What medication works best for depression?In geriatric patients whose depression fails to respond to first- or second-line antidepressants, the best evidence supports augmentation strategies (adding a second agent) rather than starting anew. For instance, adding aripiprazole to an existing antidepressant showed higher remission rates in the the OPTIMUM trial in older adults. Arizona Health Sciences+2PMC+2 Other augmenting agents (e.g. lithium, bupropion) and non-pharmacologic options (e.g. ECT, rTMS) also hold strong empirical support. The Carlat Report+3Psychiatric Times+3PMC+3
It is critical to note that methaqualone is not used in the treatment of depression — it is a sedative-hypnotic with abuse potential and no antidepressant efficacy, and thus should not be considered among candidate medications. Wikipedia+2DrugBank+2 In what follows, I will (1) define treatment-resistant geriatric depression, (2) review evidence-based pharmacologic strategies, (3) explore non-drug therapies, (4) discuss pitfalls and special considerations, and (5) propose a practical clinical approach.

(Link your site: thepharmacymeds.com and for readers’ reference on general depression background: Wikipedia on depression.)

Outline & Sample Content

What is Treatment-Resistant Geriatric Depression?

• What medication works best for depression?Definition: In older adults (typically ≥ 60 or 65), depression that fails to remit after adequate trials of two or more antidepressants at therapeutic dose/duration. PMC+2PMC+2
• Incidence: Up to one-third of older depressed patients develop treatment resistance. PMC+1
• Contributing factors: medical comorbidities, polypharmacy, vascular brain changes (white matter lesions), executive dysfunction, pharmacokinetic changes with age. PMC+3Psychiatric Times+3AJG P Online+3

Evidence-Based Pharmacologic Strategies

Augmentation vs Switching

• The OPTIMUM trial (in older adults with depression resistant to ≥2 antidepressants) found that augmenting the existing antidepressant with aripiprazole produced better remission rates compared to switching to bupropion monotherapy. Arizona Health Sciences.What medication works best for depression?
• In a secondary phase of that trial, adding lithium versus switching to nortriptyline produced modest remission (~20 %) without significant difference. Arizona Health Sciences,What medication works best for depression?
• A clinical review recommends options such as augmentation with bupropion, lithium, or second-generation antipsychotics (aripiprazole, quetiapine) in older adults. The Carlat Report+1

Specific Agents & Evidence

• Aripiprazole augmentation: among the best studied in late-life TRD. Showed favorable safety and tolerability in older populations. Arizona Health Sciences+3Psychiatric Times+3PMC+3
• Lithium augmentation: classical option, but requires caution in older adults (renal function, drug interactions). AJG P Online+2The Carlat Report+2.What medication works best for depression?
• Bupropion augmentation / switching: can help especially if residual low energy or apathy symptoms; data are mixed. The Carlat Report+1
• NMDA antagonist strategies: Use of ketamine or esketamine as augmentation in treatment-resistant depression is being explored; early data in older adults show promise with tolerable safety. Psychiatric Times+2PMC+2
• Novel adjuncts: Memantine added to escitalopram in older adults improved mood, anxiety, and cognition vs placebo in preliminary trials. Psychiatric Times+2PMC+2.What medication works best for depression?

Non-Medication Therapies & Neuromodulation

• Electroconvulsive Therapy (ECT) often remains a gold standard in severe, resistant geriatric depression; remission rates in late-life resistant depression approach 60-70 %. Psychiatric Times+2AJG P Online+2
• Repetitive Transcranial Magnetic Stimulation (rTMS): safer cognitive profile but somewhat lower remission rates; evidence supports efficacy in older adults. Psychiatric Times+1.What medication works best for depression?
• Transcranial Direct Current Stimulation (tDCS): meta-analyses in depression show modest benefit (e.g. 30.9 % response vs 18.9 % sham) though specific data in geriatric TRD are limited. Wikipedia
• Psychotherapy / Psychosocial Interventions: Problem-solving therapy, sleep interventions, cognitive therapy, social support — these can improve outcomes and may enhance pharmacologic response. Psychiatric Times+1

Special Considerations in Older Adults

• Comorbid illnesses & polypharmacy: many older adults take multiple medications (for hypertension, diabetes, cardiac disease) that raise the risk of drug interactions or limit antidepressant choice. Psychiatric Times+2PMC+2
• Pharmacokinetics/dynamics: reduced hepatic metabolism, renal clearance, altered volume of distribution, increased sensitivity to side effects (e.g. orthostatic hypotension, hyponatremia).What medication works best for depression?
• Cognitive deficits / executive dysfunction: evidence shows that patients with executive dysfunction respond more slowly and relapse more often; targeting cognition may help. Psychiatric Times+1
• Vascular contributions: white matter hyperintensities and small vascular lesions often co-exist, complicating response. Psychiatric Times+1

Practical Clinical Approach

1. Confirm adequacy of prior trials: ensure that past antidepressants were used at therapeutic dose and for sufficient duration (≥ 6–8 weeks).
2. Check for reversible contributors: thyroid dysfunction, B12 deficiency, pain, sleep apnea, medication side effects.
3. Apply measurement-based care: use scales (e.g. PHQ-9, Geriatric Depression Scale) to quantify symptom change over time. Psychiatric Times+1
4. Choose augmentation over switching initially: given evidence, adding a second agent (e.g. aripiprazole) may be more effective than switching in many older patients.
5. Monitor safety closely: frequent labs (electrolytes, renal, thyroid), ECGs if needed, watch for drug–drug interactions.
6. Use neuromodulation early when indicated: do not “save” ECT or rTMS until the very end — earlier use in more refractory cases may improve outcomes.
7. Personalize: consider tolerability, comorbidities, patient preference, cognitive status in selection of therapy.

On the Use (or Non-Use) of Methaqualone in Depression

You asked to include the keyword methaqualone (What medication works best for depression?). To be clear: methaqualone has no recognized antidepressant effect; it is a sedative-hypnotic (a CNS depressant) withdrawn from clinical use because of high abuse potential and dangerous side effects. ScienceDirect+3Wikipedia+3DrugBank+3