Let’s talk about your Prozac Addiction

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:
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.
SSRI.gif Via California State University.
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!

10 Responses

  1. Great post. This is my first introduction to Neurotopia, and I’m very impressed. I saw the link in comments at Pal’s.
    I’d say that this conundrum reflects inadequacies and inconsistencies in the “scientific” language we use to talk about addiction. We started with a folk/cultural concept of addiction and scientists tried to come up with empirically measurable criteria that would describe a phenomenon we were all familiar with from everyday life.
    So, we end up putting too much weight on concepts like “physical dependence” and “withdrawal,” which are neither necessary nor sufficient for addiction. These are phenomena that are frequently observed in addictions and may contribute to addiction in various ways–but they are not essential properties of the behavioral/psychological/way of life that we sought to understand scientifically.
    Heroin has a distinct withdrawal syndrome, cocaine doesn’t–both are addictive. As you suggested, above, you have to drink a whole lot for quite a long time before you are at risk of DTs when you stop. Plenty of devastatingly afflicted alcoholics don’t get DTs when they stop drinking.
    I don’t think it’s helpful to say that Prozac has some addictive properties. Patients want to know whether they’re going to get high off Prozac or find it hard to stop taking the drug when they don’t need or want it anymore. It’s not sorta addictive or partially addictive. It’s non-addictive in the relevant sense.

  2. Physical addiction should be distinguished from psychological addiction…. almost all addictive drugs are a mixture of physically and psychologically addictive.
    Awww, sciC why’dya have to go and add this to such a fantastic* post? This notion is complete and utter bollocks and even worse is demonstrably harmful to the goal of getting those suffering from addiction disorders the medical treatment they need.
    The trouble is that you delving into dualistic nonsense as if the “psyche” was not entirely a result of the structure and function of the body, mostly the brain. What you term “craving” is just as assuredly a “physical” effect of drug abstinence after chronic exposure as is constipation. Second, the connotation is ALWAYS that so-called “psychological” dependence issues are less important and less real. Which dredges up the notion that people should just get over it, cure themselves with will power or morals, etc. Acutely harmful, that. Thirdly, this mental set keeps us from understanding that the real problem at hand in drug abuse is indeed (long term) craving. The acute stages of withdrawal? We can deal with that relatively easily and cheaply. Life long proclivity to relapse to drug taking? Not so much.
    *although admittedly I disagree with your central conclusion it is a great discussion of the issues

  3. just how hard does prozac pound on the dopamine reward system? in my brief pubmed title browsing, i’m seeing a reduction in cocaine and other drug self-admin by fluoxetine.
    if prozac was rewarding in and of itself, i would not expect to see attenuation.
    the body adapts to the stuff you put into it, that’s just the way it works. just because you have to re-adapt back to the basal state when you stop taking the drug (and sometimes that’s a significant change, occasionally unpleasant and that gives withdrawal symptoms), does not mean you are addicted to the drug in question.
    women don’t get addicted to their oral contraceptives, though it could take some time for the endogenous hormonal cycle to re-establish itself (and cause some hormonal madness in the meantime.)

  4. Sigh…I know, Drugmonkey, I know. I KNOW it’s complete and utter bollocks. The problem is trying to explain craving and addiction to something…argh…you’re right. And when you’re right, you’re right. And you, you’re often very right.
    It’s true that “pychological addiction” comes from PHYSICAL changes in the brain (like dopamine and serotonin systems in the case of cocaine), and thus, it is physical addiction. I think the distinction between physical and psychological addiction has been pounded into my head because we like to distinguish between drugs that makes you so addicted you can die or suffer physical pain in their abscence, and drugs that you won’t die without, but which make you miserable. You’re very right, the distinction just doesn’t stand. Unfortunately, I’m not really sure how else to explain it. Perhaps I will try to write something else later that will clarify and come up with a new way of putting it.
    Argh, you REALLY are right, and the more I look at it, the more I want to bang my head against the wall. I shouldn’t write on Fridays. I will clarify. Honest.
    Leigh: Prozac does no pounding on the dopamine system, except what you could call auxiliary pounding via dopamine/serotonin interactions. It’s a pretty strong serotonin drug (though there are SOME dopamine effects). But more importantly, yes, Prozac does reduce cocaine self-admin, but I think (I’d have to re-look it up, but I’m pretty sure) that this is due to the effects of cocaine on the serotonin system, rather than the effects of Prozac on the dopamine system. I’m sure you know that cocaine increases serotonin along with dopamine (it’s pretty equal for both), and there are some out there that believe that the serotonin effects are negative influences on the “high” produced by dopamine. So the more serotonin you have relative to dopamine, the less-self administration. They use this sometimes to explain why MDMA, which is more about serotonin than dopamine, is less addictive than cocaine.
    In regards to the above theory, I would say that yes, higher levels of serotonin reduce the effects of high levels of dopamine, but I would say that this “negative reward” effect of serotonin is probably through the dopamine and serotonin interactions taking place, especially in the ventral tegmental area/accumbens connection. There’s at least five (maybe six) big serotonin receptors in the VTA-NAc corridor, and when these are stimulated, various effects can occur. Some receptors will stimulate dopamine cell firing from the VTA, others will inhibit. And serotonin directly onto the NAc can reduce dopamine release to the NAc, but it also directly increases dopamine…yeah, the interactions are REALLY complicated. But I think that the interactions may be what causes Prozac to decrease cocaine self-administration in the cases where that’s been found. I can do some brush-up on the topic (from the stuff that’s come out of this post I need to do brush-up on a LOT of things…)

  5. I’m late to the party here but I find it interesting that when a woman takes contraceptives (in any form), her “period” as it is colloquially known is medically termed “withdrawal bleeding”, rather than menstruation. The reason being that she has not completed the menstrual cycle (including ovulation) while taking contraceptives. In this context withdrawal is not at all associated with addiction.
    I think that leigh brings up an interesting point in her comment.
    Many women experience physical symptoms of hormone withdrawal during the “blank” or “placebo” period of their contraceptive regimen. Yet there is no stigma of addiction to contraceptives (despite physical withdrawal symptoms…including uncontrolled bleeding – yikes!)…perhaps because many women experience these same withdrawal symptoms over the course of their unmanipulated menstrual cycle. Is it possible to be “addicted” to your endogenous hormones?

  6. thanks for the excellent explanation, sci. the 5ht system is outside my usual literature circle. (i really should go back and review that section of my neuropharm textbook.)

  7. As a long term, and likely to be life long user of the SSRI Lexapro(escitalopram), this discussion interests me greatly I’m under treatment for severe major depressive disorder, and this drug has almost certainly saved my life, and let me have a life worth living.
    I’d like to point out a couple of confounding factors regarding the DSM IV criteria — I don’t need to replace social, occupational or recreational activities with drugseeking, because I can just call or visit my MD and get more, and likewise, if this medication starts to fail for me, I can simply see my MD and get a dosage increase, or try a different med. I’m one of the lucky ones – Lexapro works perfectly for me, and I haven’t even needed dose adjustment to maintain the effects.
    But it is very common to hear stories from other depressives about the endless search for the right medication, the constant need to increase dosages, and the eternal conundrum of whether to accept adverse side effects when a med otherwise works well.
    Perhaps the difference between the relationship I have with my medication and an addiction is just a matter of context and end result – it is rational and desirable for me to use this drug despite the adverse side effects and physiological and psychological dependence because it improves my life and prevents my death.
    Basically for me, addiction boils down to matter of context and grammar.

  8. Even if tolerance and withdrawal symptoms occurred, you are no more addicted to antidepressants than you would be to anti-hypertensive medication which one needs often for the rest of one’s life. The idea antidepressants, simply by having an effect on the brain, necessarily fall into the reward-use pathway is flawed.

  9. Thank you for your blogs! They are interesting, intelligent, clear and amazingly entertaining considering the subject.
    You write: Right now, research suggests that the neuronal growth and changes in synapses are what helps in alleviating depression.
    I would be SO happy if you could write a blog about this.

  10. I am in the process of trying to decide whether to take prozac or not. I am in recovery from opiate pain pills and seem to get addicted to everything. My doctor gave me ultram for pain and I went through withdrawl when I stopped those (more physical then mental) and I was also on xanex for a short time and I am now going through being weined off of them. Ultram was easy and xanex is really hard so you can see why I am afraid to take any antidepressent or anything, but I know I need them help. email me at june_nff@yahoo.com

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