Tormenting Thoughts and Secret Rituals Page 11

  The medications that are most useful for OCD are the serotonin reuptake inhibitors (SRIs), including clomipramine (Anafranil), fluoxetine (Prozac), fluvoxamine (Luvox), sertraline (Zoloft), and paroxetine (Paxil). These drugs, which had previously been known to have antidepressant effects, have now been discovered to possess distinct, specific anti-OCD effects as well. Over a hundred well-controlled research studies involving thousands of patients have now conclusively proven that the SRIs are both safe and effective in the treatment of OCD.

  Unfortunately, the intense media coverage of these medications, particularly Prozac, has left many people scared to take them. On television, it seems, a few dramatic, personal testimonies that Prozac has caused addiction or suicidal ideas speaks louder than the therapeutic experiences of millions of people. But among the leading psychiatrists in America there is unanimous agreement that these medications are both very helpful and very safe in the treatment of OCD.

  The serotonin reuptake inhibitor medications take their name from a unique, biochemical action: their ability to influence a certain brain chemical that has been found to play a key role in the production of obsessions and compulsions. Serotonin is a neurotransmitter; it serves as a messenger between brain cells. Molecules of serotonin are released from one brain cell, carry impulses to a second, and then are reabsorbed back into the first, to be used again.

  The SRIs specifically interfere with the reabsorption, or reuptake, of serotonin. Research into how they do so has yielded two outstanding findings. First, SRIs are extremely selective in their effect; they have little impact on other neurotransmitters in the brain, of which over a hundred have been identified to date. Second, in the treatment of OCD, the SRI medications have their major therapeutic activity in one small area of the brain. Brain-imaging techniques, able to show the brain at work, reveal that OCD is caused by a hyperactive circuit of nerve cells running from the basal ganglia to the orbital frontal area of the brain (see Chapter 9). SRI medications decrease the firing of nerve impulses in this circuit.

  From a practical standpoint, what patients report is that the SRIs allow them to let go of obsessions more easily and to resist the urge to do compulsions more readily.

  Five members of the SRI group are currently marketed in the United States, and all are now approved by the Federal Drug Administration for the treatment of OCD. They are classified under the general heading of “antidepressants” because even before their anti-OCD effect was discovered, all had been shown to reverse the severe states of depression characterized by loss of energy, interests, appetite, and sleep. The antidepressant effect, interestingly enough, appears to be unrelated to the anti-OCD effect.

  GENERIC NAME TRADE NAME EFFECTIVE DOSE

  Clomipramine Anafranil 200–300 mgs

  Fluoxetine Prozac 20–80 mgs

  Fluvoxamine Luvox 200–300 mgs

  Paroxetine Paxil 40–60 mgs

  Sertraline Zoloft 50–200 mgs

  Clomipramine (Anafranil), the oldest of these drugs, was first discovered to be useful in the treatment of OCD in Spain in 1967. Since 1980 there have been more than fifteen double-blind and placebo-controlled studies that have demonstrated its efficacy beyond a doubt. The largest study, the Clomipramine Collaborative Study Group, a model of modern pharmacological research, examined the effect of Anafranil versus placebo in 520 OCD patients over a twelve-week period. The results, published in the Archives of General Psychiatry in August 1991, showed that 60 percent of patients improved markedly with Anafranil, whereas placebo was effective in less than 5 percent of patients. Prozac—first introduced in the United States in 1987—and Luvox, Paxil, and Zoloft, which were introduced in the early 1990s, have also been demonstrated to be effective anti-OCD medications by large multi-center studies similar in design and outcome to the clomipramine study.

  Does any of the SRIs work better than the others? Few “head to head” studies have been undertaken, but those that have been done failed to show any one drug superior. A statistical review of a large number of studies published in January 1995 suggested that Anafranil is slightly superior to the others. This result, however, has been questioned, since the Anafranil studies included a much higher percentage of patients who had never before been tried on medications and who were therefore more likely to respond. What is clear is that all of these medications significantly help 60–70 percent of patients with OCD—a figure remarkably similar to the percentage of people helped by behavior therapy.

  When is it appropriate to use SRIs? The decision to initiate drug treatment should be made on an individual basis, balancing the true risks of side effects against the probability of therapeutic gain, and taking into consideration the severity of symptoms, the age of the patient, and the chronicity of the disorder.

  In general, when OCD is moderate to severe—when the sufferer is experiencing significant distress and is substantially impaired by obsessions and compulsions—medication should be used right away. In these situations, anti-OCD medications not only provide relief of symptoms, they also help a person to get a good start on behavior therapy, which is sometimes difficult when obsessions and compulsions are at their absolute peak.

  In some cases, even when OCD may be fairly severe, it may be better first to try behavior therapy alone. For children and adolescents, medication treatment should be avoided, if possible, because the effects of these drugs on the developing brain are not fully known. For children with severe OCD who do not respond to behavior therapy, however, the data are very encouraging that the SRIs are both effective and safe. Another situation in which medication should be a last resort is the treatment of pregnant women. Again, however, the data are encouraging that these medications can be safely used.

  What about young adults and college-age OCDers? I like to try behavior therapy first in this age group, as they often respond especially well to psychological therapies. If OCD is affecting a student’s performance in class, however, I do not hesitate to use medications right away.

  In general, when OCD is mild—when the sufferer has troublesome symptoms but is getting along satisfactorily despite them—it is best to try behavior therapy alone before medications. Yet if behavior therapy is not effective, and particularly if the symptoms have been present for a year or more, medications should definitely be given a try. No one should have to put up with OCD—a medical, neurological disorder—when good treatments are available.

  Once the decision has been made to use SRI medications to treat obsessive-compulsive disorder, a number of general principles must be kept in mind.

  Complete versus Partial Cure

  Some patients, after hearing of the great advances in treatment of OCD, expect that their OCD can be completely cured by SRIs, just as penicillin eliminates pneumonia. Unfortunately, this rarely happens. A closer parallel for the manner in which SRIs work is the use of anticonvulsants for treating epilepsy, or insulin for treating diabetes: They bring symptoms under control but do not eliminate the underlying disorder.

  Studies such as the Clomipramine Collaborative Study Group demonstrate that SRIs usually bring about a drop in OCD symptoms in the range of 30 percent—from a Yale-Brown Obsessive Compulsive Scale rating (see Appendix A) in the mid-twenties, for instance, to a level in the mid-teens. This might mean a change from performing rituals three hours a day to doing them for one hour. Typically, what SRIs do when they work is to free a person from being disabled by obsessions and compulsions, allowing a return to a relatively normal life. Although this is a great boon to the OCD sufferer, it is not a complete cure.

  Trial and Error

  When treating epilepsy or diabetes, tests can indicate which drug will work best and what dose is likely to be effective, but prescribing for OCD is still more of an art than a science. Studies have shown that one SRI medication will work when another does not and that there is no clear way to predict effectiveness. Further, adding a second medication, an “augmenting agent,” to an SRI can often “kick-start” a treatment that at
first seemed ineffective. The OCD sufferer, therefore, must be prepared to view medication treatment as a process of trial and error. I find it helpful to say to patients: “Let’s agree to give medication treatment a try, and we may need to use several different agents, or combinations of agents, before we find the right one.”

  Medication treatment should generally begin with one of the five SRIs used alone. Different teaching centers have differing opinions as to which to use first. Whichever one is chosen, it should be given sufficient time to work. Although OCD sufferers often report a beneficial effect from medication after only a week or two, studies indicate that it may take four to six weeks before an effect is obvious, and much longer, up to three months, before it is maximal. Therefore, a reasonable trial period for a given drug is often ten to twelve weeks.

  If there is no improvement after the initial trial, then an augmenting agent should be added in an attempt to bolster the anti-OCD effect. If this, too, fails, then a second SRI should be tried, and after that a third, and perhaps even a fourth and fifth. Studies have demonstrated that a particular SRI can work where others have failed. A recent study, for instance, showed that 20 percent of patients who had not responded to either clomipramine (Anafranil) or fluoxetine (Prozac) did well on fluvoxamine (Luvox). When it is necessary to try several SRIs, one of them should always be clomipramine (Anafranil), which is the only one that can be accurately measured in the blood, allowing a test of whether a therapeutic amount of medication is getting into the body.

  After trials on at least three SRIs, with augmenting agents, combinations of SRIs may be tried. Although there are few good studies to date on the combined use of SRIs, clinical experience shows that this can be an effective strategy. A number of my patients, for example, have benefited from the combination of Anafranil with another SRI.

  An important consideration in prescribing for OCD is whether a second, distinct psychiatric disorder is present along with OCD. If so, then it is imperative that this second condition be treated as well. Severe depression, panic disorder, bipolar disorder, and tics all occur with an increased frequency among OCD sufferers. For reasons not well understood—psychological, biological, or a combination of the two—OCD often will not respond to treatment until after these accompanying disorders have been addressed.

  Dose Variability

  There are large variations in the dose of medication required to treat OCD effectively. This is due to a number of factors, including how well a drug is absorbed into the body, how efficiently it is metabolized by the liver, how quickly it passes through the blood–brain barrier, and how strongly it affects serotonin. It is known that with standard antidepressants there are tenfold differences in effective doses between patients. The same probably holds true for SRIs.

  Finding the optimal dose of medication must be approached with the same “whatever works best” strategy as finding the right type. Studies suggest that higher doses of SRIs are needed to treat OCD than to treat depression. Quite commonly, OCD sufferers require 80 milligrams per day of fluoxetine (Prozac), and I have had patients on up to 150 milligrams. Many patients, on the other hand, respond well to the standard antidepressant dose of just 20 milligrams a day. A few people with OCD respond to ultra-low doses of medication. I have patients doing well on just 2 milligrams a day of Prozac. To take such a low dose, the liquid form of medication can be used; or the capsule can be taken apart and the contents mixed in juice and saved in the refrigerator.

  Two different approaches are used to begin people on anti-OCD medications: Start low and increase slowly, or move quickly to the highest safe dose. The advantage of the latter, of course, is that it saves time. Trials on a number of different agents, if the dose is slowly increased, could easily last up to a year. The advantage of going slowly, on the other hand, is that no one suffers harsh side effects, and therefore medications that might work if given enough time will not be quickly abandoned. Both approaches have their place. Academic centers, perhaps because many of their patients have already been tried on several medications, tend to prefer the faster approach, whereas psychiatrists in primary care, such as myself, usually start slowly.

  Maintenance Treatment

  The period of time from when medications are started to when a good therapeutic effect occurs is referred to as the acute phase of treatment. The period after that, during which medications are continued in order to maintain therapeutic gains, is referred to as the maintenance phase. In OCD it is clearly wise to continue medications for some period of time after acute treatment, but there is disagreement as to how long.

  A number of studies have shown that when SRIs are stopped, relapse is highly likely. In a 1991 investigation of moderate to severe OCD, for instance, 89 percent of patients who had responded to clomipramine (Anafranil) relapsed within seven weeks of stopping the drug; all patients subsequently responded again when Anafranil was reinstituted. As mentioned above, the SRI medications work like anticonvulsants or insulin: They bring symptoms under control but do not eliminate the underlying disorder. The effects of SRIs last only as long as the drug is being administered.

  More recent studies, however, show that it is often possible to discontinue medications, even in cases of fairly severe OCD, if effective behavior therapy has been implemented. Studies from England, in particular, suggest that a majority of patients can stop medications if they practice behavior therapy faithfully. My clinical experience is that many OCD patients can, indeed, stop medications. Some work hard at behavior therapy; others, it seems, experience such a lessening of life stresses that drug therapy is no longer necessary. Still, I find that more than half of patients need long-term maintenance treatment.

  In maintenance treatment, happily, the medication dose can usually be decreased without losing therapeutic effect. A study of the use of Anafranil in long-term treatment of OCD, for instance, demonstrated that the average dose of medication required during acute treatment was 270 mgs, whereas the average dose needed to maintain treatment was only 164 mgs. Such a decrease is often enough to eliminate any remaining side effects.

  A reasonable approach to maintenance treatment is to stay on an SRI for at least six to twelve months after symptoms have been brought under good control. During this time, maximal effort should be invested in behavior therapy. The medication dose can then be slowly lowered. If there is no recurrence of symptoms, medication can be discontinued. Yet OCD sufferers should be ready to accept the possibility that long-term treatment with an SRI, with regular trials at obtaining the lowest effective dose, may be best.

  SIDE EFFECTS

  Perhaps the main reason why SRIs are among the most widely prescribed drugs in the world is that they have relatively few side effects. A recent study involving more than six thousand patients showed that far fewer patients (13.9 percent) stopped SRIs because of side effects than stopped standard antidepressants. In my own clinical practice I have treated hundreds of patients with SRIs. The dose has usually needed to be adjusted, the type of SRI has often needed to be changed, and on occasion medication has needed to be stopped all together. But I have never had a patient who experienced either a nonreversible or a medically harmful side effect.

  Unfortunately, misinformation abounds regarding the side effects of these drugs. Probably the most common unfounded belief about SRIs is that they cause addiction. The truth is that not a single study has shown them to be habit-forming. Furthermore, the personality of the OCDer, guilt-prone and overly responsible, tends to prevent addiction to anything. I have never treated, nor even heard of, a patient who became addicted to an SRI prescribed for OCD.

  Another common but unfounded fear is that the SRIs can cause suicidal, or even homicidal, behaviors. This specter was raised by a 1990 article in the American Journal of Psychiatry which reported that 6 out of 172 hospitalized patients on Prozac had become preoccupied with suicidal thoughts. Subsequent studies on many thousands of patients, however, proved that suicidal and homicidal thoughts are no more common wit
h Prozac than with other antidepressants. The number of people who have been prescribed Prozac to date—over 40 million—dictates that almost everything will have happened to someone while on the drug, simply by chance. Yet the mistaken idea that Prozac causes Jekyll-and-Hyde personality changes surfaced once again when defense lawyers tried to argue that David Wisbecker, who in 1989 killed eight of his coworkers in a plant in Kentucky with an assault rifle, did it because he was on Prozac. The issue, hopefully, was put to rest permanently in 1995, when the courts completely discredited the “Prozac defense” in the Wisbecker case. The Federal Drug Administration, whose mission it is to oversee the safety of medications prescribed in the United States, and which is often criticized for being too restrictive, subsequently rejected a petition that the Prozac label include even a warning about suicidal or violent behavior. The FDA has repeatedly reaffirmed the safety of Prozac and the other SRIs.

  Some widely available books do a good job of realistically appraising the risks of side effects of SRIs and other psychiatric medications. I found three good ones in my local bookstore: Complete Drug Reference (Consumer’s Reports Books, 1994); Essential Guide to Psychiatric Drugs by Jack Gorman (St. Martin’s Press, 1995); and Prozac: Questions and Answers by Ronald Fieve, M.D. (Avon Books, 1994), the eminent psychiatrist at Columbia University who did much of the pioneering work on bipolar disorder. Unfortunately, the “product inserts” that accompany medications and the Physicians Desk Reference, a compilation of product inserts, do a poor job of appraising side effects. They are designed largely to prevent malpractice suits against pharmaceutical companies and simply list every side effect that has ever been reported.