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How common is treatment-resistant depression? Up to 30% of people with depression have treatment-resistant depression, meaning that they haven’t gotten better after trying at least two antidepressant medications for an appropriate length of time and in an adequate dose. How is a treatment-resistant depression diagnosis made? Your doctor will evaluate you on an ongoing basis to see whether your medications are working. If you don’t feel significant improvement after trying at least two different medications, you’re likely to be diagnosed with treatment-resistant depression. Your doctor may also base the diagnosis on your responses to depression scales and questionnaires. ....