When Medication Alone Is Not Enough

Treatment-resistant depression, or TRD, is generally defined as major depression that has not improved after adequate trials of at least two different antidepressant medications. Roughly 30 percent of people treated for depression meet this definition. It does not mean your depression is untreatable. It means standard first-line medications have not been the right fit, and more targeted approaches may be needed.

Your psychiatrist will review your full treatment history, including which medications you have tried, the dosages used, how long you took each one, and whether you experienced any partial improvement. They will also rule out other factors that could be affecting your response, such as an incorrect initial diagnosis, medication interactions, or co-occurring conditions like anxiety or a thyroid disorder.

Several evidence-based options exist beyond standard antidepressants. TMS therapy uses magnetic pulses to stimulate brain regions involved in mood regulation and is FDA-cleared for depression. Spravato (esketamine) is an FDA-approved nasal spray that works through a different brain pathway than traditional antidepressants. Ketamine therapy combines the rapid-acting effects of ketamine with structured therapeutic support. Your psychiatrist may also explore medication augmentation or combination strategies.

Many insurance plans now cover TMS therapy specifically for treatment-resistant depression. Coverage typically requires documentation of prior medication trials that did not provide adequate relief. Spravato is also covered by many insurers as an FDA-approved treatment. CARMAhealth accepts 15+ insurance plans and handles verification on your behalf. Visit our insurance page or call (512) 212-4670 for details.

Timelines vary by treatment. TMS therapy typically involves daily sessions over four to six weeks, with many patients noticing improvement within the first two to three weeks. Spravato is administered twice weekly initially, with some patients reporting improvement within hours to days. Ketamine therapy often shows results within one to six sessions. Your psychiatrist will monitor your progress and adjust the plan as needed.