Ok, I tried to post this earlier, but then Sci’s wireless internet went out (grrr). So Sci bore herself back to the lab at 8pm on a Friday night to prove how dedicated she is to SCIENCE.
I saw an interesting post from PalMD over at denialism today on the withdrawal effects of antidepressants. He made some very good points, that the “side effects” associated with stopping an anti-depressant drug in the SSRI class can be pretty severe, resulting in headaches, dizziness, nausea, muscle aches, and of course, depression. Doctors have apparently been calling this “SSRI discontinuation syndrome” for some time. And sure, that’s what it is. But not being a doctor, being a grad student in pharmacology, the phrase I learned was “withdrawal”. Why not call it withdrawal? Because “withdrawal” implies addiction, and addiction implies all sorts of bad things like selling your children on the street for their next hit. So here we run into some issues. Is Prozac “addictive” because it causes withdrawal? It is “addictive” in the sense that, say, cocaine is addictive? Unfortunately, this is where the comments led, with things like “Thank you, I’ve been saying this for YEARS. This is exactly why I’ve refused to take antidepressants, not to mention doctors seem eager to dope me up after knowing me all of ten minutes.” (Frasque, comment #2). So I just want to clarify some semantics when we’re talking about antidepressants, though of course word use and meaning may vary from the research lab to the clinic (as it clearly does).
The big question: Is Prozac “addictive”?
In the most strict, DSM IV criteria way, no. The DSM IV criterion for “drug addiction” are as follows:
SUBSTANCE DEPENDENCE (ADDICTION/ALCOHOLISM)
Three or more of the following:
– Tolerance
– Wthdrawal
– Large amounts over a long period
– Unsuccessful efforts to cut back
– Time spent obtaining the substance replaces social, occupational, or recreational activities
– Continued use despite adverse consequences
You have to fulfill three of the above criteria to be considered addicted. Prozac only fulfills two of those criteria, that there is a withdrawal syndrome associated with the drug, and that taking the drug again will alleviate the syndrome, and that there can be tolerance associated with longterm Prozac use. No one has even sold their children on the street for their next hit of Prozac, and no one will seek out Prozac at the expense of other things like food, sleep, and housing. People do not accidentally overdose on Prozac trying to get the desired effect, and attempts to cut back are usually successful. Even in the full throes of withdrawal.
However, could we say that Prozac has some addictive properties to it? Absolutely. SSRIs change your brain chemistry drastically. SSRI stands for “selective serotonin reuptake inhibitor”, which I’ve written a bit about in my various posts on depression over at my old site. There is a serotonin theory of depression, which states that depressive symptoms are caused by low levels of serotonin. Therefore, using a drug that elevates serotonin levels in your brain should alleviate your symptoms of depression. Unfortunately, this theory is most likely wrong, or at least seriously simplified. But it doesn’t really matter (at least for the drug companies, it doesn’t matter), because SSRIs WORK. They block the recycling of serotonin back into the neurons that released it, increasing the levels of serotonin in the extracellular spaces in your brain. Over time, these increases in extracellular serotonin levels appear to help the symptoms of depression in many people.
You will note that I said “over time”. SSRIs do not alleviate depression immediately, they require between 2-4 weeks to achieve their effects. During this time, your brain is exposed to much higher extracellular levels of serotonin than it is used to. These high levels of serotonin can have some far reaching effects, changing synapses and even promoting neuronal growth in various areas of the brain. Right now, research suggests that the neuronal growth and changes in synapses are what helps in alleviating depression. So the serotonin theory might be wrong, but hell, it works. Let’s not look a gift horse in the mouth, at least not until we have drugs that are better and more selective and more effective, anyway.
However, these changes that are taking place in the brain require the higher amounts of serotonin produced by the SSRIs to maintain them. This means that when you stop taking an SSRI, your serotonin levels will drop, possibly even below the levels at which they started (this has a lot to do with negative feedback, and perhaps I will have time to explain it with pictures sometime). When those artificial high levels of serotonin produced by the SSRIs are gone, the brain needs time to adjust to working under lower serotonin levels again. Since serotonin acts at many levels in the brain, this can be some profound adjustment, affecting things like nausea and dizziness, as well as things like appetite and circadian rhythm. So in this way, we can say that Prozac has addictive properties to it. Your brain adapts to more serotonin, and when that extra serotonin is gone, withdrawal symptoms will result. We could call this effect something more like “physical addiction” than “psychological addiction”.
Physical addiction is the result of the direct effects of drugs on your body, producing withdrawal symptoms, which may make you take more of the drug to keep you functioning. Examples of this would be things like alcohol. If you’re REALLY addicted to alcohol, your body can come to depend on it so much that you can suffer seizures and death if the drug is not present. Another example of this would be the opiates, like morphine, which can cause things like severe constipation during withdrawal due to their effects on the GI system.
Physical addiction should be distinguished from psychological addiction. Psychological addiction (though it can include brain changes and therefore may technically be a kind of physical addiction), is more about your craving for the drug and desire for it than your body’s physical need for it. Cocaine, for example, is severely psychologically addictive. There’s not a lot of withdrawal associated with cocaine (though some people complain of depression), but what most people complain of is their overpowering craving for a hit. Of course, you have to keep in mind that almost all addictive drugs are a mixture of physically and psychologically addictive. So when you’re addicted to morphine, you both crave it AND desperately want to relieve your constipation.
So what can we say about Prozac? I personally would say (though some people might disagree with me), that the withdrawal suffered from discontinuation of SSRIs is a physical withdrawal due to the physical changes that occurred in your brain, and the results of a drug that is physically addictive. But there is no “high” associated with Prozac, and no one is going out roving for their next hit. There are no psychological cravings for the drug associated with previous highs from former use. If there is psychological craving, it’s knowing that it made you feel better in the past, and having been told that these effects were part of the discontinuation syndrome.
Your take home message? There is more than one type of addiction, and more than one type of withdrawal. Just because there is a “discontinuation syndrome” associated with a drug does not mean that it is “addictive” in the common sense, and neither does it mean that prescription of the drug is a bad thing (see morphine). And much thanks to DrPal for bringing this up! It was enough to make me blog on a Friday night!
