Effectiveness of BBT-I and Zopiclone for Chronic Insomnia

Effectiveness of Nonspecific Methods of Treatment and Zopiclone for Chronic Insomnia

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03339583

Enrollment

Registered

2017-11-13

Start date

2015-04-07

Completion date

2017-03-14

Last updated

2019-09-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Insomnia Chronic

Keywords

chronic insomnia, brief behavioral treatment, behavioral treatment, insomnia severity index, predictors, treatment response

Brief summary

Background: Importance of chronic insomnia (CI) problem is determined by its high prevalence rate, comorbidity and resistance to the treatment. Although cognitive behavior treatment of insomnia (CBT-I) remains the recommended treatment for CI it has disadvantages of time consuming and low treatment response. Hence shortened and simplified behavioral approaches such as Brief Behavioral therapy of insomnia (BBT-I) are developed. The aim of the present study is to test the effectiveness of BBT-I program for chronic insomnia in comparison with zopiclone in Russian population. The anthropometric, psychological and polysomnographic characteristics of patients were measured to find predictors of effectiveness of each method. Participants: 42 adults (14 males, 28 females, mean age 54 years) meeting the criteria for CI according International classification of sleep disorders-3 Methods: Participants were randomized into two groups. Each group passed 2-week courses of treatment by brief behavior treatment of insomnia (BBT-I) and zopiclone in different orders with 2-week washout period between the courses. Participants underwent in-lab polysomnography prior to the treatment and completed questionnaires (Insomnia Severity Index (ISI), Dysfunctional beliefs about sleep scale (DBAS), Beck Depression Inventory (BDI) and others) in the beginning and the end of each course

Detailed description

The study had a crossover design implying that every patient underwent two different treatment courses in random sequence: hypnotic or structured educational program (BBT-I) delivered in two sessions. Each treatment course was separated by 2-weeks washout period that provided the opportunity to evaluate the sustainability of treatment effect. Before and after each treatment course and after each washout period subjects completed set of questionnaires. The total duration of the study was 8 weeks in which 6 visits including 1 night polysomnography (PSG), 2 face-to-face structured educational program sessions and 5 diagnostic interviews have been performed. Participants A sample of 42 adults (14 males, 28 females, mean age 54 years from 29 to 80 years) meeting the criteria for chronic insomnia according ICSD-3 was recruited from outpatient care of Department of sleep medicine of University Hospital №3 of I.M. Sechenov First Moscow State Medical University. All participants were informed about the nature, purpose, risks, and discomforts that could arise from their participation, and about their right to withdraw at any time. Subjects documented their willingness to participate by signing the informed consent form, approved by local Ethic Committee. Treatment methods. BBT-I program includes two weekly one hour individual sessions; Hypnotic (zopiclone) in a dose of 7,5 mg has to be taken 30 minutes before bedtime for two weeks Measures Questionnaires. During the first visit patients underwent structured clinical interview and filled in self-report questionnaires: Beck Depression Inventory (BDI), State-trait anxiety inventory (STAI), Toronto Alexithymia Scale - short version (TAS-20) , Big Five Questionnaire (BFQ-2R), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Dysfunctional beliefs about sleep scale (DBAS), Sleep hygiene index (SHI). During the next 4 visits participants repeatedly underwent diagnostic tests included BDI, STAI, PSQI, ISI, DBAS, SHI. Participants kept daily sleep diaries where they recorded bedtime and morning rise time, sleep onset latency (SOL), number of night awakenings and time of wakefulness after sleep onset before waking up (WASO) for the whole study period. On the last visit participants completed questionnaire for assessment of effectiveness of treatment along with diagnostic routine. Patients were asked to rank the effectiveness of proposed methods of treatment (didactic presentation, stimulus control, sleep restriction, relaxing recording and zopiclone) in ascending order from 1 to 5 points (5 seems most effective). Polysomnography. Participants underwent in-lab PSG (1 night without adaptation night) prior to the treatment in order to exclude other disorders producing subjective sleep complaints (sleep apnea, periodic limb movements disorder). Standard polysomnography montage including 6 monopolar electroencephalography (EEG) channels; 1 submental electromyogram (EMG) channel; 2 electrooculogram (EOG) channels; 2 EMG channels of the right and left tibialis anterior muscles; 1 electrocardiogram channel; oronasal airflow pressure; thoracic and abdominal efforts; respiratory sound; oxygen saturation; body position with videomonitoring was performed. The objective sleep measures included total sleep time (TST), sleep-onset latency, wake time after sleep onset (WASO), number of awakenings, sleep efficiency (the ratio of TST to time spent in bed multiplied on 100%, SE), percentage of sleep stages. PSG data were analysed according the 2007 American Academy of Sleep Medicine criteria including its revision in 2012.

Interventions

BEHAVIORALBrief behavioral therapy

program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording Relaxation and refreshment session for insomnia created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off.

DRUGZopiclone

zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Study design implied that every patient underwent two different treatment courses in random sequence: hypnotic or structured educational program (BBT-I) delivered in two sessions. Subjects were randomly assigned to one of treatment sequences by card sorting method. Patients of the zopiclone-first group underwent the medication therapy for the first two weeks followed by educational program. Patients of the BBT-I-first group received two-week educational program followed by medication therapy. Each treatment course was separated by 2-weeks washout period that provided the opportunity to evaluate the sustainability of treatment effect. Before and after each treatment course and after each washout period subjects completed set of questionnaires.

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

meeting the criteria for chronic insomnia according ICSD-3 willingness to take part in the study and signed informed consent form

Exclusion criteria

1. unability to stop taking medications that have a proven impact on sleep at least one week before and during the study; 2. history of alcohol or drug abuse; 3. major depressive disorder or other severe mental disorder identified by a clinical assessment and medical history; 4. dementia; 5. pregnancy or lactation; 6. shift or night work; 7. medical problems that would be a direct cause of sleep complaints: moderate/severe sleep apnea, defined as an apnea-hypopnea index of ≥15 events per hour, periodic limb movement disorder defined as a periodic leg movement index ≥15 events per hour or restless legs syndrome; 8. other serious chronic conditions or exacerbation of chronic disorder preventing further participation.

Design outcomes

Primary

Measure	Time frame	Description
Insomnia Severity Index	For BBT-I-first group: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/Month 1); For zopiclone-first group: after washout period (Day 28/Week 4/Month 1) after second treatment course (Day 42/Week 6/Month 2)	self reported insomnia symptoms severity by Insomnia severity index . Each item is scored 0 (no problem) - 4 (very big problem) with total between 0-28 (absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).

Secondary

Measure	Time frame	Description
State Anxiety Subscale (STAI)	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)	State trait anxiety scale is a 2-part questionnaire assessing state (situational) and trait anxiety. State anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms
Dysfunctional Beliefs About Sleep Scale	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)	questionnaire assessing sleep related cognitions in 16 item rated on a 10-point Likert scale. Minimum score is 0, maximum score is 160 points. Higher total score represents more intensive disfunctional beliefs
Beck Depression Inventory	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)	21-item questionnaire assessing (on 4-point Likert scales) the intensity of depressive symptoms in the past week. Minimum score 0, maximum score 63 points. Higher total score represents more severe depressive symptoms
Pittsburgh Sleep Quality Index	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)	19-item questionnaire evaluating sleep quality over the past month. The first 4 items are open questions, items 5 to 19 are rated on a 4-point Likert scale. A total score range from 0 to 21. A score \> 5 suggests poor sleep quality.
Trait Anxiety Subscale (STAI)	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)	STAI is a 2-part questionnaire assessing state (situational) and trait anxiety. Trait anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for each subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms
Sleep Hygiene Index	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)	questionnaire assessing sleep related behavior in 13 item rated on a 5-point Likert scale.Minimum score 13 points and maximum score 65 points. Higher total score represents worse sleep hygiene

Other

Measure	Time frame	Description
N2 NREM Sleep Percentage	once at baseline assessment	Percentage of Total Sleep Time
Toronto Alexithymia Scale (TAS-20)	once at baseline assessment	Degree of alexithymia evaluated by Toronto Alexithymia scale (20 questions) Measure Description: 0-100 scores. higher values represent worse outcome
REM Sleep Percentage	once at baseline assessment	Percentage of Total Sleep Time
N3 NREM Sleep Percentage	once at baseline assessment	Percentage of Total Sleep Time
Sleep Latency	once at baseline assessment	time period from bedding to sleep onset
Total Sleep Time	once at baseline assessment	total sleep episode minus wake time
Sleep Efficiency	once at baseline assessment	Prercentage of Total Bed Time
Wake After Sleep Onset	once at baseline assessment	total duration of all periods of wakefulness between sleep onset and final awakening in the morning
Amount of Awakenings	once at baseline assessment	Number of awakenings between sleep onset and final morning awakening
N1 NREM Sleep Percentage	once at baseline assessment	Percentage of Total Sleep Time

Participant flow

Pre-assignment details

The decision to recruit more patients than it was stated in protocol was made because of dropout of 3 patients and in order to get enough experimental data to provide statistical power

Participants by arm

Arm	Count
Zopiclone First Group underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording Relaxation and refreshment session for insomnia created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	19
BBT-I First Group received two-week brief behavioral therapy followed by medication therapy (zopiclone). Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording Relaxation and refreshment session for insomnia created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	23
Total	42

Withdrawals & dropouts

Period	Reason	FG000	FG001
First Intervention (14 Days)	Adverse Event	1	0
Follow-up (14 Days)	Physician Decision	6	3
Second Intervention (14 Days)	Adverse Event	0	1
Second Intervention (14 Days)	unrelated acute exacerbation	0	1

Baseline characteristics

Characteristic	BBT-I First Group	Zopiclone First Group	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	3 Participants	6 Participants	9 Participants
Age, Categorical Between 18 and 65 years	20 Participants	13 Participants	33 Participants
Age, Continuous	47.5 years STANDARD_DEVIATION 14.1	55.0 years STANDARD_DEVIATION 14.8	50.7 years STANDARD_DEVIATION 14.5
Awakenings	13.3 awakenings STANDARD_DEVIATION 6.9	13.8 awakenings STANDARD_DEVIATION 6.1	13.5 awakenings STANDARD_DEVIATION 6.5
Beck depression inventory	12.8 units on a scale STANDARD_DEVIATION 7.2	10.8 units on a scale STANDARD_DEVIATION 5	12.1 units on a scale STANDARD_DEVIATION 6.1
Dysfunctional beliefs about sleep scale	104.9 units on a scale STANDARD_DEVIATION 30.2	105.3 units on a scale STANDARD_DEVIATION 28.7	105.1 units on a scale STANDARD_DEVIATION 27.2
Insomnia severity index	17.5 units on a scale STANDARD_DEVIATION 5.4	18.7 units on a scale STANDARD_DEVIATION 4.1	18.6 units on a scale STANDARD_DEVIATION 4.6
N1 NREM sleep percentage	3.7 percentage of time STANDARD_DEVIATION 3.3	4.2 percentage of time STANDARD_DEVIATION 3.1	3.9 percentage of time STANDARD_DEVIATION 3.2
N2 NREM sleep percentage	62.6 percentage of time STANDARD_DEVIATION 8.4	64.2 percentage of time STANDARD_DEVIATION 10.2	63.3 percentage of time STANDARD_DEVIATION 9.2
N3 NREM sleep percentage	16.4 percentage of time STANDARD_DEVIATION 7	17.5 percentage of time STANDARD_DEVIATION 8.8	16.9 percentage of time STANDARD_DEVIATION 7.8
Pittsburgh sleep quality index	14.5 units on a scale STANDARD_DEVIATION 2.7	13.3 units on a scale STANDARD_DEVIATION 3.5	14.0 units on a scale STANDARD_DEVIATION 3.1
Race and Ethnicity Not Collected	—	—	0 Participants
Region of Enrollment Russia	23 Participants	19 Participants	42 Participants
REM sleep percentage	17.0 percentage of time STANDARD_DEVIATION 7.7	14.1 percentage of time STANDARD_DEVIATION 5.5	15.6 percentage of time STANDARD_DEVIATION 6.8
Sex: Female, Male Female	16 Participants	11 Participants	27 Participants
Sex: Female, Male Male	7 Participants	8 Participants	15 Participants
Sleep efficiency	63.3 percentage of polysomnogram time STANDARD_DEVIATION 18	64.68 percentage of polysomnogram time STANDARD_DEVIATION 17.9	63.9 percentage of polysomnogram time STANDARD_DEVIATION 17.7
Sleep hygiene index	28.7 units on a scale STANDARD_DEVIATION 7.3	26.7 units on a scale STANDARD_DEVIATION 6.3	27.9 units on a scale STANDARD_DEVIATION 6.1
sleep latency	54.5 minutes STANDARD_DEVIATION 51	38.5 minutes STANDARD_DEVIATION 21.7	47.0 minutes STANDARD_DEVIATION 40.2
State anxiety inventory	46.9 units on a scale STANDARD_DEVIATION 6.9	43.5 units on a scale STANDARD_DEVIATION 8.7	45.3 units on a scale STANDARD_DEVIATION 8.1
Toronto Alexithymia scale-20	49.3 units on a scale STANDARD_DEVIATION 10	49.8 units on a scale STANDARD_DEVIATION 15.9	49.5 units on a scale STANDARD_DEVIATION 12.9
Total sleep time	5.5 hours STANDARD_DEVIATION 1.6	5.7 hours STANDARD_DEVIATION 1.6	5.6 hours STANDARD_DEVIATION 1.6
trait anxiety inventory	49.1 units on a scale STANDARD_DEVIATION 7.2	49.6 units on a scale STANDARD_DEVIATION 8.3	49.3 units on a scale STANDARD_DEVIATION 7.5
Wake after sleep onset	104.8 minutes STANDARD_DEVIATION 76.1	102.4 minutes STANDARD_DEVIATION 69	103.6 minutes STANDARD_DEVIATION 71.9

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 42	0 / 41
other Total, other adverse events	0 / 42	2 / 41
serious Total, serious adverse events	0 / 42	0 / 41

Outcome results

Primary

Insomnia Severity Index

self reported insomnia symptoms severity by Insomnia severity index . Each item is scored 0 (no problem) - 4 (very big problem) with total between 0-28 (absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).

Time frame: For BBT-I-first group: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/Month 1); For zopiclone-first group: after washout period (Day 28/Week 4/Month 1) after second treatment course (Day 42/Week 6/Month 2)

Population: Participants dropped out during the first treatment course and therefore not completed the second treatment course were included only in the analysis for first treatment course and were not analyzed for treatment sequence effect

Arm	Measure	Group	Value (MEAN)	Dispersion
BBT-I First Group	Insomnia Severity Index	First treatment course	13.1 units on a scale	Standard Deviation 5.2
BBT-I First Group	Insomnia Severity Index	Second treatment course	12.1 units on a scale	Standard Deviation 6.1
BBT-I First Group	Insomnia Severity Index	After washout	14.3 units on a scale	Standard Deviation 6.3
BBT-I First Group	Insomnia Severity Index	After follow-up	13.1 units on a scale	Standard Deviation 4.7
BBT-I First Group	Insomnia Severity Index	Baseline/initial examination	18.6 units on a scale	Standard Deviation 5.2
Zopiclone First Group	Insomnia Severity Index	After follow-up	12.7 units on a scale	Standard Deviation 5.9
Zopiclone First Group	Insomnia Severity Index	Baseline/initial examination	18.9 units on a scale	Standard Deviation 3.9
Zopiclone First Group	Insomnia Severity Index	First treatment course	14.0 units on a scale	Standard Deviation 5.7
Zopiclone First Group	Insomnia Severity Index	After washout	16.1 units on a scale	Standard Deviation 4.7
Zopiclone First Group	Insomnia Severity Index	Second treatment course	12.8 units on a scale	Standard Deviation 5.4

Secondary

Beck Depression Inventory

21-item questionnaire assessing (on 4-point Likert scales) the intensity of depressive symptoms in the past week. Minimum score 0, maximum score 63 points. Higher total score represents more severe depressive symptoms

Time frame: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

Arm	Measure	Group	Value (MEAN)	Dispersion
BBT-I First Group	Beck Depression Inventory	first treatment course	8.4 units on a scale	Standard Deviation 6.8
BBT-I First Group	Beck Depression Inventory	Second treatment course	9.2 units on a scale	Standard Deviation 9
BBT-I First Group	Beck Depression Inventory	After washout	8.4 units on a scale	Standard Deviation 8.2
BBT-I First Group	Beck Depression Inventory	After follow-up	9.0 units on a scale	Standard Deviation 8.1
BBT-I First Group	Beck Depression Inventory	Baseline/initial examination	11.5 units on a scale	Standard Deviation 6.8
Zopiclone First Group	Beck Depression Inventory	After follow-up	7.4 units on a scale	Standard Deviation 6.2
Zopiclone First Group	Beck Depression Inventory	Baseline/initial examination	9.3 units on a scale	Standard Deviation 7.3
Zopiclone First Group	Beck Depression Inventory	first treatment course	9.4 units on a scale	Standard Deviation 8.2
Zopiclone First Group	Beck Depression Inventory	After washout	9.8 units on a scale	Standard Deviation 5.1
Zopiclone First Group	Beck Depression Inventory	Second treatment course	8.5 units on a scale	Standard Deviation 6.2

Secondary

Dysfunctional Beliefs About Sleep Scale

questionnaire assessing sleep related cognitions in 16 item rated on a 10-point Likert scale. Minimum score is 0, maximum score is 160 points. Higher total score represents more intensive disfunctional beliefs

Arm	Measure	Group	Value (MEAN)	Dispersion
BBT-I First Group	Dysfunctional Beliefs About Sleep Scale	First treatment course	83.8 units on a scale	Standard Deviation 34.8
BBT-I First Group	Dysfunctional Beliefs About Sleep Scale	Second treatment course	84.5 units on a scale	Standard Deviation 39.8
BBT-I First Group	Dysfunctional Beliefs About Sleep Scale	After washout	84.76 units on a scale	Standard Deviation 36.9
BBT-I First Group	Dysfunctional Beliefs About Sleep Scale	After follow-up	62.8 units on a scale	Standard Deviation 34.5
BBT-I First Group	Dysfunctional Beliefs About Sleep Scale	Baseline/initial examination	105.2 units on a scale	Standard Deviation 29
Zopiclone First Group	Dysfunctional Beliefs About Sleep Scale	After follow-up	92.0 units on a scale	Standard Deviation 34.5
Zopiclone First Group	Dysfunctional Beliefs About Sleep Scale	Baseline/initial examination	93.2 units on a scale	Standard Deviation 35
Zopiclone First Group	Dysfunctional Beliefs About Sleep Scale	First treatment course	96.4 units on a scale	Standard Deviation 36.4
Zopiclone First Group	Dysfunctional Beliefs About Sleep Scale	After washout	103.6 units on a scale	Standard Deviation 32.2
Zopiclone First Group	Dysfunctional Beliefs About Sleep Scale	Second treatment course	89.2 units on a scale	Standard Deviation 35.4

Secondary

Pittsburgh Sleep Quality Index

19-item questionnaire evaluating sleep quality over the past month. The first 4 items are open questions, items 5 to 19 are rated on a 4-point Likert scale. A total score range from 0 to 21. A score \> 5 suggests poor sleep quality.

Arm	Measure	Group	Value (MEAN)	Dispersion
BBT-I First Group	Pittsburgh Sleep Quality Index	After follow-up	11.2 units on a scale	Standard Deviation 4.9
BBT-I First Group	Pittsburgh Sleep Quality Index	Baseline/initial examination	13.4 units on a scale	Standard Deviation 3.6
BBT-I First Group	Pittsburgh Sleep Quality Index	First treatment course	10.5 units on a scale	Standard Deviation 4.5
BBT-I First Group	Pittsburgh Sleep Quality Index	After washout	11.3 units on a scale	Standard Deviation 4.4
BBT-I First Group	Pittsburgh Sleep Quality Index	Second treatment course	10.8 units on a scale	Standard Deviation 4.4
Zopiclone First Group	Pittsburgh Sleep Quality Index	Second treatment course	11.7 units on a scale	Standard Deviation 4.8
Zopiclone First Group	Pittsburgh Sleep Quality Index	After washout	12.7 units on a scale	Standard Deviation 3.8
Zopiclone First Group	Pittsburgh Sleep Quality Index	Baseline/initial examination	11.9 units on a scale	Standard Deviation 4.1
Zopiclone First Group	Pittsburgh Sleep Quality Index	After follow-up	11.1 units on a scale	Standard Deviation 4.7
Zopiclone First Group	Pittsburgh Sleep Quality Index	First treatment course	11.3 units on a scale	Standard Deviation 4.1

Secondary

Sleep Hygiene Index

questionnaire assessing sleep related behavior in 13 item rated on a 5-point Likert scale.Minimum score 13 points and maximum score 65 points. Higher total score represents worse sleep hygiene

Arm	Measure	Group	Value (MEAN)	Dispersion
BBT-I First Group	Sleep Hygiene Index	First treatment course	24.0 units on a scale	Standard Deviation 5.6
BBT-I First Group	Sleep Hygiene Index	Second treatment course	24.7 units on a scale	Standard Deviation 6.6
BBT-I First Group	Sleep Hygiene Index	After washout	24.7 units on a scale	Standard Deviation 6
BBT-I First Group	Sleep Hygiene Index	After follow-up	23.8 units on a scale	Standard Deviation 6.5
BBT-I First Group	Sleep Hygiene Index	Baseline/initial examination	26.8 units on a scale	Standard Deviation 7.4
Zopiclone First Group	Sleep Hygiene Index	After follow-up	25.2 units on a scale	Standard Deviation 7.6
Zopiclone First Group	Sleep Hygiene Index	Baseline/initial examination	25.2 units on a scale	Standard Deviation 5.9
Zopiclone First Group	Sleep Hygiene Index	First treatment course	25.0 units on a scale	Standard Deviation 6.9
Zopiclone First Group	Sleep Hygiene Index	After washout	25.5 units on a scale	Standard Deviation 7.4
Zopiclone First Group	Sleep Hygiene Index	Second treatment course	24.3 units on a scale	Standard Deviation 6.6

Secondary

State Anxiety Subscale (STAI)

State trait anxiety scale is a 2-part questionnaire assessing state (situational) and trait anxiety. State anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms

Arm	Measure	Group	Value (MEAN)	Dispersion
BBT-I First Group	State Anxiety Subscale (STAI)	First treatment course	43.8 units on a scale	Standard Deviation 8.6
BBT-I First Group	State Anxiety Subscale (STAI)	Second treatment course	45.1 units on a scale	Standard Deviation 9.1
BBT-I First Group	State Anxiety Subscale (STAI)	After washout	45.5 units on a scale	Standard Deviation 9
BBT-I First Group	State Anxiety Subscale (STAI)	After follow-up	46.9 units on a scale	Standard Deviation 6.5
BBT-I First Group	State Anxiety Subscale (STAI)	Baseline/initial examination	45.1 units on a scale	Standard Deviation 8.8
Zopiclone First Group	State Anxiety Subscale (STAI)	After follow-up	44.2 units on a scale	Standard Deviation 10.4
Zopiclone First Group	State Anxiety Subscale (STAI)	Baseline/initial examination	43.2 units on a scale	Standard Deviation 8.5
Zopiclone First Group	State Anxiety Subscale (STAI)	First treatment course	44.3 units on a scale	Standard Deviation 9.1
Zopiclone First Group	State Anxiety Subscale (STAI)	After washout	44.5 units on a scale	Standard Deviation 9.8
Zopiclone First Group	State Anxiety Subscale (STAI)	Second treatment course	44.0 units on a scale	Standard Deviation 9.6

Secondary

Trait Anxiety Subscale (STAI)

STAI is a 2-part questionnaire assessing state (situational) and trait anxiety. Trait anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for each subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms

Arm	Measure	Group	Value (MEAN)	Dispersion
BBT-I First Group	Trait Anxiety Subscale (STAI)	First treatment course	48.3 units on a scale	Standard Deviation 8.1
BBT-I First Group	Trait Anxiety Subscale (STAI)	Second treatment course	46.3 units on a scale	Standard Deviation 9.5
BBT-I First Group	Trait Anxiety Subscale (STAI)	After washout	48.6 units on a scale	Standard Deviation 7.6
BBT-I First Group	Trait Anxiety Subscale (STAI)	After follow-up	46.3 units on a scale	Standard Deviation 8.6
BBT-I First Group	Trait Anxiety Subscale (STAI)	Baseline/initial examination	48.7 units on a scale	Standard Deviation 6.9
Zopiclone First Group	Trait Anxiety Subscale (STAI)	After follow-up	48.8 units on a scale	Standard Deviation 10.7
Zopiclone First Group	Trait Anxiety Subscale (STAI)	Baseline/initial examination	48.3 units on a scale	Standard Deviation 8.1
Zopiclone First Group	Trait Anxiety Subscale (STAI)	First treatment course	48.3 units on a scale	Standard Deviation 8.6
Zopiclone First Group	Trait Anxiety Subscale (STAI)	After washout	49.3 units on a scale	Standard Deviation 7
Zopiclone First Group	Trait Anxiety Subscale (STAI)	Second treatment course	48.5 units on a scale	Standard Deviation 8.3

Other Pre-specified