Management Approach
Increase duloxetine to 60 mg daily immediately and address insomnia with evidence-based non-pharmacologic and pharmacologic strategies, while continuing alprazolam as needed for breakthrough anxiety. 1
Optimize Antidepressant Therapy
Duloxetine 30 mg is suboptimal for both major depressive disorder and generalized anxiety disorder; the FDA-approved therapeutic dose is 60 mg once daily, which has demonstrated consistent efficacy in clinical trials for both conditions. 1, 2
Increase duloxetine from 30 mg to 60 mg daily now; this dose escalation addresses the persistent anxiety, low motivation, and depressive symptoms that have not improved on the current regimen. 1, 2
The fatigue and lightheadedness may be dose-related or reflect inadequate treatment of depression; monitor blood pressure (sitting and standing) at the next visit to rule out orthostatic hypotension, which is a known adverse effect of duloxetine. 1
Duloxetine 60 mg once daily is the established first-line dose for generalized anxiety disorder, with randomized controlled trials showing statistically significant reductions in Hamilton Anxiety Rating Scale scores compared with placebo. 2, 3
Nausea is the most common adverse effect when initiating or increasing duloxetine; it typically resolves within 1–2 weeks and can be minimized by taking the medication with food. 4
Reassess response after 4 weeks at 60 mg; if anxiety and depressive symptoms remain inadequately controlled, consider titration to 90 mg or 120 mg daily (maximum FDA-approved dose). 1, 2
Address Insomnia with Behavioral Therapy First
Initiate Cognitive Behavioral Therapy for Insomnia (CBT-I) immediately as the standard of care; it provides superior long-term efficacy compared with medication alone and maintains benefits after treatment discontinuation. 5
CBT-I core components include:
- Stimulus control: use the bed only for sleep; leave the bed if unable to fall asleep within 20 minutes. 5
- Sleep restriction: limit time in bed to approximate actual sleep time plus 30 minutes (e.g., if sleeping 5 hours, allow 5.5 hours in bed). 5
- Cognitive restructuring: address negative beliefs about sleep (e.g., "I must get 8 hours or I'll be dysfunctional"). 5
- Sleep hygiene: maintain a consistent wake time every day (including weekends), avoid caffeine after 2 PM, eliminate screens 1 hour before bedtime, and keep the bedroom cool and dark. 5
CBT-I can be delivered via individual therapy, group sessions, telephone, web-based modules, or self-help books—all formats demonstrate comparable efficacy. 5
Do not prescribe hypnotic medication without concurrent CBT-I; behavioral therapy is mandated as first-line treatment by the American Academy of Sleep Medicine and the American College of Physicians. 5
Add Pharmacologic Sleep Aid Only After CBT-I Initiation
First-Line Pharmacologic Option for Sleep Maintenance Insomnia
Prescribe low-dose doxepin 3 mg at bedtime as the preferred first-line hypnotic for this patient's frequent nocturnal awakenings and inability to return to sleep. 5
Doxepin 3–6 mg reduces wake after sleep onset by 22–23 minutes, improves sleep efficiency and total sleep time, and has minimal anticholinergic effects at hypnotic doses. 5
Doxepin has no abuse potential and no DEA scheduling, making it appropriate for long-term use when needed. 5
If doxepin 3 mg is insufficient after 1–2 weeks, increase to 6 mg; this dose maintains the favorable safety profile while providing additional efficacy. 5
Reassess sleep parameters after 1–2 weeks: evaluate sleep-onset latency, total sleep time, number of nocturnal awakenings, daytime functioning, and adverse effects (morning sedation, dry mouth). 5
Alternative Second-Line Options (If Doxepin Fails or Is Contraindicated)
Suvorexant 10 mg (orexin-receptor antagonist) reduces wake after sleep onset by 16–28 minutes and carries a lower risk of cognitive and psychomotor impairment than benzodiazepine-type agents. 5
Eszopiclone 2 mg (1 mg if age ≥65 years) improves both sleep onset and maintenance, increasing total sleep time by 28–57 minutes; however, it carries higher risks of complex sleep behaviors, falls, and cognitive impairment compared with doxepin. 5
Ramelteon 8 mg (melatonin-receptor agonist) is appropriate for sleep-onset insomnia and has no abuse potential, but it is less effective for sleep-maintenance problems. 5
Agents Explicitly NOT Recommended
Do not prescribe trazodone; it yields only ~10 minutes reduction in sleep latency and ~8 minutes reduction in wake after sleep onset, with no improvement in subjective sleep quality and adverse events in ~75% of older adults. 5
Do not prescribe over-the-counter antihistamines (diphenhydramine, doxylamine); they lack efficacy data, cause strong anticholinergic effects (confusion, urinary retention, falls, daytime sedation), and develop tolerance within 3–4 days. 5
Do not prescribe traditional benzodiazepines (lorazepam, clonazepam, diazepam) for insomnia; they have long half-lives leading to drug accumulation, prolonged daytime sedation, higher fall and cognitive-impairment risk, and are linked to dementia and fractures. 5
Do not prescribe antipsychotics (quetiapine, olanzapine) for insomnia; they have weak evidence for benefit and significant risks including weight gain, metabolic dysregulation, extrapyramidal symptoms, and increased mortality in elderly patients with dementia. 5
Continue Alprazolam for Breakthrough Anxiety
Continue alprazolam 0.25 mg as needed for acute anxiety symptoms; the patient is using it sparingly (2 pills remaining) and denies panic attacks, indicating appropriate PRN use. 6
Alprazolam 0.5 mg may be used if 0.25 mg is insufficient for breakthrough anxiety; however, encourage the patient to use the lowest effective dose to minimize tolerance and dependence risk. 6
Once duloxetine 60 mg reaches steady state (4–6 weeks), reassess the need for alprazolam; many patients experience reduced anxiety symptoms and require less frequent benzodiazepine use. 2
Do not prescribe alprazolam for insomnia; benzodiazepines are not recommended as first-line treatment for sleep-maintenance problems and carry significant risks of dependence, falls, and cognitive impairment. 5
Monitor for Adverse Effects and Treatment Response
Schedule follow-up in 2 weeks (not 4 weeks) to assess tolerability of duloxetine 60 mg; early reassessment allows prompt management of nausea, dizziness, or worsening anxiety. 1, 4
At the 2-week visit, evaluate:
- Orthostatic vital signs (sitting and standing blood pressure) to assess for orthostatic hypotension causing lightheadedness. 1
- Anxiety symptoms using a standardized scale (e.g., GAD-7) to quantify improvement. 2
- Depressive symptoms using PHQ-9 or similar tool to track motivation and mood. 1
- Sleep parameters: sleep-onset latency, total sleep time, number of nocturnal awakenings, daytime functioning. 5
- Appetite and weight: duloxetine can cause decreased appetite; monitor for clinically significant weight loss. 1
Screen for emergent suicidality at every visit; antidepressants carry a black-box warning for increased suicidal thinking in adults aged 18–24 years, though this patient is 34 years old and at lower risk. 1
Monitor for activation symptoms (agitation, irritability, insomnia, impulsivity, hypomania) that may signal emerging bipolar disorder or antidepressant-induced activation. 1
Address Decreased Appetite
Decreased appetite is a common adverse effect of duloxetine, occurring in up to 10% of patients in clinical trials. 1
If appetite does not improve after 2–4 weeks at duloxetine 60 mg, consider:
- Adding mirtazapine 7.5–15 mg at bedtime, which promotes appetite and weight gain while also improving sleep; however, this should only be considered if the patient develops clinically significant weight loss or if insomnia persists despite doxepin. 5
- Switching to an alternative SSRI or SNRI with a lower risk of appetite suppression (e.g., sertraline, escitalopram) if appetite loss becomes clinically significant. 6
Common Pitfalls to Avoid
Do not continue duloxetine 30 mg indefinitely; this dose is subtherapeutic for both major depressive disorder and generalized anxiety disorder and will not adequately address the patient's symptoms. 1, 2
Do not prescribe a hypnotic without first implementing CBT-I; behavioral therapy is the standard of care and provides more durable benefits than medication alone. 5
Do not combine multiple sedating agents (e.g., adding a benzodiazepine to doxepin); this markedly increases the risk of respiratory depression, falls, cognitive impairment, and complex sleep behaviors. 5
Do not use trazodone, over-the-counter antihistamines, or antipsychotics for insomnia; these agents lack efficacy and carry significant safety concerns. 5
Do not prescribe long-acting benzodiazepines (e.g., clonazepam, diazepam) for insomnia; they accumulate with repeated dosing, cause prolonged daytime sedation, and increase fall risk. 5
Do not ignore orthostatic hypotension; duloxetine can cause orthostatic blood pressure changes, particularly in the first week of therapy or after dose increases. 1
Do not fail to reassess pharmacotherapy regularly; efficacy, side effects, and continued need should be evaluated every 2–4 weeks during the acute phase. 5, 1