Approximately 40% of bipolar patients experience rapid cycling, and half of these suffer from ultra-rapid or ultradian cycling. These patterns are also common in children. Rapid-cycling bipolar disorder is difficult to bring to remission and often requires treatment with four or more classes of psychotropic medications. Lithium, even in combination with anticonvulsants or antidepressants, is often associated with residual episodic depressions. Concerns with adjunctive antidepressant treatment include their low response and remission rates and their tendency to cause switch into mania. Atypical antipsychotics and selected agents within the anticonvulsant class are becoming increasingly important in the treatment of rapid cycling. In the absence of clear treatment guidelines, the use and sequencing of drugs in complex combination treatment remains exploratory, but should be individualized based on careful prospective mood charting by the patient. Use of several drugs below their side-effect thresholds may prevent certain side effects. In children, long-term safety considerations are particularly important in the absence of a strong controlled clinical trials database.

Presence of rapid cycling appears to be the rule rather that the exception in children with bipolar disorder, although there is not much data to support this clinical notion. Geller and colleagues studied 93 pediatric patients with bipolar disorder, mean age 10.9 years. They found that 87% had rapid cycling defined as ≥4 episodes/year and 77% had ultradian cycling, defined as >365 episodes/year. In addition, Findling and colleaguesstudied 90 bipolar patients with a mean age of 10.8 years and found that 50% had rapid cycling by veteran CV criteria. (The study did not look at ultra-rapid or ultradian cycling.) Finally, using clinical interviews to study children with affective illness, Schraufnagel and colleagues found that 41% experienced >365 cycles/year (Slide 6).

It is difficult to figure out the difference between a cycle and an episode when children are cycling so quickly. Tillman and Geller proposed that any kind of mood switching constitutes a cycle. An episode, they proposed, is defined as having ≥2 weeks of mood symptoms with either onset and offset of one mood state within that 2 weeks, or onset and offset of a period of ultra-rapid or ultradian cycling. It appears that with younger age comes more rapid cycling and more mixed states, which can be confused with ultra-rapid cycling. In turn, the older the child gets, the less rapid cycling occurs, and the more episodic the disorder becomes with more euphoria and less irritability. However, this tendency has not been well studied.

While rapid cycling was first identified by Dunner and Fieve in 1974, there is quite a good historical background on the concept. In the 1800s Falret and colleagues identified what they called a “circular course distinct from alternating.” What they meant by “alternating” was a period of remission following an episode. Currently, all types and ranges of cycling are lumped under one rubric; the spectrum ranges from having >4 cycling episodes, the minimum required for rapid cycling, through ultradian cycling, which is far more severe.

While some patients manifest chronic depression with periodic hypermania, which is known as bipolar II, others have ultradian cycles, which are often seen as pure affective instability. We do not know whether these types represent different stages of a disorder that exists on a spectrum or whether they are actually distinct categories of the disorder: one being patients who experience mania, depression, and then remission; the second being those with more continuous cycling that includes ultradian cycling. Greater understanding of the biological underpinnings of the illness will help to determine whether these conditions exist on a spectrum.

Rapid cycling may become less prevalent with age. In the Depression Collaborative Study, Coryell and colleagues found a diminishment of rapid cycling over the course of 13 years. Studies from the Stanley Bipolar Foundation group suggest that the cycling may accelerate in some, but not others. Over a long observation period in ~100 patients, Koukopoulos and colleagues found that once a pattern of rapid cycling is established in a patient, this pattern may become a hallmark of their illness.