Treatment Approach for Treatment-Resistant Depression with Suicidal Ideation in an Elderly Patient
Given the treatment failures with two SSRIs (sertraline and escitalopram), intolerable sedation with brexpiprazole augmentation, and the need to discontinue benzodiazepines, I recommend switching to either venlafaxine (an SNRI) or mirtazapine as the next antidepressant trial, while simultaneously considering electroconvulsive therapy (ECT) consultation given the severity of suicidal ideation and multiple treatment failures. 1
Immediate Safety and Benzodiazepine Management
The suicidal ideation requires close monitoring and potentially more intensive intervention, particularly during the lorazepam taper and antidepressant transition, as elderly patients are at lower risk for antidepressant-induced suicidal ideation compared to younger patients (6 fewer cases per 1000 patients ≥65 years) 2
Taper lorazepam gradually over 10-14 days minimum to limit withdrawal symptoms, which could exacerbate depression and suicidal thoughts 1
The patient's subjective improvement with lorazepam likely reflects anxiolytic effects rather than true antidepressant response, and continued benzodiazepine use poses significant risks in elderly patients including cognitive impairment and falls
Next Antidepressant Selection
Switch to a medication with dual noradrenergic and serotonergic action, as this represents one of the most effective strategies after SSRI failure 3:
Primary Options:
Venlafaxine (starting 37.5 mg daily, maximum 225 mg): An SNRI that targets both serotonin and norepinephrine systems, with moderate-quality evidence showing no difference in efficacy when switching between antidepressants, but the dual mechanism may provide benefit after pure SSRI failures 1
Mirtazapine (starting 7.5 mg at bedtime, maximum 30 mg): Particularly advantageous in this patient as it is "potent and well tolerated; promotes sleep, appetite, and weight gain" - addressing potential insomnia from benzodiazepine withdrawal 1
Bupropion SR (starting 100 mg daily, maximum 400 mg): An activating option that works through dopamine/norepinephrine mechanisms, completely different from prior SSRIs. However, avoid if the patient has significant agitation 1
Dosing Considerations for Elderly Patients:
Start at approximately 50% of standard adult starting doses due to significantly greater risk of adverse drug reactions in older adults 1
Why Not Continue Augmentation Strategies
Brexpiprazole caused excessive somnolence, which is a known adverse effect of this adjunctive antipsychotic 4, 5
Low-quality evidence shows no difference between augmentation with other agents (bupropion, buspirone) versus switching strategies after initial SSRI failure 1
Given two SSRI failures, switching to a different mechanism is more rational than augmenting a failed SSRI 3
Electroconvulsive Therapy Consideration
ECT should be strongly considered and discussed with the patient, as it "may be required in patients who are at risk of injuring or starving themselves, patients who are severely psychotic, and patients who cannot tolerate or do not respond to antidepressants" 1
Evidence suggests ECT may be more effective than antidepressant drugs in reducing the frequency of suicide attempts 6
This is particularly relevant given the combination of suicidal ideation and multiple medication failures
Monitoring During Transition
Close surveillance is essential during the medication switch, particularly in the first 4-8 weeks:
Monitor for worsening suicidal ideation, though risk is lower in elderly patients compared to younger adults 2, 7
The patient experienced worsening with sertraline, which occurred in approximately 4% of patients in large trials, with 7% experiencing treatment-emergent suicidal ideation 7
Risk factors for treatment-emergent suicidal ideation include severe depression, which this patient likely has given multiple treatment failures 7
Alternative Considerations if First Switch Fails
If venlafaxine or mirtazapine fails after adequate trial (6-8 weeks at therapeutic dose):
Nortriptyline (10 mg at bedtime, maximum 40 mg daily): A secondary-amine tricyclic with "tolerance profile similar to desipramine, but more sedating; may be useful in patients with agitated depression and insomnia" with therapeutic blood level window of 50-150 ng/mL 1
Avoid tertiary-amine tricyclics (amitriptyline, imipramine) as they are considered potentially inappropriate in elderly patients per Beers Criteria due to significant anticholinergic effects 1
Non-Pharmacologic Augmentation
Cognitive behavioral therapy (CBT) should be offered concurrently with medication changes, as moderate-quality evidence shows similar efficacy between switching to another antidepressant versus switching to CBT, and combination therapy may provide additive benefits 1
Supervised aerobic exercise could be considered as adjunctive therapy, with evidence showing no difference in remission compared to sertraline monotherapy but lower discontinuation rates due to adverse events 1
Treatment Duration
Continue treatment for at least 4-12 months after achieving remission for a first episode, though this patient with treatment-resistant depression and suicidal ideation may require prolonged or indefinite treatment given the high recurrence risk 1