Refer for ketamine immediately, as her long history of depression with multiple failed SSRI trials and passive suicidal ideation meets criteria for treatment-resistant depression warranting escalation to novel interventions.

Escalating to ketamine without verifying that prior treatments were adequate may skip effective and less intensive interventions. Many patients labeled 'treatment-resistant' actually had inadequate trials — subtherapeutic doses, short durations, or poor adherence.

Start ketamine immediately given her passive suicidal ideation and lengthy treatment history, as these clinical features together indicate urgent need for rapid-acting antidepressant intervention.

Passive SI ("wouldn't mind not waking up") requires risk assessment but does not mandate immediate ketamine. Ketamine has a specific evidence base and requires appropriate patient selection after confirming true treatment resistance.

Check a CYP2D6 genotype to determine her metabolizer status, as pharmacogenomic variation in drug metabolism is the most likely explanation for multiple SSRI failures in a patient with a 15-year history.

Pharmacogenomic testing may be useful but is not the most important assessment before ketamine. Most treatment failures result from inadequate trials or incorrect diagnoses, not genetic metabolism issues.

Verify that treatment resistance is genuine by confirming prior SSRI trials were adequate in dose and duration, the diagnosis is correct, and evidence-based augmentation strategies have been attempted.

"Treatment resistance" requires at least 2 adequate antidepressant trials (different classes, therapeutic doses, sufficient duration of 4-6 weeks with confirmed adherence). Many patients labeled "treatment-resistant" actually had inadequate trials — subtherapeutic doses, short durations, or poor adherence. Before pursuing ketamine, confirm: Were prior trials truly adequate? Is the diagnosis correct (screen for bipolar spectrum, personality disorders, chronic PTSD, substance use, and medical contributors)? Have augmentation strategies been tried (lithium, atypical antipsychotic augmentation, psychotherapy)? True treatment-resistant depression requires at least 2 adequate trials of different antidepressant classes.