PsychEducation - The Blog

Bipolar Diagnosis Rules Have Been Changed

Wed, 02 Apr 2008 12:46:18 PDT

Well, that might be a bit of an overstatement. But that's journalism, right?

Here's what really happened. The International Society for Bipolar Disorders (ISBD) is a group of researchers and clinicians interested in bipolar disorder, with members from all around the world. The leadership of this organization decided several years ago that we needed an update on the DSM (Diagnostic and Statistical Manual), because the next edition of that official rulebook won't come out for another three or four years.

The current DSM was written about 15 years ago. You would hope that by now we might have some additional insight into the nature of bipolar disorder and how it should be diagnosed.

So the ISBD commissioned 25 mood specialists to look at the existing literature on bipolar disorder and make recommendations in a different areas of controversy: mixed states, Bipolar II, bipolar depression (how is it different, if at all, from unipolar depression?), rapid cycling, children and adolescents, and the "bipolar spectrum" perspective.

For intrepid interested readers, I have posted a summary of these guidelines, with the relevant links, on my PsychEducation website. The bottom line, from my point of view: virtually all of the papers prepared by this committee of bipolar specialists acknowledge that the DSM system of discrete categories -- in which one either has unipolar depression, for example, or bipolar depression, but nothing in between -- is causing some trouble. While switching over to a "spectrum" perspective, as reflected on my website, is not a solution either (all sorts of logistic problems would follow), the validity of that way of thinking is supported by the work of these experts.

Dr. Phelps

So although the official rules for bipolar diagnosis have not literally changed, an important update on those rules has been issued. Anyone who depends on the rule system -- which hopefully includes a broad array of patients and practitioners -- should be interested in further details on the work of the ISBD Committee on Diagnosis. Here is the summary link again.

The Value of Low-Dose Lithium

Sat, 08 Dec 2007 17:52:23 PST

A reader asked if I would comment on whether low doses of lithium, well below the high-risk levels that can swing up into "lithium toxicity", might still have benefit -- particularly in Bipolar II depression.

The answer is clearly yes. Indeed, lithium has shown value at low doses as an add-on treatment for "unipolar" depression. In other words, lithium has value even if there is no obvious bipolar component to one's depression. And, it has value at low doses: when added to other medications that are not working well enough, it can boost their effects.

(On the other hand, we could wonder whether there might perhaps have been an "bipolar component" in the person's depression, and that is why the antidepressant was not working well enough -- and why lithium helped. In other words, does lithium helping mean that there might have been some degree of bipolarity in the depression? For the moment, until we have a better way of knowing when bipolar disorder is present, in any degree, we should assume that the answer to this question is no. That is, we should assume lithium can treat depression of any kind, not just bipolar depression.)

Recent data suggest that lithium's benefit in bipolar disorder is stronger against preventing manic recurrences, than against preventing depression recurrences. Nevertheless, many of us use it for a very different purpose, namely adding some antidepressant "oomph" when other treatments have not effectively treated depression. In this role, sometimes tiny doses of lithium are sufficient. One of my patients even responded to 150 mg, half of the usual smallest dose. Her response was unequivocal, and has been sustained for over three years now.

What about blood levels? At these low doses, the level of lithium can be far below the "therapeutic range". On the laboratory data sheet, such a result is often marked with an L, indicating an abnormal value, in this case too low. This can worry people who don't really understand what we are doing here. When lithium is used at a low dose, as an add-on medication, we are usually targeting a particular symptom that is already present -- usually depression (as opposed to targeting the prevention of recurrence when a patient is well. That requires knowing that the lithium level is sufficient to award that benefit. We know from research and experience that this requires requires being in the "therapeutic range". Indeed, that range is defined by a lower limit below which the preventive benefit is unlikely to occur; and an upper limit beyond which dangerous side effects become common).

In the low- dose approach, one simply turns the dose up until the target symptom is responding, or until a side effect appears, or until the patient reaches 600-900 mg, at which point we get our first blood test to make sure that she/he is not approaching the upper end of the therapeutic range.

If a good response occurs at a very low dose, e.g. 300-600 mg, the blood level is likely to be low -- so it is important to be prepared for that low number, prepared to disregard it. The main reason for the test is simply to establish that the level is not near the upper end of the therapeutic range, which even at low doses can occur sometimes. It is safe to be at that upper level, but then one has to be more careful about anything that can raise lithium levels spontaneously (for example: dehydration, adding a blood pressure medication, using ibuprofen, getting the flu). One has to be careful about such factors in any case, but when the lithium level is known to be high, then any such changes may warrant repeating the lithium level to be sure it has not gone too high. Knowing that the level is "low" allows for a little more breathing room in this respect.

In summary: low-dose lithium is a great medication. It is inexpensive, and under these circumstances can often be taken with no side effects at all. The risk to one's thyroid production is still there, and long-term monitoring of kidney safety is still warranted (although that risk is likely to be much lower with the lower dose).

I tell my patients: lithium is like two different medications. Low- dose lithium is a "low-maintenance" medication, whereas high- dose lithium warrants careful attention to levels and other variables. Unfortunately, when most people think of lithium, they think of the high-dose approach and may therefore overlook a really excellent medication option.

Thanks to anonymous for the question.
Dr. Phelps

Dr. Drug Rep: Thoughts on Working Too Closely with Pharmaceutical Companies

Thu, 29 Nov 2007 09:23:35 PST

For a first-hand account of how physicians are working with pharmaceutical companies as speakers -- which I have done extensively in the last several years -- read a very frank one published last week in New York Times Magazine, by Dr. Daniel Carlat: Dr. Drug Rep.

Having had the privilege of meeting Dr. Carlat, I know that he holds himself to a firm ethical standard. You can see that in his article. But I have continued to give talks for a few select pharmaceutical companies, whereas he found the process ethically unacceptable. Am I violating a standard? Am I only fooling myself, to think that I have not?

Linking his essay, I posted the following paragraphs on my website on the page in which I explain how I use pharmaceutical company funding. I'm trying to be quite public about taking money for giving talks about bipolar disorder, to force myself to be as honest as possible about this practice. (Or am I using these posts as another false shield? I don't think so, but I must admit there is no way for me to really know.)

From the website, revised today:
You would have to ask someone who has attended one of my talks to confirm this, but I still think -- after going through the exact same thought process that Dr. Carlat describes -- that I am managing to stay neutral. Oh, I still show the company slides where required, and emphasize (for example) "this is what AstraZeneca wants you to know". But as quickly as possible we move to a discussion of bipolar diagnosis; and when we come around to treatment, I moderate an open-ended discussion in which I try to emphasize treatment approaches with solid, well accepted evidence for their efficacy. I only give talks for companies whose medications meet that criterion, so I am not -- I don't think -- in Dr. Carlat's position.

Indeed, I once gave talks for Wyeth, the company he uses as an example. When they required that I use their slides, as he describes, I declined any further invitations to speak for them. But before that, I did give a talk once for Wyeth in which I found myself promoting Effexor, just as Dr. Carlat did (after the same training experience with Drs. Thase and Sussman, who had a similar influence on me). I had the same feeling he describes: "whoops, I just went over the line". I remember that particular talk vividly (Dr. Robert Burton, a local internist colleague, was there, for example). I still feel guilty about that one. I don't want to have that feeling again.

Dr. Phelps

Antidepressants and Suicide: Biologic Marker?

Tue, 06 Nov 2007 17:53:40 PST

Once in a while a single research study really advances our field. I think it just happened again.

Psychiatry is making major advances in terms of understanding the genetic, molecular, and brain-structure basis of some of the illness is that we treat. Frankly, this is the best field and medicine to be in right now -- at least in terms of watching good science happen. (It might be one of the worst in terms of how badly our current health care system is treating people with mental illnesses).

In any case, here is an interesting new result. The study was made possible as part of a huge study of depression in the United States (funded by our taxpayer dollars, one of the best uses I can think of -- in some ways this was like the Hubble telescope of mood disorder research).

The bottom line: even though many psychiatrists have criticized the FDA for placing a warning label on antidepressants about their potential for inducing suicidal thinking; and even though some evidence has emerged suggesting that the warning may have increased suicide rates by decreasing antidepressant use (this is still quite controversial); it would be nice to know if antidepressants really cause suicidality at all, even if rarely. This new study provides further evidence that indeed such a phenomenon occurs, as a result of the antidepressants.

But the study goes one step further: it identifies two genes which seemed to be associated with this new onset of suicidal thinking when an antidepressant is used (interestingly, the genes are not associated with suicidal thinking itself, which none of the patients in the study had before they received the antidepressant).

For more, see my Antidepressants and Suicide webpage.
Dr. Phelps

See? Sleep deprivation is not good: look at this picture

Thu, 25 Oct 2007 12:00:50 PDT

Evidence implicating sleep deprivation as one of the central ingredients in bipolar mood problems just keeps racking up. Thanks to Nancy and John for sending me a link with a remarkable picture I hope many readers here will take a moment to view.

Sleep deprivation increases activity in the amygdala, a brain region associated with strong emotions such as fear and agitation. In some ways, this is no surprise: getting more emotional, less able to control one's expressions of anger or sadness, is a familiar consequence of getting too little sleep. But if you want to see a dramatic demonstration of the brain basis of this phenomenon, see a brief explanation of this new research on my webpage about sleep and the biological clock, part of the Biological Basis of Bipolar Disorder series. Or see Dr. Walker's press release.

Dr. Phelps

Why Does It Take so Long?

Sat, 20 Oct 2007 13:42:35 PDT

You may know the story about lithium. It was discovered from a mistaken focus on urate. Until today, however, I did not realize that the first use of lithium was not in 1948 by Dr. John Cage in Australia -- but rather, nearly a century before, in 1871. (Here is a very brief little history of lithium).

Why does it take so long for an effective treatment to be recognized?

Certainly it helps if there is a pharmaceutical company spending millions of dollars on advertising. A medication like olanzapine (Zyprexa), for example, sprung into widespread use within a few years after its release -- in part because one only needs to prescribe it a few times before recognizing that it has remarkable effectiveness. (Unfortunately, one only has to prescribe it a few times more than that before discovering that it has remarkable weight gain effects as well).

Recently I have become interested in two treatment approaches for bipolar disorder which, lacking pharmaceutical company advertising, could easily go several decades relatively unnoticed. Neither of them is clearly established as an effective treatment yet, in part because there is no pharmaceutical company funding research.

First, we have the new data arriving about use of thyroid hormone as a mood stabilizer. This is a very unusual approach relative to the standard recommendations. Learn more on my webpage posted today about high-dose thyroid hormone.

Second, regular readers here will probably have come across my enthusiasm for darkness as a potential mood stabilizer. This too has very limited data supporting its use, but it is cheap and widely available and unlikely to be harmful and therefore worth knowing about. See my webpages on Dark Therapy, and the related big-picture view of this approach, Light and Darkness In Bipolar Disorder.

Maybe in this age of aggressive patient self-education, and widespread Internet access, it will not take so long for a treatment -- even one without $millions in advertising -- to become widely known.

Dr. Phelps

Fibromyalgia And Bipolar Disorder

Mon, 15 Oct 2007 08:36:44 PDT

Courtesy of a brave man who has bipolar disorder, and whose son has both bipolar disorder and fibromyalgia, here's a remarkable statistic.
Patients with fibromyalgia are twice as likely to have Major Depression as are patients with rheumatoid arthritis. (The latter, RA, was selected in this study as a comparison group because it has a relatively well-established basis in an immune system malfunction; or as the basis for fibromyalgia is still very unclear but does not appear to be a straightforward autoimmune problem like RA).

But here is the remarkable part: by comparison, patients with fibromyalgia are 153 times more likely than those with RA to have bipolar disorder.

Makes you wonder what is going on, doesn't it? The fellow who forwarded this to me wonders if exposure to antidepressant medications, in people who have bipolar disorder, might be the basis for this connection. So far, to my knowledge, there is nothing more than that striking statistic above to even raise that possibility. It does make you think, though, doesn't it?

Dr. Phelps

Misdiagnosis and Antidepressants: Any Progress?

Sun, 14 Oct 2007 12:47:38 PDT

A reader who appears to have been following my website for years writes:

"It is still astounding to me that so many psychiatrists seem to not know that treating someone with (undiagnosed) bipolar disorder, in a severe depression, can cause a 'tipping' into mania."

So we might ask: how bad is this mis-or under-diagnosis problem? Is it still as bad as it was? And how many psychiatrists really are unaware that antidepressants can precipitate a manic episode?

As we proceed, we might also wonder if there is any evidence that the pendulum swing toward increased diagnosis of bipolar disorder has gone too far, causing unintended consequences on the opposite side -- people being treated with medications for bipolar disorder, with their known risks and side effects, who really do not need this treatment.

Taking each of these questions, and summarizing very briefly (one could write nearly an entire book summarizing the research and opinions on each of these questions):

1. How bad is the problem? A few years ago, it was this bad (the graph below reflects one study, but several showed a nearly identical result):

Well drat. Can't get that image to upload. Suffice to say that in a study published in 2000, presumably reflecting trends in late 1990's, at that time it took 6 years to get a correct diagnosis of Bipolar I, and 12 years for Bipolar II.

To my knowledge, there have been no similar studies published more recently that might show us changes in this problem.

2. Is there any evidence that the pendulum has swung too far in the opposite direction?

If judging simply on the basis of public outcry,certainly there is reason to worry.There is a lot of noise these days about overdiagnosis of bipolar disorder, particularly in children. There is one study (Soutullo et al) which seriously questions the rate of diagnosis of bipolar disorder in children in the United States.

In talking with doctors who are worried about overdiagnosis,it seems that the main concern isabout exposing people -- especially children --to the risks of medications we use for bipolar disorder. In particular, the risk of weight gain, which comes along with so many of the medications for bipolar disorder, is concerning -- given the prevalence of weight gain even without such medications in our society, and the evidence that severe mood disorders themselves seem to be associated with weight gain. This is a very valid concern.

Nevertheless, we should probably not be positioning our diagnostic pendulum based on medication risks, or at least that is not supposed to be another process works. Alternatively, if we are to let medication risks influence our diagnostic judgment, then the issue of how much risk antidepressants pose in the short and long run is a very important variable. Readers who have gotten this far might be interested in my essay for psychiatrists along these lines, which appeared in a journal called Psychiatric Times.

3. How many psychiatrists are unaware that antidepressants can trigger manic episodes?

Frankly, I think this number is probably quite low. The problem lies more with the primary care providers who are struggling to cope when they cannot refer patients to a psychiatrist (because in many regions of the country, particularly here in the West, it is difficult to find a psychiatrist who can see a patient within a few weeks, and for many it is months, and some not at all). These current care providers have not had good training in the diagnosis of bipolar disorder. And they have very little experience in using the mood stabilizers for this condition. That makes them reluctant to make the diagnosis, because they are reluctant about being led into having to treat it. The result is an over-reliance on antidepressant medications, which makes them perhaps reluctant to look at potential risks of these medications.

All of this was the basis, in part, for writing my website on bipolar II (PsychEducation.org). Since that time, six years ago, I think there has been substantial improvement. But it is slow, and there is a long way to go. On top of all this, we now have to counter that concerned that greater diagnosis of bipolar disorder will lead to many children being placed on medications that will lead to massive weight gain and other problems. If all we did was simply demand that anyone who is about to receive an antidepressant medication be screened with accepted instrument for bipolar disorder, such as the Mood Disorders Questionnaire, that would be a big step forward.

Dr. Phelps

Does Aripiprazole (Abilify) Have Antidepressant Effects?

Thu, 11 Oct 2007 13:21:40 PDT

The short answer is: probably yes. A much longer answer has just been posted as an update to my webpage about aripiprazole and the "atypical antipsychotic" family of which it is a member.

If for one reason or another you are interested in the data on aripiprazole in bipolar depression, or Major (unipolar) Depression, I've summarized four studies, the three of them unpublished so far, which have recently been made available by the manufacturer.

See New Data on Aripiprazole.

Worsening Over Time: The Progression of Bipolar Disorder

Thu, 11 Oct 2007 13:13:39 PDT

In some people, bipolar disorder gets worse over time. Not everyone. And treatment is supposed to prevent this, at least in the best of cases.

The graph above shows one hypothetical patient's experience, where depression is shown as a bar below the line, a manic episode as a bar above the line, and hospitalizations in red. The height of the bar indicates the severity of the episode. Fortunately, few cases are as bad as this, but the pattern is obvious -- and that pattern is very common.

In Bipolar I, where episodes tend to be separated by "well intervals", one can see a progression like the one shown above: episodes become more severe, and the length of time in between episodes become shorter. In Bipolar II, more continuous symptoms are common. In this case, illness progression is characterized by an increasing severity of mood swings, and sometimes more rapid cycling. In many people, manic and depression symptoms occur at the same time, and what is called a "mixed state". In other words, the pattern shown in the graph above is not easily seen in people who have more complex and mixed symptoms. Yet the progression toward more severe symptoms over time is still going on.

Unfortunately, this also means that sometimes a treatment which worked at one point is no longer sufficient to provide complete symptom control later. Sometimes a person who symptoms were quite well-controlled on one medication ends up on three a few years later.

What causes this progression? This is not well understood, in part because we do not know what causes the illness itself; we do not know what the molecular and genetic basis of bipolar disorder is (although we know a lot more than we did 10 years ago, as outlined on my webpage about "what causes bipolar disorder?"). However, we do know some of the factors which seem to influence whether people experience this can progression or not, and how fast.

Basically, mood specialists currently presume that anything which has a "destabilizing influence" is likely to be one of the causes of progression. You can imagine how hard it is to do research on this: people continue to live their lives, and thus expose themselves to all sorts of influences. How could you tell whether the influence you are studying was truly the "cause" of worsening? There are always too many variables to really know.

For now, we are extrapolating from our experience with the obvious triggers. Probably the biggest one is substance use. Methamphetamine and cocaine might be the worst. Alcohol comes along shortly after that: even though in the short run it can damp down symptoms, in the long run it tends to cause more cycling in most people. Pain medications are not as bad, and it seems, at least in our current understanding. They can cause trouble in some people but nowhere near as often as street stimulants and alcohol.

What about marijuana? Evidence has accumulated that this can lead to psychotic episodes in susceptible individuals. In Bipolar I, therefore, it might be best avoided entirely. At the same time, many patients who see me in our local free clinic have been using marijuana for years, just a puff or two at night, because they have found that it helps them sleep. They are quite certain they would be worse without it, although they tend to give it up if they get a very good response to a mood stabilizer medication (in which case I can claim"my drugs are better than your drugs").

The other big destabilizing influence is sleep deprivation. People who take on erratic schedules, such as shift work, often see a dramatic worsening in mood stability. Even just a plane flight across time zones can be a major trigger in some susceptible individuals. Evidence is accumulating that careful attention to sleep schedule, and even light exposure, is very important in self-management of bipolar disorder. See my essay on Light and Darkness in Bipolar Disorder for some interesting data about the role of darkness independent of sleep.

Finally,without necessarily having exhausted this list, a word about antidepressants. One of my greatest fears about current psychiatric practice is that 10 years or more from now we might discover that widespread use of antidepressants has led to an acceleration in bipolar progression in people receiving these medications, in those who were later discovered to have bipolar disorder (let alone those who were known at the time to have bipolar disorder). This acceleration has been called "kindling", after a similar phenomenon seen in epilepsy. I sure hope that I'm wrong about this. Until we have a good biological marker of Bipolar Disorder which can show us where a person is on this illness progression, so that we might be able to see -- literally -- progression associated with antidepressants, this kindling worry is likely to remain just that, a background worry, not a known problem. See more about this on my page about Antidepressant Controversies, the section on kindling.

(This entry was composed in response to a reader's request for information on this topic. Thank you for the inquiry)

Dr. Phelps

What Causes Bipolar Disorder?

Wed, 03 Oct 2007 13:22:32 PDT

The answer to this question has never been entirely clear. But it is getting better.

Indeed, if you ask "what causes depression?", the answer is getting pretty good; and right now, it appears that this answer also applies to bipolar depression.

But that leaves mania. However, new research is beginning to shed more light on this. I just revised the essay on this subject on my website to reflect that new research. The bottom line: first, there is clearly a genetic component, but instead of one gene, there clearly are many that can be part of the problem, which is one reason why there are so many different versions of bipolar disorder. Secondly, at least one of the genes involved is part of the biological clock, the mechanism of which is now understood to a remarkable degree. Third, new research has revealed clues about the basic differences between the brains of people with bipolar disorder and those who do not have this illness.

If bipolar disorder can be so lethal sometimes, why is it still around? Why hasn't evolution selected it out long ago? Some speculations on this are offered at the end of the Web essay linked above.

Dr. Phelps

B/C>K : Cooperation and Evolution

Wed, 26 Sep 2007 22:16:27 PDT

What does psychiatry have to do with evolution?

Or, the other way around, what does evolution have to do with psychiatry?

Granted, the connection is not direct. On the other hand, the mood disorders I treat are intimately embedded deeply in the way we interact with one another, our social context. Some theorists have speculated that both depression and mania are some form of our social hierarchy system gone awry.

Dedicated readers of my website know that I have been writing there about evolution in several contexts. I am interested in good science, and it is nearly impossible to do good science without ending up looking at evolutionary principles, if you are dealing with living creatures.

In any case, I am most interested in the evolution of cooperation, particularly since at this stage in human history we had better figure out how to be much better at it, or we are all cooked, so to speak.

Therefore, anyone who is paying attention to world affairs like the warming of our planet might be quite interested to know that cooperation is under good scientific study from an evolutionary point of view, with a recent result that makes sense intuitively as well as fitting very well with the research in this area so far. A nice summary article about this appeared in the New York Times recently; linked below.

The "bottom line" of that article is this (e.g. if you are not registered and so cannot read it there): from a research point of view, the likelihood of cooperation seems to be reducible to an equation B/C>K , where (B) represents the benefits of cooperation, (C) represents the costs, and (K) represents the size of the population involved, which you can think of as how many neighbors are around. In other words, the benefits must be greater than the costs, but that ratio must be particularly large if there are many individuals involved. In a small group, cooperation is more likely.

This research has also shown that a person's reputation strongly affects how they interact with others, how much people will cooperate with them or not. You can imagine that reputation quickly comes to substitute for direct personal experience with an individual, when the size of the group goes up.

As one of my friends says, "science is the rigorous demonstration of the obvious". On the other hand, perhaps this equation (from Dr. Nowak at Harvard) also helps make it more obvious what must now happen to avoid the incredible social disasters that face us as the planet warms. Because K, in this case, is so large, B will have to be much greater than C. We are going to need a culture that places cooperative behavior at the very pinnacle of social respect.

If we were to expect our public systems -- our political system, for example -- to use available science to insure that our safety and that of our children will not decrease rapidly in the face of global changes, then we should expect those systems to incorporate this simple equation into their planning processes.

I know, that is sort of a joke. What politicians do you know that focus on long-term risks and safety for all humanity? What political system do you know that rewards cooperative behavior far more than "personal freedom"? Perhaps worse yet, what corporations do you know that focus on their long-term success, not their short-term return to stockholders?

Ah, here is one, perhaps: organized religion, at least some forms of it. Okay, okay, there are many exceptions and many egregious examples of the opposite, of greed and personal interest and narrow-mindedness and all that, in nearly any religion. But most religions include some form of group cooperation, at least within their own particular group. They focus on taking care of one another, looking after those who are suffering or struggling, and seeing that the group as a whole prospers in the long run (in the past this often included making many more members by having many children, the foolishness of which in our current circumstances has yet to become incorporated in religious culture, unfortunately).

What an odd pairing, religion and evolutionary science. But here is one realm in which they both seem to agree without any hesitation or qualification: cooperation is at the very core of being human.

Dr. Phelps

link to NY Times article

Antidepressant Risks in Children: a balanced view

Fri, 14 Sep 2007 13:46:57 PDT

The debate about use of antidepressants in children continues. It is one of the most vigorous in psychiatry.

The two sides, roughly:
A) antidepressants can increase suicidal thinking in some susceptible individuals with depression, probably particularly in bipolar depression. Therefore, physicians should warn patients and families about this risk before antidepressants are started.

B) since the FDA (and the Brits as well) posted their warnings along these lines, antidepressant use has declined sharply in children and adolescents. Now research has been published suggesting that the suicide rate in children and adolescents might actually be going up, possibly as a result. If true, this is a most unfortunate unintended consequence in the FDA should change their warning.

As in most such matters, this issue is much more complicated than these two opposing views suggest. A balanced view on this issue was just published along with one of the studies suggesting the increase in suicide risk. A link to that essay, and a translation into non-medical English, is available on my education website for those interested in this topic.

Dr. Phelps

Resuming The Blog

Thu, 16 Aug 2007 11:18:10 PDT

If there are any regular readers out there, they've either noticed that I have been silent for a long time, or they have disappeared.

I hope it might strike as good news that I am setting out now to change that. Part of the problem is that I have never mastered this blog process. So please put up with me now while I put up a few posts to get the rhythm going.

Dr. Phelps

What Causes Weight Gain From Mood Medications

Sat, 17 Feb 2007 17:30:10 PST

Finally a significant advance seems to have occurred in the understanding of the mechanism by which Zyprexa and other similar medications for bipolar disorder cause weight gain. The article in which this advance is described as not quite yet been published, but a news release which describes the results in plain English is available (thanks to N.H. for the heads up). It speaks for itself. Hopefully this will create a cascade of new results that might lead to some solutions we can use to try to prevent this huge problem.
JP

Do Antidepressants Cause Worsening of Bipolar Disorder? Two Direct Looks For Switching

Wed, 22 Nov 2006 14:45:09 PST

Antidepressants are known to cause switching from depression to mania in some people with bipolar disorder; the only remaining question is how often this happens. A very important study recently studied the switch rates on venlafaxine (Effexor in the U.S.) versus bupropion (formerly Wellbutrin). By some interpretations (including mine) this study shows that bupropion does indeed have a much lower rate than venlafaxine (Post and Leverich and colleagues). Because there was no control group in this study, we don't know how close bupropion might have been to some "natural" switch rate, which is very likely not zero even in a 10-week study like this one. (We're lucky to have even these data, and should be grateful to Drs. Post and Leverich and their colleagues in the Stanley Bipolar Network that conducted this research; there was no control group because in this study, people in regular treatment agreed to be randomized, when they were going to be given an antidepressant, to one of three (sertaline/Zoloft was the other one).

Since then another study has been published on this subject. This is not a randomized trial either. A team of researchers looked at patients in ongoing treatment for bipolar disorder who were using a slick program called ChronoRecord, which keeps a mood chart automatically; all the patient has to do is enter a number or two every day (chronorecord.org). They compared the experience of patients on antidepressants to those not on antidepressants. The main point of their paper, by my reading, is that they did not see any more switching amongst those on antidepressants than those not so treated (nearly everybody was on a mood stabilizer) (Bauer and Rasgon and colleagues).

However, as the authors point out, they too did not have a control group and indeed, those patients who are on antidepressants could easily be different than those who are not -- more depressed, for example. That is the other thing which stands out in this paper, as the authors also point out: the patients on the antidepressants are more depressed than those who are not. Odd, isn't it. But on this basis, it seems to me at least that we have to decide: either we're going to accept the design of this study and conclude that antidepressants don't work, and may even make patients more depressed; or we can say that there was so much potential for some sort of selection operating in this study that the patients who got the antidepressants were just so different from those who were not on them, that we can't conclude anything from these data.

I have not corresponded with Dr. Bauer, whose work I greatly respect but who doesn't know me well, and whom I don't want to bother with my little objection. But it did bother me that one conclusion could be presented as though it means perhaps a little something, while this other conclusion about antidepressants associated with greater depression was mentioned but not focused upon. Overall, if either worth noting, this latter one seems to me to be the more powerful finding, or at least both together, but not just the "no increased cycling on antidepressants" finding.

And so with two more studies of the issue, unfortunately nothing is much clearer as regards antidepressant safety in bipolar disorder -- other than to strongly suggest that bupropion is better, if an antidepressant is going to be used, than venlafaxine. That is probably important, as a preliminary conclusion while we await more data (although frankly, this is likely to hammer venlafaxine so hard it would take years to recover even if the next study showed a more neutral finding).

Dr. Phelps
(I've been working on a big article on the Bipolar Spectrum concept so haven't been posting much lately, but will get back to it here soon I hope.)

Light Therapy: Timing Matters?

Tue, 21 Nov 2006 21:07:27 PST

Research in the realm of light therapy seems to be accelerating. There are several groups now suggesting specific times of day for use of a light box -- not just "first thing in the morning" as we've been advising people for years.

There are at least two systems for determining when a light box ought to be used. One is a research group, led by Drs. Terman and colleagues in New York. The other is also online -- but comes from a light box company! That usually would make so suspicious I'd be looking elsewhere. Worse yet, to get the results after you take their test, you have to enter a valid email address (I tried to sneak around that, no go. Of course you could use that junk email address you're using for all the other online things you sign up for...).

However, this time I think the light box company may have the better of the two tests -- in part because I've had telephone and email conversations with the research leader there, Dan Adams, who is very knowledgeable in this realm (somewhat overwhelmingly so) and who seems really dedicated to getting doing accurate, valid research as well as selling a very good product.

In any case, if you're using or thinking about using a light box, have a look at my updated page on Light Therapy, including particularly the section on When To Use It. Good luck with the process of figuring it out -- which I say not as a joke, but as a well-wish, knowing that we don't know yet all we need to know about this.

Dr. Phelps

A Great Book on What Bipolar Depression is Really Like

Wed, 18 Oct 2006 16:08:10 PDT

There are many good books out there about bipolar disorder. Several have been written by people with this condition. They're good writers, entertaining. But here's one that I think really warrants attention -- and you can get a lovely sample of it by reading the author's blog before you buy.

John McManamy is one of the most respected writers about bipolar disorder. He's been a member of the International Society for Bipolar Disorders for years and is well known to many of the researchers in the field through his work there. But his greatest asset, and thus his book's greatest value, is in his ability to put into words the experience of bipolar depression.

So if for any reason you would find useful a thoughtful, well-crafted description of what life is like for people who know despair like most of us don't -- but one which also captures the funny, creative, brilliant side of the experience: this is a great one.

His information on treatment is most useful for those who need an introductory overview. This is not the strength of the book; and in not too long, as is the fate of any such book, this section will be out of date. But the most valuable part of this book -- the first half, describing the experience-- will remain valuable for years. Indeed as doctors are pressured to spend less and less time with patients, Mr. McManamy's book will become even more important for them. I can't think of a better book for third-year medical students rotating in Psychiatry, for example. It ought to be required reading there, worthy of replacing nearly any textbook currently recommended.

After all, what is the most important thing for anyone (medical student or otherwise) who is just beginning to try to understand a new subject? You don't need the physiology first, nor the molecular explanations. You need to get a good feel for the thing you're studying, as though you could experience it yourself. Mercifully, Mr. McManamy has supplied this for you, saving you this hard learning. Indeed, perhaps if you understand it like he does, you'll be less likely to find yourself there. At minimum you won't be there without a map, as has so long been the case (as it remains, even now for some, in the realm of bipolar depression when the hypomanic or manic side is minimal or absent).

If you've already "been there" yourself, I think you'll find great comfort in seeing your experience so artfully described. I can imagine people who've struggled with depression buying this book so that they could hand it to a loved one and say "here, read this: it will help you understand me better than I can explain myself". Although first you'll want to go through it yourself, several times I'll bet, gleaning all the gems of self-care the author has collected from his website readers, and his own experience.

You'll see: have a taste of his writing. And order his book right from there. Bon appetit.
JP

Serotonin Transporter Lab Testing?

Sun, 08 Oct 2006 14:31:54 PDT

A reader just emailed to let me know he'd found a lab which offers a test which will determine your gene type for the "serotonin transporter". The significance of this particular gene is a long but very interesting story, which I've tried to tell in plain english on my webpage about "Yellow People and Blue People". This story is a young one. There is a lot more to learn. But for now it looks pretty clear: this is a gene which has an impact on mood, and probably anxiety -- in some people.

Most people, upon hearing this story, want to know where they can get tested. At least that's a first reaction. But whether to get tested or not is a tricky decision. That warrants another page on my site, considering the pro's and con's.

This used to be a theoretical issue, but with at least one lab actually offering the test, it's time for a more deliberate consideration of these pro's and con's. The justification being offered for the test by the lab is strong -- but very narrow. There is one particular purpose the test may indeed serve well (it's a little early to conclude even that much). But now that the test is available, I fear people will start using it for other reasons. This is going to be tricky.

For now I think it's so tricky I'm not even going to link the lab. You could probably figure it out if you really wanted. Read the pro/con essay first though. Good luck thinking that through.

Antidepressant Risks

Tue, 14 Nov 2006 08:19:27 PST

Two interesting new articles on this issue (about which I've written extensively on my Antidepressant Controversies page):

First, a review by Dr. Joe Goldberg, well-known expert in this area, cites the latest data on the issue and arrives at conclusions very similar to mine: antidepressant-induced switching into mania is disturbingly common and risky; and antidepressant-induced cycling, meaning more episodes per time, is also clearly associated with antidepressants, a second reason to avoid them if possible. He recommends using mood stabilizers with antidepressant effects, and maximizing non-medication tools like exercise and psychotherapy, before turning to antidepressants. Same as my recommendations. So this is affirming, to find an expert like Dr. Goldberg reaching the same conclusions at which I've arrived by seeing lots of patients.

However, from Australia comes a report of 10 patients with Bipolar II, some of whom seem to get a "mood stabilizer" effect from an antidepressant, used with no other mood stabilizer! This is paradoxical, quite the opposite of the effect Dr. Goldberg is writing about.

Taken together, these two articles do not shift the debate much: one is clearly warning about antidepressant risks and counseling against using them even with a mood stabilizer on board; the other is suggesting that at least for some patients, antidepressants might themselves be "mood stabilizers".

My opinion: they are probably both right. I think Dr. Parker's data from Australia are convincing, looking at the graphs: there are some patients who do indeed look more stable on an antidepressant alone -- in the short run. This leaves open the question of what will happen to them in the longer term. Meanwhile, Dr. Goldberg's review again emphasizes that for the majority of patients, the opposite holds: antidepressants can be destabilizing. He concludes with this list of factors which suggest which patients might do better on antidepressants (in other words, if you're not like this, using an antidepressant may carry more risk):

no previous episode of antidepressant-induced hypomania or mania
no current or recent episode of hypomania or mania
no rapid cycling in the past year
Bipolar II (Bipolar I may have more risk)
no substance use, now or even in the past

Dr. Phelps

Hair Loss With Lamotrigine (Lamictal) Treatment

Wed, 06 Sep 2006 20:53:40 PDT

Months ago someone asked me, on Bipolar World's "Ask-a-doc" page, about whether lamotrigine causes hair loss. At the time I had trouble finding much to go on, to answer that question. It is listed (at the less than 1% level) in the prescribing information from the manufacturer.

But now comes a very clear report of the phenomenon in a respected journal. (Hillemacher) This augments the numerous reports one can find online (e.g. Googling lamotrigine hair loss). It does seem clear that lamotrigine can be associated with substantial hair loss.

The same vitamins which have been recommended for valproate (Depakote)-associated hair loss (as that medication is well-known to cause this problem) were suggested informally by one person who felt they had helped: selenium and zinc, which can be found together in the (expensive) vitamin called Centrum Silver.

International Meeting Over; Back to Light and Dark!

Sat, 02 Sep 2006 07:35:35 PDT

After two weeks in London and Scotland, which included attending the International Society for Bipolar Disorders meeting in Edinburgh, I'm back to the computer. Interesting how life looks without one. Same as it used to look, frankly. Can't put one's thoughts immediately into print, is the big difference. So now I have a backlog of writing to put up.

I started with several changes/updates on my website. The page on Light and Dark: Therapy Implications is changing almost weekly with new information sent by readers. A collaboration is developing with the John Carroll University light engineers whose website, www.lowbluelights.com, presents their products for nearly eliminating exposure to blue light at night. (The reason for the emphasis on blue light is explained in my Light and Dark essay above.) They are research scientists, primarily, and so are already interested in helping get the idea of blue-blocking technology for bipolar disorder into testing.

I've advocated trying their lights and glasses even without such testing because the downside -- cost and risk -- is almost nil and the potential benefit is great. You'd have to be skeptical about that advocacy if I was selling the glasses, but I'm not: I have no connection with the sale of any such products.

Recent changes include a study the JCU researchers' website lists, which -- to my great surprise -- shows that this idea of blocking blue light at night has already been tested! Well, it was tested to the extent of showing that using a pair of glasses, such as the JCU team's website sells, does indeed change the sleep chemical melatonin, just as we would hope were this whole idea to really be true.^Kayumov This study showed that wearing blue-blocking lenses allowed evening melatonin production to begin just when it should, and continue normally, when the person wearing them was exposed to moderately bright light at intervals between 8 pm and 8 am. In contrast, those who were randomly assigned to wear a clear lensed pair of glasses instead had substantial changes in their melatonin production. Since the onset of your own melatonin production is supposed to help get you to sleep, interfering with it means interfering with one of the main signals your body is using to know that it's time to be asleep.

The next step will be to see if people with bipolar disorder have improved sleep (easier to get to sleep, especially) if they wear the blue-blocking lenses. Several readers are already trying this and attempting to "serve as their own controls" by wearing the lenses for two weeks, then not wearing them, then wearing them again, charting information about their sleep all the while.

If you're going to do this yourself, make sure to include that step about charting. For an amazing tool to gather such information using your computer (if you're on it every day -- otherwise this would be a bit of a hassle), see www.chronorecord.org. Go to "Get Started", select the patient option; and when you get to the "referred by" box, enter Dr. Jim Phelps.

Yellow lenses at night for sleep: Not Such a Strange Idea

Thu, 10 Aug 2006 22:58:26 PDT

A previous post here referred readers to information on blue light as the particular form of light which affects our biological clock timing. That's why the newest light boxes, for light treatment of SAD (seasonal affective disorder), use just blue light.

But there's a little known flip-side to that story, about avoiding too much light at night, to preserve normal biological clock timing. I've written about this in an essay about "Dark Therapy", an interesting idea, but not well-tested.

Combining the blue-light story for SAD treatment with the Dark Therapy idea leads to a very odd -- but safe and cheap! -- idea for improving sleep. This would be most useful for people who have difficulty falling asleep because their mind is still wide awake; or people who have "rapid-cycling" bipolar disorder, which the dark-therapy research (such as we have to go on) suggests that quality darkness might be a "mood stabilizer" for them.

The combination of these two research threads suggests this: blocking exposure to blue light at night might be sufficient, rather than blocking all light as in the Dark Therapy approach, to allow easier falling off to sleep, or perhaps even gain the "mood stabilizer" effect of being in complete darkness. That's because of the selectivity of the biological clock for blue light, a story told in more detail on my page about why blue light is the one that matters in this business.

Blocking blue light is pretty easy -- and cheap -- because special glasses, with yellow lenses, for this purpose have already been developed, for other medical conditions . What I did not think had been done yet, in research, was to study the effect of those glasses on sleep.

But yesterday I found, courtesy of a reader (RH), that this approach has already been studied! A research team has already shown that using yellow-lensed glasses at night preserves normal biological clock timing even during late night light exposure. (Kayumov)

All that remains to be shown is that these lenses might actually help people fall asleep, by using them earlier in the evening, for people who can't get their mind to shut off when they're ready to try to go to sleep. Or that using these lenses might act like a "mood stabilizer" for people with rapid cycling bipolar disorder. That will be exciting research to watch for.

In the meantime I can imagine that some people are going to try it anyway, figuring that $40 for a pair of these glasses is worth a go (there are less expensive ones, but they block less blue light). If it seemed to work, it's pretty cheap -- and it's hard to imagine a risk that might go along with this, except looking rather geeky in the privacy of your own home at night. But hey, Jonathon, another reader, is already trying them at work! He works nights and is trying them to see if he can get to sleep easier after his shift when he uses the glasses. So far? He thinks they might be working but is going to conduct some on-off trials: 2 weeks with the glasses, 2 weeks without, to see if he can tell the difference. He's kindly sharing his results with me as he goes along. I'll post them.

For more on all this, try my essay on Light and Dark in Bipolar Disorder.

Free, online, computerized (research-tested) Cognitive-Behavioral Therapy

Thu, 24 Aug 2006 23:08:18 PDT

"Free" ought to have your skeptic force-fields on full power, right? But this is for real; there are no hidden costs or obligations. It grew out of a research program in Australia.

One of these days I hope we'll get a head-to-head, John Henry test: the computer versus the live therapist (for those of you without the benefit of a classical education, John Henry was the guy in folk legend who tried to outperform the steam engine back in the days of railroad construction) (the part about the classical education was supposed to be a joke, mind you. I learned about John Henry from the song by the John Mitchell trio...).

As you may know, cognitive-behavioral therapy (CBT) is one of the forms of psychotherapy which has been shown to be as good as medications for the treatment of most kinds of depression, including a version of CBT used in bipolar depression. But many people can't afford it, or think they can't (don't forget to add up those medication co-pays).

And there are plenty of folks who can't find a good, live CBT therapist (none in the area; none covered by insurance, and can't afford to pay for it without insurance; that kind of thing). And finally, there are people who just wouldn't go even if they could afford and find one -- but could still benefit from CBT.

If you know of anyone in that position, they might want to know about the free, online CBT program with no strings or loss of privacy. Here's my brief introduction (including some of the research studies that have been done on this approach).

How the Biological Clock Works

Fri, 14 Jul 2006 22:05:08 PDT

This is one of the most impressive science stories I know. Everybody knows they have a clock -- because everyone knows what it's like to try to get up at 4 am when you're used to getting up at 7! You just don't feel right.

How does your body know what time it is? How does your clock shift, if you fly to London? (okay, you Londoners; how about when you fly to San Francisco?)

Turns out your body is using a biological version of an ancient trick, the water clock: a process that takes a very consistent amount of time can be used as a clock. Your body is using some very basic cellular tools as a clock: transcribing DNA, and turning the resulting mRNA into a protein.

The cool part is what happens next: how that protein regulates the process itself. And the coolest part is being able to see how the whole thing works, thanks to the work of some dedicated biologic researchers. For some basic illustrations, and the rest of the story, try this essay on How the Biological Clock Works.