Table 4 Studies of actigraphic recordings of treatment outcome or course of illness in samples that include individuals diagnosed with bipolar disorders (BD)

Kupfer,

USA

(1974)

4

N = 11;

Bipolar Depression (N = 4) & Unipolar Depression (n = 7)

 ~ 52 ^b;

80%

3d at baseline & 3d at wk 3

Baseline (pre-treatment) mean levels of daytime motor activity in un-medicated unipolar depression > BD depression, with significant differences between 19:00 & mid-day (but not mid-day until 19:00)

BD cases treated with lithium; UP cases treated with amitriptyline

Post-treatment activity differences were no longer evident; (response in Unipolar Depression showed the greatest improvement in activity)

Weiss,

USA

(1974)

6

Mania (N = 3) & Bipolar Agitated Depression (N = 3)

 ~ 38 ^b;

66%

7-9d; additional recording

at 20 wks

3 manic inpatients were assessed pre-treatment; then all 6 inpatients were assessed before & after initiation of Lithium. Some individuals repeated actigraphy recordings at 5 months

Baseline (pre-treatment) levels of motor activity (counts per minute) in un-medicated mania > agitated depressed, with the most significant differences reported between 22:00 and 02:00 h

Heninger,

USA

(1977)

13

N = 15;

BD-I = 11;

BD-II = 2; Unipolar Disorder = 2

55^b

84%

2d pre-lithium & 2d at 2 wks

All participants were inpatients who initiated lithium treatment

Duration of sleep increased by > 60 min after starting lithium (~ 6.3 h to 7.5 h). When data were reviewed for mania and depression separately, individuals with mania showed reduction in motor activity in parallel with symptom reduction, whilst individuals with depression showed increased motor activity with reduction in symptoms

Kripke,

USA

(1978)

7

BD:

across episodes

28% ^b

3d

(repeated)

Adults assessed through complete cycles of mania and depression. In 5 individuals there was evidence that a circadian rhythm ‘free-ran’ fast & in 5 individuals, evidence suggested that lithium slowed a circadian rhythm. The authors concluded that the prophylactic benefit of lithium may derive from slowing or delaying an overfast circadian clock to prevent desynchronization

Wehr,

USA

(1980)#

10

Mania &

Bipolar Depression

 ~ 40^b

2d

Motor activity levels were significantly different across 24 h and indicated ‘phase advance’ of 1–3 h in mania or depression (compared with 14 HC)

Acrophase for motor activity was significantly earlier in Mania (13:37 h) & Depression (14:10 h) compared to HC (15:57 h)

Acrophase did not differ in 8 BD cases that were assessed in both the Manic & Depressive phases of illness

Godfrey,

New Zealand

(1984)

4

N = 9;

Unipolar Disorder = 5;

BD-II, Hypomania = 4

77%^b

Median

 ~ 12d

Inpatients wore an actiwatch during the daytime only for 7-27d of the admission. Data were also collected on 9 HC. Daytime activity level was lowest in Depression and highest in HC. During actigraphy, mean daytime activity level increased in Depression & reduced in Hypomania. Change in activity was not correlated with change in depressed mood (no measures reported for hypomania). However, patients continued to show much lower levels of activity compared with HC. (The study abandoned some speech recordings due to low cooperation by some hypomanic patients)

Wolff,

USA (1984)#

30

Mania,

Bipolar Depression or Euthymia

42 ± 13; 66%

3d

Intra-individual recordings demonstrated that:

Mean amount of motor activity in Mania > Depression with the most significant differences being early & later in the daytime

Activity levels did not differ significantly in Mania versus Euthymia

Total activity (count/24 h) in 18 HC > Euthymic BD

Joffe,

USA

(1987)

15

N = 19,

BD Depression = 15;

Unipolar Disorder = 2;

Schizoaffective = 1

43 ± 3; 58%

3d pre- & 3d post-initiation of -carbamazepine

Inpatients were included who began carbamazepine treatment after a placebo washout of > 2 wks; actigraphy was undertaken during washout and ~ 35 days later. 7 individuals (37%) met response criteria. Baseline patterns of motor activity were not significantly different in Responders vs. Non-responders

Mean 24 h activity increased over time (& mean depression score decreased), with a trend toward greater change in Responder. When time of day was considered, Responders showed higher activity from 13:00 h onwards, with significantly greater activity during evening & night-time

Klein,

USA

(1991)

4

BD,

in remission

Not reported^b

3d with lithium;

3d at ~ 3 wks post-lithium withdrawal

Long-term lithium was discontinued, and outpatients were followed for 3 months of placebo treatment and up to 12 months. Two individuals experienced manic relapse with symptoms commencing within 2 wks of discontinuation, 2 remained well. Relapse was characterized by fragmentation of sleep–wake patterns, disorganization of 24 h rest-activity cycles & increased motor activity, especially at night. The latter was accompanied by a marked reduction in SE

Klein,

USA

(1992)

10

BD,

in remission

49 ± 12^b

3d with lithium;

3d at ~ 3 wks post- lithium withdrawal

As with the previous publication, long-term lithium was discontinued, and outpatients were followed for 3 months of placebo treatment. Seven experienced manic relapse: 4 within 3 weeks and all 7 within 3 months of lithium discontinuation. These individuals had higher baseline levels of motor activity (daytime) even though asymptomatic and showed higher daytime & night-time activity (during follow-up) than individuals who remained well (N = 3)

Raoux,

France,

(1994)

5

N = 26;

Unipolar Depression = 21;

BD Depression = 5

44 ± 21; 77%

3d treatment-onset &

3d pre-discharge

Inpatients were assessed at beginning & end of admission for melancholic depression (median stay = 26d). All patients had current or past exposure to benzodiazepines. Diurnal hypoactivity, reduced amplitude & longer TST were found at admission. Overall activity level and amplitude increased by discharge. There was an inverse correlation between baseline activity level & clinical improvement (daytime hypoactivity), with a trend for Responders (N = 21) to a lower baseline activity levels than Non-responders (N = 5). Amplitude was a robust marker of response, but acrophase was difficult to interpret because of large intragroup phase variability (~ 25% showed a phase shift of ~ 1 hr)

Todder (2006) & Baune,

Germany

(2007)

6

N = 26;

Treatment-resistant depression:

Unipolar = 21;

BD-II = 6

49 ± 13; 58%

2 × 11d

with 6d gap

Todder reported 4-week follow-up of patients & 27 HC. Sleep parameters in patients showed significant change in the 1st week of follow-up (increased TST & reduced SOL). Even with depression improvement, many sleep parameters differed from HC

Baune reported the 4-week study of anti-depressant & quetiapine. At final follow-up, 16 individuals were classified as Responders. Amount of activity had increased significantly at follow-up (& depression score had decreased)

Benedetti,

Italy

(2007)

39

BD-I

Depression

44 ± 10; 54%

7d

Study examined antidepressant effects of sleep deprivation & light therapy; 14 individuals were receiving lithium (36%)

Responders (N = 26) & Non-responders (N = 13) did not differ on actigraphy parameters at baseline (although mesor was higher in Responders). Responders showed increase in daytime activity especially in the morning compared with Non-responders. Total sleep was shorter in Responders. Acrophase was advanced in Responders (of ~ 57 min) but delayed by 5 min in Non-responders

Salvatore,

USA (2008)#

36

BD-I: Mania/ Mixed States & Remission

44 ± 10; 81%

3d in episode & 3d in remission

BD-I cases were in and outpatients; 72% were prescribed lithium

36 acutely ill BD-I cases were compared with 32 HC at baseline. Then recordings from the BD-I cases when ill & in remission were compared

Manic cases showed phase advance (~ 2 h) compared with HC & lower amplitude (mesor & TST did not differ from HC)

Mean daytime activity (counts/minute were higher in HC (67 ± 10) than Mania/Mixed States (59 ± 32; but Mania ~ Remission (60 ± 11)

Total sleep was significantly longer in remission (Remission > HC; HC = Mania/Mixed States)

Acrophase was significantly earlier in Mania/Mixed States (14:01hrs) < Remission (14:26 h) < HC (16:05 h)

Scott,

UK

(2011)$

10

N = 18

Unipolar Disorder = 8;

BD-I = 10

43 ± 12;

60%

30-200d

Naturalistic longitudinal follow-up of individuals attending a lithium clinic who were invited to wear actiwatch for > 1 month (many continued for > 6 months)

Lower mean daytime activity (counts/minute) and variability in sleep pattern/duration (alongside psychological measures such as self-esteem) was associated with shorter time to hospital admission during ~ 15-month follow-up (but admissions according to polarity were not reported)

Kim,

(2014) & Hwang (2017)

South Korea

29

BD-II = 26;

BD Depression

36 ± 10; 55%

56d

Open label trial of lithium v. quetiapine (actual N for each group included in analyses varied slightly between the two publications). Individuals were drug free at baseline

Quetiapine group (N = 10–12): SE increased (~ 6%) & WASO decreased at 6 weeks follow-up & SE improvement maintained at final follow-up (8 weeks)

Lithium group (N = 15–17): Modest improvement in SE (~ 1.5%), other parameters showed some fluctuation without obvious improvement

Both quetiapine & lithium affected several circadian parameters, including peak activity time and robustness of circadian rhythm, but exerted different effects on acrophase; clinical depressive symptoms were associated with robustness of circadian rhythm during the 8-week treatment phase

Novak,

Czech Republic

(2014)

6

BD-I

 ~ 37 ^b;

66%

Median

 ~ 210d

8 individuals were recruited, 7 agreed to participate and 6 of them provided long-term recordings (5–80 months, but about 30% loss of data). 4 individuals reported no relapses, one reported 3 episodes (over 37 months) & one reported 14 (over 80 months). No manic relapses occurred

The best signal for identifying relapse was for IS (inter-daily stability)- a marker of regularity of rest-activity patterns (overall classification ~ 66%)

Kaplan,

USA

(2015)

75

N = 159,

BD- I = 143,

BD-II = 13;

BD NOS = 3

36 ± 11;

66%

7d

159 individuals with BD spectrum disorders were assessed for hypersomnia & followed-up at 7 months later (222 ± 73d). Baseline actigraphy recordings in 75 individuals identified 2 forms of hypersomnia: ‘long sleepers’ (although actigraphy showed these individuals spent longer in bed but did not have longer TST) and those with excessive sleepiness (lower daytime activity)

During follow-up, 21 individuals (17.5%) had a hypomanic/manic & 37 (30.1%) a major depressive episode. Self-reported ‘Excessive daytime sleepiness’ predicted relapse into hypomania/mania (p < 0.01); actigraphy was not used to directly assess objective markers of relapse

Gershon,

USA

(2016)

37

BD-I

35 ± 10;

62%

42d

Lower amount of daytime activity & later daily onset of activity were both associated with greater likelihood of onset of a depressive episode &/or increase in depressive symptom severity. Weaker evidence suggested a slightly elevated mid-day peak & less evening activity were also noted

Moon,

South Korea

(2016)

26

BD-I = 23

Manic = 21; Depressed = 4. (Manic & Depressive Episodes = 1)

30 ± 11;

62%

At admission; 2 wks, 4 wks & recovery

All BD cases were recruited during a hospital admission. Analyses included 26 manic and 5 depressive episodes. Final wake time was delayed by ~ 1 h and SE improved by ~ 4% during admission

Advanced phase was recorded in mania but returned to normal after treatment; likewise, delayed phase in depression returned to normal after treatment. These shifts led to BD cases more closely resembling HC (N = 18)

Phase advance or delay observed in biochemical rhythms (such as cortisol) were much greater than sleep–wake cycle changes identified by actigraphy

Bewernick,

Germany

(2017)

2

N = 16;

Unipolar Depression = 14;

BD Depression = 2

49 ± 9;

66%

7d

12 individuals (10 inpatients) completed the study. Actigraphy was not undertaken during sleep. Individuals with higher activity levels at baseline showed a larger reduction in symptoms of depression after one week. Change in severity of depression correlated with increased in amount of daytime activity (with significance for some but not all ratings). Activity also showed a lagged correlation with mood rating in the following hours (but not vice versa)

Duncan,

USA

(2017)

21

N = 51;

Bipolar Depression = 21;

Unipolar Depression = 30

 ~ 42;

59%

9d:

(4-days pre- & 5 days post-ketamine

Data from 51 trial participants receiving ketamine (21 responders; 30 non-responders) were compared with data from 38 who received placebo

Pre-ketamine infusion: evidence of phase advanced activity pattern (acrophase) & lower mesor (144 vs. 167) was associated with good response. Persistent response (day 1 & 3 post-infusion) was characterized by higher amplitude & increased mesor

Krane-Gartiser,

Norway (2018)

3

Series of BD-I cases with >  = 2 admissions (over 1–6 months)

 ~ 50^b

1d per admission

Intra-individual 24-h activity patterns for recurrences of the same polarity show similar patterns; but episodes with different polarity show intra-individual differences in activity patterns. Acute phases were characterized by greater variation between rest-activity and periods with distinct irregularity in activity (measured by sample entropy) in all cases

Averill,

New Zealand (2018)

2

N = 24;

22 Unipolar Depression;

2 BD Depression

38 ± 14;

37%

17d

Inpatients were recruited to a study of activity, psychomotor speed & treatment response; usable actigraphy data available from 16 individuals (2 receiving lithium)

Change in 24-h activity count was correlated with treatment response

Data from consumer grade activity monitor did not correlate with outcomes

Kaplan,

USA

(2018)

40

Inter-episode

BD I

(with insomnia)

39 ± 14;

70%

14d

(7d pre- & 7d post-intervention)

58 patients were randomized to a two-arm trial; 40 participated in a one session intervention experiment actigraphy data were available on 29

A behavioural intervention (Rise-Up: aimed at overcoming sleep inertia) was compared with a control condition (education: PE)

Individuals in the Rise-Up group were significantly more active in the 1^st hour upon waking compared to PE

Henriksen,

Norway (2020)

20

BD-I,

Mania

45 ± 13;

70%

2d (baseline & day 5)

The trail recruited 32 individuals: this study reports data for 20; 10 inpatients were allocated to the blue blocking glasses (BBG) & 10 to placebo glasses

60% of all cases were receiving lithium

At day 5: SE improved more in the BBG compared with the control group (4% v 0%). The BBG group showed lower activity count during the sleep period (L5) & lower WASO & a trend for lower FI

Knapen,

Netherlands

(2020)

14

BD-I

45 ± 12;

79%

 ~ 180d

Continuous monitoring of temporal relationship between sleep, daily rhythm (measured by actigraphy) and mood changes. Time-lagged association showed significant negative correlation between depression and fractal patterns of motor activity (a measure of rigidity or adaptability of physiological systems) with higher level of depression associated with greater rigidity (with 5–7-day delay)