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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.






not statistically different

not statistically different


not statistically different

not statistically different




Elated Mood



Daredevil Acts



Flight of Ideas



Racing Thoughts




   45% of entire BP group
     before puberty:  24%
        after puberty:  70%


Decreased Need
for Sleep



Suicidal thoughts with plan or intent



 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 hypo-manic episodes.

What I didn’t realize is the definition of Bipolar II, a relatively new diagnosis that is different from the huge mood swings from elated to depressed. It also has a very common link, it seems, to Borderline Disorder tendencies. As it appears now, my anxiety is a type of mania. And I definitely have a tendency toward depression, which I’ve been diagnosed with for many years. Of course, I went home that day, new prescription in hand, and researched this the rest of the afternoon. I will include some of the most pertinent documents here that I found relating to my condition, and of course I have showed them to my doctor, who is awesome as far as letting me do my own research and then asking questions. The most interesting article was on Medscape, which I copied in its entirety below, and hopefully they don’t mind.

I am not angry with my doctor, even though it states right in the article that people often suffered from bipolar disorder for 10 years before they are diagnosed. I know when I came to him in 1996 that I was so severely depressed and suicidal that he had no choice at all but to treat me for my major depression. First things first, obviously. I have no qualms about that at all. But I do believe I’ve had the hypo-manic symptoms the whole time. My mind is never blank, even in the worst states of depression. It spins and spins and drives me crazy, sometimes even to over-medicate and just sleep the day away to escape the constant overactivity of my brain.

After my studying, my doctor asked me my opinion on which medication to try first. I really had no idea. I know some of the side effects of the major Bipolar medications frightened me. Finally I asked him truthfully, “If I was your daughter, which would you put me on”. After pondering a moment, and I know he has a young daughter, he had an answer: Lamictal. Lamictal (lamotrigine) is described below in the article. I brought this article to him at my next appointment and he was happy with it. Dr. Joseph Goldberg, who is mentioned in the article, was someone he worked closely with at one time. And the fact that Lamictal is suggested to work BELOW baseline to control depressive symptoms, drugs like Lithium control mania better than depression.

I am now in limbo with medications, slowly coming down on Effexor and moving up on Lamictal. So far I have not experienced the common Effexor withdrawal symptoms, and my biggest concern, falling into a depression once again. I don’t notice a tremendous effect yet of the Lamictal, but I have been able to get through the occasional day without my “panic pill” Klonopin, which very atypical for me.

Bipolar Depression and Rapid Cycling: The Latest Pharmacologic Strategies

The Brown University Psychopharmacology Update 13(7):1, 10-12, 2002. © 2002 Manisses Communications Group, Inc.

Posted 07/09/2002


Our 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.

The most 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.

Presenter Mark A. Frye, M.D., director of the Bipolar Disorder Research Program at UCLA, examined the problem of unmet need more closely.

"Bipolar 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.

Joseph F. 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.

"The 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.

Goldberg 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 depression.

"Lithium 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."

Limitations of the current bipolar pharmacopoeia include:

  • Drug development in bipolar disorder has primarily focused on mania.
  • No treatment is specifically indicated by the FDA for bipolar depression.
  • Bipolar patients usually excluded from antidepressant FDA application studies.
  • Unimodal antidepressants can destabilize bipolar disorder (i.e., induction of mania or rapid cycling).

Lithium vs. Lamotrigine for Bipolar Depression

Data 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.

Goldberg also 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.

Rapid Cycling

Robert 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.

"Although 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 time."

Clinical outcomes 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.

Newer agents 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.

Efficacy with 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.

"Lamotrigine 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.

"We are 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

  • Depression is the predominant pole;
  • typically first presentation of the illness;
  • episodes are longer and more frequent than mania;
  • in controlled maintenance studies, patients more commonly relapse into depression than mania.
  • Persistent early depressive symptoms predict depressive symptoms 15 years later and poor prognosis.
  • 90 percent completed suicides in depression or mixed mania.

[Judd LL, et al.: Arch Gen Psychiatry, in press.]

Sidebar: One Schema for Treatment of Rapid Cyclers

Combination Treatment

  • Lithium + Valproate (Dysphoric Mania)
  • Lithium + Carbamazepine/Oxcarbamazepine (Schizoaffective, BPII, Substance Abuse)
  • Lithium + Lamotrigine (Depressions predominate)


A.       For Agitation/Insomnia -- 1) Clonazepam or Lorazepam; 2) Gabapentin (Social Phobia, GAD).

B.       For Psychosis -- Atypical Antipsychotic

C.      For Persistent Cycling -- Third Mood Stabilizer


1.       Weight Loss -- Topiramate

2.       Cognitive Slowing -- T3/T4 (esp with lithium); Dihydropyridine; Ca++ blocker; Donepezil

3.       Mania -- Third Mood Stabilizer; Atypical Antipsychotic; High-dose Thyroid

4.       Depression -- Lamotrigine; Antidepressants (Bupropion, SSRI, SNRI, Folate, Omega-3 Fatty Acids, High Intensity Light)

5.       Alcoholism -- Naltrexone

6.       Atypical Depression -- MAOI; SNRI + Bupropion

7.       Ultradian Cycling -- Dihydropyridine;Ca++ blocker

8.       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.