Transcription
15 years ago, scientists put over 60 baby monkeys on Prozac. Now, this wasn't some kind of sick science experiment. It was due to concerns about how SSRIs might alter the normal trajectory of brain development in human children.
Now, for obvious ethical reasons, we can't just grab a bunch of human kids and randomize them to drug and placebo and see what happens. But we can do that with monkeys and then keep them in a controlled environment and watch them. And so, that's what we did. And so today we're going to talk about what happened to those 60 baby monkeys that were put on Prozac in childhood and what this might mean for human kids.
For those of you who don't know me, I'm Dr. Yseph. I'm a board-certified psychiatrist. I used to study drugs at the FDA and I'm an expert in drug safety.
Now the data we're going to be discussing today comes from Gula Vadal. These were the researchers who looked at the monkeys at UC Davis, about 30 of them. and Sherethsa. This was another group of researchers from the NIH um in Maryland who looked at the monkeys.
So, let's start here. Why did these researchers pick juvenile monkeys for this? Well, for a couple clear reasons. Baby monkeys have a long childhood period before they hit puberty. Their brains also develop complex cognitive functions just like human kids, like emotional functions, attentional, and social behavior. And also, their serotonin system responds to SSRI drugs very similarly to humans.
And so these two studies had very similar designs. They grabbed anywhere from 30 to 36 baby monkeys and they looked at them and half of the monkeys got fluoxitine and the other half got placebo. And these monkeys were given them at about 1 years old. And to put that in monkey terms, we live about four to four times longer than monkeys. So that's the equivalent of being about, you know, 4 to 6 years if you were like a human.
And the monkeys were given these drugs for about 2 years, meaning they kind of got off them at around maybe, you know, 12 years of age just before they hit adolescence. And then after that period, they were followed for another year to about 18 months. And so that's, you know, equivalent of like maybe another 4 to 6 years in human years. And that's when a lot of these post treatment follow-ups were done to see, hey, you know, were some of the changes we observed when they were on the drug, did they stick around afterwards or did they gradually go away over time?
And one more thing you should know about the design of these studies was that the monkeys were given doses of Prozac that would have been equivalent to the uh serum concentration in normal doses given to kids um therapeutically.
Now the researchers in these studies they looked at five major areas and that was sleep patterns, changes in social behavior, attention and cognitive functioning, emotional responsiveness and also changes in brain structure.
So let's jump into it. We're going to start by looking at the Golab group in UC Davis and what they found with sleep. So they were tracking sleep in the monkeys with activity monitors and these tracked nighttime awakenings or sleep fragmentation and also daytime naps. And here was the main finding. They found that Prozac was causing clear sleep disruption and that the monkeys on these medications woke up more often during the night and that sleep was more fragmented and there was less deep or restorative sleep. And these effects were present for the whole duration of treatment. But importantly as well, sleep disruption actually persisted after the Prozac was stopped in that 1 year to 18month follow-up. Now, we don't know what happened after that period of time, but it does suggest that that effect may be enduring in some of the monkeys.
Now, the next issue that Golab looked at in the Yushi Davis primate study was social behavior. And what they found was that monkeys who were on the medication, they actually had increased social interaction. And they characterized it as especially quiet and non-aggressive. However, these social changes did not persist after the monkeys came off the medication.
Now, this was actually different from the other study that was done by Shesta at the NIH because what they found was that during treatment with the medications, they saw reduced dominance behaviors amongst the monkeys on the medication, both during and after being on the medication. And this was with a fairly large effect size. This is 0.8. That's considered a moderate to large effect size to put it into context. anti-depressants in clinical trials, they usually have an effect size of 0.3. To have something of 0.8 is quite large. They also saw an increase in submissive behaviors as well and this continued after the drug was discontinued. The authors did note in the paper that this was a small study and they can't be certain statistically of those results, but the trends were certainly noteworthy.
And for me, this makes a lot of sense because one of the main effects of SSRI medications that you see with kids and adults is that for many of them, they can be blunting and they can reduce anxiety. And when that is happening to you, you might be a bit more mellow, a little bit less confrontational, a little bit less assertive. So that makes sense that they saw signs of decreased dominance and more submissiveness in those monkeys on those medications.
The next issue studied was attention and cognition. So going back to the UC Davis study. So the Golab program actually used computerized tests for the monkeys to assess the cognitive function of the monkeys over time. They wanted to to look at how they maintained focus and how accurately they responded to test questions. And what they found was that the monkeys on Prozac made more errors of omission. And this really reflected a reduction in sustained attention. They found that this effect was modest. It was consistent and [clears throat] it actually got worse when the task became more demanding. And this actually increased to about a 20% difference between the monkeys on the medications and the monkeys not on the medications. They also found that after the monkeys came off this the attention deficits persisted. However, on a positive note, two areas were not affected by the medication, and that was short-term memory and cognitive flexibility.
And so, the main thing to take away from this is that Prozac seemed to selectively impair sustained attention during treatment and after treatment for these baby monkeys. Now, this is relevant for young kids who get put on this medication because if this effect is actually carrying over, you may be at an increased risk of being diagnosed with ADHD. Now many people when they get that diagnosis they think oh you know I've just developed this neurological condition but it may actually be the result of neurological changes that have been caused by the drug during this period of critical development.
Moving on now let's talk about this emotional responsiveness. So going to the UC Davis program they assess this by showing the monkeys three different types of images. They showed them neutral images and also fear-provoking images. And then researchers would sit there and they would score the facial expressions of the monkeys, their vocalizations as well and how they responded to these images. And here's what they found. They found that fluoxitine caused a clear reduction in emotional expressiveness when they were looking at these images. The emotional response was essentially blunted across all image types. And this reduction was large. There were roughly 40 to 45% fewer observable emotional reactions. And what they found was that even after stopping the medication, the emotional blunting showed a trend towards persistence that did not reach statistical significance.
Now to me, this isn't surprising at all because when we look at kids and adults on these medications, they often report emotional blunting. And this is actually the therapeutic effect of the drug. You know, SSRI type medications are usually anxiety reducing medications that work through this mechanism. Now, some people like that a lot and that's very therapeutic, but other people say that, you know, it decreases their ability to feel joy. Now, I don't actually think this is going to be a persistent effect even though it was trending that way in monkeys because I've taken so many people off SSRIs and often times, you know, everything comes rushing back. So perhaps one of the reasons they didn't see this resolve was it might take a little bit longer than the follow-up period um in these studies which was about a year. Now that kind of surprises me that they didn't see it resolved but that's what I would suspect because I do not see emotional blunting uh continuing in adults and kids who are on these medications.
Now moving on. So the final issue was what happened to the structure of the brain on these medications. Now firstly starting with the goal lab program with the monkeys at UC Davis they took brain tissue samples from eight to nine monkeys from each group. So the prozac group and the nonprozac group and they looked at dendritic spine density. Now this is a complicated word. Essentially what it means was they were looking at the connections between the neurons in the preffrontal cortex. And this really reflects how brain connections are refined during neurological development. you know uh synaptic pruning and changes in dendrites is very characteristic of brain maturation. So they wanted to see how that was affected by you know the brains being on these drugs and what they found was that there was a pattern towards lower spine density. So this is decreased connections in the Prozac treated monkeys. However, this did not reach statistical significance likely due to the small sample size. And so what they're saying is there was a trend in that direction which probably would have hit statistical significance if they had more monkeys. And so that study on its own is is kind of concerning. It is showing that there is changes in the structure of the brain from from these medications.
But let's move on now and look at the NIH study by Sha and they looked at the brain differently. They used PET brain imaging. And so all of the monkeys were scanned in this study. The PET brain scan was done while they were on the drug and then also 18 months after they came off. And they were really interested in the serotonin system. And what they found was that Prozac caused persistent increases in serotonin transporter binding even after they came off the medications. These effects were seen in the lateral temporal cortex, the singulate cortex and the hippocampus. So these are multiple different uh brain regions which are now essentially showing uh different wiring in the serotonin system. And all of these changes were still present well into young monkey adulthood.
And so to recap what the two largest primate studies in baby monkeys found was that there were sleep disruption, social behavioral changes, attentional changes, changes in emotional responsiveness or blunting, and also changes in brain structure. And most of these things persisted into young monkey adulthood.
And so what does this mean for human children? So obviously monkeys aren't kids, but honestly they're the closest thing that we have to human kids in hypothesizing what might happen. And so what I think is very clear and what I think would translate clearly to human kids is that these drugs if you give them during this critical period of neurological maturation there can be some changes one in the brain biology but also in the behaviors of these kids.
Now one of the clear limitations of this study was that the monkeys were only studied for up to 18 months after they came off the drug. And so that's about six human years later. Would these changes have persisted afterwards? We don't really know but at least the findings now are suggesting that some of them may be enduring.
So I think the clear takeaway from this study is that taking medications you know firstly if you're a pregnant woman and you have a baby on board or you know giving medications to your young children who are going through neurological development. So I would say this is clearly under age 18. This should be a very big decision and a very very serious one and you should not let a doctor rush you into putting your kid on one of these medications and you should work with someone to find all of the non-drug approaches that may help you or your child avoid taking a medication that could cause some of these enduring issues afterwards.
So, we're going to leave it there for now. If you found this video interesting, please consider liking it if you think someone may enjoy it. Share it with a friend and also subscribe to the channel if you enjoy hearing about psychiatric research that many doctors don't share with their patients. And finally, although we don't treat monkeys in our medical practice, we actually help humans. And so, if you are someone who wants help coming off these medications and also finding non-drug approaches to them, be sure to check the link below where we have our website and you can see if we're a good fit for you. Thank you.