My doctor tells me that I am “drug resistant” and I can’t seem to find a medication that helps. Any suggestions?

Before talking about next steps, we should be careful to use words that put the blame where it belongs. I wouldn’t say that you are “drug resistant”. I suspect you really do want medications to work for you, and you’re probably doing everything you can to help out. If the medications haven’t helped you, it may mean that your mood disorder is “drug resistant”. Or maybe some of your brain receptors are “drug resistant”. This may sound like splitting hairs, but I think the difference is important. We certainly need to move away from old-fashioned ideas that patients’ “resistance” is the reason why treatments sometimes don’t work. Unfortunately, the treatments you’ve tried have failed. But you haven’t failed.

When medications that are usually effective for treatment of mood disorders don’t work, there are some questions we should be sure to ask:

1. Do we have the wrong diagnosis? Standard antidepressant medications may not help if the correct diagnosis is actually bipolar disorder. Many people with bipolar disorder have taken medication for depression for years before arriving at a correct diagnosis.
2. Is some other chemical getting in the way? Alcohol and street drugs (including marijuana) can certainly interfere with the effectiveness of antidepressant or mood stabilizer medication.
3. Did we give it a good enough try? Most medications for depression or bipolar disorder take two weeks or more to really work. The full benefit may not be clear for a month or more. And the dose needs to be high enough.  For several mood stabilizer medications and some antidepressant medications, measuring blood levels can clearly indicate if the dose is high enough to be effective.

And sometimes, we just have to keep trying. Research on “drug resistant” depression shows that persistence can pay off.  Only about 40% of people who start taking an antidepressant have a significant benefit from it. Another 25% will benefit from a second medication. If we continue to try a third and even fourth medication, the percent of people who benefit does go down, but it’s still more than zero.

Some day we hope to have more scientific methods of predicting what medication to try when other medications have not worked. For now, the best tools we have are persistence, hope, and paying attention.