Tuesday, February 10, 2009

Bipolar Depression

The depression which occurs in the context of bipolar disorder may have a variety of unique features (sometimes such a depression may occur BEFORE a clear manic episode has ever happened, so a depression with these features can sometimes be a warning sign of latent bipolarity, or a risk sign that bipolar disorder may develop in the future):

1) excessive sleep (rather than insomnia), along with marked physical lethargy
2) depression beginning early in life (during teenage or young adult years)
3) depressive episodes of short duration
4) depressive episodes having psychotic features (e.g. delusions)
5) other "atypical" depressive features, such as increased eating
6) Sometimes a very rapid response to antidepressants (e.g. within one or two doses)

Nevertheless, these features are not invariably present in bipolar depression; and many people may have depressive episodes with these features, who do not have bipolar disorder.

Conversely, in my opinion, there is one significant element from a person's history which points strongly away from a diagnosis of bipolar depression:

If a person has taken an antidepressant, especially at a high dose, and especially for a long period of time (over 3 months), and especially a tricyclic antidepressant or venlafaxine -- if a person has taken such an antidepressant on its own, without a mood stabilizer, and WITHOUT developing overt symptoms of mania, this is fairly strong evidence against underlying bipolarity.

Some of the recent evidence about treating bipolar depression leads us to question the role, value, or safety of antidepressants in the bipolar population.

(a 2008 review, showing little effect of antidepressants when added to mood stabilizers in treating bipolar disorder over at least 6 months of follow-up)


(this is from the New England Journal of Medicine--one of the world's leading medical journals--in 2007, and it showed, over 26 weeks of follow-up, that adding antidepressants to a mood stabilizer regime did not improve outcome, in fact the antidepressant group did not do quite as well)

Which treatments have an evidence base in bipolar depression?

1) Lamotrigine. It has the advantage of helping modestly with depressive symptoms with a low risk of causing mania. It may be true that some of the studies over the past few years have exaggerated the benefit of lamotrigine, however. In any case, it appears quite safe, and can be helpful for some people. There is a small risk of a very serious skin rash with this drug, otherwise it is quite safe and well-tolerated.

(a recent study looking at Lithium + Lamotrigine vs. Lithium + Placebo over 8 weeks of follow-up; the benefits of lamotrigine are significant but modest)


(this study also showed a benefit from lamotrigine, over a whole year, but there was no placebo group, so the results carry much less weight)

2) Other mood stabilizers, e.g. lithium, valproate, and carbamazepine. Unfortunately these drugs are probably more effective for preventing manic episodes than for preventing or treating depression. Yet, the combination of a standard mood stabilizer with another agent such as lamotrigine could be a valid step.

3) Atypical antipsychotics, e.g. olanzapine, quetiapine, and risperidone. These drugs undoubtedly are beneficial as mood stabilizers, possibly more so than the standard mood stabilizers such as lithium or valproate. There is evidence that antipsychotics + other mood stabilizers are additively effective in combination. They can be worth a try for treating bipolar depression. Unfortunately, if the bipolar depression is already characterized by excessive sleep, tiredness, and appetite, antipsychotics can sometimes make these symptoms worse. But if there are psychotic features with the depression, an antipsychotic can be an essential part of the treatment.

4) Omega-3 supplements : see my previous post

5) Light therapy: I have seen this be helpful at times. The light exposure may need to be carefully titrated (e.g. just a few minutes at a time), to prevent overstimulation or agitation. Light therapy requires the purchase of a 10 000 Lux light box, which could cost about $200-300.

6) Cognitive-behavioural therapy. Elements of CBT help with most anything, it seems to me (from learning to play the violin, to doing mathematics, to treating anxiety or depression from any cause). CBT can be adapted so as to be more tolerable and interesting (some of the workbooks can be hard to get through). I think its core features require daily written work, journaling, conducting a dialog with oneself about thoughts and emotions (hopefully to work at identifying forms of depressive thinking, and being willing to challenge such thoughts if they occur), and deliberately challenging oneself behaviourally to face fears, a little at a time. In bipolar disorder CBT may work best in conjunction with ideas that help to stabilize or structure daily behavioural rhythms (e.g. getting up regularly in the morning, having a routine, eating regularly, exercising, doing some intellectually challenging work, doing some creative work, going to bed around the same time, etc.). Of course, in depression of any sort, it can be extremely hard to initiate or maintain such lifestyle habits--if there is too much fatigue or lack of motivation to get started with very much, I encourage getting started with the very smallest of tasks or daily structures, and building from there; consistency is more important than amount.


7) Other psychotherapy: basic supportive care can be very important, provided there is a resilient, trusting therapeutic relationship

8) Antidepressants: despite the negative results of late, there are selected individuals for whom antidepressants may be very helpful. Over the past decade, bupropion has perhaps been the first antidepressant to consider, due to its lower rate of causing a manic switch, and possibly its higher likelihood of helping with the low energy states characteristic of bipolar depression. SSRI antidepressants have been the second-choice agents. MAOI's are probably lower risk with respect to causing manic switch, and the reversible MAOI moclobemide could be a good option. Venlafaxine and tricyclic antidepressants have been agents to avoid, due to their high risk of causing a manic switch.



9) Stimulants: I have found that stimulants can be quite useful in bipolar depression, provided that they are not increasing psychotic symptoms or agitation. They have the advantage of working quickly, helping immediately with energy and attention, and often helping with mood. Furthermore, they can be withdrawn quickly if manic symptoms or agitation arises; if stimulants are withdrawn quickly, it causes a relative state of sedation. (Note that there is some evidence from a few older studies that stimulant treatment can actually reduce symptoms of mania) There are several older stimulants, such as methylphenidate (Ritalin), and dextroamphetamine (Dexedrine), and several newer formulations of these older drugs (e.g. Adderall). A newer, atypical stimulant called modafinil can be an option as well. However, modafinil is quite expensive and often not covered by medication plans in Canada.





(the above two references are to older, interesting studies showing that stimulant treatments actually helped REDUCE manic symptoms acutely--I cite this as evidence that stimulants are reasonable to use in bipolar patients, however I would not go so far as to recommend stimulants in the treatment of mania, as other anti-manic treatments are much more effective and accepted as a standard of care)

10) ECT:electroconvulsive therapy is unequivocally effective for treating both depression and mania. However, there may be a higher risk of mild but persistent cognitive side-effects in the bipolar population:

If there are "borderline" phenomena occuring in the context of bipolar depression, once again some of Dawson's ideas may be helpful (see my previous postings about borderline personality); these involve emphasizing the role and competence of the individual patient in choosing treatment options, and avoiding an authoritarian stance on the part of the therapist.

Other references:

(A recent study correlating early age of onset for depression with bipolarity, severity, recurrence, etc.)


(A review of diagnostic issues regarding bipolar depression)

1 comment:

L said...

Hi Dr K.,
This is interesting information. Thanks .

I'd be interested in an article about the type of mood cycling that happens outside bipolar. It seems there is are all kinds of descriptions for different types of cycling (bipolarI, II, cyclothymia etc., but nowhere do I find information about people who have major depression and a mood that cycles up right below hypomania. I must not be the only one with this difficulty:
- Why is there no description for this?
- Do treatments differ from treating BPII?
- Do other psychiatrists recognize this kind of cycling?
- Do symptoms really differ or is it a matter of increments below hypomania that makes it not BP?
- Is there a stigma attached to having BP that isn't attached to Major Depression?
Does this influence doctors "labeling" of an illness?
- Does it influence your decisions to label?
I know...lots of questions...but I find it really frustrating to be somewhere inbetween and unable to really find any consistent information.