An elderly patient with diabetes, depression, and hypertension on fluoxetine, metformin, and Lisinopril presents with insomnia and irritability, what is the next best step in management?

Evaluate for Medication-Induced Insomnia First: Check TSH and Consider Changing Fluoxetine

The most appropriate next step is A - TSH and thyroxine level, followed by consideration of changing fluoxetine (option C) if thyroid function is normal, as SSRIs are a well-documented cause of insomnia and irritability in elderly patients. 1, 2

Rationale for TSH Testing First

The combination of insomnia and irritability in an elderly patient warrants immediate evaluation for thyroid dysfunction, as these are classic presenting symptoms of hyperthyroidism that can develop at any time. 3 Additionally:

• Thyroid disorders are common medical causes of insomnia that must be ruled out before attributing symptoms to medication side effects or psychiatric causes. 4
• Hyperthyroidism directly causes both insomnia and irritability through metabolic mechanisms, making it a critical differential diagnosis. 3
• TSH testing is straightforward, inexpensive, and immediately actionable, providing definitive information to guide next steps. 3

Why Fluoxetine is the Likely Culprit if Thyroid is Normal

Fluoxetine is explicitly listed as a common contributor to insomnia in elderly patients, and the FDA label specifically warns about insomnia and irritability as adverse effects requiring monitoring. 1, 2

Evidence Against Fluoxetine:

• SSRIs including fluoxetine are documented to cause or exacerbate insomnia in the American Academy of Sleep Medicine guidelines. 1
• The FDA label for fluoxetine explicitly lists insomnia, irritability, agitation, and anxiety as symptoms that should prompt evaluation and possible medication adjustment. 2
• These symptoms can emerge at any time during treatment, not just at initiation, and may indicate need for medication changes. 2

Why Other Medications Are Less Likely:

• Metformin does not cause insomnia or irritability; in fact, research suggests it may have mild antidepressant effects and improve depression symptoms in diabetic patients. 5, 6, 7
• Lisinopril is not associated with insomnia or irritability as primary side effects. 1

Why NOT Psychiatric Referral (Option B) at This Stage

Psychiatric referral is premature before ruling out medical and medication-induced causes, as this represents standard medical evaluation rather than primary psychiatric pathology. 1, 4

• Medical causes including thyroid dysfunction and medication side effects must be excluded first before attributing symptoms to psychiatric disease progression. 4
• The patient already has established depression treatment with fluoxetine, making medication adjustment more appropriate than referral if symptoms are medication-induced. 2
• Referral would be appropriate only after medical causes are ruled out and medication adjustments fail to resolve symptoms. 1

Recommended Management Algorithm

Step 1: Immediate Laboratory Evaluation

• Order TSH and free T4 to rule out hyperthyroidism as the cause of insomnia and irritability. 3
• If TSH is abnormal, treat thyroid disorder appropriately and reassess symptoms. 3

Step 2: If Thyroid Function is Normal

• Consider switching from fluoxetine to an alternative antidepressant with lower insomnia risk, such as mirtazapine (which is sedating and may help both depression and sleep). 8
• Alternative approach: Add low-dose doxepin 3-6mg specifically for sleep maintenance if continuing fluoxetine is preferred for depression control. 8, 9

Step 3: Implement Cognitive Behavioral Therapy for Insomnia (CBT-I)

• CBT-I should be initiated regardless of medication changes, as it provides superior long-term outcomes for insomnia. 1, 8
• Key components include: stimulus control (use bedroom only for sleep), sleep restriction (limit time in bed to actual sleep time), sleep hygiene education (avoid caffeine, maintain regular schedule), and relaxation techniques. 1

Step 4: Avoid Common Pitfalls

• Do not add benzodiazepines or Z-drugs (zolpidem, eszopiclone) in elderly patients due to fall risk, cognitive impairment, and dependency concerns. 8, 9
• Do not use over-the-counter antihistamines (diphenhydramine) due to anticholinergic effects and delirium risk in elderly. 8, 9
• Do not continue fluoxetine unchanged if it is the cause, as symptoms will persist and quality of life will remain impaired. 2

Special Considerations for This Patient Population

Elderly diabetic patients on multiple medications require careful evaluation of drug-drug interactions and medication-induced symptoms before adding new treatments. 1, 4

• Fluoxetine's long half-life (4-6 days) and active metabolite (7-9 days) mean symptoms may persist for weeks after discontinuation, requiring patience during medication transitions. 2
• Depression in diabetic patients is associated with poor glycemic control, making effective antidepressant treatment essential, but not at the cost of severe insomnia. 10, 6
• If switching antidepressants, consider mirtazapine as it treats depression, aids sleep, and has favorable metabolic profile in diabetic patients. 8, 9