Jump to Bipolar II and Rapid Cycling
Attention Deficit Vs. Bipolar Disorder
In 2001, I was put on Ritalin to treat ADHD (Attention Deficit Hyperactivity Disorder). I took the medication for nearly a year, noticing only that my road rage had ceased. I still had severe anxiety that was interfering with the rest of my life. After completing months of mood charting (which forms can be found on the web), my psych doctor took me off the Ritalin, noticing little or no difference in the charts. He did, however, notice something that I found shocking.
I had done research on the similarities in symptoms of
ADD/ADHD and Bipolar disorder when it was suggested to me. I was extremely
surprised at the commonalities of the two problems.
What I didn’t see in those mood charts was what Dr.
T called “Rapid Cycling”, ups and downs in the course of a week. When I
heard this I admit I was in a bit of a panic – I never thought myself
“Manic-Depressive”. My mind raced to blood tests, kidney failure,
uncontrollable shaking and Lithium, which scared the hell out of me. The
descriptions of Mania always sounded intriguing: Too high, too happy, feeling
like you can do anything, lack of need for sleep… blah blah blah, that did NOT
describe me. As much as I hate being labeled with this disorder or that, I do
realize that it is a necessity for doctors to classify your symptoms in order to
use other doctors’ successful treatments as a start for treating my particular
problems. I just never thought in a million years that I’d be diagnosed as
Manic-Depressive – and that the very drug, Effexor, that had so very much
controlled my depression for years now may be creating or stimulating the
University Psychopharmacology Update 13(7):1, 10-12, 2002. © 2002 Manisses
Communications Group, Inc.
ability to treat and manage patients with bipolar disorder -- both adequately
and inadequately -- was the focus of several well-attended industry symposiums
at the recent 155th American Psychiatric Association Annual meeting in Philadelphia.
The latest data put the lifetime prevalence of bipolar disorder up to around 6.5
percent, with medical costs of up to $476,000 per year per patient. Astounding
figures, and when one adds the fact that about 25 to 50 percent of those
diagnosed with bipolar disorder attempt suicide, and that as many as 40 percent
are not diagnosed or are misdiagnosed, the picture can look fairly grim for
patients and families.
exciting of the bipolar disorder symposiums -- "Bipolar depression and
rapid cycling: current management strategies" -- attempted to elucidate
some of the most telling treatment deficiencies and explore the latest
approaches to addressing them. Joseph R. Calabrese, M.D., Director of the Mood
Disorders Program at the University Hospitals of Cleveland, and Professor of
Psychiatry at Case Western University, chaired the symposium and said that the
recognition and treatment of bipolar disorder has improved in recent years.
However, he urged attendees to help eradicate the underdiagnosing and
misdiagnosing of a disorder that takes such a personal and economic toll.
A. Frye, M.D., director of the Bipolar Disorder Research Program at UCLA,
examined the problem of unmet need more closely.
disorder is commonly unrecognized, hypomania is often overlooked, and bipolar
depression is frequently not differentiated from unipolar depression," said
Frye. "In one survey of 400 patients, 69 percent of patients with bipolar
disorder had not been diagnosed initially, and bipolar disorder was most
commonly mistaken for depression, anxiety and schizophrenia.
More than one third of respondents had suffered symptoms of bipolar disorder for
at least 10 years before they were diagnosed."
Frye also said
that current treatment of bipolar disorder is inadequate.
Treatment of the disorder as unipolar depression is particularly worrying
because antidepressants may destabilize bipolar depression and may even cause
mania and/or rapid cycling in some patients.
Goldberg, M.D., Director of the Bipolar Disorders Research Clinic at New York
Presbyterian Hospital and Assistant Professor of Psychiatry at Cornell
University, addressed the issue of stabilizing mood over long periods. He
presented information on current treatment options, ranging from typical mood
stabilizers such as lithium (Eskalith and others) and divalproex (Depakote,
Depakene) that work from above baseline to help mania, hypomania and
mixed episodes, to the newer atypical antipsychotics (see page 8). He also
explored the possibilities offered by novel mood stabilizers like lamotrigine (Lamictal), that
work from below baseline to help major depressive episodes and
subsyndromal depressive symptoms -- a relatively novel concept.
three goals of mood stabilizer therapy is to treat manias without causing or
worsening them, treat depressions without causing or worsening them and
effective prophylaxis for manias and depressions," said Goldberg. "I'm
hard pressed to find one agent that does all three of these things in an
excellent way," he added.
stressed the need to conceptualize mood stabilizers as primary antidepressants,
and not just anti-manic drugs. He also recommends using antidepressants when
needed for depression and the sustained use of antidepressants to prevent
is the only agent approved for long-term treatment of bipolar disorder, but
where depression precedes mania, it may not work as well," said
Goldberg."lithium prophylaxes mania better than it does depression."
the current bipolar pharmacopoeia include:
Lithium vs. Lamotrigine for Bipolar Depression
suggest that lithium will prevent or attenuate depression better if it has been
effective first in the mania phase, according to Goldberg. Though results for
divalproex and carbamazepine (Tegretol) for depression prophylaxis have been
adequate, the most excitement has been generated by recent studies of
lamotrigine for both bipolar depression and rapid cycling. Brand new data
[Bowden CL, et al.: in press] comparing lamotrigine (LTG; N=69) and lithium (Li;
N=58) to placebo (PBO; N=44), found both drugs superior to placebo in time to
intervention for depression (LTG vs. PBO, P=0.015; Li vs. PBO, P=0.167; LTG vs.
Li, P=0.355) when the index episode was mania.
In a second
new open-label double-blind study [Calabrese JR, et al.: submitted for
publication 2002] looking at the same comparison where polarity of entry was
depression, lithium did not fair as well as lamotrigine in time to intervention
for depression (LTG vs. PBO, P=0.047; Li vs. PBO, P=0.209; LTG vs. Li, P=0.434).
In both trials, lithium was superior to lamotrigine and placebo in time to
intervention for manic and mood episodes.
presented new data on factors associated with antidepressant-induced mania
(Goldberg JF, J Clin Psychiatry, in press). Results showed that
predictors of antidepressant-induced mania include substance use or dependence
and having been on several antidepressant trials, particularly when there was a
lack of response.
M. Post, M.D., released new data from two studies looking at the efficacy of
lamotrigine for rapid cycling, as well as the use of combination therapy for
this subset of patients.
rapid cycling was once viewed as a rare presentation for bipolar disorder,
recent data suggest that it may present in as many as 30 to 50 percent of
patients," said Post. "We really have to revise our notions about
rapid cycling; it is much more prevalent then it used to be and up to one
quarter of one recent study sample remained ill three quarters of the
in rapid cyclers is often poor and these patients may be non-responsive or only
partially responsive to lithium, according to Post. Treatment limited to antimanic agents
that stabilize mood from above baseline usually only improves hypomania and
mania, but not the depression phase, he added.
in monotherapy or in combination with typical mood stabilizers may be able to
effectively manage patients with rapid cycling. Across nine different studies,
lithium has proven less effective in rapid cycling bipolar disorder, and more
rapid cycling episodes prior to starting lithium is associated with poor
response. Likewise, results have not been stellar for carbamazepine or
combination carbamazepine/lithium treatment for rapid cycling.
valproate has been a little better, says Post, but again results for the
depression phase of the cycling have been relatively poor. "In one study
comparing lithium and valproate in rapid cycling," said Post, "we
couldn't get more than 25 percent of the patients well enough to get them into
the study -- with our two best drugs!"
Calling this a
terrible statement for our field, Post added that most patients are relapsing
through monotherapy. He presented data from the two new studies by Bowden et al.
and Calabrese et al. mentioned above to offer some hope that lamotrigine might
be effective for treating rapid cycling in bipolar I. An earlier study found the
drug superior to placebo for rapid cycling in bipolar II patients only.
looks like it is better for the depressive side of rapid cycling and it appears
to do it without any induction of mania," said Post.
He also noted
that topiramate (Topamax) and quetiapine (Seroquel) look promising, but more
data is needed.
left with a lot of guesses with these patients and my own bias is to get the
patient involved in tracking their own moods," concluded Post. "In the
absence of randomized clinical trial data, we must use all these medications as
best we can."
Sidebar: Bipolar Depression is the Greatest Unmet Need
[Judd LL, et
al.: Arch Gen Psychiatry, in press.]
Sidebar: One Schema for Treatment of Rapid Cyclers
For Agitation/Insomnia -- 1) Clonazepam
or Lorazepam; 2) Gabapentin (Social Phobia, GAD).
For Psychosis -- Atypical Antipsychotic
For Persistent Cycling -- Third Mood Stabilizer
Weight Loss -- Topiramate
Cognitive Slowing -- T3/T4
(esp with lithium); Dihydropyridine; Ca++ blocker; Donepezil
Mania -- Third Mood Stabilizer; Atypical Antipsychotic; High-dose Thyroid
Depression -- Lamotrigine; Antidepressants (Bupropion, SSRI, SNRI, Folate,
Omega-3 Fatty Acids, High Intensity Light)
Alcoholism -- Naltrexone
Atypical Depression -- MAOI; SNRI + Bupropion
Ultradian Cycling -- Dihydropyridine;Ca++ blocker
Highly Refractory Mania or Depression -- ECT
Post RM; Rapid
cycling: clinical presentation and treatment approaches. New research presented
at the 155th Annual Meeting of the American Psychiatric Association,
Philadelphia, May 2002.