects may actually decrease at higher doses due to increased noradrenergic activity. 3
Alternative Consideration: Quetiapine Dose Adjustment
The current quetiapine dose of 400 mg is within the therapeutic range (400-800 mg/day) for bipolar disorder, but could be increased if mirtazapine optimization proves insufficient. 5
Quetiapine has demonstrated efficacy for PTSD symptoms including re-experiencing, avoidance, hyperarousal, insomnia, and nightmares, though evidence is primarily from open-label and retrospective studies. 6 It may be particularly beneficial given this patient's PTSD diagnosis.
If increasing quetiapine, titrate in increments of 100-200 mg/day up to 600-800 mg/day, monitoring for sedation which is the most common adverse effect and primary cause of discontinuation. 5, 6
Lamotrigine Considerations
The current lamotrigine dose of 75 mg is subtherapeutic for bipolar disorder, where typical maintenance doses range from 200-400 mg/day for mood stabilization. This low dose may be contributing to inadequate mood stability and breakthrough anxiety.
Consider gradual titration of lamotrigine to therapeutic levels (typically 200 mg/day minimum) following standard escalation protocols to minimize rash risk, which would provide better mood stabilization and potentially reduce anxiety symptoms.
Common Pitfalls to Avoid
Do not add benzodiazepines as first-line treatment for the insomnia and anxiety, as they should be avoided in patients with cognitive concerns and can worsen depression in bipolar disorder. 7
Avoid using the current mirtazapine dose as evidence that "mirtazapine doesn't work" for this patient—7.5 mg is a subtherapeutic dose that provides sedation without adequate antidepressant or anxiolytic effects. 1, 4
Monitor for increased sedation when optimizing doses, particularly if both mirtazapine and quetiapine are increased simultaneously. Consider sequential adjustments rather than concurrent increases.
Reassess in 2-4 weeks after mirtazapine optimization, as full therapeutic effects require 4-6 weeks but initial improvements in sleep and anxiety may occur within 1-2 weeks. 3, 4