Posted by Scott L. Schofield on March 7, 2000, at 10:09:02
In reply to Re: Rapid Cycling Bipolar Disorder, posted by judy on March 6, 2000, at 22:38:18
Judy:
I think Scott suggested the best mood stabilizer combo I was ever on- depakote and lamictal. Lamictal had an excellent anti-depressant effect at 200mgs and as Scott said you need to carefully monitor your depakote levels. The regularity of your cycles are really unique, mine vary greatly in length, mania 1-2 weeks, depressions about a month. When I lived in northern U.S., my depressions lasted the entire winter and light therapy also helped significantly. I've been told by a prominent bipolar expert that I have "a difficult variation of what is already a difficult disease to treat." I wish you the best of luck.
Janice:
So right now since it's February, and I do live in Canada and it's Monday, I am fairly stable and moderately depressed. But I need to be more stable before an AD, otherwise I will be up and down again.
Me:
Before beginning any of these things, I think you should first establish a dosage of lithium that produces therapeutic blood-levels. This is the minimum "mood-stabilizing" action you must take so as to try preventing a manic reaction to any antidepressant drug trials. You may be pleasantly surprised. At this point, you may want to test the waters of using an antidepressant. Given your history of SAD-type stuff, an SSRI might be a good starting point. Lithium and SSRIs may act synergistically (1+1=3). I might be inclined to add Depakote first, though. Using lithium plus Depakote in combination sort of covers the two major categories of bipolar disorder.I think that Judy is on the mark regarding the Depakote and Lamictal combo. I suggested to my doctor that this could be a hell of a combination globally. I was close to making that my first recommendation, but I thought the dosing interaction (the need to use only half the usual Lamictal dosage) might be unpalatable to your doctor. Lamictal definitely possesses significant antidepressant properties, although this might be limited to bipolar disorder (which it seems you do have). My gut feeling is that Neurontin may be a somewhat better choice to address rapid cyclicity (only an uneducated guess). Again, you and your doctor must determine how desirable using a combination of Lithium+Depakote+Lamictal+Neurontin would be. It would certainly save a lot of time. Of course, severe negative reactions upon the addition of each drug must be anticipated as a possibility. The only thing that I see as a concern, though, is the appearance of a rash when introducing Lamictal. I think it is wise to use the titration schedule listed in the PDR. I should note that when Lamictal is started to rapidly and produces this reaction, many times it can be discontinued and restarted successfully.
The dosing of each drug can be accomplished clinically, using side-effects as a determinant (as tolerated). One very important factor that must be considered is how each drug affects the other's blood levels (pharmacokinetics). Many anticonvulsants (used here as mood-stabilizers) have the tendency to cause the body to increase the rate at which it eliminates them. The Depakote - Lamictal interaction is the exception. The PDR offers some good guidelines to follow, and details the extent to which the clearance of each drug affects the others. Many of these drugs even affect their own clearance after a while (autoinduction of metabolism).
Janice:
My cycle's lowest day is usually always Saturday (except maybe twice a year), and highest day is either Tuesday or Wednesday.
Yes my circadian rhythm has been off, as far as I know, my whole life. I try to keep my sleep as regular as possible, but this, so far, has been almost impossible. AFter decades of the Monday to Friday thing, my body's clock seems to have developed its own rhythm. Just recently, I've been noticing I sleep very little on Sunday nights (regardless of whether I am exhausted or well rested)...Monday to Friday, I sleep more and more until Saturday - the sleeping day. There is no phase-shift that causes my cycle to move forward or backward through the week. My circadian rhytm is such that I cannot get to sleep at night and have troubles getting out of bed.Sleep causes depression.
Little sleep shifts me into mania. and I seem to have very little control over the whole thing.
It sounds like a ridiculously easy problem to solve - but for me, it's very difficult. I do my best but am uncertain if I will ever be able to get my sleep and moods regular.
Me again:
Circadian rhythms - fascinating, but often a pain-in-the-ass. One interesting and important feature of many cases of depression is that sleep-deprivation can exert an antidepressant effect. This is sometimes used as a prognosticator of which drugs may have a better chance of working. Sleep-deprivation is sometimes used to potentiate the antidepressant response to a drug. However, sleep-deprivation can also precipitate mania. One must be careful to try to minimize this possibility if there is a history of mania.One suggestion comes to mind. Once you optimize your dosage of lithium (and possibly add Depakote), you may want to try total sleep-deprivation for one night. This will serve as a test to see if it produces an antidepressant effect. I would suggest doing it Friday night going into Saturday. Hopefully, you will feel modestly better towards morning and up until early afternoon. At this point, you may begin to lose the improvement, and will certainly feel sleep-deprived. It is important that you stay awake until you go to bed at your normal time. If you can't help yourself, you can take naps that last no longer that 20 minutes. Use an alarm clock to prevent going over 20 minutes. Do not oversleep Sunday morning!
If this stuff works, you may be able to develop a strategy that uses sleep-deprivation to manipulate your circadian rhythm. However, this should not require *total* sleep-deprivation. On Friday night, go to bed at your normal time, or at least at a reasonable hour. Wake up at 2:00 AM, and remain awake thereafter. You can try to stretch it to 3:00 AM, but use 2:00 AM initially to establish whether it works or not. The same rules apply regarding naps, and you must wait until your usual bedtime to go to sleep.
Even if this regime doesn't work, I feel that it is *extremely* important to maintain good sleep hygiene. It is probably most important to wake up at the same time every day and not oversleep. Saturday mornings are probably the culprit here. If you work a "regular" 9 - 5 job, my suggestion is to use a sleeping schedule of 11:00pm - 7:00am or 10:00pm - 6:00am, except for any therapeutic sleep-deprivation.
I hope something here helps.
- Scott-------------------------------------------------
Depress Anxiety 1997;5(4):175-89
Alternative approaches to refractory depression in bipolar illness.
Post RM, Leverich GS, Denicoff KD, Frye MA, Kimbrell TA, Dunn R
Biological Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda, MD 20892-1272, USA.
Thus, there appears to be a large variety of approaches to refractory bipolar depression. In contrast to several decades ago, wherein augmentation of lithium with antidepressants and neuroleptics was essentially the only treatment mode available, a panoply of treatment options now exist. However, their relative efficacy in different illness subtypes and stages remains to be better delineated, as do their optimal sequencing and use in combination in individual patients. It is the opinion of these authors and many of our colleagues in the field that initial use of several mood stabilizer drugs in combination may have a preferable long-term outcome in some rapid cycling patients, compared with the immediate use of a unimodal antidepressant with an inadequate single mood stabilizer, although this remains to be systematically studied. The use of thyroid augmentation strategies would appear to have merit in relationship to not only the potential treatment of lithium-related hypothyroidism, but also in augmenting antimanic and antidepressant effects. As one moves toward some of the complex combination treatment strategies discussed in this chapter, one has to be particularly careful about drug interactions and their potential for toxicity as well as therapeutic effects. Perhaps a prevailing guideline would be to use these agents more carefully in combination therapy than in monotherapy, with slow upward titration of dose to individual patients' side effects thresholds, even in preference to targeting of conventional blood level windows. In this way, side effects can be avoided during the assessment of complex combination regimens. In addition, one should be aware of potential pharmacokinetic interactions. For example, with the addition of valproate to carbamazenine, one should reduce the dose of carbamazepine, as valproate will not only increase the free fraction of carbamazepine based on displacement of protein binding, but will lead to increased accumulation of carbamazepine-10,11-epoxide. This epoxide is not measured in conventional assays but could contribute to the side effects profile (Ketter and Post, 1994). Similarly, valproate will markedly increase blood levels of lamotrigine; the starting dose of this agent should be substantially lower than conventional dosage when these two drugs are used in combination. We suggest the utility of detailed mapping with a formal system-such as the Life Chart Methodology (LCM) (Leverich and Post, 1996)-of mood fluctuation vs. medications in order to optimize and rationalize complex combination therapy. In this way, not only can the nuances of partial response be better defined, but also basic decisions about the therapeutic index and relative likelihood of response can be more readily assessed. We have discussed the other merits of the life chart method as an important clinical treatment tool as well as a research tool in other venues, but reemphasize its potential great importance in the treatment of refractory cyclic bipolar patients, in whom an initial period of remission of depression may, in many instances, be as likely attributable to the natural course of illness as the current intervention being offered. As such, it behooves the clinician to have a systematic database for the more subtle issues of dose titration and sequential addition of medications in complex combination regimens. In the face of inefficiency to one combination strategy, how one moves to the next strategy remains a highly individualized, clinically-based algorithm. We suggest the potential utility of moving towards a new set of mood stabilizers and then repeating some of the unimodal antidepressant additions and augmentation trials in an attempt to overcome refractory depression. Refractory depression in bipolar patients should be viewed as a medical emergency in light of the high potential for suicide in the illness in general (Chen and Dilsaver, 1996) and in patients who have either sustained or episodic refractory depression.
poster:Scott L. Schofield
thread:25437
URL: http://www.dr-bob.org/babble/20000302/msgs/26230.html