I've been on zoloft for about two years one time, and about a year and a half this time. I've heard you can take it forever. I think you're asking how long one can safely be on this medication and about what the long-term effects on the brain are. I'm not sure about this, and honestly don't know if the psychiatric world has a clear answer. I may just ask my pdoc the next time I see him and see what he says. Maybe others who have been on these drugs long-term, for years, might have an oppinion.