By Rhona Finkel
If you feel depression has come to predominate your bipolar existence, you're
in good company.
Research indicates that, at a minimum, three times as many days are spent in
depressive episodes than in manic or hypomanic ones for bipolar 1.
And Joseph R. Calabrese, MD, director of the Mood Disorders Program at
the Case Western Reserve University School of Medicine in Cleveland, Ohio,
estimates that for bipolar II the ratio is 40 to 1.
Now if only there was a good way out of those debilitating episodes.
But there just might be.
For just when you thought you'd tried it all--done the SSRI's, been talked into
paying more for Prozac and Zyprexa together in one pill form (Symbyax), tried
Seroquel and Abilify, been on Lamictal twice--and thought you'd continue
to have unremitting bipolar depression for as far as the future can see, well,
there's still hope.
It just comes from some unusual venues.
Known as pramipexole in its generic form, Mirapex is used to treat the
symptoms of Parkinson's Disease, and, quirkily enough, Restless Leg
That wouldn't necessarily make it an obvious choice for bipolar depression,
but it's what's called a dopamine agonist, acting in place of dopamine, which
is a substance in the brain that controls movement.
However, a paucity of dopamine has strongly been related to depression
(Wellbutrin, for example, is a well-known dopamine agonist), since dopamine
also controls emotional response, and the ability to experience pleasure and
It didn't take too long for researchers to put the two uses of dopamine
together, and in 2004 the first preliminary randomized, placebo-controlled
trial was published in the American Journal of Psychiatry by Joseph
Goldberg, MD, associate clinical professor of psychiatry at the Mount Sinai
School of Medicine in New York City and director of the Affective Disorders
Research Program at Silver Hill Hospital in New Canaan, Conn.
They studied a group of patients for whom mood stabilizers and standard
antidepressants had failed. And the results looked good. 67% of patients had a
reduction of 50% or more from their baseline depression scores, which is none
Mirapex is particularly helpful in re-invigorating motivation, all too often
sucked away by the depths of depression.
Still today, 8 years after the first study, Mirapex remains relatively unheard of
as a treatment for bipolar depression, but that's much the pity.
One well-known Atlanta psychiatrist, however, Dr. Darvin Hege, had such
good results from it that he incorporated his experiences into his blog, in the
post "Mirapex – A New Medicine for Depression", which is definitely worth a
It is safe in conjunction with lithium and other mood stabilizers.
In one case with which I'm familiar, introducing Provigil to the medication
regime was like bringing back the dead.
Approved by the Food and Drug Administration for improving wakefulness
in patients with excessive sleepiness due to narcolepsy, sleep apnea, and shift-
work disorder, this young woman's depression was so severe that she spent 20
out of 24 hours sleeping. An introduction of Provigil, a tweaking of the dosage-
-she was out of bed and back with the living, although of course with a lot of
work to do.
Her situation is not unusual, since bipolar depression is often typified by
So Dr. Mark Frye, head of the Mayo Mood Clinic which focuses exclusively on
treatment-resistant depression and bipolar disorders and a team of 11 other
researchers set out to study the efficacy of modafinil (Provigil) in bipolar
depression, again, like with Mirapex, as an adjunct to other treatments.
In their ground-breaking study on Provigil in the August 2007 issue of
the American Journal of Psychiatry, they found that, using three scales for
assessment, depression severity was "significantly reduced in the modafinil
group compared with the placebo group."
In another of Provigil's big sells, the drug didn't cause "switching," where
patients flip to a manic episode, which is a hazard with a number of standard
Interestingly the study concludes that doses of 100-200 mg a day may
improve the symptomatology, while the woman I know didn't achieve full
relief until 400 mg.
We're once again reminded how psychiatry is a field with much art
commingled with its science.
Just to clarify, I'm not one of those people who believes you can treat major
psychiatric disorders with vitamins and herbs.
It's be nice, I agree--but it's a bit of a fantasy.
So when I address this herbal supplement, know that I've got real, double-
blinded research behind me, not just a wing and a prayer.
N-acetylcysteine produces something called glutathione (and I promise to stop
using such technical terms for the rest of this discussion--really all we care
about is that it works, right?)
Anyway, this glutathione protects the outer layer of brain cells, as well the (ok-
-I'm hoping you know this word back from high school bio, so I won't have
lied) mitochondria of brain cells. Mitochondria, as I'm sure we all remember,
are the energy-producers of the cell. So this glutathione lets the brain cells
function better, and it particularly improves their functioning (warning: 2
big words coming but I feel confident they're familiar) when transmitting
messages through brain chemical messengers like dopamine and seratonin.
These messengers are big players in mood regulation, and improving
It's had a number of uses as a supplement, and then, as recently as the
September 2008 issue of Biological Psychiatry, there's has a study by Berk
et al that indicates it’s an effective add-on drug for bipolar depression. Their
conclusion was surprisingly definitive in the world of research studies, ending
with "NAC appears a safe and effective augmentation strategy for depressive
symptoms in bipolar disorder."
Big plusses? No known reports of adverse side effects (and when do you
hear that in discussions about bipolar medications?) and it’s a score
economically, with a 60-tablet bottle of 1000 mg pills sold online by Source
Naturals for $11.00.
#4) Synthroid (levothyroxine)
A 1999 paper in the American Journal of Psychiatry found that people with
lower thyroid levels were less likely to come out of their bipolar depression
when compared with those with higher thyroid levels.
It's well-known that if your thyroid levels are low, you can get depressed.
But here's where the surprise comes in: Thyroid hormones can act as a
treatment for bipolar depression, even if your thyroid levels seem normal.
They act like mood stabilizers by helping to stop mood cycling, and seem to do
this particularly well among rapid cyclers.
Levothyroxine, or T4, or Synthroid, is a synthetic form of the thyroid hormone.
And so far research is indicating that adding levothroxine to mood stabilizers
increases the stabilizers' efficacy.
As far back as 1990, two researchers studied 11 treatment-resistant bipolar
patients. Levothyroxine was added to their medication regimen, and, while the
patients took it, their scores on both depressive and manic symptom rating
scales decreased significantly.
A 2003 article reviewing the evidence thus far on synthroid and treatment-
resistant mood disorders found that "open-label studies have consistently
demonstrated that the behavioral expression of bipolar disorder can be
modified by a change in thyroid status. In many instances, the course
of illness is improved through use of supraphysiologic doses of L-T4
If you believe this treatment might be for you, print out the article above and
bring it to your doctor, so he's got a run-down of the facts.
And be aware, as with all hormone supplementation, that there might be
serious side effects, some long-term.
This one got more press than the marriage of Kate and William, so you may
in fact be aware of it, but it comes under the heading of new and unusual
treatments for bipolar depression.
In what could turn out to be one of the biggest break-throughs in treatment
of bipolar depression, if scientists can figure out what's going on and make
the changes permanent, researchers found that a single inclusion with of the
anesthetic ketamine can improve the mood within minutes of a depressed
Dr. Carlos A. Zarate Jr. of the National Institutes of Health in Bethesda,
Maryland, and his colleagues gave a single dose of ketamine and a single dose
of placebo to a group of patients on two different days, and then assessed the
patients for depressive symptoms.
When the patients received the dose of ketamine, their depression improved
significantly within an astonishing 40 minutes--and remained better for 3
79% of patients improved with the ketamine [a staggering number in
depression treatments], and 0% with the placebo.
While clearly a drug that allows you to relapse after 72 hours isn't going to be
a best-seller anytime soon, Zarate believes it can be useful in several ways. He
said it could be used to "jump-start" regular antidepressant treatment, or as
an anesthetic before ECT, thus contributing its antidepressant qualities just
when they're most needed.
Zarate and a co-author have filed a patent for use of ketamine in depression.
While he believes more research is needed to develop guidelines, he also
suspects doctors might already be using it in certain particularly refractory
I must say that the idea of a 40-minute wait for improvement, instead of the
4-6 weeks standard with antidepressants, has to be a big sell.
And I haven't even addressed Rilutek, celexocib, or insulin sensitizers (for
real), which you can read about here.
Depression makes it seem that there is no hope, that you will continue to
flounder in your darkness forever. But sometimes it just takes a look outside
of the box--and a drug meant for Parkinson’s, or thyroid disorder, or to put
you under during surgery, is waiting there for you, to bring back the light and
joy in your life.