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Depression and Bipolar Disorder

Mood disorders are common, deadly and treatable. The prevalence for bipolar mood disorder is 1-3% of the population. Bipolar disorder accounts for very small subgroup of patients compared to those who have depression, who account for 8 to 15% of the population. Depression has a much worse outcome for untreated disorders than even some forms of cancer. 15-20% will die by suicide if untreated. The good news is that mood disorders are highly treatable depression, bipolar disorder, manic, mania, manic disorder, depresion.

The frequency of suicide has a bimodal distribution. We have a low peak in the year over the spring months and a secondary peak in the fall. Hippocrates wrote that spring is the time the black pile runs, right? The black pile being melancholia and the reason Hippocrates said that is because his teachers taught him that it was autumn and you can see that both of them were right. We have two peaks during the year. This is very consistent and itís not just the shape of the curve for suicide but also for suicide attempts. The new onset of affective episodes tends to be in the spring and the fall all over the world although the spring peak is obviously October/November in the

People have looked very carefully at why this might be happening and you notice that the peaks are centered on May and October, months when you might say if ever psychiatrists should be there to return the phone calls of their 

So mood disorders are common. Unipolar thereís a 2:1 ratio of female to male where bipolars, at least for most forms of bipolar illness and most studies find a 1:1 ratio. If you are ever asked about the gender ratio for rapid cycling, itís 3:1, maybe even 4:1 in favor of females where bipolar IIs there may be a 2:1 females but overall most studies donít find that. Most studies find that thereís a 1:1 ratio for most forms of bipolar illness as 

Bipolar I you see it has got 1% of the population. When people ask questions about the prevalence of bipolar illness they often mean what is now termed bipolar I and weíre going to clarify that later. But for now I just want you to get the idea that there are subtypes within the mood disorders and weíll come back to that.

Because the importance of these numbers to me is not so much the numbers themselves. I donít think we worry a lot about epidemiology but there are some important lessons to be learned from how these numbers are collected. We could do various kinds of psychiatric assessments. Thereís great limits on the validity and reliability because thereís no gold standard. We canít go out and draw a

How long do episodes last? Another very important issue and this is data from my colleagues at Pittsburgh but it happens to be almost precisely the same as the data from our collection. Time to remission for pure manic episodes, half the episodes have remitted at 20 weeks. Now that may not sound so good to you and you should know their definition Ė that 20 weeks required them to have eight 

So thatís kind of good news and then even better by 40 weeks, everybody who had an acute episode of mania is well. Maybe that doesnít sound so good to you but look at the alternatives. What if you had an episode of depression? You are going to have a much more crowded course. For people with pure depressive episodes the median duration now is out at 40 weeks and we never get to here. At the end of a year, 42% of these patients are still ill. In our clinic at the end of two years 23% are still ill and youíre getting borderline 

If that isnít bad enough, what if you have a mixed episode? If you have a mixed episode, now the median duration is out to 50 weeks and 45% are still ill at a year. Well, thatís pretty bad. So depression confers chronicity.

Thatís a quick overview of development of the concept and the course of symptoms. Now letís go and talk quickly about core concepts in the DSM. The single most important concept to make sense of the DSM-IV is that the DSM-IV distinguishes the episodes from the illnesses comprising those episodes and it also gives us so-called course specifiers. So these are three separate concepts to understand.

The course specifiers are rapid cycling, meaning the patients have had four episodes a year, post partum onset which is having an episode of mania depression within a month of delivery and then seasonal patterns simply means over several years the episodes have the same onset and offset in the time of the year predominantly. It doesnít have to be that every episode occurred in the fall or winter but predominantly. Youíre left to make a judgment about that. So those are the four specifiers.

These are specifiers because somebody with bipolar illness could be rapid cycling or a unipolar could have a seasonal pattern and they are not separate illnesses. Any unipolar or bipolar could have any of these.

The acute episodes, as you know well, are depression, hypermania, mania and mixed. These are acute episodes but you canít give a diagnosis code for one of these four. Theyíre always coded relative to a disorder so the mood disorders are categorized as primary. Weíre going to talk a lot about unipolar and bipolar in a minute but worth noting the other category secondary Ė induced by a substance or a general medical condition. This means you think that is etiologically important in the development of that episode. So if somebody were using alcohol or cocaine, antihypertensives, steroids, they would have a substance induced secondary episode but the episode would be diagnosed using the same criteria as it would be for a primary episode.

So depression is depression. Mania is mania. If you have a pancreatic cancer and get depressed we diagnose depression because it meets the criteria for major depression but we call it secondary because of the pancreatic cancer or this drug or the TLB.

"Residual mood disorder not otherwise specified" is seldom used but it simply means there are prominent mood symptoms and it doesnít meet criteria for any of these.

On the unipolar side, looking at the primary mood disorders, we have major depression and its little brother dysthymia. Major depression and dysthymia are unipolar because notice there is never any period of abnormal mood elevation. For major depressive disorder we have to have at least one episode that meets criteria for major depression. It is as simple as that.

Dysthymia is a chronic condition where we have low level mood symptoms, disinterest, dysphoria and this goes on for a period of one year in children and adolescents, two years in adults where more than half their days they have either depression or disinterest and half their days two symptoms of major depression. Anytime that their mood is normal in this year or two year period lasts less than eight weeks and during this whole time they didnít meet criteria for major depression. Now that could have happened to somebody when they were age 18 and now when theyíre 24 they have major depression. They would have so-called double depression. They had the prior dysthymia and we donít take dysthymia away because years later they got an episode of major depression. We would only take it away if during this period of one to two years they got major depression.

On the bipolar side, we have three defined conditions, bipolar I, bipolar II and their little brother psychothymia. Bipolar I requires at least one full manic episode. No depressions are required but mostly patients have had lots of depression. In fact, bipolar patients tend to have more depressions by far than they do manic episodes but itís not required to diagnose bipolar I.

Bipolar II, on the other hand, patients suffer a hypomanic episode but never mania and must have at least one episode of major depression. Why do they require major depression for bipolar II and not bipolar I? Very simple. If you go to Yale at the end of four years thereís a 96% chance that you would endure symptoms sufficient to diagnose an episode of hypomania but very few of them actually get depressed. So what is that they were describing? They were describing falling in love, winning an award, getting good grades, the things that happen to them and there really isnít much specificity to hypomania particularly during those years until you add that depression in. Then itís a lot more meaningful particularly if it was recurrent and I know if Hugo Pakiska was here he would say you can always tell the difference between bipolar illness and falling in love because bipolar illness is always recurrent.

Cyclothymia, like dysthymia, the patient has had it a year for children or adolescents, two years for adult where they have frequent hypomanic symptoms. It doesnít say frequent hypomania just frequent hypomanic symptoms and half the days are either too high or too low. That can mean you have 20 days of dysphoria and two days of mood elevation each month and you would be cyclothymic not dysthymic as long as any period of euthymia was less than eight weeks, you never meet criteria for mania or you would be bipolar I. During this period of time again you donít meet criteria for a major depressive episode.

It sounds like it would cover the waterfront but it doesnít. Itís worth knowing about bipolar NOS which is in the book. This is somebodyís got some period of clear-cut abnormal mood elevation. Maybe theyíve had one, two or three or more hypomanias but never depression, thatís a bipolar NOS not a bipolar II. Maybe theyíve had a period where they look cyclothymic but it only lasted 10 months. Weíre not going to ignore that theyíre bipolar NOS. Even if itís for less than two months theyíre bipolar NOS.

You often hear the term bipolar III bandied about. There are ten definitions in the literature for bipolar III. It is not in the DSM but when you hear it you can know that some people mean cyclothymia, some people mean antidepressant induced mood elevation but actually one that we find useful is this one. Bipolar III is somebody who themselves has never had any period of abnormal mood elevation but they have a first degree relative, a parent, child or sibling, who does have bipolar illness and they themselves have recurrent major depression. That is to say if my brother and I have both been depressed and you find out that my brother has been manic, when I come to you for treatment you might want to say to me, "Your chances of having the same illness your brother has are very high. We might characterize you as bipolar III and maybe we shouldnít just give you an antidepressant alone for your treatment."

Now, Iíve been talking about 35 minutes and Iíve probably said the word "mood" over a hundred times giving you the idea that these are mood disorders. Why, if theyíre mood disorders, do we see that 30-40% of these patients receive chronic treatments Ė at least bipolar patients Ė with antipsychotics. This is not in the days of atypicals. This is data from before that when every expert recommended not giving neuroleptics to affectively ill patients chronically.

Well, there are some reasons for that. One of them is that psychosis is not uncommon as a part of mood disorder. This is data for bipolars and you see in twenty studies since 1970 about half the patients in any episode had delusions, 15% hallucinations, 18% or just about 1 in 5 patients have the Schneiderian first rank symptom. Right? Thatís what I was taught discriminates schizophrenia from affective psychosis which is not the case.

Over the course of a lifetime more than half the patients have some history of psychosis and you can see in some studies itís three-quarters of the patients depending on how you define it when you break them up. So psychosis is common as part of affective illness and it tends to be more common the earlier the age the person is when they first get ill. So this age of onset, we see three or more

Diagnostic criteria for mania. Here we require a distinct period of abnormal mood that must be euphoric, expansive or irritable. If euphoria or expansive mood is part of it, you only need three of these associated symptoms but if itís only irritable then you need four. Now remember when I told you the criteria for major depression. It says the symptoms need to be there most of the day nearly every day. Thatís not what it says here. Associated symptoms must be present to a significant degree during a week. Now, that leaves you to figure out what "to a significant degree" means. Thatís your judgment call. It doesnít mean that they were constantly talking. But whatís 

These associated features include increased self esteem or grandiosity, decreased need for sleep as opposed to simple insomnia, pressured speech or just going on and on and saying more than anybody else in the room. Flight of ideas or racing thoughts, distractibility, increased goal directed activity and then there is my favorite criteria, participation in pleasurable activities with potentially painful consequences. This is risk taking and this is here because of the word "potentially".

Why? Because if you are participating in activities that are potentially dangerous, whether you get caught or not is immaterial to the diagnosis. So if you are embezzling money from your hospital and you donít get caught, you still meet this criteria. If you were driving down the street here in the city at 90 mph and you donít get a ticket, you meet this criteria. Remember the word is "potentially". That means we have an opportunity to intervene before thereís a disaster if we make the diagnosis. This criteria is often what helps you discriminate mania from hypomania as youíll see in a bit.

Lots of times patients have no idea how to evaluate the risks that theyíre taking. This is a guy that I always wondered did he ever have a psychiatric exam. Remember David Wolf the astronaut physician who went up and just before he went up on the shuttle to dock with MIR he said, "Flying MIR seems perfectly safe to him." Well, I donít know about him but I would rather be on the Budweiser blimp. 

Sometimes patients present with excessive talking and when you ask them about pressured speech they say no. This gives you some idea about insight but more often they will endorse pressured speech outside of the interview if you simply ask about it. Theyíll tell you that people cross the street to avoid having conversations with them. Theyíre often very aware of it. Donít rate that as absent because you donít see it in the office. Take their word for it. Theyíre telling you the truth.

Sometimes you will be the target of the patientís being easily annoyed by everything you say but more often itís somebody else so ask about that even if they seem perfectly fine to you if any little thing gets them going. Sometimes itís a cop and often the art of interacting with these patients is when you see that youíve just waved that red flag to change the subject or things are going to deteriorate fast often 

A couple of words here that fit over all the patients but most particularly for adolescents where we get into this question of differential diagnosis versus comorbidity. Once the patient has met criteria for mood disorder, theyíre very likely to have a comorbid condition. The only one on this list that is inconsistent with the mood disorder diagnosis is schizophrenia. Patients often have disruptive behavior disorders, anxiety disorders, substance abuse.

What is the significance of having that comorbidity? Again, this is one of the key points to remember. Remember those epidemiological studies? Remember all the people that got diagnosed? Well, 86% of people who got any diagnosis only met it for a period for one or two. The other 14% who had the diagnosis actually had three or more diagnoses. What does that mean? Well, if you focus on this slice of the pie, what you see is if you follow them up for a year this group accounts for nearly 60% of those who have a new episode in any year and if we look just at severe episodes, 90% of severe episodes come out in this group.

So when you have a patient, when you do your evaluation and you say, "Oh, my goodness. They have an anxiety disorder. They also seem to have a comorbid ADHD and they clearly meet criteria for mood disorder, thatís not good." Theyíll need to be watched closely. Maybe that shows us our cookie cutter diagnostic system is inadequate because if you look carefully at the symptom overlap for mania, ADHD and letís say conduct disorder, what might impress you is for instance if you have increased goal directed activity and psychomotor agitation that overlaps with six symptoms of ADHD, three of conduct disorder and this pleasurable activities overlaps with ten symptoms in conduct disorder.

So if you were to have five, six and seven, you would definitely meet criteria for all three of these. Right? That would be kind of worrisome. Can we disentangle them? Well, data from Janet Wolzniak, I think, showed you that in the case of ADHD you really can. She looked at consecutive referrals to the child psych unit with mood problems and when they had bipolar illness 96% of those who had hypomania or mania also met criteria for ADHD. But when she went down to those referred in for ADHD, only 19% met criteria for bipolar illness.

What does that mean? Well, if you think about this for a minute, I think we might agree, what we can say here is that if people really seem to meet criteria for both, the least likely thing is ADHD alone. They may just have bipolar illness, they may have both but the least likely thing is this is just an ADHD kid. So when youíre confused the first thing to do is not reach for the Ritalin. Itís better to reach for the Lithium or Depakote to treat that and see how much improvement that brings and then add stimulant if you still need to.

Also from Jo Mirianís group we see the risk of new onset of bipolar illness over a four year followup, presentation has all three of these disruptive behavior disorders Ė ADHD, oppositional defiant and conduct disorder. If you diagnose that, you may not want to be around for the next four years treating this patient because within four years more than 40% of these patients with have a hypomanic or manic episode. But if we just take away the conduct disorder you see itís less than 10% if they just have oppositional defiant ADHD. ADHD alone is about 6%. So having these are bad but really the worst thing is to have a comorbid conduct disorder. That foreshadows for you where the difficulties are.

How can you tell ADHD from bipolar disorder? Itís pretty difficult. People will look at the hyperactivity and say thatís more goal directed for bipolar and more scattered with ADHD. The sleep disturbance is episodic with bipolar, consistent with ADHD. Impulsivity here is reactive versus it seems consistent and self generated.

Those three things, to be completely honest with you, I think are hit and miss. I canít really feel good relying on them. What I rely on if I have to make this discrimination is the last one Ė social or academic function Ė and I donít ask about the year that they failed out. I want to know about the year that they did best, socially and academically because an ADHD kid, the bipolar kid will definitely have bad times that look indistinguishable but the bipolar kid often has periods of above average function even without treatment. So somebody who is on the outs with all their friends in fifth grade but in eighth grade was voted most popular, thatís rare with an ADHD kid. If they were spelling bee champion in the fifth grade and failing in the sixth grade, thatís rare for an ADHD kid. That ADHD kid they failed both grades without treatment. So weíre looking for the period of best function and I do find that to be helpful.

I canít really find anything helpful to discriminate conduct disorder from bipolar disorder and this may be telling us something but lifetime comorbidity is about 70% in the studies from Kovax and Pollock. Episode comorbidity is 54% with any one episode. Conduct disorder gets diagnosed first in about 40% of kids and about a quarter of them bipolar first and maybe thatís a little bit helpful.

How to do the assessment. You want to have multiple sources of history if at all possible. We do not rely on a patientís self reporting for the diagnosis and we will not treat people although we will do a consult and that will be it if we canít have another source of information. You want to get a good family history, a good medication and substance abuse inventory.

Physical exam, you donít just go and do a head to foot evaluation of everybody but your physical is directed by the findings of your history. You want to do a good cognitive status exam. At least some brief cognitive test and evaluate their mood state.

Then what about labs? Well, labs are going to help you sort out the secondary issue very often. Here I think as a minimum youíre going to get serochemistries, a TSH and a CBC and then if necessary you can get a sed rate, BDR and all, HIV, toxicology screen and then some people would say imaging. Some people would also say you should get an EEG. I really believe that all of these should be done at least once per patient. You donít have to do them every episode but if somebodyís presented with mania, you might want to do this and see whatís going on there.

Differential diagnosis. In most areas we concentrate on the psychiatric illness first and you always start by ruling out the secondary causes so we are looking to our physical exam and labs to help us figure out what of these things might be going on.

We can also look at the difference between drug and placebo of these trials. 15, 23 and 18%. Not significantly different and then we can look between any two drugs of the same class, less than 2%, about 2%. Here this is the difference between bupropion and a tricyclic. Actually favored bupropion being 7% more effective. So we can see whichever of these criteria we set thereís not much difference between these drugs. That is not to say the individual wouldnít respond preferentially. It is to say that if you took a thousand patients and you gave them all any of these treatments you would get a very similar percentage getting well. But any one patient thatís not necessarily the case.

We can use our definition to generate this "menu of reasonable choices" and so you can see here there are ten or so first line choices based on our low risk of serious morbidity, tolerable side effects and pretty good efficacy. If you look at this list, I donít know if it jumps out at you, but when I show this around the country people say, "Look, you guys have missed the boat on something very important here." Drug safety in overdose.

If you use that criteria you must eliminate the two tricyclics because these drugs are in fact deadly in overdose. We felt we should leave them on because of lot of physicians feel like they can manage this by assuring they give limited supply of medication. So if youíre going to use that medication you need to know that these are deadly in overdose.

So in each case here, with the exception of these two, we have medications where there a drug with similar profiles thatís better tolerated over here. The reason ECT is on this list of available and preferred is because some people think that it is an ethical imperative to offer the safest, fastest most effective treatment we have to any patient whoís not doing well. So you may start with one of these but if this isnít working you should make patients aware that ECT is available at any point if they prefer,

And there are also other reasons why you might prefer one of these. You might prefer it because the patientís sister responded to lithium so youíre going to use it. The patient might have ulcers and allergies so you might decide to use doxepin. They might have sleep apnea so you might decide youíre going to use protriptyline. There could be lots of reasons to choose. Nobodyís going to sue you if you choose to start with one of these.

In this case, second line treatments there is an issue. These drugs all have some significant risk thatís completely avoidable so why would you start with amoxapine when it has a risk of tardive dyskinesia even if itís small when you have two dozen other drugs to choose from? Clomipramine Iím not so worried that itís not approved for depression but it has the highest rate of seizures of any drug up here. The MAOIs, we have a risk of hypertensive crisis. Thereís lots of other things that you might decide to use.

How do you decide what to do? We can look at these various guidelines and we come up with our own menu of reasonable choices. Iím not trying to convince you to use the one Iíve just showed you but just to come up with one of your own. If you did, you might have a list like this that you show patients and this is what we actually do at our clinic. I will show a little profile of these drugs that I regard as first line treatments.

How do we do a course of treatment? Well, weíre going to begin with our acute phase treatment plan and that means negotiating to choose that first line treatment and I need to teach the patient and their family member what to expect about it. Then weíre going to start the treatment and Iím going to monitor the response and adverse effects every one to two weeks. Now there is no established legal standard for how often you need to monitor patients but I can tell you that if you decide you should give them a medication because the

So what happens when they do come back for their followup in one or two weeks? Well, then weíre going to evaluate them and if they have minimal symptoms, theyíre recovering, then they go into the continuation phase of treatment and Iíll see them in two weeks. Even if I started a drug with a dose initially that I donít think is adequate I donít advance the dose at that point. If the patient is well, I pat them on the back, "Congratulations, Iíll see you in two weeks."

Often though, thatís not the case early in the course of treatment. Instead, I look to see are they at all better at a couple of weeks. Looking for maybe 30% improvement. When that is the case, then go on and pat them on the back there, continuation phase treatment, we just leave them where they are.

But, again, quite often early in the course of treatment patients are actually no better and if the patients are no better, what I do with that followup is determined by the adverse effects. When patients have serious adverse effects I have to manage that. That may require a week or two to intervene so that they can tolerate the treatment whatever I do. Now again, early in the course of treatment that doesnít tend to be the issue.

So what if somebody is absolutely no better and theyíre tolerating a drug well? We think that what you may need to do is to increase the dose of their medications. So often what youíre doing early on is continuing this acute treatment path, seeing them back every one to two weeks and titrating the dose, escalating it as they will tolerate until you get to a maximal dose. Now that may seem to you to be a bit aggressive.

Why do we do it? Well, when youíre doing this, you may jump off of the treatment plan at several different places based in the patientís clinical status, if theyíre recovering ____ continuation. But if you were dosing somebody and they became manic or even hypomanic you would take them off the antidepressant. If they came back and they were depressed, still fully depressed or even close to it but maybe they donít quite meet the full DSM criteria, then, again, based on their ability to tolerate you might switch treatments, go to ECT, a different standard antidepressant or some innovative treatment. In the reverse, you might also, if you carry out a trial up to sixteen weeks, you might add a new treatment. Again, ECT, standard or 

Why? Well if you read the literature the literature tells you in some studies offering a second, third or fourth SSRI seems to work and in others it clearly doesnít. It may either be valueless to choose a drug of a different class or it might really be a winner. Itís just if the cost of going to a different class is the same as going to the same class, Iíd rather go to a different one. You can also add stimulant precursors or anything else you like. This will allow you to add tincture of time and give the patient the maximal chance to fail drug A before you go to drug B.

So weíre going to do that. Weíre going to carry out this trial. The patientís been doing well, we optimize their treatment, adding a second antidepressant if itís not working. If that doesnít work weíre going to switch to the different class and, of course, if necessary go to ETC.

Now all of you have probably worked through these strategies and youíve had some patients who donít do well. What do you do at this point? Well, you could say, "Mr. Jones, tough luck. Iíve done everything I can. Why donít you find somebody else? I donít think I can get you better." That is also not a very good thing for your therapeutic alliance, needless to say.

If you read William Stirin or Kay Jameson or any of the other very well written books describing this interaction between patient and doctor trial after trial, remember I told you about the patient I had 23 failed trials? What you see they describe is "The only reason I took that 24th trial is to kind of humor my foolish psychopharmacologist. I didnít think I was going to get better. But you know what? I eventually did." Patients literally live off of your therapeutic optimism. That will keep them alive and it should always be offered so if we get here and itís not working, what we do is we go back and we do it again. One maxim of treatment that I always try to keep in mind is life is short and the PDR is long. Thereís always something more.

Now we get to the continuation phase. Remember that means the patient has had remission of their acute symptoms, weíre going to continue the successful treatments at the full dose to maintain effective serum levels in the cases where thatís known which usually itís not and weíre going to adjust things so that they can tolerate their medications. Someone whoís got such severe dry mouth that they canít speak, keeping them at that dose is not the way to go. How long are we going to do this? Weíd like to choose a duration based on some estimate of the natural course of their illness. Now, if I know how long the last episode was that means Iím going to go at least that long, usually double that duration but if I know nothing, weíre going to use this handy, dandy 6/12 rule. Six to twelve months after remission of symptoms for a first episode and probably if itís the second, Iíd say at least a year.

So hereís how we use this rule. With unipolars, letís say itís 6 to 12 months. If they have multiple episodes weíll probably decide not to taper after the continuation phase but to maintain them. For bipolar patients the 6/12 rule goes like this. If they have monophasic episodes, so isolated depressions without mood elevation before during or after, or a kind of biphasic episode that starts manic and goes to depression those patients Iím comfortable 6 to 12 weeks. Taper them off and during the taper, they relapse, I go back and Iíll go another 6 to 12 weeks.

If they relapse again, theyíre 6 to 12 months and after that theyíre getting maintenance dose. 21% of our bipolar patients get maintained on antidepressants so Iím not telling you you canít maintain people. Iím saying give them a chance to get off the drug. Biphasic episodes for our bipolar patients who have depression that goes spontaneously to mania, rapid cycling, history of iatrogenic mania, for those folks, 6 to 12 days it means and then these tapers Iím doing at about 25% of the dose a month. So itís a very gradual kind of taper. Now, we get to the maintenance phase and thatís where we would be doing this taper after we have declared victory because the patient has a sustained remission for at least eight weeks. Weíll do our slow 25% a month taper. Could you do 25% a week? Could you taper it over 4 days? Well, obviously you really could but there really is no need to be in a foot race and the slower you go with this the more likely you are to be successful.

During this time youíre going to keep them on whatever prophylactic treatments you decide are necessary to ward off recurrence and then youíre going to followup. Whatís reasonable followup? In our clinic, through the first year once a month, every other month the next year and then four times a year thereafter. Weíre watching them to manage adverse effects, keeping the prophylactic medications in the therapeutic range. We encourage people to do daily mood charting so that we can determine their cycling.

Weíre also looking out for this thing called roughening. Roughening refers to after the patient has had this period of eight weeks, maybe itís 18 weeks or 118 weeks with smooth sailing, now they hit a point where theyíre not doing so well. That is often the herald of the next episode so weíre looking out for that. The breakthrough episodes that occur during prophylactic treatment, the patientís roughening, they have a new episode, these are much more worrisome than episodes that occur in the absence of any treatment. These breakthrough episodes tend to be more severe, more chronic and less responsive to treatment. Any bipolar patients, they will tend, if they have a new episode off treatment, respond well to mood stabilizers but not so well if they were on the mood stabilizer. If theyíre on lithium at 0.8, going up 1.0 when they get depressed tends not to work.

For mania, we make sure patients are safe just like we did for depression. We get rid of any secondary causes, whether theyíre medications or medical problems that are there. Then we institute specific antimanic therapies. So weíre always going to begin with lithium, Depakote or Tegretol. Weíre going to add other agents as necessary to control the acuity of the symptoms, clonazepam, antipsychotics, if necessary, bilateral ETC.

The question you might have is how fast do you go from here to there? Well, we might start these all on day 1 if patients are really very agitated and if on Tuesday night that patient is tearing the ward to pieces we would certainly offer ECT Wednesday morning.

In the acute phase, what weíre really targeting is hyperarousal and weíre trying to, in our acute phase, bring down the amplitude and the duration of the hyperarousal symptoms so that we can get accurate continuation. So there might be an indication to use, not just benzodiazepines but antipsychotics as well if patients are psychotic, very agitated, they have a history of being refractory with mood stabilizers or they just wonít take one. Somebody who would rather have Risperdal than lithium, absolutely. Right there. What we will do here if there is this kind of agitated hyperactive psychotic patient is we will offer the mood stabilizer and the antipsychotic at the same time. Whichever we didnít give here, within a few days or a week if theyíre not doing well we offer it there and then of course progressing to bilateral ETC. The rest is the same.

Good news in managing mania is that you can treat very aggressively with antipsychotics. You can also treat very aggressively with Depakote. You canít do that with Tegretol or lithium. So itís worth knowing the oral loading strategy for Depakote and in this case what you do on the first day, you can give 20 and some people even give 30 mg/kg. If youíre thinking do I need a calculator to figure it out? No. You can take the patients weight in pounds, letís say 130 pound woman, we add a 0 and we round to the nearest 250, sheís going to get 1250 mg on day 1, then I would give her maybe 500 in the morning step and 50 in the evening, day 2, get the labs, on day 4 see where she is. If you do this, you will find very reliably with people who are between 20 and 60 years of age you get a blood level of 80 +/- 10. Often you will need to push beyond this and be more aggressive with people but at least thatís a good rapid way to get people into the therapeutic range. Does this work better or faster? I donít know that to be honest with you but I can tell you itís actually very well tolerated. Thereís no reason I would see not to do this with an inpatients. You might be a little bit less cavalier with outpatients.

Continuation phase of mania looks just like the continuation phase for depression. So if we know the natural course, weíre going to choose a duration double the last episode of mania. 12 weeks if we have no reliable history, at least 12 weeks. The question that comes up this time of year, let me emphasize this to you because we see this every fall and also early in the winter, Johnny is going off to