Basically, your neurotransmitters (whatever those are) aren’t doing a very good job of getting your brain cells to communicate (synapse) with each other. To remedy this sorry state of affairs, there are: Tricyclics which keep all kinds of neurotransmitters from being sucked back (re-uptaken) too soon from whence they came; “Selective” reuptake inhibitors (SRIs) which target the reuptake of specific neurotransmitters, and MAO blockers which forcibly restrain the enzymes that are trying to devour those same well-meaning neurotransmitters before they’ve done their jobs.
Since then, researchers have learned a lot more about these processes. And, although it’s not a bad overview, I’ve learned a lot more about how little I know.
Brain cells (a.k.a. neurons) can’t stop talking. Even after you’re dead, they keep talking. For a day or more. Until the last one realizes there’s no one left to talk to, gets bored, and sends its molecules off to greener pastures.
What with there being ±100 billion neurons up there, you’d think they could just communicate by rubbing up against each other. Unfortunately, they’re not allowed to touch. It’s against the rules. Instead, each one is separated by a “great” divide called a synapse. Synapses are 20–40 billionth of a meter across. That might not sound like very much to you and me, but for a little neuron, it’s quite a leap.
Fortunately, neurons know how to make molecules that can leap across that great divide. Those molecules are called neurotransmitters, because they transmit information between neurons.
If you’ve seen one neurotransmitter, you definitely haven’t seen them all. Depending on who’s counting, there are more than a hundred different kinds, and each one is a slightly different size and shape. However, in terms of whether you are optimistic, pessimistic, paranoid, confident, compulsive, or laid back, there are only a few we need to worry about. Actually, there’s no reason to worry. Although, if your neurotransmitters are a little off-kilter, you might not have a lot of choice.
As far as depression goes, the most famous and prolific neurotransmitter is serotonin. Norepinephrine and dopamine also get a lot of play. A little GABA and glutamate come in handy. And then there’s acetylcholine, which, for some reason, you don’t hear about as much—probably ’cause it’s even harder to pronounce than the others.
Neurons shoot these and other neurotransmitting molecules out of hairs at the end of an umbilical-like cable called an axon.
The rest of the neuron is covered with little receptive filaments called dendrites. You’d think dendrites would be the end of the line, size-wise. But each one features even tinier receptors. They also come in a variety of sizes and shapes, which bear a suspicious similarity to the different sizes and shapes of the neurotransmitters. This ensures that only certain kinds of neurotransmitters can hook up with certain kinds of receptors to transmit certain kinds of signals.
There are, for example, about 13 or 14 subtypes of receptors for serotonin alone. The scientists can’t seem to decide. And each one is part of a specific neural pathway that’s responsible for relaying certain types of messages. That’s why the activity of a single neurotransmitter or type of receptor can affect so many different aspects of your life. And, in turn, why everyone responds a little differently to meds that increase synaptic levels.
Once a neurotransmitter finds a compatible receptor, it settles in for a quickie, and gives the “target” cell a charge. Some scientists call this neurotransmitter-receptor relationship a lock-and-key kind of thing. Seems more like kamikaze speed-dating to me. Especially since, as soon as an individual neurotransmitting molecule has made its point, it skedaddles. Which it quickly lives to regret because (like drone bees who mate with the queen), once it’s done, it gets eaten up by an enzyme which breaks it into smaller molecules. They, in turn, become the raw materials for more neurotransmitters. Elegant, huh?
This complex dance doesn’t happen one synapse at a time. Every axon of every neuron has ±1000 synaptic endings spewing out neurotransmitters like there’s no tomorrow; as well as ±1000 of those dendrites which are receiving those messenger molecules from other neurons. Axons can be up to 12 feet long, so we’re not exactly talking a bucket brigade. More like a switching station that would blow even Bill Gates’ mind. Fortunately, most of those axons and dendrites know what they’re doing. So, with minimal, if any, conscious help from you, they usually do a good job of helping you digest your food, type on your laptop, or try to explain something inexplicable.
Put a few of those puppies together, do a little algebra, and you realize that one little neuron can share synapses with tens of thousands of other neurons. Move on up to Algebra II, add all those billion or so brain cells, and we’re talking like a quadrillion synapses in all—give or take a trillion every second (or less). What a racket! Pretty amazing when you think of it. Which, hopefully, you can, even if one of those neural pathways is slow on the uptake.
What’s even more amazing is that your brain is able to assemble this unceasing barrage of synapses into experiences and thoughts such as: “I’m happy.” “I’m sad.” “I’m starving.” “I’m full.” “I want a beer.” “I’m freaked out.” “I can’t wait to get to work.” “I can’t wake up.” “Ouch, that hurts.” “Mmmm, that feels good.” “I need to buy 1,000 copies of this book and give it to all my friends.”
When you feel “off” in any which way, one or more of the following things is probably happening:
1. Your axons aren’t shooting enough neurotransmitters out into the wide open synaptic space. It’s enough to make you want to sleep all day.
2. A bunch of shy or lazy neurotransmitters have been sneaking back into the neuron they came from. That is, they don’t bother sticking around in the synaptic space long enough to see if they can find a willing receptor.
3. A voracious MAO enzyme eats them up before they can hook up with a receptor. (MAO stands for monoamineoxidase. Aren’t you glad you asked?)
4. Too many neurotransmitters are flooding the synapses because the neurons just can’t keep them under control. It’s enough to make you crazy!
5. The neurotransmitter keys don’t fit so good. Or more likely, some of the receptors are hard to open.
You might be wondering why, instead of taking little pills, we don’t just flash flood our brains with neurotransmitting molecules and hope for the best—i.e., take a pill filled with a balanced combination of neurotransmitters themselves instead of something that inhibits their reuptake or their ultimate demise. Unfortunately, in the “How-to-Make-a-Human” manual, they put in something called the “blood-brain” barrier. Only neurons have the right stuff to make neurotransmitters. We can eat or drink more of the ingredients they need to make them. But they have to do the work.
Dealing with the blood-brain barrier is the raison d’être for a lot of natural/dietary treatments for depression. Supplements like tryptophan, SAM-e, and 5-HTP can get through the blood-brain barrier. And they’re just what a productive neuron needs to make more neurotransmitters. Although even supplements with the best of intentions might get detoured into some other job on their way to your brain, or throw something else out of balance.
Things like alcohol, nicotine, and heroin are really good at messing around with receptors and encouraging your neurons to release more neurotransmitters. This can make neurons kind of lazy, because they figure it’s only a matter of time before you give them another hit. That’s one reason withdrawal can really suck.
One of the latest theories for why it can take a while for meds to work is that they’re actually not directly affecting the synaptic success rate of neurotransmitters, they’re actually cajoling your brain into making more neurons. Either theory implies a third: that antidepressants cause significant changes in your brain’s electro-vibrational frequency. I never had electro-shock treatment, but that clearly affects the connections between neurons, and definitely helps some people. Ditto for, say, acupuncture. And, perhaps, even homeopathy.
All these theories don’t matter a
whole lot as far as we head-cases are concerned, except as a reminder that most know-it-alls don’t.
Let’s not forget about hormones. In the midst of my extremis, a friend who was in the process of setting the world record for hot flashes, wrote: “Have you thought about how your mental state might have a relationship to your hormones?” This was and is a really good question. Particularly when discussing a 53-year-old guy having a nervous breakdown … not to mention a mother dealing with postpartum depression, an anorexic teenager, or hyperactive child.
I wasn’t exactly thrilled with the idea that my fragile mental states were being exacerbated by a virulent case of rapidly vanishing testosterone, but I figured I might as well man up and do more research.
Both hormonal and neurotransmitting molecules pass messages between cells. The difference is that, instead of being created in neurons and leaping across a synaptic divide like neurotransmitters, hormones are created in glands and travel through your bloodstream in search of receptive cells.
Norepinephrine, for example, tends to be attracted to cells that deal with stress. So, if your neurons do a better job of making norepinephrines, and give them a good swift kick across the synapse, they might help you get out of that catatonic funk. However, norepinephrine is also synthesized in the adrenals and travels through your bloodstream, in which case it’s considered a hormone. Those norepinephrine molecules know how to spread the word that you need to increase your heart rate and blood flow. This helps you leap into action whenever you feel threatened: like when a car is heading right at you or—if you’re in the state I was in—you can’t find the top to the yogurt container.
This hormonal/neurotransmitter connection explains why adolescence and menopause in particular can trigger big-time mood changes in both men and women. It also makes you wonder how people could question the diagnosis of “postpartum depression.” Telling a new mother—whose hormonal system is thinking, “What the heck just happened?”—that she’ll get over it seems remarkably insensitive considering that “it” can last months or years. Just as with any depression, there are numerous options for treating it—although paying attention to the warnings and caveats would seem particularly important in that case, especially if you’re nursing.
Bottom line: It’s a real good idea to tell your psychiatrist if you just had your first period, are starting to grow your first beard, are pregnant, nursing, showing signs of male or female menopause, or are in the middle of a sex change procedure.
Prescription Medicines
If you do need to take medication the math is really simple: which sucks less?
Taking an imperfect medication that controls the symptoms of a condition that puts your life somewhere in the spectrum of “barely tolerable” to “dear God please kill me now;” or trying to get through life with that same condition … which will keep getting worse the longer you go without treating it?
—JEROD POORE
YOU’VE DECIDED to take the plunge. Actually, you’ve already taken the plunge and you’re in way over your head.
So you’ve finally gone to see someone with an M.D. or N.P. tacked on their name who, thankfully, appears to have heard most of it before. And, more important, appears to have a reasonable idea how to deal with it. They’ve taken their notes. They’ve handed you Kleenex. They’ve looked in their big books to check on potential interactions. And then … then … they get out the pad and start scribbling. Yes!
They hand you the piece of paper with an expression that combines concern and optimism: “This should work. Remember, you might feel something right away, but it could take a couple of weeks. Don’t worry. We’ll figure this out. Make an appointment for next Wednesday. Try to get some rest.”
“Rest?” You say with a pitiful choking sigh.
And then … then … they get out the pad and start scribbling again! Yes!
You walk out and go back to the receptionist’s window. He or she sees folks like you all day, and struggles between sympathy and professionalism, with a hint of job fatigue. You make the appointment. A reminder card? Well, sure. But there ain’t no way you’re going to forget this appointment. For the next week, it’s going to be a faint lighthouse of hope. On the way from the doctor’s office to downtown, you clutch those two pieces of paper like lottery tickets with a winning number.
You take the first pill as soon as you leave the drugstore—unless you are dissuaded by those warnings that say not to drive until you see if you have side effects. In that case, you rush home. Or to the office if you have to go back there. Get some water. And swallow. Full stomach. Empty stomach. Whatever.
And then, in spite of all the warnings that it could take weeks for the drug to be effective, you sit down and wait to “get off.” The same way you’d wait, and expect, an ibuprofen to take away pain.
After a while, you accept that it’s really not going to work right away, and reluctantly go about doing whatever it is you do. Later that evening, you tell your spouse, partner, or friends what happened at your appointment and what drug(s) you’re taking. There’s a good chance you go online and read everything you possibly can about those drugs.
At the end of the day, you get into bed and reach for the other bottle (remember that second slip of paper?) and take one. With any luck, you get some sleep.
As a one-man clinical trial, I’m often asked about specific meds. After trying to answer those questions for a while, I realized that while I could toss around acronyms like SSRI, NDRI, TCA, MAO, AED, and CNS with the best of them, there was something about the way that antidepressants are classified that didn’t make sense.
All those years I thought I’d been trying to understand the difference between apples and apples, it turns out I was actually dealing with apples and oranges—with a few fish and fowl thrown in for good measure. As best I can tell, this is how it breaks down: Drugs classified based on what they do in the brain. Anything with an RI (that doesn’t refer to the state where I was born) acts on the brain by Inhibiting the Reuptake of neurotransmitters. Those are the various Selective Reuptake Inhibitors (SRIs).
MAOIs (Monoamine Oxidase Inhibitors) are also named based on what they do in the brain. They inhibit the enzymes that are waiting to chow down some nice juicy used-up neurotransmitters.
In both cases, the goal is to have more synaptic connections.
Drugs classified based on the condition they treat. Or, in many cases, the condition they were originally designed to treat. An AED, for example, is an Anti-Epileptic Drug. However, I, and many other people who have never had an epileptic fit, take them as mood stabilizers. They’re also prescribed for bipolar. Still they’re called AEDs.
Drugs classified based on their chemical structure. For example, the “tricyclics.” This is the classification that’s the most annoying. The researchers should be ashamed of themselves. Tricyclics are Reuptake Inhibitors too. They’re just not as selective. They’re named for what they are, not what they do. Their molecules have three (tri) rings of atoms—whatever that means. The cyclic part comes from the citric-acid cycle which is made up of seven chemical reactions, or maybe it’s nine. I can’t remember. Regardless, what goes around comes around. It’s also known as the tricarboxylic acid cycle (TCA) or the Krebs cycle—and I don’t think they mean Maynard G! Bottom line: tricyclics should be called PRIs: Promiscuous Reuptake Inhibitors.
Neither fish nor fowl. The notorious “Atypicals.” This is almost as much of a scientific cop-out as the diagnosis NOS (Not Otherwise Specified). Atypical antidepressants and antipsychotics are called atypical because, at one time, they were different from the typical ones prescribed for a certain purpose. Although now they are often now prescribed more typically for that and other purposes.
To make matters worse, doctors often use brand and generic names interchangeably. And prescribe them for both FDA-approved and off-label conditions. So, for example, you might be taking a drug named sertaline, which is the generic version of Zoloft. It boosts serotonin levels by
blocking reuptake and makes certain serotonin receptors more or less receptive. While it’s selective for serotonin (i.e., an SSRI), it also blocks more dopamine reuptake than the other SSRIs. So you could call it an SDRI. Maybe that’s why it seems to cause fewer problems with sexuality and weight gain. And why it’s sometimes prescribed “off-label” for eating disorders, fibromyalgia, hot flashes, and migraines.
See? It’s hard enough to figure out what’s what and why without having to figure out what the heck it’s supposed to do. So, if you’re curious why your doctor prescribed what he or she prescribed for what ails you … ask. And keep asking. I mean, it’s your mind. Even though it occasionally feels like someone else’s.
Drug companies put a lot of effort into coming up with names. They need something with an obtuseness only a doctor could love (and prescribe). At the same time, they want to give patients at least a subliminal message of encouragement. Typically, they spend more than a million dollars to achieve these goals.
In retrospect, the name Prozac doesn’t seem to fit that bill. Allegedly, it’s just a mishmash of positive sounds. (I get the “pro” part. But “zac”?) Doesn’t matter. The word has become so much a part of the lexicon that we don’t question it anymore. The names Zoloft and Paxil are more calming and uplifting. Effexor certainly sounds effective. Wellbutrin suggests it may actually tame the beast. And, for some reason, Cymbalta has a relaxing ring, even though the image of crashing cymbals isn’t exactly soothing. The name BuSpar seems unpleasantly Germanic, but does imply it’ll put up a good fight. Abilify sounds like a performance-enhancing drug trying to pass as a mild-mannered pick-me-up.
Like Prozac, the brand named Valium has become so ingrained in our vocabulary that it makes most folks feel faintly drowsy just hearing the word. At least it’s a whole lot less sexist than “mother’s little helper.” (Which included Librium and Quaaludes as well as Valium.)
David's Inferno Page 10
