Role of adjunctive nonpharmacological strategies for treatment of rapid-cycling bipolar disorder

Table 1 Studies of adjunctive electroconvulsive therapy in rapid-cycling bipolar disorder

Ref.	Sample	Results
Case reports
Berman and Wolpert[56], 1987	18-yr-old woman with medication-resistant RCBD	ECT during mania led to complete remission, which was maintained for 14 mo without medications
Mizukawa et al[57], 1991	81-yr-old woman with medication-resistant ultra-RCBD	ECT did not prevent the recurrence of episodes over a period of 35 yr of observation
Benjamin and Zohar[58], 1992	45-yr-old man with treatment-resistant RCBD	Depressive episodes responded transiently to total sleep deprivation and psychotherapy but complete remission was only achieved with acute ECT
Kho[59], 2002	79-yr-old woman with medication-resistant RCBD	ECT and lithium was used successfully during acute and maintenance treatment
Zavorotnyy et al[60], 2009	63-yr-old woman with medication-resistant bipolar disorder	The patient developed ultra-rapid cycling during acute ECT, which responded to the continuation of ECT and addition of lithium
Amino et al[61], 2011	63-yr-old woman with medication-resistant RCBD	Continuation-ECT for 12 mo prevented rehospitalization
Huber and Burke[62], 2015	67-year-old woman with medication-resistant ultra-RCBD	ECT was used to successfully treat depression and manic episodes that developed on discontinuation of lithium
Kranaster et al[63], 2017	21-yr-old woman with medication-resistant ultra-RCBD	ECT was used to successfully treat a treatment-resistant depressive episode
Observational studies
Kukopulos et al[64], 1980	87 patients with RCBD	11 patients treated only with ECT for 7–35 yr remained in remission for long periods
Kukopulos et al[65], 1983	87 patients with RCBD	ECT was more effective than antidepressants in treating severe depression and when combined with lithium led to longer remissions
Wehr et al[66], 1988	24 patients with medication-resistant RCBD	None of the patients remitted with ECT
Mosolov and Moshchevitin[67], 1990	8 patients with mood stabilizer-resistant RCBD	Acute ECT lead to remission for 6 mo in 3 patients. The number of episodes and the time spent in mood episodes was reduced. Mood stabilizers were more effective following acute ECT treatment
Vanelle et al[68], 1994	Four patients with medication-resistant RCBD	Maintenance ECT for 18 mo led to full or partial remission in all 4 patients. Time spent in the hospital was reduced. Response was better in depressive episodes with psychotic symptoms
Wolpert et al[69], 2013	Six patients with continuous cycling	ECT started early in the course of cycling was effective in reducing recurrences
Koukopoulos et al[70], 2003	43 patients of RCBD who received ECT	11 patients remitted with ECT and mood stabilizer combinations and maintained in this state for 2–36 yr. Temporary improvement was noted in the others. Two out of 3 patients on maintenance ECT had good response
Minnai et al[71], 2011	14 patients with medication-resistant RCBD treated with maintenance ECT. Comparisons of 2-yr periods before and after ECT	All patients improved. Eight did not relapse over 2 yr and 6 had only one episode annually. Time spent ill was reduced and interepisodic periods were longer. Young males with type II BD and hyperthymic temperament had better outcome
Mosolov et al[72], 2021	1-year prospective study of 30 patients with RCBD and ultra RCBD with poor response to mood stabilizer treatment. Comparisons of 1-yr periods before and after acute ECT	40% achieved and maintained remission with ECT and lithium treatment; 30% showed partial response with the combination and 30% did not respond. Duration of mood episodes was significantly reduced with ECT. Mixed depression with/without catatonia had better response to acute ECT

ECT: Electroconvulsive therapy; RCBD: Rapid-cycling bipolar disorder; type II BD: Bipolar disorder type II; Ultra-RCBD: Ultra-rapid-cycling with shorter cycles of days to weeks; Ultradian-RCBD: Ultradian rapid-cycling with episodes lasting less than a day.

Table 2 Studies of adjunctive chronotherapy in rapid-cycling bipolar disorder

Ref.	Sample	Results
Case reports
Christodoulou et al[131], 1978	26-yr-old woman with rapid-cycling episodes of severe recurrent depression resistant to medications	Inpatient and outpatient total sleep deprivation every week for 36 wk led to remission for a period of 10 mo. The patient committed suicide after stopping the maintenance sleep deprivation treatments
Lovett Doust and Christie[132], 1980	48-yr-old woman with medication-resistant RCBD	Five nights of total sleep deprivation combined with medications during depressive episodes for 8 mo led to reduction in intensity and duration of depression. Switches into hypomania were recorded
Churchill and Dilsaver[133], 1990	47-yr-old woman with rapid-cycling episodes of severe recurrent depression	Partial sleep deprivation on alternate nights combined with an antidepressant led to complete remission from depression for 6 wk
Benjamin and Zohar[58], 1992	45-yr-old man with treatment-resistant RCBD resistant to antidepressants	One night of sleep deprivation was successful in aborting depressive episodes, but led to prolonged hypomania on one occasion and did not prevent the rapid-cycling pattern
Gann et al[134], 1993	64-yr-old man with ultradian-RCBD	Total sleep deprivation for 3 nights led to reduction of depressive symptoms for 2 wk. Further improvement occurred with carbamazepine
Eagles[135], 1994	50-yr-old man with medication-resistant ultradian-RCBD	Daily morning BLT for 2 mo produced sustained remission without hypomanic switches
Kusumi et al[136], 1995	2 patients with medication-resistant RCBD and nonseasonal depressions	Morning BLT led to improvement in sleep and mood. Withdrawal of BLT did not result in relapse. Remission was maintained for several months
Wehr et al[137], 1998	51-yr-old man with medication-resistant RCBD treated with 10–14 h of darkness, rest, and sleep over 1.5 yr	Dark therapy helped in stabilizing sleep, reducing hypomanic symptoms, and attenuating rapid cycling for the period of treatment. Lower doses of antipsychotics were required and hospital stay was shorter
Wirz-Justice et al[138], 1999	70-yr-old woman with medication-resistant ultra-RCBD	Rapid-cycling ceased on initiation of 10–14 h of darkness, rest, and sleep. Depression improved with mid-day BLT and remission was achieved with morning BLT. Patient remained on valproate and was stable for a year
Leibenluft and Suppes[127], 1999	42-yr-old woman with medication resistant ultra-RCBD	A lifestyle intervention that ensured a regular sleep–wake schedule in combination with medications led to decrease in rapid cycling
Observational studies
Papadimitriou et al[139], 1981	5 patients with treatment-resistant RCBD	Weekly regimens of total sleep deprivation administered over several months reduced relapses and increased the duration of remissions
Wehr et al[140], 1982	9 patients with RCBD treated with 1 night of total sleep deprivation during depressive episodes	Depressive symptoms improved in 8 patients with sleep deprivation but 7 developed mania or hypomania
Papadimitriou et al[141], 1993	5 medication-free patients with RCBD treated with total sleep deprivation twice a week for 4 wk	All 5 patients responded to sleep deprivation treatment with > 50% improvement in depressive symptoms and remained in remission for a year with weekly sleep deprivation treatments. Rapid-cycling, young age, female sex, family history of mood disorder and illness duration < 10 yr predicted response. Hypomania was observed in 1 patient
Gill et al[142], 1993	3 patients with treatment-resistant RCBD treated with total sleep deprivation and mood stabilizers and antidepressants	Duration of response was significantly better when sleep deprivation treatment was administered late rather than early in the depressive episodes
Leibenluft et al[143], 1995	9 patients with RCBD treated with 3 mo of BLT and medications versus 3 mo of only medication treatment	Mid-day BLT was more effective in reducing depressive symptoms and days spent depressed than morning or evening BLT. Morning BLT precipitated hypomanic switches
Koukopoulos et al[70], 2003	2 women with RCBD	Sleep deprivation resulted in a temporary improvement of depression

BLT: Bright light therapy; RCBD: Rapid-cycling bipolar disorder; Ultra-RCBD: Ultra-rapid-cycling with shorter cycles of days to weeks; Ultradian-RCBD: Ultradian rapid-cycling with episodes lasting less than a day; Partial sleep deprivation: Sleep deprivation during the second half of the night; Total sleep deprivation: Sleep deprivation for 36 h.

Table 3 Studies of adjunctive psychotherapy in rapid-cycling bipolar disorder

Ref.	Type of study	Sample	Intervention	Results
Levy and Remick[51], 1986	Observational study	8 women with RCBD	Supportive psychotherapy with patients and family regarding treatment response and adherence	Complete remission in 5 patients and partial remission in 3 patients for 7–40 mo with combined psychotherapy and medications
Spurkland and Vandvik[150], 1989	Case report	13-yr-old girl with RCBD	Family therapy to reduce conflicts and improve adherence	Family therapy combined with medications led to lasting remission
Benjamin and Zohar[58], 1992	Case report	45-yr-old man with treatment-resistant RCBD	Supportive psychotherapy	Psychotherapy provided relief from the rapid-cycling pattern for 3 mo
Satterfield[151], 1999	Case report	33-yr-old man with medication-resistant RCBD	Pharmacotherapy and concomitant CBT	Significant reductions in the severity of manic, depressive, and anxiety symptoms with adjunctive CBT
Reilly-Harrington et al[152], 2007	Uncontrolled trial	10 patients with RCBD	CBT included psychoeducation, cognitive restructuring, and teaching illness-management skills	CBT over 5 mo led to significant improvements in depressive symptoms for 2 mo after the treatment in 6 patients who completed the trial
Lenz et al[153], 2016	Controlled trial	16 patients with RCBD; 14 wk of adjunctive psychotherapy and 12-mo follow-up	CPT vs BT. CPT included psychoeducation and CBT; BT consisted of reading and discussing a book on bipolar disorder	Significant effects of both treatments - reductions in illness severity, reductions in the number of all episodes with CPT and depressive episodes with BT, reductions in the number and duration of hospitalizations, reductions in disability, and improvement in medication adherence and illness concepts. CPT was better than BT

BT: Bibliotherapy; CBT: Cognitive behavioural therapy; CPT: Cognitive psychoeducational therapy; RCBD: Rapid-cycling bipolar disorder.

Table 4 Suggestions for the use of adjunctive nonpharmacological treatments in rapid-cycling bipolar disorder

	Suggestions
Goals of acute treatment[18,45]	The priority for acute treatment is to ensure that patients respond to treatment and no longer meet criteria for an acute mood episode
	A rapid response is necessary to provide relief for patients and their families and reduce the risks of self-harm, aggression, and physical complications
	The concurrent and early use of treatments such as ECT or wake therapy for depression, and dark therapy for mania may be considered if there is inadequate response to pharmacotherapy
	Treatments that are likely to be useful during long-term treatment should guide the use of treatments in the acute phases
Goals for long-term treatment[29,30,45,51,55]	Rather than focusing on acute treatment, the primary objective should be to prevent further episodes of rapid cycling
	The model for a chronic medical disorder with acute exacerbations should guide the long-term treatment plan for RCBD
	Adjunctive maintenance ECT, wake therapy, bright light treatment, dark therapy, and triple chronotherapy can be considered at this stage
	Education, support, and the involvement of the family is useful for all patients. Psychoeducational treatments, CBT, family treatment can be implemented if required
Improved functioning rather than complete remission should be the goal of long-term treatment[18,20,25,30]	Full remission and complete absence of recurrences is an unrealistic goal
	Clinicians should focus on an enduring response that consists of reduced frequency, intensity, and duration of mood episodes
	Clinicians should attempt to restore optimal functioning in the occupational, family, and social spheres
Basic tasks[2,4,54,55,162]	Careful diagnosis and comprehensive assessment of the patient including psychosocial factors
	Avoidance of precipitants such as stress, irregular sleep routines, and antidepressant medications when it worsens the course of RCBD
	Treatment of physical and psychiatric comorbidities especially hypothyroidism and substance use
Longitudinal approach and use of life charts[2,26,45,55,163]	Acute episodes should be viewed in the context of the long-term course of bipolar disorder/RCBD
	Life charts may be used to delineate the course of illness, possible precipitants, and treatment response. They might help patients and families understand the course of RCBD and the longitudinal approach to treatment
Use of treatments effective in bipolar disorder[27,30,45,49]	Options for adjunctive nonpharmacological treatment should be chosen based on the evidence for their efficacy in BD
Sequential trials of treatment for long durations[25-27,30,51]	Treatment of RCBD requires several trials of each treatment regimen lasting for about 3–4 mo before the acute-phase efficacy of the treatment regimen can be determined
	Frequent changes in treatment should be avoided since they might worsen rapid cycling
Combining pharmacological and nonpharmacological treatments[25,30,32,45,163]	One option is to add nonpharmacological treatments only in refractory patients in whom several medications have been tried and have failed
	An alternative option recommends the early use of adjunctive nonpharmacological patients even in those patients who are not medication resistant
Monitoring treatment response[17,18,25,35,51]	More intensive monitoring during acute phases which can be relaxed once the patient becomes more stable
	Mood charts can be used to assess response to treatment
	At least 12 mo of treatment is required to determine the efficacy of long-term treatment
Working with patients and families[4,32,45,51,127]	Education: explaining RCBD, its causes, and the treatment approach including lifestyle changes is necessary for ensuring the collaboration of patients and families. Psychoeducational treatments that reduce stress, improve attitudes to treatment, enhance treatment engagement, and reduce caregiver burden can be tried. CBT is another option
	Support: ongoing support for patients and families is essential. This can be provided by developing a strong collaborative relationship. Nonadherence can also be addressed by fostering a strong treatment alliance
	Patience: the protracted nature of the illness requires the clinician to accept that it will take a long time for the results to become apparent. Patience and perseverance on the part of patients and families has to be stressed repeatedly so that they learn to focus on long-term goals
	Sleep hygiene: regular sleep routines can be advised in all patients. Chronotherapeutic techniques can be tried when required and feasible

CBT: Cognitive behavioural therapy; ECT: Electroconvulsive therapy; RCBD: Rapid-cycling bipolar disorder.