We're going to talk here about medications used for the treatment of OCD. You may read some things here that sound a little different from things you've heard on the subject from other doctors. That may be due to a number of reasons that we will talk about later. But it's very important that if you have questions about medications, go first to your doctor or psychiatrist, whoever is prescribing medications for you presently. He or she knows you best, and knows your personal physiology and reactions to medications, so he or she should be your first resource for answers. For instance, you might be reading here that there is now a statistical preference for certain medications over the one(s) you're now taking. If the medication you are now taking is working, ignore the statistical things you read here, because all of the comments about medications we will make here will be true for some or most people, but not for everyone. But do ask your doctor if you have questions, and remember: you are the consumer of his or her services, as well as ours, and you have the right to make informed choices. That means you have the obligation to become informed about the medical things that affect you. Here, that means please ask your doctor if you have a question about medications.

Brain Biochemistry. Let's talk a bit about the brain biochemistry of OCD first, so that we all have a common place to start from. Thanks to a lot of basic and clinical research in the areas of OCD, Neuroscience and Pharmacology, we now have a rudimentary understanding of some of the things that may be going on in OCD. That may sound sort of vague, but that really is the level of our current knowledge. We do know that certain cells in the brain called neurons seem to be responsible for most of the transmission of information within the nervous system. These neurons "talk to" each other primarily by means of chemical substances that get secreted from the finger-like extensions of these cells. These chemicals, called neurotransmitters, diffuse or float across a tiny gap between the processes of one cell and those of another. This tiny gap is called a synapse; neurotransmitters that cross a synapse cause a very small change in the membrane of the "receiving" cell, and that cell understands this change as information. This tiny bit of information gets multiplied by millions of cells interacting in this way for each thought, movement or function, and by each cell sending information across synapses of many other cells thousands of times a second. Add this all up, and somehow this explains human nature. Or so the theory goes.

Well, back to our story. One of the chemicals that we know acts as a neurotransmitter is called serotonin. Once serotonin delivers its message to the "receiving" cell, it is removed from the synapse by a vacuum cleaner-like process called the Serotonin Re-uptake system. Certain medications specifically block or inhibit this system. This allows serotonin to stay in the synapse longer and to stimulate the "receiving" cell over and over. These medications are known to reduce obsessions and compulsions, and are called Serotonin-Selective Re-uptake Inhibitors, or SSRIs. We'll come back to these in a minute. From this bit of pharmacology comes the hypothesis that serotonin is somehow involved in OCD, most probably by being insufficiently active at certain crucial places in the brain. This is called the Serotonin Hypothesis of OCD, and it is the most prominent current working model of how the disease works. It's important to remember that this is only a hypothesis, that is, a well-educated guess still needing to be further tested. Not all of the finer points of this hypothesis have been proven yet, and other explanations of OCD are also possible.

PET Scans. One of the questions for which we now have some answers concerns which sites in the brain are affected in OCD. Studies using PET scans are based on averages of many people in each group. This is important because there is probably a range of activities in both groups with some overlap, and no statistics ever apply to any individual case. A PET scanner is sort of like a fancy X-ray machine that shows which areas of the brain are active or inactive by imaging cellular metabolism. These studies show us that there seem to be three areas of interest in this disorder. The part of the brain right behind the eyes, called the orbito-frontal cortex, seems to be over-active in patients with OCD compared to people without OCD. This part of the brain can be thought of as being responsible for gathering all of the sensory information about your internal and external environments, and packaging it for further processing in the rest of the brain. In addition, in the middle of the brain is an area called the striatum (specifically, the caudate nucleus) which is also over-active in patients with OCD. This part of the brain can be thought of as acting like a gate, or a filtering mechanism, separating out the things you need to pay attention to from those you don't. With this part of the mechanisms over-active, it's as if the gate has been stuck open, and nothing can be kept out. So, statistically speaking, people with OCD are likely to be both over-stimulated and have a reduced ability to filter out irrelevant information. Kind of a double-whammy, huh? Well, guess what happens when you treat these people with anti-OCD medications? Both of these activities normalize; the over-activity in both areas decreases, so that the PET scans of the person treated for OCD and the normal person look about the same. The third area of over-activity in the brains of OCD patients appears to be in a very primitive part of the brain called the amygdala (latin for "almond" because of its shape). This area is responsible for fear among other things, and we don't yet know if its activity changes in response to medications. This suggests that, as most of us would probably agree, people with OCD have more fears, and are more sensitive to fearful subjects, than are other people.

The next big question is, what happens if you administer behavior therapy to the person with OCD instead of medications? The same two changes in the PET scans occur. Let me restate that: both medications alone and behavior therapy alone can change the PET scan image, and therefore the brain biochemistry, of someone with OCD to that much closer to the normal range. Imagine that - you can change you brain biochemistry by learning a few techniques and practicing them over and over! "Designer brain chemistry" may sound like an incredible concept, but memory works the same way. Everything you've ever encountered has left it's biochemical imprint on your brain in the form of a memory, and the more you rehearse something the better memory of it you have. And as we understand more about the brain, we may find that many more brain functions are malleable this way, as long as we know what approaches to use.

So now you might be asking, which one is better treatment for my OCD, medications or behavior therapy? The exact answer to that will vary a lot from person to person. However, a couple of things are certain. Even if you have a good response to medications, once you go off the meds your symptoms will probably return. On the other hand, people who learn E & RP techniques seem to maintain their improvements for years. Certain physicians say that medication is a treatment for OCD, while behavior therapy is a cure for OCD, even though responses to behavior therapy vary a lot. But there are lots of reasons that one might consider using both approaches together, especially at first. For instance, if someone's anxiety is too high to allow then to sit and listen to this type of presentation, or to do the homework assignments of behavior therapy, then they might benefit from medication that would reduce their anxiety. If someone's obsessions or compulsions were so consuming that they couldn't get to group or do their assignments, then again they might want to start anti-anxiety medication first, just to make it possible for them to do the behavior therapy. Finally, if other factors are keeping them from being able to do behavior therapy (for instance, a concurrent depression), medications designed to treat the other problem might be a good starting place as well. Fortunately, most of the medications that we use for OCD are good for treating anxiety and depression as well, so often it's possible to treat several problems with one medication.

Medications for OCD. Lets introduce some of the names of these medications now. I've mentioned the SSRIs already. In this group are fluoxetine, also called Prozac; sertroline, also called Zoloft; paroxetine, also called Paxil; and fluvoxamine, also called Luvox. These are the medications that we refer to as the SSRIs, and the list is growing by about one every 6-12 months. In fact, a new one called Citalopram should be out by the end of 1998. There are two other, relatively new medications out that are hybrids of these drugs, in that they are not completely serotonin-specific. Effexor (venlafaxine) and Serzone (nefadizone) also work on the dopamine and norepinephrine systems; at least Effexor is turning out to be effective for certain types of OCD-related symptoms. But before I go on with these medications, let me mention the oldest, and for some people still the best, of the anti-OCD medications. This is clomipramine, also called Anafranil. This one is sort of an SRI, since it acts on other systems in addition to serotonin and therefore isn't as specific. It is a member of class of medications that has been around for a long time called the tricyclic anti-depressants, and is related to the anti-depressant called imipramine. These are called tricyclics because their chemical structure includes three rings of carbon atoms. The side effects of these tricyclics are similar to each other, and there are more of them than for the SSRIs. Side effects are often the reasons people don't like taking them, even though they work very well. But for most people, these side effects can be managed with not too much difficulty. The side effects most often complained about include sedation or tiredness, dry mouth, constipation, dizziness and blurry vision. Rarely these side effects include increased liklihood of seizures, changes in heart function, sexual side effects (I'll talk about these along with the side effects for the SSRIs in a minute), urinary hesitancy and weight gain.

Sounds like a pretty impressive list, huh? Some of you may be thinking after hearing this, "Boy, none of that for me, thank you!" But it really isn't as bad as it may sound at first. No one gets all these side effects, and some people don't get any of them. Many of these side effects go away over the first few days to weeks of treatment. Most important is that the majority of them can be easily managed. For instance, if your medication makes you sleepy, your doctor may instruct you to take it at night. You're going to be asleep anyway, so why not have your drowsiness occur then? If you get dry mouth, you might carry around hard candy (sugarless, of course) in your pocket, or never pass up a water fountain. If you are constipated, add more fruits and green leafy vegetables to your diet. These do your body good in lots of ways that other laxatives can't. Dizziness is usually experienced when getting up from a prone position. This is due to the tendency of these medications to slow down the body's natural mechanism that raises your blood pressure slightly when you get up after lying down. Normally, this mechanism allows you to continue to get enough blood to your brain, even though the system has to work harder to pump the blood uphill when you are standing than it did when you were lying down. So if you get up quickly, the system lags a bit before catching up. You end up with a few moments of insufficient blood to your brain, and you feel lightheaded or dizzy. What can you do about it? You can get up more slowly, especially at night when your blood pressure is normally at its lowest of the day.

Blurry vision is related as a potential side effect to most of the others we've covered, since it results from action of the medication on the same non-serotonin system (called the cholinergic system because it uses the neurotransmitter acetylcholine). It's slightly more complicated to manage as a side effect, and you should talk to your doctor about your specific case (as you should if you experience any of these effects). Seizures, if they occur, are primarily found in people with a personal or family seizure history, so it's important that your doctor take a thorough history from you before starting you on these meds. Heart complications primarily occur in older men or men with a history of cardiovascular illness; in higher risk cases, or just to be sure, your doctor may recommend a heart scan (or EKG) before you start. Even weight gain can often be managed by some simply dietary adjustments. So you can see that most of the potential side effects of medications like Anafranil can be managed by adjusting a few of your habits.

Before we talk about sexual side effects (which, if present, are similar in all of these medications), let's talk about the potential side effects of the SSRIs. Of these medications, Zoloft and Luvox are the weakest and probably the least specific, followed by Prozac with Paxil being the strongest and most specific. By this I mean that 50 milligrams (mg) of Zoloft has about the same effect as 12 mg of Prozac or 10 mg of Paxil. Now it's important to remember that the number of milligrams is not an indicator of how well a medication may work for you. For example, a single aspirin is 325 mg. And your physiology is unique, meaning that everyone will have different responses to each medication. In terms of side effects, these medications are pretty similar, with the primary complaints being headaches, stomach upset and restlessness. Again, most of these go away after a few days to two weeks. Some people that take Prozac find that they feel activated, and may have some mild insomnia. One of the best ways to deal with this is to take the medication in the morning. Some people complain of weight loss with Prozac, but some people experience just the opposite problem. Neither weight loss nor insomnia appear to be frequent problems with Zoloft or Paxil, although Paxil and Luvox may be more likely to cause drowsiness. One other difference between these SSRIs is the half-life of the medication, or the time it takes your body to reduce the effective amount of medication in your system to about half. The longer the half-life, the longer the medication remains active; if the half life for some medication is 24 hours, then in one day the effectiveness of the medication is reduced by half, in two days it is reduced by three-fourths, etc. The half-lives of Zoloft and Paxil are each about 24 hours; the half-life of Luvox is about 12-15 hours, and the half life of Prozac is about 7-10 days. This concept is important if you are waiting for the drug to be washed out of your system before switching meds, and also in managing some side effects.

OK, now let's spend a few minutes talking about the sexual side effects of these medications. The primary complaint in this department is delayed orgasm, or the inability to experience orgasm. This seems to be more often reported as a problem by women. This is not likely due to women experiencing this effect more; it seems that many men find it a positive side effect. One fellow went as far as to say "My wife loves it this way, so don't change my meds!" However, another possible sexual side effect is the lowering of your libido, your sex drive. One way to deal with this if it is a problem is to try reducing the amount of medications, again with your doctor's consent, to see if there is a dose that will control your OC symptoms but not result in these side effects. Often this sort of adjustment is all that is needed. Alternatively, you can change the time of day that you take the medication. Since the half-life of Zoloft and Paxil is about 24 hours (and even shorter for Luvox), you can take the medication just before you go to sleep if you are normally sexually active at night. That way it will be at its weakest 23 hours later when you are about to be sexually active. Or you could plan your sexual activity and not take the medication for that day (this is called a "drug holiday," not to be confused with the 1960's meaning of the phrase). For Prozac the story is a little different. Because Prozac has an active metabolite, which means even when it gets broken down in your system it is still active, the half-life is 10 days. So if you get sexual side effects from Prozac, a different strategy is required. You may need to experiment with these possibilities with the advice of your doctor to find out what works best for you.

This different strategy can be used for the other SSRIs also if the other changes don't help enough, and this basically involves the use of short-term antidotes for the SSRIs. One of these is called Bethanicol or urecholine. It's normally given in 1-4 pill doses, and you might take it about 30 minutes before sexual activity. This will block the effects of the SSRI for about 2 hours. Another such short-term antidotes is the anti-histamine Periactin. Some people are also finding that their SSRIs can be supplemented over the long term with either another type of antidepressant called bupropion, or Wellbutrin, or with an anti-anxiety drug called buspirone, or Buspar, and that these reduce the sexual side effects of these medications. Other medication antidotes that must be taken over the long term to be effective, but appear to have more potential side effects, include amantadine, and bromocryptine. So you see that there are quite a few ways to deal with the sexual side effects of these drugs. This is important, because these sexual side effects are the ones most likely to cause people not to take their medications for their OCD symptoms. One other thing that's important about sexual side effects of these meds is that you NEED to talk about these with your doctor. Of course you need to talk about all side effects with your doctor, but doctors are often reluctant to talk about sexual side effects of meds with their patients, so if you notice them it may become your responsibility to bring it up. And if you do bring it up, do so with conviction - it's much better to run the risk of overdoing it and making the doctor think it's a major problem (because it probably is) than to end up not taking the meds because your doctor didn't think it was really bothering you very much and didn't intervene.

All of these side effects that we've been talking about stop when you stop taking the medications. None of these effects are permanent. Many of the potential side effects are what we call idiosyncratic; that means they depend completely on the individual. Most of the side effects diminish or disappear in the first two weeks, and that means that you get the side effects first, then they go away and then you get the beneficial effects. If you don't know this ahead of time you may be more likely to quit taking them, thinking, "All I get is this lousy headache, and I still have my obsessions. I'm not going to wait for even two weeks of this!" These meds don't work in 30-60 minutes like aspirin, and you have to give them a fair chance. We'll talk more about this in a minute.

Medications for related problems. Now let's talk a bit about adjunctive treatment, or other meds that are useful in supplementing the anti-OCD meds. One of the reasons to do this is that there are many variations in the OCD spectrum, and treatments will vary a lot within this spectrum. Also, certain other problems seem to occur with higher frequency in people with OCD than in the general public. We already mentioned that all of these medications are in the class of anti-depressants, which is a good thing because depression seems to occur in a high percentage of people with OCD, at least at some time in their lives. So if we can treat OCD with Prozac or one of the other anti-depressants, then we can also protect against depression at the same time. While we're on Prozac, let me say a little about some of the press that Prozac has received, because I'm sure many of you have heard some things about it that you may question. Prozac is a very powerful anti-depressant. It does not make you crazy, it does not make you kill other people, and it does not make you kill yourself. However, some people who are severely depressed are so down that they don't even have the energy or motivation to kill themselves. Often these people are given Prozac for their depression. Since Prozac works gradually, the first thing that these people notice is a return of some energy as they start to recover from their depression. So people who are severely depressed must be watched very carefully during this period, as their risk for suicide gets a little higher before it gets lower, just because now they have enough energy to do what they had been wanting to do for a while. This is really only a problem for severely depressed and actively suicidal patients, not for most people with OCD.

Some depressions need to be treated with agents called mood stabilizers instead of, or in addition to, anti-depressants. This is especially true of depressions that are cyclic in nature, when highs and lows come and go on a repeating basis and can complicate OCD or recovery from it. Among the class of mood stabilizers are lithium, Tegretol, valproate (or Depakote), Lamictal and Neurontin. These are very effective medications for helping with mood symptoms, but do not directly affect OCD symptoms. However, many people with mood instability also have what seems to be a rapid repsonse or hypersensitivity to the SSRIs, and can feel that even 10mg of Prozac makes them more anxious. If you've noticed both things (mood variations, between depressed and euphoric, or between depressed and irritable, as well as hypersensitivity to SSRIs), you might want to check with your doctor about the possibility of trying a mood stabilizer before adding one of the more traditional anti-OCD drugs.

Anxiety is another part of OCD that we sometimes treat independently. The SSRIs are pretty good anti-anxiety medications (or anxiolytics), and often they affect three problems all at once, those being compulsions, anxiety and depression. Most other medications that are useful for managing anxiety are in the Valium class, and the are called hypnotics because they induce sleep as well as reduce anxiety. These are good medications, and when used as directed are very safe; however, they all have the potential to be addictive if used irresponsibly. The strongest of these is Xanax; it has the shortest half-life, and because it disappears from your system so quickly, it has the highest potential for addiction. The one with the longest half-life is Klonopin, and so it is the least addictive. Valium itself is in the middle of these two, and there are several others in this class. One note about Luvox here - since Luvox can increase the effect of the Valium family of drugs, it's better not to take Luvox along with medications in the Valium family. Another medication you may have heard about is called buspirone, or Buspar. It also acts on the serotonin system. It isn't quite an SSRI because it doesn't act to limit serotonin uptake. Instead, it makes the cell believe that it is serotonin itself, and so it can boost the actions of the SSRIs. This med has very few side effects, but often takes 6-8 weeks to start having anti-anxiety effects.

Another class of medicines that often help augment the anti-OCD meds are the neuroleptics, also called anti-psychotics. These are not used because people with OCD are considered to be psychotic; clearly, most are not. But these meds act on the dopamine system, and can help make very sticky obsessions loose their power over your thoughts. They are also the same medications that are often used to control tics, both motor and vocal. The newest of these neuroleptics are called Zyprexa and Resperdol.