Your experience that an antidepressant seems to wear out after several years is, unfortunately, fairly common. At this time, we don’t understand the biology of antidepressants “pooping out” (as some have called it). But we certainly know that it happens. If it does, we first ask if there’s some underlying reason—like a major loss or stressful event, some other health problem, using alcohol or street drugs, or a change in some other medication. If there’s a specific reason, then there may be a way to turn things around, like counseling to deal with a stressful situation or cutting down on alcohol use.
It’s also important to be sure that an “old faithful” medication is at the most effective dose. Increasing the dose is simple, usually safe, and often helpful. Recent research shows that the most effective doses of many antidepressants may be higher than those doses recommended in the past.
If those steps aren’t appropriate or aren’t effective, then changing medication can certainly be helpful. We do know that trying a different medication or adding a “booster” medication both have a reasonable chance of success. And if a second medication isn’t helpful, it’s reasonable to try a third or even a fourth. While we know that trying a different medication can work, we don’t yet know much about which one is best. Research about choosing the best specific medication for any individual has not yet provided much useful guidance. For now, the best we can do is to be persistent and logical about trying a different medication and giving it enough time to work.
It may seem discouraging that the newer medications you’ve tried have all caused you problems or side effects. But that situation is actually more hopeful than if they were all ineffective at a full dose. If a first medication “fails” because of side effects, that means that a different medication has a higher chance of working, compared to that first medication that just doesn’t work).
In general, we recommend combined treatment (antidepressant medication and psychotherapy) for people with more recurrent or chronic depression. When multiple antidepressant medications really have been ineffective, there are other physical treatments, like transcranial magnetic stimulation or vagal nerve stimulation that may be effective.