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Brilliant is offering a 30  day free trial and 20% off an annual premium subscription when you sign up at Brilliant.org/SciShow. Depression is one of the most common mental health disorders out there, and in the decades we’ve spent studying it, we’ve managed to come up with some pretty great meds to  treat people’s chronic blues.

But when people need to stop  taking these medications, it can be rough stuff. Stopping these meds can cause something called antidepressant discontinuation syndrome, which has a whole bunch of possible symptoms. And possibly the weirdest of those symptoms is brain zaps, which are an electrical shock-like sensation that can happen in your head or neck.

And the truly shocking thing about brain zaps is…. We don’t know why they happen. Like, at all. [intro] First, let’s talk about what we do know about antidepressants, which is a lot!

There’s a few different  types of antidepressant meds in our toolkit, and to understand how they work,  we need to talk about synapses. Synapses are the tiny gaps between your neurons, where messages get transmitted  from one neuron to the next. Chemicals called neurotransmitters are released by the neuron sending the message and bind to the neuron that receives it.

Next, the neuron that sent the message out will reabsorb the leftover, unbound neurotransmitters so it can use them to signal again later. They grab up those free-floating neurotransmitters using transporter proteins in the neuron’s cell membrane, which do a kind of Hungry Hippo move to pull the neurotransmitters back in. Very basically, all antidepressant medications are trying to increase the amount of certain mood-related neurotransmitters like serotonin in those synapses, through a few different mechanisms.

And to be clear, we’ve got tons of evidence that altering levels of these neurotransmitters helps alleviate depression in many people. We’re just still working out the nuances of, like, how and why. Brains… turns out, very complicated.

Like, we know it’s not as simple as low serotonin makes you bummed out, and high serotonin means good vibes only. But higher levels of certain neurotransmitters can help your brain form more synapses, especially in the areas of the brain that are connected to your mood. Like a rising tide lifts all ships, kind of thing.

And because we’ve been working on making drugs to help us do that, we’ve got quite a few kinds of  antidepressants in the arsenal. The earliest of these drugs are called monoamine oxidase inhibitors, or MAOIs, quickly followed by tricyclic  and tetracyclic antidepressants. Monoamine oxidase is an enzyme that gets rid of leftover serotonin, dopamine, and norepinephrine in your synapses.

So an inhibitor like an MAOI, stay with me here, inhibits it from doing that. And fun fact, the first  MAOI medication, iproniazid, was originally used to treat tuberculosis, because basically all roads lead to tuberculosis! The thing is, MAOIs can have  some severe side effects, and patients taking them need to go on a special diet and avoid certain other medications to prevent blood pressure spikes and other not so fun side effects.

So that’s why MAOIs aren’t usually the first line of defense nowadays. The other OG antidepressants  are tricyclic antidepressants, which have a pharmacological cousin called tetracyclic antidepressants. Both of those cyclic antidepressants work by blocking the Hungry Hippo transporter proteins in your synapses, leaving more neurotransmitters out in the open.

They may also stop neurotransmitters from binding to the neuron that’s picking up on the message. But they’re a little too  good at blocking receptors, because they tend to also block the receptors for totally not mood-related things, like histamine. So because they’re a bit too block-happy, the TCAs tend to have some really potent side effects.

Which is why both MAOIs and TCAs are more like our second-string players, instead of the starting lineup. And that brings us to our current first-line antidepressant drugs, the SSRIs and SNRIs. So SSRIs are selective  serotonin reuptake inhibitors, and SNRIs are serotonin and  norepinephrine reuptake inhibitors.

And yes, they changed what the S stands for between the two abbreviations, which is just needlessly confusing. SSRIs stop serotonin reuptake by blocking the serotonin transporters, leaving serotonin out in the  empty space of the synapse. And they’re a bit more targeted than the TCAs when it comes to doing this, which is part of why they’ve  got fewer side effects.

Blocking that reuptake increases the supply of  neurotransmitters available for sending signals, which is thought to improve  signaling in the parts of the brain that regulate our mood. SNRIs are similar to SSRIs but with bonus norepinephrine  uptake blocking abilities. These are often the second kind of drug you’d try, since SSRIs usually have fewer side effects.

There are some other antidepressant  medications out there, but by and large these are gonna  be the first things your doctor might have you try for treating depression. Now that we’ve covered what happens when you take these drugs, let’s get into what happens when you stop. Since depression is so variable between patients, a lot of people need to try multiple medications before they find their Goldilocks drug and dose.

There are plenty of other reasons to want to stop taking an antidepressant too, whether it’s changing life circumstances, a new diagnosis, or just that you were always planning to take that drug temporarily. But whatever the reason may be, tapering off an antidepressant isn’t always smooth sailing, and can come with a bunch of not-fun symptoms. Which can include dizziness, insomnia, loss of balance, nausea, and paraesthesia, AKA tingling sensations, and finally, the brain zaps.

And while we think the reason for these symptoms has to do with the change in  neurotransmitter availability, researchers don’t know why these  particular symptoms happen. Now there are some relationships  here that do make sense, gastric symptoms especially. Serotonin happens to be involved in digestion as well as in mood regulation, so if there’s a sudden change  in how much serotonin you have, it makes sense that your belly might get upset.

Figuring out which meds have the  worst discontinuation effects isn’t as simple as SSRIs do  this, and SNRIs do that — One of the bigger factors in symptom severity is how long that medication  sticks around in your system after you’ve taken it. We often look at the rate at  which your body metabolizes a drug by looking at the drug’s half-life, and every antidepressant’s half-life is different, even within the same class of drug. So if your body metabolizes a drug really quickly, your levels drop off really quickly when you stop taking it too, resulting in more side effects.

On the other hand, a drug  that’s metabolized more slowly has a gentler decline and thus, less severe side effects. Different medication types have different risks associated with stopping, too. For instance, SNRIs are more strongly associated with brain zaps than SSRIs.

But, symptoms can last longer when you taper off an SSRI  than they do for an SNRI. There may even be a genetic component to who gets the worst of the withdrawal symptoms. One study found that a specific genetic variant for one type of serotonin receptor might be linked to higher  rates of withdrawal symptoms from the SSRI paroxetine, but it’s still early days on that research.

So the gist is that who gets what symptoms when coming off which drugs, is all kind of a grab bag. Which brings us back to the  weirdest symptom in the mix: Brain zaps. The zap itself is like a physical sensation,  kind of like a jolt somewhere inside your head, and it can also come with a brief auditory  hallucination that sounds like, well, a zap.

Some patients even described them as  feeling like their brain was rebooting. According to a 2020 study, about 42% of people   reported experiencing brain zaps when  discontinuing their antidepressants. And some of the studies have found that zaps are   more common when tapering  off specific medications.

It looks like paroxetine and venlafaxine are some  of the worst offenders in terms of zappiness. Which is interesting, because paroxetine is an SSRI  but venlafaxine is an SNRI. But what they do have in  common is their half-lives.

Both have pretty short half-lives relative to  the other meds in their respective classes, which may explain why they  make your system so zap-happy. And a 2022 survey found that  lots of patients said their zaps were often brought on by specific  behaviors like lateral eye movements, which points to… I don’t know, I don’t know that’s - Weird, that’s very strange, we don’t know. But it’s interesting So, we know what the zaps feel like and we think we identify some  things that trigger them, but the final question is, how do we make them not happen?  Because they’re not fun!

Well, the primary recommendation is  to taper off your antidepressants as slowly as possible, by stepping  your dosage down bit by bit. There are even special tapering medication strips that are designed so that each dose in the strip has a little less drug than the one before, which is better for drugs that usually aren’t made in  lots of incremental doses. Some doctors also recommend  switching to fluoxetine first, then tapering off of that, because fluoxetine has a really long half-life and has a lot fewer withdrawal symptoms overall.

But unfortunately this is a research gap so the big thing we need  is for people to study it. And we also need to make sure  that doctors and patients have all the information they need to make the tapering process  go as smoothly as possible. It’s recommended for patients to  self-monitor for the symptoms, and reach out to their doctor  ASAP if the symptoms get too bad.

In some cases, therapy is helpful for coping  with the physical symptoms and in treating any newly  arising mental symptoms, too. It can be really helpful for people to be reminded that their symptoms are temporary, and that they won’t be getting zapped forever. As we learn more about treating depression and other mental health conditions, we may stumble our way into new medications that don’t come with all of these side effects.

So while there’s no question that they’ve helped millions of people, maybe the SSRIs and SNRIs will end up on the bench with the MAOIs and TCAs, when some hot new drug that isn’t  so zappy takes center stage. Sometimes we come up with really  cool solutions to big problems that just don’t pan out when they’re released into the real world. Because in the real world, side  effects like brain zaps enter the chat.

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