According to Dr Joseph Glenmullen in
Prozac Backlash studies have shown that some serotonin boosters exhibit signs of neurotoxicity. A study on a drug called Redux (abruptly recalled from the market in 1997 because of heart valve damage) examined the possibility of neurotoxicity.
Under the microscope, as they are injured, the axons look "swollen," "irregularly shaped," and "seemingly fragmented." In one study, monkeys treated with the drug for just four days showed evidence of "persistent" and "possibly permanent" damage more than a year later... If the damage is not too severe, the neurons sprout new branches in what literally amounts to a rewiring of the brain.
Prozac Backlash, p. 96.
Those experiments were done with a dose similar to what humans take for 6 months... a year... sometimes a decade or more. The "antipsychotics" (also known as major tranquilizers) fell out of favor once severe, permanent side effects such as tardive dyskinesia were revealed over a span of 20-30 years. Prozac and many SSRIs came into fashion in the 1990s, which means we are just now at the cusp where the long term effects will begin to be revealed. Conveniently, just after the patent expires, but that's a different story. The main problem is that the brain can sustain quite a bit of damage and still function. You can think of it as sort of a buffer or safety margin that has to be consumed until problems show up. However, aging has detrimental effects on the brain as well. This means that damage may be done by drugs earlier in life that won't reveal themselves until later, once the brain starts deteriorating from aging effects.
Studies of Ecstasy [MDMA] have shown that when damaged neurons sprout new branches, the rewiring of the brain is "highly abnormal," a chaotic jumble that does not follow the original pattern. Most alarming, researchers are concerned that the neurotoxicity could cause "increased risk for developing age-related cognitive impairment." Indeed, they are explicit that the "aberant reinnervation [abnormal rewiring of brain cells] such as that seen after MDMA injury may also occur during the course of neurodegenerative diseases [e.g., Parkinson's and Alzheimer's disease]. This is especially worrysome because patient with Alzheimer's type dementia "have significant 5-HT [serotonin] deficits in brain regions implicated in learning and memory" as well as deficits in other neurotransmitters.
Prozac Backlash, pp. 96-97
To be fair, Ecstacy is a serotonin releaser that will cause a sudden release of massive amounts of serotonin. However, most Ecstacy users don't pop pills every day, so it is an acute case vs the chronic case of SSRIs. Dr. Monika Wrona, writing in a June 1997 article published in the National Institude on Drug Abuse Research Monnograph Series, stated that serotonin is "very easily oxidized into a serotonergic neurotoxin." Dr. McCann at NIMH speculated that such damage to the brain caused by serotonin toxicity may be why the effect of the drugs wear off over time.
Regardless of whether it is brain damage from neurotoxicity or simply the brain adapting to the presence of a foreign drug, the before and after pictures are dramatic. Would you take a pill every day for months or years that did this?