Emily4040 - There seems to be some validity in the phenomenon of when stopping an SSRI and then taking it again, the SSRI often doesn't work as well as an antidepressant as it did when it was first taken. I have seen this with all the SSRIs at least once, including Zoloft™ (sertraline), Paxil™ (paroxetine), Prozac™ (fluoxetine), Luvox™ (fluvoxamine) and Celexa™ (citalopram). I haven't "personally" seen it occur with Lexapro™ (escitalopram), but I do assume that it has happened.

This is not to say that an SSRI never works as well as on the second trial, just that sometimes it definitely does happen. I have seen it happen when someone has stopped an SSRI too soon (ie. before the body has had a chance to adjust from a depressive state to a euthymic state) and also when that SSRI had work for an initial deppressive, but when tried for a subsequent depressive episode (eg relapse of depression). This can be frustrating for both the person with depression and for the clinician.

There is no obvious reason for an antidepressant not to work a second time, but it does happen; and although it does not happen all of the time, it is not a rare occurance, but then again it does not happen every time.

When using an SSRI, I do suggest that, if the SSRI is controlling the depression (ie. helps to alleviate depressive symptoms), one should remain on that SSRI for at least 9 months after euthymia (ie. absence of depression) is acheived. This (hopefully) gives the body the time it needs to start producing enough serotonin on it's own. Since I do not know why this happens I always recommend staying on an SSRI, if it is working, for at least a year after attaining euthymia.

The old adage of "don't fix it if it ain't broken" definitely applies to SSRI. I have seen other psychiatric meds not work as well on retrial, with lithium being the classic medication that seems not to work second time around. Many clinicians (eg psychiatrists) do not believe that this is true. Many studies show that lithium works just as well the second time; many psych nurses that I know will disagree.

I have seen this effect wih other psychiatic medication like the atypical antipsychotics. (eg. Zyprexa™ - olanzapine and Risperdal™ -ripseridone) and even mood stabilizers like Tegretol™ (carbamazepine) and Epival™/Depakote™ (divalproex), but to nowhere near the extent that it happens with lithium and the SSRIs.

That said, I really do not have scientific proof of this happening, but I suspect that most clinicians have seen it at least once. Often a failure upon second trial has been explained away as noncompliance on the part of the patient, but I know that this is not true in a majority of cases.

Another problem with SSRIs is the phenomenon of "poop-out". Someone taking an SSRI initially experiences some degree of remission of their depressive symptoms, but after 6 or 8 months the medication stops working, for seemingly no apparent reason. Like the above situation, this can be terribly frustrating, but, alas, it does happen. Again, I have no proven scientific explanation of why this happens. Raising the dose in both cases does not seem to fix the problem; Interestingly, a couple of times I have seen that a slight lowering in SSRI dose after poop-out did result in restored antidepressant activity. Alas, I have only seen this work a few times; most times lowering the dose did nothing.

Unfortunately, all I can say is that these phenomenon do apparently exist, and one must change medications. Sometimes changing from one SSRI to another fixes both poop-out and retrial failure, which is also puzzling.

Another thing that I should mention is that SSRIs to not "cure" depression. They are only a tool that resolves depressive symptoms enough so that one can "fix" the problems in their life that brought on the depression in the first place. In chronic depression, resulting in large part from genetic factors, one may have to stay on the SSRI for life, but a change of lifestyle to reduce stress does seem to help someone remain euthymic longer and also improve the quality of one's life.

I hope that this is sorta clear. - Cam