Treatment FAQ

Table of Contents

You don’t have bipolar disorder, necessarily, but you’ve got something more than plain depression: that’s why you’re here.

Most of the ideas below apply to anyone with a mood problem, so don’t let “bipolar” labels throw you.  Almost all the research outside “Major Depression” has been with full-on bipolar disorders, very rarely on people in the middle of the Mood Spectrum.  We have to stretch the research to apply to you, perhaps.

Lots to learn.  Make sure you have the basics of treatment first. But then… the summaries below will introduce you to many other things I think are important.  Maybe you too. Use the links to read the stuff that catches your eye.

Basic self-care of bipolar disorders: minimizing pills, managing suicidal thoughts; how long do I have to take pills? Can I have a job? 

What can I do, without pills?

Some aspects of treatment rely on you. In the many books about that, you’ll find common ingredients.  For example, look at the right-hand column below:

Focus Title Author Section
Bipolar I The Bipolar Disorder Survival Guide David Miklowitz, Ph.D. Ch. 8: How can I manage my disorder:
practical ways to maintain wellness
Ch. 9: What can I do if I think I’m getting manic?
Ch.10: What can I do if I think I’m getting depressed?
Ch.11: Dealing with suicidal thoughts and feelings
Ch.12: Coping effectively in family and work settings
Bipolar II and Mood Spectrum Why Am I Still Depressed? Jim Phelps, M.D. Ch.11: Simple lifestyle changes that can improve symptoms
Ch.12: How to use psychotherapy across the mood spectrum
Ch. 13: Exercise, not the usual rap
Ch. 14: How family and friends can help
Bipolar and Major Depression Living Well With Depression and Bipolar Disorder  John McManamy
The voice of experience
Ch. 4.Lifestyle: Food and Mood; Messing with the Food Chain; Diet and Obesity; Exercise; Sleep; Staying Well; Suicide Prevention; Coping with Work; Support; Using Your Bag of Tricks; Meditation and Yoga; God PowerCh. 15 Complementary Treatments: Nutritional Supplements; Amino Acids; Omega-3; St John’s Wort; Sam-e; Bright Light Therapy; Acupuncture; Experimental Therapies

Common recommendations in these books, as you can tell from the chapter headings:

  1. Maintain a regular daily schedule — especially sleep hours, exposure to light, and very probably more darkness!
  2. Get exercise nearly every single day: clearly it’s an antidepressant, and it probably also has mood stabilizing effects
  3. Have a social support system: family, or friends, or a therapist; preferably all of the above if possible
  4. Have a plan for when you’re having a lot of symptoms
  5. Have a means for figuring out what’s you, and what’s your bipolar disorder (many use a therapist for this)
  6. Work, or volunteer, or go to church/mosque/synagogue:  have some other focus outside yourself

What are the most important self-care steps?

Three essentials you’ll hear about over and over (well, two, plus one of my favorites, the light part…)

  1. Sleep: regular hours, enough sleep, protect sleep, yada yada. You’re going to hear this one a lot. It’s true too, but focusing there is hard. I think it’s easier to focus on…
  2. Light: regular hours of light and dark exposure will help you get regular sleep. It’s amazing how powerful this is. To the point that if you don’t control light and dark, you’re working uphill when trying to make sleep regular. Don’t get lost, come on back, but you gotta read the story about Dark Therapy to really appreciate this, and then maybe the Light and Darkness in Bipolar Disorder essay.
  3. Drugs (yours): here, let’s trade your drugs for my drugs. Mine are supposed to work better. If they don’t, you could decide, perhaps, to go back to yours (not the meth’, please, or the cocaine or heroin, but people go back to marijuana rather often, thinking it better than my stuff. Short term, maybe so. For a few folks, longer.)We can all agree that alcohol in large amounts is not a good idea for mood or mood stability. Caffeine? not horrible but probably makes the PTSD side of things (very common) worse.In general, how about “while you’re trying my drugs, why don’t you cool it with yours so you can see what’s doing what.”

Show me some small steps toward better self-care

Three types of psychotherapy have been shown in randomized trials to be useful in bipolar disorder:  cognitive, behavioral (these two are often combined), and interpersonal psychotherapy.

Here are some key parts of these therapies, which you can apply yourself:

S = Schedule (activities) — Behavioral
P = Pleasurable Activities — Behavioral
E = Exercise — Behavioral
A = Assertiveness — Interpersonal
K = Kind Thoughts About You — Cognitive

Schedule: make a plan now and have a calendar or log for behaviors you intend to pursue. Here is a sample log you can change to suit you:

Day Time of Day Activity planned With whom? Where? Planning needed

When you make a log like this, and keep it up to date, you have a good record of exactly what you have done for your own health. If you are trying to increase your activity, this log could show you whether you are making progress! Even if you can see a small increase, this can be a big “boost”, to see that you are able to move yourself forward. It may give you the motivation and energy to move further yet.

Pleasurable: as many people experience loss of pleasure due to their mood state, they can stop arranging for activities that used to provide enjoyment, leading to a vicious downward spiral. Many people can reverse this trend, though it’s slow at first, by deliberately scheduling pleasurable activities. In the beginning you’ll have to force yourself, and it won’t be fun like it used to. But with some repetition, you might notice a hint of improvement, and if you do, take advantage of that by trying to do a little more. That’s how some people turn the spiral around, into a slowly improving one.

Exercise may have a mood stabilizing effect in bipolar disorder  I think so, but that’s not been studied. It clearly has an antidepressant effect, beating sertraline/Zoloft in a randomized trial.Babyak Exercise has not been shown to cause mania, unlike all available antidepressants (including light therapy, St. John’s Wort, SAM-e, rTMS, etc.). You are probably aware of the many health benefits of regular physical activity. I tell patients, “if these benefits could be put in a pill, everyone would be taking it!”. Obviously the hard part is getting yourself to do it, but as one woman says, “it’s possible! it’s essential!”

So, trying to do this exercise thing is an extremely difficult challenge, especially if you have symptoms now, and you may need some help (from friends, family, therapist, pastor, doctor).

Make a plan and a chart like this:

Day Time of Day Type of exercise How Long? Intensity 1-5 How I felt before (1-10) After (1-10)

Start with just a little bit.   Harvard’s mood recommendation: go to your door and open it, with your shoes on (that’s the hard part). Walk for 7.5 minutes in any direction, then walk home.  Do that every day. Rate your mood on a scale of 1-10, where 1 is the worst you get, and 10 is the best, before and after. See your primary care physician if you have been very inactive, before you begin, for an okay and more guidelines.

Assertiveness means asking for what you want. When two people are in conflict over something, four things can happen:

  1. I win, you lose.
  2. You win, I lose.
  3. We both lose.
  4. We both win.

Assertiveness means trying to get what you want, where hopefully the other person still gets what he/she wants. There is a lovely book about negotiating skills by Harvard experts on this topic, called “Getting to Yes“, but there are also many “self-help” books about this in your local bookstore. Many people with mood problems have lost, or never had, good assertiveness skills. A good therapist (e.g. MSW, LCSW, Ph.D.) can often help a lot with this.

Kind thoughts about you: many people with mood problems can be extremely unrealistic in their view of themselves. They minimize their skills while magnifying their weaknesses; inflating small errors into major gaffs; overlooking their successes, and so forth. “Cognitive therapy” tries to help people be realistic in their view of themselves, calling attention to such “cognitive errors”. In most cases, this eventually means treating oneself as one would likely treat others: with kind thoughts, rather than harsh negative assessments. At one level, this is “think positive”, but at a more sophisticated level, it is “think fair/realistic/evidence-based”. A good book about cognitive techniques is Feeling GoodBurns (a friend of mine says “great book, terrible title”). If you’re really motivated, you may be able to work through this book on your own. It costs less than an insurance co-pay. This book contains all the ingredients of good cognitive therapy (written by a master). However, most people do this kind of work with a therapist who knows the technique.

If you’re really motivated there is even a free online version of cognitive therapy. It works as well as seeing a therapist, if you can get through it. (One study even says maybe betterWagner  but these are early data in ongoing research). You could use it with a therapist who doesn’t know cognitive therapy as a “booster” for your sessions.

What if I have thoughts about suicide?

If you are not just thinking about it but actually planning something and afraid you might act on that plan, click here. If you’re still afraid you’ll act, it’s time to call 911 unless you have an easier way to get yourself safe now.

Thoughts are thoughts. You can think about suicide, but if you don’t act about suicide, you’ll stay alive long enough to find out if there’s a treatment for you out there. So thinking about it is okay, if that’s all that ever happens. Most people with severe bipolar symptoms do indeed think about suicide, sometimes a lot. If you do, read the Metanoia page about this, best I’ve ever seen.

How long do I have to take this stuff?

Nearly everyone thinks about just stopping their medications at some point. It’s hard for most people to imagine taking this stuff for years and years.

Many patients will be told  “you have to take these pills for the rest of your life”. Most don’t really buy that. They will take the pills for a while. Then, if they’re doing well, they think “why am I still taking this stuff? Maybe I don’t really need it anymore.”

So let’s be realistic. You may indeed think that. BUT WHEN YOU DO, here are some things to consider:

  1. How bad were my symptoms? how much do I have to lose by having them return? (for some people, this is not a huge risk, just a loss in their own quality of life, perhaps)
  2. Am I willing to risk having those symptoms return? is this a good time for that?  Who will be affected? Will I tell them I’m doing this? If not, am I being honest with them?
  3. Will I tell the doc’ or NP , or my psychotherapist, that I’m doing this?  Am I afraid of their reaction?

Here’s my usual recommendation.  If you’ve thought through all those questions, and still want to try going off your medications, then ideally you would tell the person who’s prescribing them that this is what you want to do and they will work with you to make a plan.  They might try to teach you something about the risks that you haven’t figured on. They might try to convince you not to do this. At least give them that chance; after all, they’re supposed to be doing what they think is in your best interests.

You’re still determined to stop, even when you’ve been advised not to? Here’s what I tell my patients then:

  • Think about it: are you doing this because you’re having symptoms?  Like you’re depressed so it all looks hopeless, including taking these pills (or getting exercise, or doing some volunteer work, etc)? Is it a good idea to listen to your own mind under those circumstances? Better to listen to someone you trust, someone you know has your interests in mind?
  • Still going to stop? Well then at least do it one medication at a time!  — be a scientist about this.  Gather information about which med’s do what as you taper them.
  • Tell somebody. Who’s going to help you figure out if you’re getting worse?  Don’t rely on yourself on this one. If you’re sure you’re going to be fine, then there’s no risk in letting someone help you make sure that’s so.
  • Have a plan for what to do if you are getting worse: go back up on your meds or switch to something else? (it’s my job to lay out those alternatives, pro’s and con’s of each)
  • At the very least, taper, don’t stop. This is your brain we’re working with here. If you’re going to get worse, with a taper you could see it coming before it’s fully as bad as before, and change course. And if you want your best shot at staying well off medications, don’t do it with a sudden shock to your system, eh? (Ask your prescriber for a taper plan. They can’t make you take the pills, and they know it. So they might prescribe a taper if you’re determined to do so, then work with you to catch any signs of relapse early. They might also say “bad idea, I want no part of it”. That’s their call).

Can I keep a job with this illness?

Yes! That’s the short answer. Actually, for most people, having a regular job seems to be an important ingredient in maintaining mood stability. It forces you to keep a regular schedule, for one thing. It also gives you a focus, and perhaps for some, a feeling of accomplishment or productivity (and if you actually get enough money out of the process, that would be good too, right?). So, in my view, it’s important to really try hard to get a job, or keep a job. It is actually like taking a mood stabilizer medication.

Granted, for some people, this just is not going to work out. The job has to be sustainable. You have to consider how much stress to tolerate because at some point it may be that the job is actually making things worse, not better. So this is worth an extended discussion with your psychologist/psychiatrist, if you have one, or at least with a trusted friend who can give you a neutral point of view on job stress. Again let me emphasize that even for a job that is really no fun, the regular schedule that it requires can be a tremendous benefit for mood stability, and should not be given up lightly.

Finally, may I show you some research data from a colleague here in Corvallis, OR which might be of use to you. Dr. Carol Tremblay conducted a survey of people with bipolar disorder, asking about their experience working. Here are some of her results, quoting from her paper:

Key contributors to job success for the majority of the participants are flexibility in work schedule policies, autonomy, and supervisor willingness to accommodate individuals. Specific examples of helpful characteristics reported are freedom to work at home, allowances for leaves of absence, frequent breaks, barriers between work spaces, control over goal-setting, creativity required on the job, and avoidance of jobs with pace set by machinery. More than half of the respondents indicated that bipolar disorder was detrimental to their job performance, but all reported at least a satisfactory job evaluation from their employer.

Destabilizing factors: alcohol, steroids, sleep loss, travel, stress,  stopping antidepressants, “kindling”

How much alcohol is ok?

Zero would be nice. However, zero forever is more than most people think they can realistically do. Still, I strongly suggest that you try 1-2 months with no alcohol at all, so that you can then evaluate how destabilizing alcohol is for you personally, and in what amounts. Most people find that about 1 drink per week does not affect them, but that more than one at a time, or more than one per week total, does. You must also be aware that the mood stabilizer medications will often make just one drink a lot more powerful. If you do drink while on these medications, don’t drive or do things where judgement and performance are crucial (the example that always seems to be listed is “operate heavy machinery”, but using a kitchen slicer counts too!)If you are not getting better with mood stabilizers but are still drinking, it’s time to start the trial of these medications over again, while clean and sober. Zero alcohol is a must for people whose mood remains unstable, while looking for an effective treatment.

Are steroids really bad?

“Steroids” include prednisone, cortisone, and several other forms, even including steroid eye drops (and I had one patient who did not stabilize until he stopped those drops!). They are used for everything from poison oak to severe asthma, to decrease immune system response when the response itself is causing problems.

The risk of making mood unstable with steroid medications has been clearly described and repeatedly observed.Young and Preskorn How frequently does this occur? In one study of people with no prior history of mood symptoms, 2% got “mental disturbance” with a low dosage (prednisone equivalent less than 10 mg in most of the subjects). In this study, only severe psychiatric disturbance was counted. In another study which used a very high dose (prednisone equivalent of 120 mg), the authors found 26% with manic symptoms and 10% with depression symptoms during the 8 days of treatment.

Testosterone can induce mania or hypomania, including in about 10% of volunteer men.Pope Obviously I don’t get to see the many patients who have done fine on predisone for their poison oak, but I have seen multiple patients who have had severe manic episodes when given steroids by their (well-meaning) primary care physician. There are reports of a testosterone patchWeiss and dihydroepiandosterone (DHEA) inducing manic episodes.Markowitz, Vacheron

If it becomes clear through treatment that you do indeed have a bipolar variation, be very, very cautious about using any steroid medication. Many physicians are not aware of the risk this poses in bipolar disorder (causing quite severe symptoms of the type you went on mood stabilizers to treat!) So if you think the medication you are being offered is a steroid, politely explain your concern (referring the doctor here, if needed; here are some thoughts about talking with doctors). If there are no treatment options other than steroids, you will probably need more mood stabilizer while taking the them.

What about steroid inhalers for asthma, or steroid nasal sprays for allergies? There are several case reports of inhaled steroids causing symptoms. Since these are widely used medications, I’ll take the liberty here to reproduce a paragraph from a review you might have trouble finding.Brown As you can see, the “bottom line” is that inhaled steroids can be a problem, but probably not very often:

There are several case reports that suggest psychiatric disturbances may occasionally occur with steroid inhalers. A 5-year-old child with asthma developed symptoms of mania including agitation, irritability, and insomnia 2 days following the addition of inhaled budesonide at 200 µg/day. The psychiatric symptoms observed in the child resolved with dose reduction. Phelan found that a 69-year-old man who had previously developed protracted manic symptoms with oral prednisolone became euphoric with pressured speech and visual hallucinations after receiving 400 µg/day of inhaled beclomethasone for 3 weeks.

Similarly, a bipolar disorder patient who was stable on lithium therapy promptly developed severe mania requiring hospitalization after the addition of a beclomethasone inhaler (eg, 1 puff prn) for asthmatic symptoms. Inhaled corticosteroids are widely used, thus, the paucity of case reports of psychiatric symptoms associated with their use suggests that severe reactions are uncommon.
No study, however, has formally examined the global psychiatric side effects of inhaled steroid use, therefore the incidence of mild to moderate mood changes is unknown.

Update 12/2010: in addition to another review with the same conclusions, Brown 2002, here is one more striking case report from a reader, about nasal use of a steroid (nasal fluticasone/Flonase):

I already had bad experiences when taking prednisone for my rheumatoid arthritis. Turned me into a monster – yelling at husband, irritable, cleaning the house at 2 am. So after my bipolar diagnosis, I just say no to prednisone. I am stable on a nice cocktail of lithium, Seroquel, Neurontin, and a dash of Canax and Ambien. I work full time and am happily married, and active in my community. High functioning so to speak. It took years to find this combo for me. Last week a bad cold/sinus infection/ear ache brought me to my GP. She gave me a Z-Pak [an antibiotic, zithromax] and Flonase. She mentioned that it might, just might maybe make me a little manic. And don’t be mad at her if it does. And so, as agreed I did just one sniff in each nostril. Within 30 mins my mood changed, elevated, high energy, strong moods, burst into tears. Felt sort of sexy and wound up. Felt too energized to notice my ear ache…. wasn’t sure whether I wanted to dance to hits from the 70’s or cry.

This woman also pointed out: “I am the type of bipolar who had years and years of hypomania, plus some pure mania/delusions/paranoia. Plus some depression. Sort of the graduate from college at age 20 with honors type of high energy person… Many of my bipolar friends tell me that they can take Flonase no problem. But they are mainly depressed BP 2.” (Thanks Ms. L).

What are other destabilizing factors?

You have already encountered the major recognized destabilizing factors: antidepressants, alcohol, and steroids. Now for the more subtle ones: sleep loss, travel, stress, stopping antidepressants.

Sleep deprivation is pro-manic, even in people without “bipolar disorder”. Do you know that feeling you get the middle of the day after a night up much too late? The giddy, loose, hilarious, on the edge feelings? And how a few hours later it’s switching into irritability, disorganization, anxiety? Just a single night of sleep loss can do that (e.g. doctors know this from being on call). For people with bipolar variations, night after night of too little sleep is clearly part of the whole problem. Generally, when people get better they sleep much better.

In fact, I use sleep as one of the best single markers of whether a patient has enough mood stabilizer: when they do, they will sleep well (6-8 hours, unbroken or able easily to go back to sleep if awakened). If they still need some sleeping medication, that’s a warning sign that we still don’t have enough lithium/valproate type effects. Once a patient is finally sleeping well on these medications, they can use poor sleep as a “marker” for trouble. When they start to sleep less than 6 hours, it’s time to watch closely for any other symptom of bipolar disorder, and increase the mood stabilizer if such a symptom shows up.

Travel crossing time zones creates automatic potential for sleep change: deprivation when traveling east, additional time when going west. Two studies report symptoms brought on by travel, with mania more common going east, and depression going west.Young,
Major travel within the same time zone (e.g. my Oregon patient who became manic in Mexico) may be destabilizing due to stress alone.

Stress alters many nervous system chemicals, including corticotropin releasing hormone (CRH) which releases the body’s own steroids. Reproductive steroids such as estrogen and progesterone respond to stress; for example, women may stop menstruating when severely stressed. Serotonin, the mood-related neurotransmitter, also clearly changes with stress.Duman All of these brain chemicals influence mood.

Stress is part of modern life (some would say more so in recent centuries?). Achieving a stress free life is not realistic for anyone (one could wonder what that would look like). People with bipolar disorder can be expected to show mood instability even during positive stresses such as moving into a new house or accepting a new job, let alone after trauma or losses. So while lowering stress levels may help maintain mood stability, people with bipolar disorder need to have enough mood stability from their medications to be able to handle at least some stresses.

In bipolar I it has been shown that the first episodes are commonly associated with a severe stress, whereas later episodes often appear “out of the blue”, i.e. with no apparent stressor to bring them on. This raised the concern that somehow earlier episodes were making subsequent episodes easier to trigger. For more on this, read the next section.

Stopping antidepressants fast can significantly destabilize bipolar disorder. Even though we know antidepressants can cause cycling, it looks like stopping them fast can do so also. There is even a phenomenon called “antidepressant-discontinuation induced mania”: causing mania by stopping an antidepressant suddenly.Goldstein Dr. Sachs, the Harvard bipolar expert, recommends taking four months to taper off an antidepressant if things are going pretty well otherwise. Since following this recommendation, I have seen much smoother courses for folks stopping their antidepressants. (more on slow antidepressant tapers)

Does bipolar disorder get worse over time?  (kindling theory)

Many people with Bipolar I have more episodes of mania or depression as time goes on, as shown in this man’s pattern (his age is shown at the bottom of the timeline; red means hospitalized, up is manic and down is depressed, of course):

This observation led to the so-called “kindling theory”. The idea of “kindling” is based on the finding that a region of mouse brain repeatedly exposed to small electric shocks will eventually start to have spontaneous seizure-like electrical events. That is, repeated episodes seem to make subsequent episodes more likely to occur spontaneously. This is precisely the pattern observed in bipolar I.

Three out of five of the currently recognized “mood stabilizers” are anticonvulsants (valproate, carbamazepine, lamotrigine; as opposed to lithium and olanzapine). So it has been tempting to assume that bipolar phenomena might be “seizure-like” in some way. Unfortunately, there still is no clear understanding, nor even dominant guess, as to the basis of bipolar disorder, although it’s improving. The accuracy of a seizure-like model is unknown. However, as estrogen has been shown to increase seizures, and progesterone to decrease them; and both seem also to modulate mood; there is further support for a seizure/bipolar relationship of some kind.

Bipolar II seems to get worse with time in many people, especially women. Some researchersLeibenluft have guessed that each menstrual cycle is somehow driving the illness toward greater severity, and that’s why it looks so different in women compared to men.

As the illness gets worse, medications that seemed to have helped a person in the past don’t seem to “work” anymore. Antidepressants start to cause mixed state symptoms (can’t sleep, anxious, can’t concentrate, irritable — as well as depressed) and rapid cycling, where at first they were actually very helpful.

Because of this potential worsening with time, you should not count on being able to “go back” to a previously effective medication. Though I have not heard it stated as such, as I read the experts, and watching what happens to my patients, the “name of the game” may be to prevent cycling. That might be how you keep from getting worse. If that’s true, now you have two reasons to get your symptoms controlled: first, because you’d rather not have symptoms; but also because they could mark a worsening process that you might be able to interrupt with a fully effective treatment.

Some possibly reassuring news:  a major review of the “kindling” idea did not find strong support for this concern.Bender  Oh, that’s good. But the authors note that the research is slim on the question at issue here: can one episode make later episodes more likely?  They cite one of the originators of the kindling hypothesis, Dr. Robert Post, whose 2007 review is not as reassuring.

More on mood stabilizer use: problems, solutions, labs, other meds; too many meds? 

Problems and solutions: lithium and divalproex (Depakote)

Problems with lithium can be grouped into two major categories: nasty events and minor side effects. The most common problems with valproate/divalproex are nausea, weight gain and hair loss.

Lithium: nasty events

Lithium definitely can interfere with thyroid function. . About one person in every tenGittoes taking lithium has to take thyroid hormone replacement because lithium lowers thyroid hormone levels. Because this is so common, and because becoming “hypothyroid” can have its own mood effects, it is very important to have your thyroid checked at least once a year, and most experts recommend every six months.

Lithium can cause kidney damage, and when it gets very high, people have died. These problems are avoided by very close monitoring of blood levels. Lithium can cause changes in kidney function that are potentially life threatening. Standard lithium levels only do this very rarely, but over decades of use can cause a slower, more easily recognized decrease in function that usually requires switching to a different medication.

If at any time while taking lithium you get side effects such as feeling unsteady, slurring your speech, or becoming confused, you need your blood lithium level checked right away. These are usually signs of the level being too high. If these symptoms persist, there is danger to brain and kidney cells.  If your lithium is in the low range (e.g. 0.6-0.7 mmol/L) , it is generally unlikely to reach these “toxic” levels.

However, if you start from a high level such as 0.9 or 1.0 mmol/L, becoming dehydrated can raise your level to the point where you might start to experience serious side effects . So can adding ibuprofen/Motrin and its cousins (“non-steroidal antiinflammatories” or NSAIDS), or some kinds of blood-pressure medications. Check with your pharmacist to avoid these kinds of interactions. And make sure you have access to fluids if you’re exercising hard or driving or working many hours in a row.

Lithium: side effects

Side effects most likely to cause you to give up on lithium are (in roughly decreasing order of severity):

  • feeling flat, blah, dull
  • diarrhea
  • tremor
  • nausea
  • frequent urination

Feeling flat or dull or “blah” happens to about 1 person in 10 taking lithium (my working guess). This does not get better with time. Working closely with my patients, I (not you…) lower the dose until this is no longer a problem. If it doesn’t go away, we have to look at other mood stabilizers: this one’s almost a guarantee of making people want to get off it.

Diarrhea rarely decreases with time on lithium: you will probably have to reduce the dose, if already on immediate release lithium. But if you’re on slow-release, ah, good news, you might be able to solve this problem by switching to the immediate release form.

Most people will put up with tremor until it interferes with function, such as signing checks in front of people (increased severity in anxious social situations is very common).  This is a reason to try the slow-release lithium, if it doesn’t then cause diarrhea.

Lowering the lithium dose will help tremor, but don’t do that on your own, you could lose the benefits for which you’re taking it . For people who can’t solve the tremor problem with dose reduction, we often use low-dose propranolol (a simple blood pressure medication). Most people find this very effective without new side effect problems.  Where the usual dose for blood pressure control is 80mg or more, a 10 mg tablet is a good starting place for tremor. I tell people to use up to 4 per day if necessary, including taking two at once if one is not enough, after they have a feel for the effects of one alone.

Some people with nausea will see a decrease in this side effect with time. If not, try a  slow release version (less nausea, but more risk of diarrhea). Sometimes splitting the dose morning and night will solve this problem. After those things are tried, nearly everyone with this side effect will have to lower the dose until nausea is gone: it would be very difficult to tolerate this long-term. If nausea appears after you’ve been doing fine, suspect too high a blood level: get it checked right away.

Frequent urination is almost universal for patients on lithium and increases with blood level. Generally having to urinate at night, sometimes several times, is the biggest problem. It should diminish somewhat if you lower the level a little, but with lithium you should not make dose adjustments without discussing what you’re doing with your physician. Most people figure out on their own: drink plenty of fluids during the day but then back off in the early evening, minimizing fluids after dinner for example, to decrease sleep interruptions.

Valproate (divalproex, Depakote)

Weight gain is the bane of this medication. Hair loss can occur when at weight gain doses, but the weight thing is what makes people really angry about this medication if it happens.

Weight: before you freak out (most people do), there’s a new weight loss medication. If divalproex is working great, maybe there’s another solution, although it means adding another pill, not generally the way we like to do things.  Here’s the news: naltrexone is an old medicine we know well, with pretty low risks . It is marketed as Contrave when combined with an antidepressant, but that’s not necessary. Naltrexone works by itself very well: in an 8 week research study, the naltrexone group averaged 7 lbs lost, while the control group gained 3.Tek  And that was while taking medications that are as bad or worse for weight gain than divalproex!]

The ER version of divalproex seems to cause a little less trouble with weight gain (but it’s still a big risk).  Remember that only 80-85% is absorbed; calculate the “real” dose versus the dose-by-stated-milligrams. I often use the 250 mg ER version to ramp up and find the best dose between 750 and 1500 mg (as much benefit as possible without appetite increase or weight gain).

Here’s how I manage the weight thing. First, I tell a patient as soon as I introduce the very idea of this medication that weight gain is a risk, but that if she/he gains any weight at all, we’re going to change the plan. Weight gain is not going to be something they’re just going to have to put up with. And, it doesn’t generally occur unless there has been a big increase in appetite, to really bizarre levels. One patient described it as “wanting to eat the refrigerator”: hungry all the time, and not full when eating, even with enormous amounts of food. If you start getting that, it’s time to change the plan.

The manufacturer says if patients don’t eat more, they won’t gain weight, but most of my patients don’t seem to believe this. How about using exercise as weight control? As discussed below, physical activity is a great health tool generally, a great antidepressant, and probably a mood stabilizer overall. But sticking with it is hard even for patients without mood disorders. Trying to use increased physical activity to handle this weight problem works only for a few folks. So, when it occurs, it’s time to change the plan, in my view.

I tell people to lower the dose to the point where this appetite effect disappears. Most people can tell when it stops, as thought there were a very discrete “threshold” beyond which the problem develops, and under which it quits. For most people this “threshold” seems to be around 750-1000 mg (or 1000-1500 using the ER version), which unfortunately is generally the lowest dose sufficient for symptom control with valproate by itself. (Some do not get the appetite increase even with as much as 2000mg per day, but this is the minority) .

Unfortunately, when people have to lower the dose they lose some effectiveness as well. You can see now why I underline the positives of both lithium and valproate: when you must lower one because of side effects, you can make up for it with a low dose of the other. This so-called “rational polypharmacy” is now a routine strategy in psychiatry.Post

Divalproex and Polycystic Ovarian Syndrome

There is concern about valproate/divalproex can cause a hormone imbalance in women called “polycystic ovarian syndrome (PCOS).” PCOS seems to be associated with both epilepsy (divalproex was first used for seizures) and perhaps even with bipolar disorder — without divalproex. But it looks like divalproex can make this risk worse.  Women with functioning ovaries ought to be aware of this issue if being offered divalproex.  This concern has evolved quickly over the last several years — so I gave it a separate page where you can learn about the latest research on divalproex and PCOS, updated 11/2014.

What labs, how often, are necessary during followup?

As described in detail above, one must watch for thyroid hormone decreasing, and keep track of kidney function. These should be checked every six months (remember, hypothyroidism is common on lithium, about 1/10). Signs of too little thyroid hormone include feeling cold when everyone around you is warm; gaining weight despite eating little; low energy; increased sleep; and even depression. Obviously this can easily be confused with or even cause mood problems itself. Checking routinely makes this less likely to develop unnoticed.

For valproate, there is no clear consensus on when or what to test. There is an FDA “black box” warning about liver problems. However, rates of liver problems for adults on one such medication are close to the rates of liver problems for adults not taking valproate at all. After your initial blood tests, which serve as a “baseline” against which to compare, it is not clear how often to test again. The “package insert” from the manufacturer, which is always the most conservative, says to test “at frequent intervals, especially in the first 6 months”. But in practice most doctors do not seem to follow this recommendation. In my experience, is seems frequent for doctors to make up their own minds, using their clinical judgement and experience regarding how much to “drive risk down” by frequent testing, versus the hassle, expense, and pain for the patient. Some experts say they don’t monitor at all unless there’s a problem, like abdominal pain or nausea.

Too high a valproate dose causes headache, blurred vision, and a foggy/fuzzy feeling — but not the “toxicity” effects like lithium. Thus we do not need to test valproate levels to keep them from going too high, as we do with lithium. Instead, we use blood tests when a person is not responding to valproate, to see if their blood level is high enough. As for when to do other lab tests for patients on valproate, see my separate essay on Lab Testing for Safety.

What about other mood stabilizers?

The list keeps evolving. Here’s a table of options, organized by the evidence we have to support their use. Click on any of the medications for more information. It’s really worth looking this over, just to see how many options we now have! I plan on keeping this table up to date frequently, as we get at least one clear new medication per year in the last several years.

I don’t want to take a lot of medication!

No one really does. How do some people end up on 2 or more medications for one problem like bipolar II?

Obviously there’s no point in taking any more medication than is needed to control your symptoms! More medications means more hassle, more co-payments, and more potential for interactions with each other or any other medication you add (including over-the-counter medications).

Simply put, the reason we sometimes end up using multiple medications in treating bipolar II is:

  • Your symptoms just won’t get better with only one; or
  • We’re trying to use several medications at low doses, to avoid the side effects of a single one at full dose.

One exception: sometimes we have to use a medication just to combat the side effects of another. For example, when lithium is working well but causing a tremor, sometimes instead of switching to another mood stabilizer (which is not guaranteed to work as well) we’ll add propanolol to block the tremor. Then if this patient becomes hypothyroid, another side effect of lithium about one time in 10, we might add thyroid hormone replacement. At some point she/he might say, “this is getting ridiculous” and we would consider switching to divalproex or carbamazepine, for example, hoping to get good control of symptoms with fewer medications. (why not just start with the ones with the fewest side effects and risks? we often do, but don’t forget “efficacy” — the treatment needs to work well too, not just have low risk!)

The use of multiple medications at low doses instead of using a single one at full dose, to avoid side effects of any kind, has been called “rational polypharmacy” and is increasingly common as a strategy, including its use by the experts at the National Institutes of Mental Health.Frye

More non-medication approaches: light, dark, exercise, social rhythm, diet, ECT

Light therapy (and dark therapy) — very important!

Light therapy clearly works as an antidepressant. It has much less likelihood of triggering mania, as the regular antidepressants do (you may have heard me rant about antidepressant risks elsewhere on this website). Light therapy is cheap now too — so I’ve offered you an entire page on its benefits, risks and how-to’s.

But to get a mood stabilizer effect, you need to consider “dark therapy“. This has much less research to support it, compared to light therapy, but it’s worth knowing. Here’s the fascinating story on “dark therapy”.

By the time you’re done with all that, I hope you’ll have read the full story of Light and Darkness in Bipolar Disorder. If not, there’s the link!

What is the role of exercise in bipolar disorder treatment?

Exercise clearly has antidepressant effects,Phelps even being shown equal to sertraline (Zoloft)Blumenthal — and perhaps better, 6 months after the end of treatment!Babyak It would be one of the most widely used antidepressant approaches, but for people’s ability to stick with it. Even people without mood problems have trouble getting regular physical activity! Unfortunately this is not a joking matter: though Oregonians are more active than almost all other states in the U.S., still half of the state’s population gets no regular physical activity. So expecting people with severe mood disturbances to get regular exercise is extremely unrealistic. However, my patients with the worst symptoms seem actually to have more regular exercise regimens. They seem to have learned from experience that it helps, and they are looking desperately for any help they can get.

One patient in her late 20’s, who has had extreme agitation and racing thoughts, described exercise as very effective for anxiety as well. She said that after about 20 minutes of vigorous aerobic effort she would feel something shift. As she “came down” from the workout, her anxiety would seem to “come down” with it. Another patient with an extensive history of self-harm (cutting, burning) found that weight work-outs seemed to provide the same kind of benefit: it would keep her from dissociating, or feeling like she was “flying apart”.

For another extensive “testimonial” direct from a patient herself, read this strong endorsement of exercise as a treatment in itself (includes my reply to her initial statement, and her follow-up).

As you can imagine, routine physical activity is an important part of an overall mood-stabilizing “lifestyle”, but I warn patients that maintaining such a plan is extremely difficult and will require great effort on their part. Here is an essay about making exercise part of your life. The more severe your symptoms, the more beneficial exercise may be. If your illness is bad enough, it may actually help motivate you to stick to the exercise.

What is Social Rhythm Therapy?

Bipolar disorder somehow disturbs how your body “clock” keeps time. Some people lose their “anchor” to real time (when the sun actually comes up and goes down). They can have their energy turn “on” in the middle of the night and be unable to sleep, often finding their mind extremely active. Or they can try to get up in the morning and feel as though their body is still completely asleep (“somebody give me some caffeine!”) This led researchers to wonder whether “anchoring” a patient’s circadian rhythm might have mood stabilizing effects.

The Western Psychiatric Clinic has been testing this idea with treatment for bipolar disorder they call Social Rhythm Therapy, which is added on to the regular medications used. Daily routines such as time of awakening, time of rising, time of first meal, time of going to bed, and time of going to sleep are kept very regular in this treatment.Results show some benefit, especially after months of keeping a very regular schedule of daily activities. This treatment was as good as a medication in one small head-to-head trial!Swartz If you have found that your sleep or work or play follow a very irregular schedule, there may be value for you in this form of psychotherapy. Staying up late to work or play, for example? (how did  I know that?) Working irregular shifts is another really tricky problem. 

Can diet do anything?

So far, to my knowledge, no one has shown in a rigorous clinical trial that any diet can treat bipolar disorder — BUT: evidence seems to be piling up that diet matters, and of course, many people (often with things to sell you) believe this is already very clear. So just be careful: ask for evidence  in this realm.  Here are a few things I know of where evidence is at hand, as of 2014.  First, about gut inflammation; and second, about ketogenic diet.

Gut inflammation seems to be associated with bipolar relapse rates. A group at Johns Hopkins is studying this. They found markers of inflammation in their gut were higher in hospitalized patients with bipolar disorder than controls (or non-hospitalized patients).Severance   Higher gliadin, associated with gluten insensitivity, was found in patients who were rehospitalized with mania.Dickerson They are now conducting a trial of giving hospitalized patients with bipolar disorder a yoghurt-like anti-inflammatory food (as well as treatment as usual), based on these earlier results.

Of course diet is not the only place that inflammation might have come from. Other potential sources include social stressors, poor diet, physical inactivity, obesity, smoking,  dental problems, sleep and vitamin D deficiency.Berk  So don’t go leaping to the grocery for yoghurt as a treatment just yet. Of course you could just buy it because you like it. Or because you’re very hopeful and heck, why not, it’s cheap and useful otherwise anyway. Just watch out for the raised hopes, those can lead to dashed hopes which hurt. If you were very very systematic about putting it in, and taking it out, keeping a log, you might be able to figure out whether yoghurt or other anti-inflammatory diet changes (e.g. gluten-free) did anything for you.

Secondly, the ketogenic diet, which is basically what happens with the rigorous Atkins Diet approach (very few carbohydrates).  There is reason to think that a ketogenic diet might have mood stabilizing properties, because this diet can help limit the frequency of seizures, and there are some remarkable similarities between epilepsy and bipolar disorder. Dr. Robert Belmaker in Israel reported on this strategy in 2004 but his patient did not become “ketogenic” (a near-zero-carbohydrate state which can be confirmed easily with a urine test) .

The same idea was also proposed by a bipolar research group in Kentucky.El-Mallakh   After that, Dr. El-Mallakh and I were contacted by a woman who clearly had maintained ketosis (she’d routinely tested her urine, as patients with diabetes sometimes have to do, and had a log of her results). She had also clearly benefited from her ketogenic diet (based on her similarly regular log of mood). Dr. El-Mallakh later found another such example and we published these two cases.Phelps

The ketogenic diet is very nearly the opposite of common American eating, which can include very high quantities of refined carbohydrates (read “sugar”). And the American diet is very clearly associated with “metabolic syndrome” (one recent study indicated as many as one quarter of the entire U.S. population has this condition Ford). And there is just a hint of evidence that metabolic syndrome may have its own mood consequences. Thus it becomes plausible to see the ketogenic diet as an extreme in one direction, while the refined carbohydrate/metabolic syndrome approach to eating represents an extreme in the opposite direction, dietarily — and perhaps even in their mood effects. A patient’s wife sent me a “case report” describing her husband’s mood changes on and off the Atkin’s Diet.

Since the long-term health consequences of an Atkin’s approach are not known, I would not want you to think I’m advocating this. Just something to think about. People often wonder if there is anything they can do dietarily, but beyond this carbohydrate issue, and the interesting data about gluten and inflammation, I am not aware of any research that would support any particular diet practices — except avoiding weight gain generally, which can be tricky with some of the medications we use.

Is ECT effective in Bipolar II? TMS?

Electro-convulsive therapy (ECT) has efficacy in bipolar disorder at least equal to medications, in the 60-70% range (improved or much improved).Kusumakar Most experts agree that ECT should stand high in treatment algorithms. Although most of the data are in Bipolar I, at least one study showed Bipolar II responding also (not as well as “unipolar”).Medda  Several of my BPII patients have had ECT with positive responses.  Less illness prior to ECT has an impact on efficacy (longer time ill correlates with lower likelihood of response, and high likelihood of relapse after treatment). Wolpert

Unfortunately, in all forms of bipolar disorder one must think about long-term prevention as well as acute treatment, and “maintenance ECT” (repeated single treatments at regular intervals, as prophylaxis) has been used in bipolar as well as unipolar disorder.Minnai 

Repetitive transcranial magnetic stimulation (rTMS) using a hand-held but very powerful magnet (similar in power to an MRI magnet) has been shown to have antidepressant effects, but exactly where to stimulate, how long, with what intensity and frequency, have yet to be worked out for bipolar disorder. Unfortunately, looking  in 2014 for an update on the 2004 paper from the Mark George group on use of TMS in bipolar disorder, I found nothing. Good old Bipolar Network News has a 2014 article but that’s only on bipolar depression. We don’t lack antidepressants for bipolar depression: we lack antidepressants that don’t induce hypomania, as TMS can, at least when added to an antidepressant.  We need to see a mood stabilizer effect as well as antidepressant effect from TMS to really make it a useful tool in bipolar disorder. That has not been shown.

(updated 11/2014)

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