Evidence-Based Reviews

Ultra-rapid cycling bipolar disorder: A critical look

Current Psychiatry. 2011 December;10(12):42-55

References

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Table 2

Evidence-based treatments for ultra-rapid cycling BD

Intervention	Strength of evidence	Comment
Antidepressant elimination	Cycling frequency may lengthen during antidepressant-free periods among patients with RC²⁰; long-term (up to 1 year) antidepressant use in RC patients may increase the likelihood of depressive recurrences¹⁹	Findings based mostly on small sample sizes; no controlled trials of antidepressant cessation as an intervention specifically for URC
Lithium	Single case report of ECT-induced URC resolved by lithium augmentation during continued ECT²²	No large-scale or randomized trials
Carbamazepine	No controlled trials or case reports	Possible anti-cycling benefits relevant for URC could be inferred from post hoc studies among patients with RC
Divalproex	Single case report describing resolution of a 48-hour cycle after augmentation of lithium with divalproex²³	No large-scale or randomized trials
Lamotrigine	Single case report of 100 mg/d lamotrigine augmentation to divalproex yielded 8 months of remission in a 25-year-old man with BD II and a long-standing pattern of 3 days of hypomania followed by 5 days of depression²⁴	No large-scale or randomized trials
Topiramate	Single case report in URC describing reduction of cycling frequency over 3 years²⁵	Multiple large scale placebo-controlled studies in bipolar mania have been negative
Second-generation antipsychotics	No controlled trials or case reports	Possible anti-cycling benefits relevant for URC could be inferred from post hoc studies in RC
Combinations of ≥2 mood stabilizing drugs	No controlled trials or case reports	Combining multiple anti-cycling agents is intuitively logical but largely unstudied
Nimodipine	1 unipolar and 11 BD patients treated in randomized, off-on-off-on fashion (begun at 90 mg/d, increased up to 720 mg/d, mean duration of 12 weeks on active drug)²⁶	Response in 5 of 9 completers. Findings await replication with larger sample sizes
Hypermetabolic thyroid hormone (levothyroxine)	Findings from a small (N = 11) study of adjunctive high-dose levothyroxine (0.15 to 0.4 mg/d, with dosages increased by 0.05 to 0.1 mg/d every 1 to 2 weeks); an unspecified subgroup had “a very rapid cycling pattern” (reviewed by Bauer et al²¹)	10 of 11 RC patients had reductions in depressive symptoms, 5 of 7 had improvement from baseline manic symptoms (observation period >60 days)
ECT	Case reports of improvement with ECT in refractory RC that was presumed secondary to tricyclic antidepressants	Reports of induction of URC by ECT²²; whether or not ECT would more likely improve or exacerbate cyclicity for a given patient may require empirical determination
BD: bipolar disorder; BD II: bipolar II disorder; ECT: electroconvulsive therapy; RC: rapid cycling; URC: ultra-rapid cycling

Treatment monitoring. Prospective life charting allows patients to systematically record manic/hypomanic and depressive symptoms day-to-day and week-to-week, thus creating a measure that may be particularly relevant for patients whose moods change rapidly. Simple mood charts (see Related Resources) typically take into account the severity of symptoms of either polarity with ratings of mild, moderate, or severe. Such visual records permit simple calculations over the course of a given interval (eg, week-by-week or across months) of several important parameters, including:

number of days euthymic
number of days with depression
number of days with abnormal mood elevation
number of occasions in which moods of both polarities occur on the same day.

Clinical Point

Prospective life charting helps clinicians determine whether meaningful changes are occurring in cyclicity

Tracking these parameters during a treatment allows clinicians to make quantitative comparisons over time as a method of determining whether or not meaningful changes are occurring in cyclicity. See the figure below for an example of a completed mood chart and its interpretation.

Additional recommendations for assessing and managing cyclicity in BD are summarized in Table 3.

Table 3

Tips for managing suspected ultra-rapid cycling BD

Do’s	Don’ts
Ascertain a history of ≥1 lifetime manic or hypomanic episode to diagnose BD	Diagnose BD solely on the presence of rapid mood fluctuations
Determine the presence of changes in sleep, energy, speech-language, and related behavior as correlates of mood to differentiate syndromes from isolated variation in mood	Ignore constellations of associated signs and symptoms of mania/hypomania
Obtain patient history to assess for head trauma or other medical and neurologic events that could have affective or other psychiatric manifestations	Disregard possible medical etiologies for new-onset affective dysregulation
Ascertain the resolution of 1 episode before counting the resurgence of symptoms as constituting a new episode; a waxing and waning course may reflect illness chronicity with incomplete recovery rather than true cyclicity	Misidentify incomplete recovery from an existing episode as the occurrence of new multiple episodes, which would inflate false-positive cases of RC or URC
Advise patients to refrain from alcohol or illicit substances that could destabilize mood	Assume that comorbid alcohol or illicit substance abuse will remit only after mood stabilization has been achieved, rather than the reverse
Monitor changes in sleep-wake cycles and the effects of erratic sleep or sleep deprivation on mood	Ignore the effects of poor sleep hygiene on mood
Minimize antidepressant exposure in patients with RC or URC	Continue long-term antidepressant maintenance therapy in patients with manic or mixed features or ongoing oscillations between mania/hypomania and depression
Assure euthyroid status and consider the potential utility of hypermetabolic levothyroxine	Assume that RC or URC will resolve solely by normalizing or optimizing thyroid function
Use rational, pharmacodynamically nonredundant anti-cycling drugs	Ignore the cumulative burden of adverse effects of multiple drugs
Consider the potential role for ECT as a strategy to arrest URC during any phase of BD	Assume ECT has value only during acute depressive phases of BD
Use prospective mood charting to document the evolution of mood changes over time, particularly when gauging treatment efficacy	Rely solely on impressionistic recall of mood states or polarity changes as reflecting distinct phasic changes
BD: bipolar disorder; ECT: electroconvulsive therapy; RC: rapid cycling; URC: ultra-rapid cycling