Journal Pre-proof

The effect of cognitive behavioural therapy for insomnia on sedative-hypnotic use: A

narrative review

Alexander Sweetman, Stacey Putland, Leon Lack, R Doug McEvoy, Robert Adams,
Ron Grunstein, Nigel Stocks, Billingsley Kaambwa, Emer Van Ryswyk, Christopher
Gordon, Andrew Vakulin, Nicole Lovato
PII: S1087-0792(20)30147-7
DOI: https://doi.org/10.1016/j.smrv.2020.101404
Reference: YSMRV 101404

To appear in: Sleep Medicine Reviews

Received Date: 28 April 2020

Revised Date: 12 July 2020
Accepted Date: 26 July 2020

Please cite this article as: Sweetman A, Putland S, Lack L, McEvoy RD, Adams R, Grunstein R, Stocks
N, Kaambwa B, Van Ryswyk E, Gordon C, Vakulin A, Lovato N, The effect of cognitive behavioural
therapy for insomnia on sedative-hypnotic use: A narrative review, Sleep Medicine Reviews, https://
doi.org/10.1016/j.smrv.2020.101404.

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Title: The effect of cognitive behavioural therapy for insomnia on sedative-hypnotic use: A

narrative review.

Word Count (including Main text, Tables, Figures and References): 11,918

Number of Tables: 4

Number of Figures: 2

Submission includes Supplementary Materials file

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Authors:

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Alexander Sweetman1,9 (Corresponding Author) alexander.sweetman@flinders.edu.au

Stacey Putland stacey.putland@gmail.com

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Leon Lack2,9 leon.lack@flinders.edu.au
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R Doug McEvoy1,9 doug.mcevoy@flinders.edu.au

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Robert Adams1,3,5,9 robert.adams@flinders.edu.au

Ron Grunstein8,9 ron.grunstein@sydney.edu.au

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Nigel Stocks6,9 nigel.stocks@adelaide.edu.au

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Billingsley Kaambwa4,9 billingsley.kaambwa@flinders.edu.au

Emer Van Ryswyk1,9 emer.vanryswyk@flinders.edu.au

Christopher Gordon7,8,9 christopher.gordon@sydney.edu.au

Andrew Vakulin (Co-Senior Author)1,9 andrew.vakulin@flinders.edu.au

Nicole Lovato (Co-Senior Author)1,9 nicole.lovato@flinders.edu.au

Affiliations:

1. The Adelaide Institute for Sleep Health: A Centre of Research Excellence, College of

Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.

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2. College of Education, Psychology and Social Work, Flinders University, Adelaide,

South Australia, Australia.

3. The Health Observatory, Discipline of Medicine, The Queen Elizabeth Hospital

Campus, University of Adelaide, Woodville, South Australia, Australia.

4. Health Economics, College of Medicine and Public Health, Bedford Park, Adelaide,

South Australia, Australia.

5. Respiratory and Sleep Service, Southern Adelaide Local Health Network, Bedford

Park, Adelaide, South Australia, Australia.

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6. Discipline of General Practice, Adelaide Medical School, University of Adelaide, South

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Australia, Australia.

7.
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Susan Wakil School of Nursing and Midwifery, Faculty of Medicine and Health,
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University of Sydney, NSW, Australia
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8. Sleep and Chronobiology Research Group, Woolcock Institute of Medical Research,

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University of Sydney, New South Wales, Australia

9. National Centre for Sleep Health Services Research: A NHMRC Centre of Research
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Excellence, Flinders University, Adelaide, South Australia. https://www.ncshsr.com/

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Corresponding Author Details:

Dr Alexander Sweetman, alexander.sweetman@flinders.edu.au

The Adelaide Institute for Sleep Health, College of Medicine and Public Health, Flinders

University, Mark Oliphant Building, Level 2A, 5 Laffer Drive, Bedford Park, South

Australia, 5042.

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Summary:

Although cognitive behavioural therapy for insomnia (CBTi) is the recommended

‘first-line’ treatment for insomnia, most patients are initially treated with sedative-hypnotic

medications. Given the risk of impaired cognitive and psychomotor performance, serious

adverse events, and long-term dependence associated with sedative-hypnotics, guidelines

recommend that prescriptions should be limited to short-term use and that patients are

provided with support for withdrawal where possible. CBTi is an effective insomnia

treatment in the presence of sedative-hypnotic use. Furthermore, guidelines recommended

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that CBTi techniques are utilised to facilitate withdrawal from sedative-hypnotics. However,

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there is very little research evaluating the effect of CBTi on reduced medication use.
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The current narrative review integrates 95 studies including over 10,000 participants,
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investigating the effect of CBTi on reduced sedative-hypnotic use in different populations
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(e.g. hypnotic-dependent patients, older adults, military personnel), settings (e.g. primary care
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settings, psychiatric inpatients), CBTi modalities (e.g. self-administered reading/audio

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materials, digital, and therapist-administered), and in combination with gradual dose

reduction programs. Based on this research, we discuss the theoretical mechanistic effects of
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CBTi in facilitating reduced sedative-hypnotic use, provide clear recommendations for future

research, and offer pragmatic clinical suggestions to increase access to CBTi to reduce

dependence on sedative-hypnotics as the ‘default’ treatment for insomnia.

Keywords:

Insomnia, cognitive behavioural therapy for insomnia, primary care, general practice,

pharmacotherapy, sleeping pill, sleeping aid, sedative-hypnotic, benzodiazepine, medication

withdrawal.

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Glossary of terms:

BZD = Benzodiazepine, CBTi = Cognitive behavioural therapy for insomnia, GDR = Gradual

dose reduction, RCT = Randomised controlled trial, SCT = Stimulus control therapy, TAU =

Treatment as usual

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1 Insomnia disorder

Insomnia disorder occurs in approximately 6-10% of the general population and is

defined by chronic (≥3 months) self-reported difficulties initiating sleep, maintaining sleep,

and/or early morning awakenings, with associated daytime functional impairment[1, 2].

Insomnia reduces quality of life, increases risk of future psychiatric diagnoses, and presents a

significant economic burden through lost work productivity and high healthcare utilisation[3-

5]. When insomnia co-occurs with other medical and psychiatric illness, it is conceptualised

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as a functionally independent ‘comorbid’ disorder, rather than a ‘secondary’ condition[6].

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Hence, insomnia is a common, debilitating and costly disorder, which demands targeted

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2 Cognitive behavioural therapy for insomnia

Cognitive behavioural therapy for insomnia (CBTi) is the most effective treatment for
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insomnia[7, 8]. CBTi includes a range of non-pharmacological cognitive, behavioural, and

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educational techniques which directly target the underlying maladaptive physiological,

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psychological, and behavioural factors thought to perpetuate the disorder[8-11]. The most

common side-effect of CBTi is an increase in daytime sleepiness during the first 2-3 weeks of

treatment, however this increased sleepiness is commonly seen as a therapeutic target and

quickly dissipates as sleep improves[12]. Hence, the sleepiness-related side-effects of CBTi

(e.g. sleepiness, headaches, reduced motivation) are relatively short-lived compared to the

large and clinically meaningful improvements in insomnia that persist long after the cessation

of therapy [8, 12-15]. CBTi has historically been delivered by trained ‘sleep’

therapists/psychologists over the course of 6-8 weekly individualised treatment sessions.

However, CBTi is also effective when administered by nurses and other healthcare

professionals[16, 17], in small-group settings[17, 18], via telemedicine[20], and through self-
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administered reading/audio materials or digital/online programs[13, 21, 22]. These CBTi

modalities differ in availability, resource requirements and assumed effectiveness. Espie[23]

suggests a ‘stepped-care’ model of treatment, progressing from readily available self-

administered CBTi modalities to more intensive but resource-demanding modalities if

required (Figure 1).

Although major sleep, primary care, and medical associations around the world

recommend CBTi as the ‘first line’ insomnia treatment[8, 24-28], the use of CBTi has been

limited by poor access to resources and qualified therapists, inadequate patient and healthcare

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provider knowledge, high costs and time demands[29, 30]. Consequently, pharmacotherapy

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remains the most common treatment for insomnia[31-34].
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<Insert Figure 1 around here>
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3 Sedative-hypnotic medications
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3.1 Overview and effectiveness

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The most commonly prescribed pharmacological agents for insomnia include

benzodiazepines (BZDs; e.g. temazepam, oxazepam, nitrazepam), non-BZD hypnotics (‘z-

drugs’; e.g. zopiclone, zolpidem, zaleplon), antidepressants/antipsychotics (e.g. trazodone,

amitriptyline, mirtazapine, quetiapine), and melatonin [25, 31, 33, 35]. BZDs and ‘z-drugs’

are psychoactive drugs that bind to specific sites of the ‘gamma-aminobutyric acid’

neurotransmitter in the central nervous system (i.e. GABA-A receptors). This binding

enhances the effect of the GABA neurotransmitter, which is responsible for inhibiting the

excitability of neurons. Therefore, BZDs and ‘z-drugs’ enhance the action of GABA

neurotransmitters to promote a sedating effect in the brain and facilitate sleep. Although ‘z-

drugs’ selectively bind to ‘alpha-1’ (assumed sleep inhibitory) GABA-A sub-units, the

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effectiveness, side-effect and risks profiles of BZDs and ‘z-drugs’ are similar[36, 37]. Most

guidelines recommend against use of antidepressant and antipsychotic medications to treat

insomnia due to limited efficacy data, however there is a growing trend for off-label

antidepressant and antipsychotic prescriptions for insomnia[31, 35, 38]. Meta-analyses and

guidelines indicate that BZDs, ‘z-drugs’, and antidepressants/antipsychotics (henceforth

collectively referred to as “sedative-hypnotics”) are associated with short-term small-to-

moderate improvements in sleep, with limited evidence to support their long-term use in the

treatment of insomnia[8, 25, 37, 39-42]. Finally, melatonin is an endogenous hormone which

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exerts influence on circadian rhythms[27, 28]. Although melatonin administration is

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associated with fewer dependence/side-effects than BZDs and ‘z-drugs’, there is limited
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efficacy evidence to support melatonin in the management of insomnia[8, 27, 28].
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3.2 Side-effects, dependence and withdrawal symptoms

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Sedative-hypnotics are associated with cognitive, psychomotor, and medical side-

effects[35, 41-45], which place patients at increased risk of serious adverse events and
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outcomes, including falls and fractures[37, 48], motor-vehicle accidents[49], health service
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use, hospital admissions[50, 51], and mortality[52]. Furthermore, clinical guidelines

commonly warn of the addictive potential of sedative-hypnotics, due to the rapid

development of tolerance effects, and withdrawal symptoms experienced during dose

reduction[8, 27, 28]. Withdrawal symptoms vary between individuals and specific

medications, and can manifest at different times during the withdrawal process, but may

include; insomnia, tremors, headaches, depression, perceptual disturbances, anxiety, and

seizures (See Ashton, 1991[47]). Rebound insomnia symptoms are withdrawal phenomena

related to the emergence or resurgence of insomnia symptoms during reduction of sedative-

hypnotic use. It is suggested that rebound insomnia symptoms are more common following

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abrupt cessation of medication (versus gradual withdrawal of medication), and are dependent

on the dosage and half-life of specific sedative-hypnotic medications[27]. After successful

withdrawal from sedative-hypnotics, patients commonly report improved sleep quality and

psychomotor functioning[53-55]. However, any attempts to reduce dose commonly result in

withdrawal symptoms that tend to discourage adherence to a withdrawal schedule (Figure 2).

Unfortunately, it is difficult to identify specific patient characteristics before treatment that

predict the development of patterns of medication dependence, or the specific types of

withdrawal symptoms experienced during medication reduction[45]. Therefore, clinical

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guidelines recommend that sedative-hypnotics are prescribed at the lowest effective dose and

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for the shortest possible duration (e.g. for no more than 4 weeks)[8, 24-27].
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<Insert Figure 2 around here>
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3.3 Prevalence of sedative-hypnotic use

Despite these recommendations, sedative-hypnotics represent the most common

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initial approach by medical practitioners to manage insomnia, and are commonly prescribed
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as a long-term treatment[31-33, 56, 57]. For example, an Australian survey of 31,000 primary

care patients in 1991 found that 90% of insomnia cases were managed with sedative-hypnotic

medications[34]. Australian data collected from 2000 to 2015 confirmed these high rates of

medication prescriptions, with data from over 14,700 Australian general practitioners

indicating that 90% of appointments with insomnia patients result in medication

prescriptions[31]. The majority of these patients received repeat prescriptions over time,

indicating patterns of long-term use[31]. Furthermore, Kaufmann and colleagues recently

investigated United States data including over 80,000 respondents, and found that 82% of

patients using sedative-hypnotics had been using medication for over 6 months, and 50% had

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been using for over 2 years[32]. These high rates of long-term sedative-hypnotic use have

also been documented in other European, Australian and North American samples[56-62].

Hence, patterns of long-term sedative-hypnotic dependence represent an important issue for

healthcare providers and their patients.

3.4 Withdrawal from sedative-hypnotics

Guidelines recommend that physicians assist patients in reducing/ceasing sedative-

hypnotic use where possible[8, 27]. Complete withdrawal from sedative-hypnotics is

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associated with improved cognitive and psychomotor functioning[55], reduced risk of

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adverse events[64], and improved sleep, health and quality of life[53, 54]. Sedative-hypnotic
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withdrawal can be a relatively simple process for some patients, achieved with written/verbal
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prompts, self-help materials, or limited support from healthcare providers to reduce dosage,
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while other patients experience the rapid re-emergence of withdrawal symptoms which
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undermine and delay the withdrawal process, and may require additional specialist support

and structured gradual dose reduction (GDR) programs[65-67]. See Figure 1 for a ‘stepped
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care’ overview of different approaches to withdraw from sedative-hypnotics[65].

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GDR programs (also called; taper schedules, stepped reduction, deprescribing

schedules, etc.) vary between studies/clinical settings, but commonly include the following

components; substitution of any sedative-hypnotics of shorter half-life for sedative-hypnotics

with a longer half-life to reduce ‘potency’ of withdrawal symptoms during taper, stabilisation

of baseline dose/frequency, gradual taper schedule (e.g. 25% dose reduction every 1-2

weeks), and slower dose reduction during final weeks with introduction of ‘medication free’

nights[27, 65]. Gradual reduction of sedative-hypnotics reduces withdrawal symptoms

compared to abrupt cessation, thereby reducing side-effects and increasing likelihood of

successful withdrawal[27].

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 Given the robust and well-established effectiveness of CBTi for improving insomnia,

it may be possible to utilise CBTi techniques to facilitate sedative-hypnotic cessation. In fact,

an increasing number of guideline statements and research groups have suggested that CBTi

should be used to facilitate sedative-hypnotics withdrawal (See Table 1). However, this

recommendation is currently based on a limited number of studies[18, 68, 69], and little is

known about the specific treatment components, timing, or mechanisms by which CBTi

facilitates reduced sedative-hypnotic use. Furthermore, there is a lack of knowledge regarding

the stability of this effect across different insomnia populations, different CBTi modalities,

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different settings, and over longer follow-up periods. For the remainder of this article, we

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present a narrative review of research investigating the effect of CBTi on sedative-hypnotic
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use, a discussion of theoretical mechanistic pathways between CBTi and sedative-hypnotic
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reduction, recommendations for future research, and suggestions to increase access to CBTi
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techniques in primary care settings to reduce sedative-hypnotic prescriptions as the ‘default’

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treatment for insomnia.

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<Insert Table 1 around here>

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4 The effect of CBTi on sedative-hypnotic use

The effect of CBTi on sedative-hypnotic use has been investigated as the primary

outcome in a handful of studies[68, 69, 74, 75], and as a secondary outcome in a large

number of case studies, chart reviews, single-arm trials, and randomised controlled trials

(RCTs). We present a brief chronological history of research in this area, before discussing

the effect of CBTi on sedative-hypnotic use in different settings and modalities (e.g. primary

care, self-administered reading/audio materials, and digital CBTi), different patient

populations (co-morbid medical/psychiatric diagnoses, military personnel, treatment-resistant

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insomnia), and with respect to specific CBTi components/interventions (bedtime restriction

therapy, stimulus control therapy [SCT], relaxation therapy, and multi-component CBTi). A

chronological list of the 95 studies contributing to this narrative review is provided in the

supplementary materials (Table S1).

Several previous reviews have examined strategies to reduce sedative-hypnotic use.

Three narrative reviews have previously reported on research published before 2012

investigating the effect of CBTi on sedative-hypnotic use[65, 70, 76]. A recent systematic

review and meta-analysis by Takaesu and colleagues, including eight RCTs, found that

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compared to GDR-alone, GDR plus CBTi was associated with an increased rate of sedative-

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hypnotic cessation by short-term (≤3 months) but not long-term follow-up (12-months)[77].
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Finally, a number of meta-analyses have also examined broader GDR strategies to facilitate
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sedative-hypnotic cessation, which are beyond the scope of this review (See Figure 1)[65-67,
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78].
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The measurement of ‘sedative-hypnotic use’ (and ‘reduction’) is complicated due to

the multiple features that have been used to define patterns of medication use. For example,
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while many studies have operationalised ‘reduction’ via the complete cessation of sedative-
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hypnotics by follow-up, others have examined reductions in dose[74], frequency of

‘medicated nights’ (e.g. nightly use, versus intermittent ‘prn’ use)[17, 112, 114], or study-

specific definitions of ‘use’ and ‘reduction’ by follow-up[15, 16, 110, 124]. Furthermore, the

assessment modality and follow-up period over which medication use is assessed differs

between studies (e.g. some studies include chart-reviews to examine medication prescriptions

throughout the whole study period, while others have assessed medication use via self-report

questionnaires, telephone interviews, or sleep diaries completed for 1-2 weeks at each

assessment period)[88, 106, 112, 130]. Where possible, we have provided data on rates of

complete sedative-hypnotic cessation (i.e. transition from any use at baseline to no use at

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follow-up). For other studies, we have described researcher-defined patterns of sedative-

hypnotic dose/frequency ‘reduction’ (e.g. the percentage of patients reporting a reduction in

the ‘number of nights of sedative-hypnotic use’ by follow-up).

4.1 Brief chronological research history

In 1974, Kales and colleagues were among the first to describe the use of

psychological strategies to reduce sedative-hypnotic dependence in two patients who

experienced improved sleep and cessation of sedative-hypnotic use following extensive

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psychotherapy and GDR[79]. In 1983 and 1985, two studies reported the effectiveness of

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relaxation/stress reduction programs on sedative-hypnotic cessation in patients with a
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prolonged history of sedative-hypnotic use[80, 81]. Although the content of these
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interventions (psychotherapy and relaxation) differs from modern multi-component CBTi
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programs, these early reports indicated a promising effect of psychological strategies to

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facilitate sedative-hypnotic withdrawal.

In 1988-89, the first research specifically examining the effect of behavioural CBTi
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components on sedative-hypnotic use reported a reduction in sedative-hypnotic use post-

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treatment[82-84]. A number of observational studies and RCTs published between 1993 and

1996, highlighted the potential benefit of relaxation techniques, and the first multi-component

CBTi programs on reduced sedative-hypnotic use[85-89]. Between 1999 and 2003, a number

of RCTs investigating relaxation therapy[90], self-administered reading/audio materials with

telephone support[91], and multicomponent nurse-administered CBTi in primary care[92]

included analyses of changes in sedative-hypnotic use.

These early mainly observational and case-control studies which indicated a

promising effect of CBTi in reducing sedative-hypnotic use were followed in 2003-2004 by

the first larger RCTs investigating the effect of multicomponent CBTi interventions[18, 68,

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69]. These RCTs indicated a substantial effect of CBTi on reduced sedative-hypnotic use

post-treatment and resulted in the widespread recommendation that CBTi should be used to

facilitate sedative-hypnotic cessation (Table 1). More recently, several studies have focused

on translating and implementing CBTi treatments into primary care settings. Given the

widespread use of sedative-hypnotic prescriptions for insomnia in primary care, many of

these trials have also reported effects of CBTi on sedative-hypnotic use[16, 93-96] (Table 2).

Finally, the development and rapid increase in research investigating digital CBTi programs

has resulted in several trials investigating the effect of digital CBTi on sedative-hypnotic

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reduction[20, 98-99].

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4.2
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Effect of CBTi on sedative-hypnotic use in primary care
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Given that many sedative-hypnotics are prescribed for sleep disturbances in primary
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care[31], it is appropriate that several studies have investigated the effect of CBTi on
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sedative-hypnotic reduction in primary care patients (Table 2). Most studies reporting the

effect of CBTi interventions on sedative-hypnotic use in primary care have been conducted in
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the UK, Canada, and Sweden. As funding mechanisms for insomnia/mental health treatments
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in primary care differ between countries, it is important to consider the feasibility of these

interventions and generalisability of results to other countries and healthcare settings.

Furthermore, multiple CBTi modalities/delivery types have also been investigated in

primary care, including; self-help booklets[100, 101], nurse-administered[16, 93, 95, 96],

general practitioner-administered[17], and counsellor/therapist-administered CBTi[69].

Given that general practitioners are commonly limited by short appointment times, most

primary care studies have focused on up-skilling practice nurses to administer CBTi[16, 17,

92, 95].

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 Of note, Morgan and colleagues conducted a RCT to compare the effect of a 6-session

CBTi program administered by primary care counsellors, versus no-treatment control, on

sedative-hypnotic frequency, dose, and cessation by post-treatment, 3-month, and 6-month

follow-up[69]. In total, 209 patients with sleep problems and at least 1-month of sedative-

hypnotic use, were referred by one of 23 participating general practitioners. Compared to

control, patients treated with CBTi reported improved sleep parameters, reduced frequency of

sedative-hypnotic use, and greater rates of sedative-hypnotic cessation (33%, versus 8.1%) by

6-month follow-up.

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Overall, there is promising evidence that different CBTi modalities administered by a

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range of healthcare professionals can facilitate reduced sedative-hypnotic use in primary care.
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This evidence ranges from single-arm trials with a small number of patients using sedative-
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hypnotics[17], to larger cluster RCTs[69]. It will be important for future research conducted
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in primary care settings to continue implementing a range of CBTi techniques and referral
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options, and to investigate the impact of different combinations of CBTi modalities and GDR

interventions on sedative-hypnotic use (Figure 1). By implementing CBTi options in primary

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care, it may be possible to reduce ‘first time’ sedative-hypnotic prescriptions (to prevent
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patterns of dependence), and facilitate sedative-hypnotic reduction (among patients with pre-

established dependence).

<Insert Table 2 around here>

4.3 Effect of self-administered CBTi on sedative-hypnotic use

4.3.1 Self-administered CBTi reading and audio materials

Self-administered CBTi packages (including CBTi booklets, eBooks, video, and audio

materials delivered over session-based components/chapters) are an effective intervention to

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treat insomnia. Consequently, several research groups have reported secondary analyses of

the effect of self-administered CBTi packages on sedative-hypnotic use (See Table S2 in

Supplementary Materials for all included studies). Overall, there is mixed evidence regarding

the effect of self-administered CBTi reading/audio interventions on sedative-hypnotic

cessation. While some studies have observed a significant reduction of sedative-hypnotics

with self-help materials compared to waitlist[91], and sleep hygiene information[22], others

have observed no difference compared to waitlist[84], and inferior outcomes compared to

GDR-alone[75], therapist-administered CBTi[84], and when combined with therapist

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support[97, 100]. Hence, although self-administered reading/audio materials may be useful as

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a first-line insomnia treatment (before commencing sedative-hypnotic use), they may be less
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appropriate for facilitating sedative-hypnotic withdrawal in patients with established
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dependence (Figure 2).
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4.3.2 Digital CBTi

Several studies have investigated the effect of digital and telehealth CBTi programs
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on sedative-hypnotic use (Table 3). Earlier studies (2009-2014) reported little effect of digital
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CBTi on sedative-hypnotic use, potentially due to the small number of patients using

sedative-hypnotics at baseline (n = 15-36)[20, 21, 102]. Larger RCTs have recently reported a

promising effect of digital CBTi programs on reduced sedative-hypnotic use in a single-arm

trial [110], and RCTs of digital CBTi compared to sleep-education[15, 99, 103, 107], and

waitlist-control[104]. Furthermore, reduced sedative-hypnotic use has been reported

following digital CBTi interventions with and without combined GDR support[104-106].

Given the potential accessibility and positive effect of digital CBTi interventions on

improved insomnia symptoms and reduced sedative-hypnotic use, these programs may also

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be a suitable intervention for primary care settings in which the majority of sedative-

hypnotics are prescribed.

<Insert Table 3 around here>

4.4 Effect of CBTi on sedative-hypnotic use in specific populations

The effect of CBTi on sedative-hypnotic use has also been investigated in samples of

insomnia patients with comorbid medical and psychiatric conditions, military

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personnel/veteran populations, and in patients with treatment-resistant insomnia (See Table

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S3, Supplementary Materials). Although there is mixed evidence regarding the effectiveness
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of CBTi on sedative-hypnotic use between these studies, the more robust RCT evidence
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suggests that CBTi has little impact on changing patterns of sedative-hypnotic use in these
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specific populations[112-114].
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Three trials have reported on the effect of CBTi in patients with comorbid psychiatric

symptoms/diagnoses. Two single-arm trials have reported a reduction of sedative-hypnotic

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use in patients with comorbid psychiatric symptoms/illness[19, 115], while no between-group

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difference was found in a small RCT comparing CBTi with treatment as usual control[113].

It is possible that among patients with co-occurring insomnia and psychiatric

symptoms/illness, sedative-hypnotics have a therapeutic effect on both insomnia and some

psychiatric symptoms (e.g. anxiety), and are therefore less likely to withdraw following CBTi

alone. Given the small and diverse samples in these studies, more research investigating the

effect of CBTi on sedative-hypnotic cessation among patients with co-occurring psychiatric

symptoms and diagnoses is warranted.

Two studies have also examined the effect of CBTi in patients with insomnia

symptoms which are resistant to sedative-hypnotic treatment. In a RCT of 79 medication-

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resistant patients, Wang[116] reported that 27% of patients treated with a brief CBTi

intervention (with optional GDR-support) ceased sedative-hypnotic medications compared to

7% of patients in a sleep hygiene control. Alternatively, Sato[111] reported no effect of a

digital CBTi intervention versus a treatment as usual control in a RCT of 23 patients resistant

to sedative-hypnotic management.

Evidence from several RCTs in cancer patients/survivors with insomnia suggests no

impact of therapist-administered CBTi[119], group CBTi[114], self-help booklet CBTi[118,

120], or nurse-administered CBTi[121] on sedative-hypnotic cessation, versus control.

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Alternatively, a recent chart-review in 32 cancer patients with insomnia indicated that a

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combined six-week CBTi and GDR intervention resulted in a 69% sedative-hypnotic
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cessation rate by post-treatment, and 56% cessation rate by 1-month follow-up[124].
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Finally, two RCTs in military personnel/veteran populations reported no effect of
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CBTi (vs control) on cessation of sedative-hypnotic use[94, 119].

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Overall, it is possible that a greater focus on GDR support/programs, or additional

comorbid symptoms/diagnoses are required to assist patients with comorbidities and/or in

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specific samples to withdraw from sedative-hypnotic medications. The limited number of

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studies in these specific populations highlights the need for more research, including

interventions with combined intervention approaches for patients with insomnia and

comorbid conditions.

4.5 Effect of single/multi-component CBTi on sedative-hypnotic use

4.5.1 Single-component in-person CBTi techniques in insomnia populations

Several studies have examined the effect of single-component SCT[17, 82, 122],

imagery training[82], relaxation[81, 85, 90], and bedtime restriction interventions[74] on

sedative-hypnotic use (See Table S4 in Supplementary Materials). Overall, there is mixed

17
evidence regarding the effectiveness of single-component CBTi therapies on sedative-

hypnotic reduction, which is further complicated by the presence/absence of combined GDR

interventions, and different comparator groups. While some have reported a positive effect of

single-component interventions when combined with GDR[74, 81], there is insufficient

evidence to recommend any single component of CBTi to facilitate medication cessation.

Pooled results from single-component CBTi studies suggest a limited effect of SCT, imagery

training, and relaxation therapy on reduced sedative-hypnotic use (See Table S4), which may

indicate that multiple-component CBTi programs are necessary to target the different

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psychological and physiological factors involved in sedative-hypnotic dependence (see

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‘mechanistic pathways’ section below).
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4.5.2 Multi-component in-person CBTi in insomnia populations
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Several studies conducted in tertiary and sleep clinic settings have also examined
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sedative-hypnotic outcomes following multi-component CBTi programs delivered by

experienced therapists. As several of these studies have been reviewed previously[65, 70, 76],
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this research is summarised in Table 4.

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Of note, Baillargeon and colleagues[18] reported one of the first RCTs comparing a

combined CBTi and physician-led GDR intervention, to GDR-alone on sedative-hypnotic

cessation in 65 primary care patients with chronic sedative-hypnotic use. They reported

significantly greater rates of medication cessation in the ‘combined’ group by post-treatment

(77%) and 12-months (70%) compared to the group receiving GDR-alone (38, and 24%,

respectively). This study provided some of the first RCT-evidence of the additive positive

effect of CBTi in facilitating reduced sedative-hypnotic use.

The following year, Morin and colleagues[68] reported a 3-arm RCT comparing the

effect of CBTi, GDR, and combined CBTi + GDR on sedative-hypnotic use by 12-months, in

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a sample of 76 patients with long-term sedative-hypnotic use. Patients in the CBTi group

were treated with a 10-session small-group CBTi program, those in the GDR group received

10-sessions with a physician to manage GDR, and those in the combined group received both

interventions. The combined group showed greater rates of sedative-hypnotic cessation by

post-treatment (85%), compared to those treated with CBTi (54%), or GDR-alone (48%), but

no difference by 12-month follow-up. Among patients who ceased sedative-hypnotics by

post-treatment, greater rates of cessation at 24-month follow-up were observed in the

combined (67%), and GDR-alone (69%) than the CBTi group (31%)[123]. Hence, this trial

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provided important RCT evidence of an additive post-treatment effect of CBTi in facilitating

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sedative-hypnotic cessation when combined with a GDR program, and non-inferiority of
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CBTi compared to GDR-alone over short-term follow-up.
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Overall, evidence from the multi-component CBTi interventions suggest that CBTi
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facilitates reduced sedative-hypnotic use by immediate post-treatment as a stand-alone

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intervention, and in combination with GDR (Tables 4 and 5). However, there is mixed

evidence regarding the maintenance of this effect over long-term follow-up in RCTs and
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other single-arm and non-randomised trials [77, 88]. Future research should also examine the
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effect of additional ‘booster’ sessions over time (including both CBTi and GDR support) on

maintenance of sedative-hypnotic cessation[18].

<Insert Table 4 around here>

5 Mechanisms between CBTi and sedative-hypnotic cessation

An overview of potential theoretical pathways between CBTi and sedative-hypnotic

cessation is provided below and in Figure 2. The mechanisms by which CBTi facilitates

sedative-hypnotic cessation likely vary between individual patients, patterns of medication

19
use (e.g. nightly use, or intermittent ‘prn’ use), established tolerance to medications (e.g.

whether the patient is continuing to derive therapeutic benefit from the medications, or is

using medications because of tolerance, dependence, and withdrawal effects), the specific

factors contributing to medication dependence (e.g. psychological, versus physiological

dependence cycles), and each specific medications (e.g. half-life, dose, profile of

dependence-risk).

The most parsimonious explanation is that CBTi directly replaces any remaining

therapeutic effect of sedative-hypnotics in the management of insomnia symptoms, thereby

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rendering the medications redundant. Indeed, CBTi is effective among patients using

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sedative-hypnotic medications[11, 132], can reduce sedative-hypnotic use in the absence of
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structured sedative-hypnotic withdrawal interventions[22, 99, 103], and results in long-lasting
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insomnia improvements which may be protective against ‘relapse’ of medication use in the
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future among some patients[109, 123]. Although this ‘therapeutic substitution’ theory may
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explain the effect of CBTi on reduced medication use among patients who continue to derive

therapeutic benefit from the medications, it does not account for the reduction of medication
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use among individuals who have developed tolerance and long-term dependence.
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Among patients with established dependence, it is possible that CBTi counteracts the

physiological withdrawal symptoms occurring during dose reduction, which otherwise

complicate withdrawal attempts[27, 47]. It is possible that commencing CBTi concurrently or

before withdrawal attenuates withdrawal symptoms[47, 90], thereby improving successful

sedative-hypnotic cessation. Further research is required to determine the most appropriate

timing of CBTi and GDR interventions to ameliorate withdrawal symptoms during gradual

withdrawal (e.g. commencing CBTi before GDR, vice versa, or concurrently[83]; investigate

the timing of specific CBTi components to target psychological versus physiological

withdrawal symptoms during different stages of GDR; See Figure 2).

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 Thirdly, CBTi may facilitate sedative-hypnotic cessation through several

psychological pathways. Patients on sedative-hypnotics may hold firm beliefs regarding the

need for medication to help them sleep at night, including expectations of poor sleep on non-

medicated or reduced-dose nights. These expectations of withdrawal symptoms upon

cessation are commonly confirmed by previous withdrawal attempts[133], and may preclude

patients from considering future withdrawal attempts. CBTi may reduce these psychological

barriers through either providing patients with an alternative treatment to sedative-hypnotics

(i.e. ‘switching’ to another treatment may be less concerning than withdrawing without any

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‘safety net’), or via educational/cognitive CBTi components which target medication-related

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maladaptive beliefs about sleep[9]. For example, discussing beliefs about the need for
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medications, homeostatic and circadian control of sleep, and night-to-night sleep variability
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may reduce anticipatory-anxiety over the effects of acute loss of sleep during withdrawal, and
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provide patients with the confidence to withdraw[81]. Two recent studies examining blind-
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tapering programs provide support for the importance of psychological factors in sedative-

hypnotic dependence[130, 134]. Furthermore, a meta-analysis of 32 studies, by Winkler and

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colleagues found that up to 64% of the effect of sedative-hypnotics on objective and

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subjective sleep outcomes are also observed in placebo conditions, indicating a major

psychological contribution to the perceived ‘effectiveness’ of sedative-hypnotics[135]. These

pathways are largely theoretical and further research is required to elucidate the mechanisms

by which CBTi facilitates sedative-hypnotic cessation.

6 Implementing CBTi to reduce sedative-hypnotic use

The above research indicates a positive effect of CBTi on improving insomnia and

reducing sedative-hypnotic use. As most sedative-hypnotics are prescribed in primary care

settings, it is appropriate to improve access to CBTi and GDR interventions at the primary

21
care level. There are several patient-level, practitioner/clinic-level, and healthcare funding-

level opportunities which may be targeted to improve access to CBTi in primary care to

reduce sedative-hypnotic prescriptions.

Given the high rates of sedative-hypnotic prescriptions as the ‘first line’ response to

manage insomnia in primary care, education efforts are required to promote the recognition

of CBTi as the recommended first-line treatment for insomnia[24, 27, 31]. CBTi should be

promoted to clinicians as the first line treatment for both acute and chronic insomnia (to

avoid ’first time’ sedative-hypnotic prescriptions), and in patients with recent sedative-

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hypnotic use who may wish to withdraw[27]. Individuals at risk of developing insomnia, and

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patients with acute/chronic insomnia or sedative-hypnotic use should also be informed of the
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effectiveness of CBTi, and the multiple ways that CBTi techniques can be accessed and
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administered.
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There are also strong economic incentives to promote access to CBTi as the ‘first line’
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treatment, and to facilitate sedative-hypnotic withdrawal. For example, although CBTi

initially incurs a high cost, the effects of CBTi on improved sleep are often maintained for
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many years[13, 109, 136]. By contrast, sedative-hypnotics incur gradually increasing costs
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over time due to patterns of sedative-hypnotic dependence and repeated prescriptions, and

risks of adverse events and healthcare utilisation (e.g. increased risk of falls and fractures

leading to hospital admissions[37, 50, 51]). Hence, healthcare funding models should be

modified to reflect the health-economic superiority of CBTi over sedative-hypnotic

prescriptions, when considering long-term cost-benefit outcomes[136].

Additional CBTi referral options, subsidised through changes to healthcare funding

models may include; improved access to psychologists trained in CBTi and management of

withdrawal symptoms with CBTi (e.g. with mental health management plans/support),

subsidised access to digital CBTi options (with optional support of practitioners or

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therapists), improved training and access to general practitioners and practice nurses up-

skilled to identify insomnia and provide session-based CBTi and GDR support, and self-

administered reading/audio materials for patients with ‘first time’ insomnia. Integration of

these CBTi modalities into primary care settings is a complex task, which will require

consideration and co-ordination of specific healthcare systems and funding models.

7 Future research

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Future research should aim to examine the most effective timing and sequence of

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CBTi and GDR interventions to improve insomnia and reduce sedative-hypnotic dependence.

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For example, it may be appropriate to either treat insomnia symptoms with CBTi before
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commencing GDR[17], to undertake a GDR program to reduce medication use followed by

CBTi to alleviate withdrawal symptoms, or to administer both interventions concurrently.

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Although different studies have examined various sequencing/concurrent interventions, very

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few studies have directly compared the efficacy of these different sequential approaches[83].
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Secondly, future research should investigate the effect of different sedative-hypnotic

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profiles/history and psychological factors, on the effectiveness of CBTi and GDR

interventions[132, 137]. For example, shorter history of sedative-hypnotic use (e.g. 1 month)

may predict greater insomnia improvement and sedative-hypnotic cessation following CBTi-

alone, while longer history of sedative-hypnotic use (e.g. 6 months) may demand combined

CBTi and GDR interventions. Alternatively, lower levels of psychological distress, anxiety,

and sedative-hypnotic dose have been found to predict successful withdrawal following

combined GDR and cognitive behavioural support[137]. These studies will be useful to

inform the most appropriate allocation of resources and interventions to the patients who

require different degrees of withdrawal support.

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 Finally, as many sedative-hypnotics are prescribed in primary care settings, it is also

critical to implement CBTi techniques and referral systems into primary care. This applies

not only to CBTi access as ‘first-line’ treatment for insomnia, but also for patients with pre-

established sedative-hypnotic use. For example, it is possible that sedative-hypnotic use

masks underlying insomnia symptoms in many patients who may benefit from CBTi, despite

the absence of current insomnia symptoms. Although CBTi has traditionally been reserved

for patients with current and chronic insomnia symptoms, it may also be appropriate to

identify and offer CBTi to patients with a recent history of sedative-hypnotic use who wish to

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withdraw, in anticipation of heightened insomnia symptoms during withdrawal.

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Given the potential effectiveness of digital CBTi programs in treating insomnia and
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reducing sedative-hypnotic use, it may be possible to integrate digital CBTi referral pathways
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into primary care for this purpose. For example, it may be possible to use electronic patient-
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management systems to identify patients using sedative-hypnotics, and present practitioners

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with referral links to digital CBTi programs and GDR materials. This would allow general

practitioners to prescribe guideline-recommended management approaches, without the

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multiple session-based in-person CBTi appointments which are difficult to implement in

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over-burdened general practice settings. Any patients with poor adherence to digital CBTi

could be ‘stepped up’ to another modality (telehealth, psychologist, etc.)[23, 106].

8 Summary

Despite guidelines recommending CBTi as the first-line treatment for insomnia, most

patients who present to primary care settings and are seen by a general practitioner/family

physician are initially managed using pharmacotherapy. Several guideline statements and

reviews recommend that CBTi should be used to facilitate sedative-hypnotic cessation;

however, this recommendation has previously been based on very little research. In this

24
narrative review, we presented a broader overview of 95 studies including over 10,000

patients, which supports the effect of CBTi on facilitating sedative-hypnotic cessation in a

range of patients, settings, treatment modalities, and in combination with gradual sedative-

hypnotic withdrawal interventions. A large body of research has reported a promising effect

of various CBTi interventions on reduced sedative-hypnotic use. Specifically, interventions

including therapist-administered/supported session-based programs, and interactive digital

multi-component CBTi programs appear to facilitate sedative-hypnotic cessation.

Alternatively, there is mixed evidence regarding the effectiveness of self-administered

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reading/audio materials and single-component CBTi interventions in patients with pre-

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established sedative-hypnotic use.
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Future research should investigate the timing and sequence of CBTi and GDR
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interventions on sedative-hypnotic reduction, investigate predictors of patients requiring
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CBTi-alone, and combined CBTi and GDR to reduce sedative-hypnotic use, and the effect of
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CBTi implemented in primary care settings to reduce reliance of healthcare professionals on

sedative-hypnotics as the ‘default’ treatment for insomnia.

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Jo

25
Practice Points:

1. CBTi facilitates sedative-hypnotic (sleeping pill) cessation, however the exact timing,

sequence, and components of CBTi which exert the greatest effect on sedative-hypnotic

cessation are unknown.

2. In-person CBTi (nurse, therapist, or psychologists administered) and interactive

digital CBTi programs treat insomnia and appear to facilitate sedative-hypnotic cessation.

Although, self-administered reading/audio CBTi materials improve insomnia symptoms they

do not appear to have an additive effect on facilitating sedative-hypnotic cessation.

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3. Despite the high comorbidity of insomnia and psychiatric/medical conditions, only a

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small amount of research has investigated the effect of CBTi on sedative-hypnotic use in
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these populations. The effect of CBTi on sedative-hypnotic cessation may be reduced in
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samples with comorbid psychiatric and medical conditions. Patients with comorbid
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psychiatric and medical symptoms/illness may require additional GDR support to achieve
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sedative-hypnotic cessation.

4. As most sedative-hypnotics are prescribed in primary care settings, it is important to

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increase CBTi knowledge and systems of care in primary care to prevent/reduce sedative-
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hypnotic use. It may be possible to integrate identification of patients with a recent history of

sedative-hypnotic use, and referral options for in-person or digital CBTi with existing

primary care computer software to reduce the time burden on practitioners.

26
Research Agenda:

1. Standardised reporting of sedative-hypnotic ‘cessation’, ‘frequency of use’, and ‘dose’

will facilitate future reviews/meta-analyses in this area. It is recommended that future

research investigating interventions for insomnia (or GDR) should report a) the

proportion of patients (between-groups) using medications for sleep at each assessment

period (to calculate ‘cessation’ rates), and b) the average frequency and diazepam-

equivalent dose of sedative-hypnotic medications consumed during each assessment

period (e.g. total number and dose of sleeping pills consumed over a 2-week follow-up

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period at baseline, post-treatment, and long-term follow-up). This later suggestion will

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also allow for comparisons of changes in frequency, dose, and ‘average daily dose’
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between studies. Finally, future studies should also identify patients using prescription
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medications (e.g. BZDs, ‘z-drugs’), versus ‘over-the-counter’ medications for sleep
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during each assessment period.

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2. Future research should examine the timing and sequence of CBTi and GDR interventions

on sedative-hypnotic cessation (e.g. CBTi before GDR, GDR before CBTi, or concurrent
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administration). These studies should also examine relationships between improved sleep,
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withdrawal symptoms and reduced sedative-hypnotic use during CBTi/GDR interventions

to better identify the mechanisms by which CBTi facilitates sedative-hypnotic cessation

(e.g. Figure 2).

3. As the majority of sedative-hypnotics are prescribed in primary care, there is a large

opportunity to utilise CBTi techniques to prevent ‘first-time’ prescriptions, and facilitate

sedative-hypnotic cessation in patients with a history of medication use. Future research

should aim to implement a suite of evidence-based CBTi options (e.g. reading materials,

digital, in-person, telehealth) into primary care settings.

27
4. More research is required to directly compare the effects of CBTi (and GDR) modalities

on insomnia improvements and sedative-hypnotic cessation (e.g. self-administered

reading/audio materials, digital, in-person, group CBTi).

5. Qualitative interview data with patients withdrawing from sedative-hypnotic medications

during/following CBTi will also provide rich in-depth data, to guide future treatment

studies/approaches and understand the mechanisms between CBTi and reduced

medication use (e.g. Figure 2).

6. Future research should aim to investigate baseline predictors of sedative-hypnotic

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cessation following combined CBTi and GDR interventions, to inform allocation of

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patients to suitable CBTi/GDR modalities (Figure 1). Given the complexity of identifying
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predictors of treatment response, this recommendation may be a long-term research goal,
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supported by multiple studies and a meta-analysis of individual patient-level data.
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8.1 Financial support

The Authors are grateful for the financial support of a grant from the National Health

Medical and Research Council, Centres of Research Excellence scheme, aiming to position

Primary Care at the centre of sleep health management (App ID: APP1134954;

https://www.ncshsr.com/).

8.2 Conflicts of interest

8.2.1 Financial conflicts of interest:

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LL and NL report receiving research funding support from Re-time Pty Ltd. LL has shares in

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Re-Time Pty Ltd Australia. The remaining authors report no relevant financial conflicts of

interest.
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8.2.2 Non-financial conflicts of interest:

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The remaining authors report no relevant non-financial conflicts of interest.

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8.3 Ten key references [Also denoted with “*” below]

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1. Morin et al., 2004[68]

2. Ong et al., 2012[76]
3. Takaesu et al., 2019[77]
4. Hintze et al., 2018[70]
5. Bélanger et al., 2009[65]
6. Blom et al., 2016[15]
7. Morgan et al., 2003[69]
8. Baillargeon et al., 2003[18]
9. RACGP, 2015[27]
10. Belleville et al., 2007[75]

29
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List of Tables and Figures

Table 1. Guidelines and articles indicating that CBTi may be used to facilitate sedative-

hypnotic reduction.

Table 2. Effect of CBTi administered in primary-care on sedative-hypnotic use.

Table 3. Effect of digital CBTi on sedative-hypnotic use.

of
ro
Table 4. Effect of multi-component in-person CBTi interventions on sedative-hypnotic use in

insomnia populations.
-p
re
lP

Figure 1. Theoretical ‘stepped care’ model of cognitive and behavioural therapy and sedative-
na

hypnotic withdrawal interventions, effectiveness, and resource requirements. CBTi =

cognitive and behavioural therapy for insomnia

ur
Jo

Figure 2. Cycle of sedative-hypnotic dependence, and potential mechanisms by which CBTi

may facilitate reduction at different stages (blue).

48
Table 1. Guidelines and articles indicating that CBTi may be used to facilitate sedative-

hypnotic reduction.

Citation Association, document Recommendation/quote

Voshaar et al., Meta-analysis “A higher success rate was found for systematic
2006[66] discontinuation with psychotherapy compared with
systematic discontinuation alone” (including CBTi
and other psychotherapy interventions)
Schutte-Rodin et al., American Academy of Sleep “Medication tapering and discontinuation are
2008[8] Medicine: Insomnia Guideline facilitated by CBT-I.”
Parr et al., 2009[67] Meta-analysis “Psychological treatment plus GDR were superior
to both routine care… and GDR alone.” (including
CBTi and other psychotherapy interventions)
RACGP, 2015[27] Royal Australian College of “Gradual dose reduction plus psychological

of
General Practitioners, interventions are the most effective for
Benzodiazepine Guideline benzodiazepine discontinuation.”

ro
Hintze et al., Review article “cognitive behavioral therapy or behavioral
2018[70] therapies alone can improve hypnotic

Pottie et al., 2018[71] Clinical Practice Guidelines

-p
discontinuation outcomes.”
“Tapering with CBT improves cessation rates
re
compared to tapering alone postintervention.”
Riemann et al., European Sleep Research “… hypnotic discontinuation should be based on
lP

2019[25] Society: Insomnia Guideline slow tapering off medication, supporting patients
… with counselling, CBT-I or, if necessary,
alternative medications.”
na

Wilson et al., British Association for “CBTi during taper improves outcome.”
2019[28] Psychopharmacology:
Insomnia Guideline
ur

Croke et al., 2019[72] Practice Guidelines, American “CBT combined with tapering improved BZRA
Family Physician cessation when compared with tapering alone.”
Jo

Grima et al., Research Group, Australia “CBT-I can be used to help patients wean off
2019[73] hypnotics.”
Takaesu et al., Meta-analysis “CBT-I is effective for the short-term (3 mo)
2019[77] discontinuation of BZD hypnotics…”
Note: BZD = benzodiazepine, CBTi/CBT-I = cognitive and behavioural therapy for insomnia, GDR = gradual
dose reduction.

49
Table 2. Effect of CBTi administered in primary-care on sedative-hypnotic use.
Citation Design n Demographics CBTi GDR Control Outcome
Baillargeon, Single 24 7 using sedative- Practitioner- GDR NA Average daily dose was reduced by 84%, and the
1998[17] arm hypnotics at baseline, administered SCT administered number of ‘medicated nights’ decreased from 6.3 to
(Canada) Age M = 44, 33% Male (10 sessions max) after SCT 0.1 nights per week by 6-month follow-up.
Espie, RCT 139 74 using sedative- Nurse-administered, GDR support Waitlist 76% of patients using medication at baseline had
2001[92] hypnotics at baseline, ceased by post-CBTi, and 84% by 12-month follow-
6-group sessions
(UK) Age M = 51, 32% Male up.

f
Morgan, RCT 209 209 using sedative- Counsellor- Practitioner- TAU Compared to control, patients treated with CBTi

oo
2003[69] hypnotics at baseline, administered, 6- administered showed reduced frequency of sedative-hypnotic use,
(UK) Age M = 65, 33% Male sessions GDR and greater rates of cessation by post-treatment, and

pr
6-month follow-up (33, versus 8.1%).
Espie, RCT 201 95 using sedative- Nurse-administered, NA TAU No group by time interaction effect on sedative-

e-
2007[95] hypnotics at baseline, 5-group sessions hypnotic use. Both groups showed reduced use by 6-

Pr
(UK) Age M = 54, 32% Male month follow-up.
Morgan, RCT 193 95 using sedative- 6-booklet CBTi Within TAU Significantly fewer patients in the CBTi than TAU

al
2012[101] hypnotics at baseline, intervention plus booklets group were consuming sedative-hypnotics at post-
Age M = 67, 34% Male telephone support treatment (33%, versus 51%). No between-group

rn
difference by 6-months.
Bothelius, RCT 66 20 using sedative-
u Nurse-administered, Within CBTi Waitlist No group by time interaction effect on sedative-
Jo
2013[96] hypnotics at baseline, 5-sessions program hypnotic use.
(Sweden) Age M = 51, 14% Male
Sandlund, RCT 165 130 using sedative- Nurse-administered, Within CBTi TAU Greater reduction in self-reported frequency of
2017[16] hypnotics at baseline, 7 x 2-hour sessions program medication use in CBTi group (48% reduction),
(Sweden) Age M = 54, 27% Male versus control (12% increase). The CBTi group
maintained reduction by 12-month follow-up.*
Davidson, Waitlist 81 51 using sedative- Psychologist/Nurse- Optional GDR Waitlist 59% of patients using sedative-hypnotics at baseline
2019[93] control hypnotics at baseline, administered 6 x 2- program control ceased by post-treatment. Among a sub-set of patients
(Canada) Age M = 57, 14% Male hour sessions data for assigned to a waitlist group, sedative-hypnotic use
subset decreased by 7% during the waitlist period, and a
further 37.5% following CBTi.
CBTi = Cognitive behaviour therapy for insomnia, GDR = Gradual dose reduction, RCT = Randomised controlled trial, SCT = Stimulus control therapy, TAU = Treatment
as usual. The term ‘sedative hypnotics’ is used to encompass any medications consumed for sleep. *Researcher-defined ‘sedative-hypnotic reduction’ outcome.

50
Table 3. Effect of digital CBTi on sedative-hypnotic use.
Citation Design n Demographics CBTi GDR Control Outcome
Ritterband, RCT 45 15 used sedative-hypnotics at SHUT-i NA Waitlist Greater cessation of sedative-hypnotics by post-
2009[102] baseline, Age M = 45, 23% Male treatment in CBTi (67% reduction) than control group
(10% increase). No change by 6-months.
Van Straten, RCT 118 36 used sedative-hypnotics at 6-session NA Waitlist No group by time interaction. Among patients using
2014[21] baseline, Age M = 49, 30% Male program sedative-hypnotics at baseline, 35% of CBTi patients
ceased use by post-treatment, while control patients
showed a 5% increase in medication use (not
statistically significant).

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Holmqvist, RCT 73 32 used sedative-hypnotics at 6-session Within Telehealth No group by time interaction. 29% of patients using
2014[20] baseline, adult sample, 25% Male program CBTi CBTi sedative-hypnotics at baseline ceased by post-

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Blom, RCT 48 30 used sedative-hypnotics at 8-session Within Group No group by time interaction. 70% of patients using
2015[105] baseline, Age M = 54, 42% Male program CBTi CBTi sedative-hypnotics at baseline ceased by post-

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treatment.
Kaldo, RCT 148 70 used sedative-hypnotics at 8-session Within Online CBTi group showed greater cessation of sedative-

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2015[107]; baseline, Age M = 48, 22% Male program CBTi education hypnotics than control patients by post-treatment (22
Blom, vs 48%), 6-, 12-, and 36-month follow-up (29 vs

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2016[15] 47%).
Ritterband, RCT 303
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146 used sedative-hypnotics at SHUT-i NA Online No group by time interaction. Significant reduction in
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2017[108] baseline, Age M = 43, 28% Male education medication use over time (means not reported).
Blom, 2015; RCT 43 Patients with both insomnia and 9-session Within 9-session By post-treatment, 92% of CBTi patients, and 50% of
2017[98, 109] depression. 27 used sedative- program CBTi depression CBT-for-depression patients ceased sedative-hypnotic
hypnotics at baseline, Age M = program use. There was no between-group difference in
47, 47% Male. sedative-hypnotic use by 3-year follow-up.
Forsell, Multi- 251 150 used sedative-hypnotics at 9-session Within NA Proof-of-concept adaptive digital/supported CBTi
2019[106] step baseline, Age M = 47, 31% Male program CBTi program. Patients identified as ‘at risk’ of treatment
RCT failure part way through digital CBTi program. A
greater proportion of patients identified as ‘not at-risk’
ceased medication during treatment (53%), compared
to those identified as ‘at-risk’ (13%).
Drake, RCT 1,232 212 used sedative-hypnotics at Sleepio NA Online Greater sedative-hypnotic cessation by post-treatment
2019[99] in CBTi (18% cessation), than control (8% increase in

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(Poster) baseline education use).
Moloney, Single 46 11 used sedative-hypnotics at SHUT-i NA NA 55% of patients ceased sedative-hypnotics after CBTi.
2019[110] arm baseline, Age M = 55, All Female
Sato, RCT 23 Age M = 50, 22% Male, sedative- 5-session NA TAU No between-group difference, or main time effect on
2019[111] hypnotic resistant insomnia program sedative-hypnotic cessation.
Luik, RCT 1,711 Age M = 48, 22% Male Sleepio NA Waitlist Intervention reduced frequency of sedative-hypnotic
2020[104] with online medication use by 25-week follow-up vs. control
education (proportion of patients ceasing medication not
reported).

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Veeda, RCT 1,721 994 used sedative-hypnotics at SHUT-i NA Online Among patients on using sedative-hypnotics at
2020[103] baseline, Age M = 44, 27% Male education baseline, the CBTi group showed a greater cessation
rate (30%), vs control (17%) by 9-weeks.

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CBTi = Cognitive behaviour therapy for insomnia, GDR = Gradual dose reduction, RCT = Randomised controlled trial, TAU = Treatment as usual. The term ‘sedative

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hypnotics’ is used to encompass any medications consumed for sleep.

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Table 4. Effect of multi-component in-person CBTi interventions on sedative-hypnotic use in insomnia populations.
Citation Design n Demographics CBTi GDR Control Outcome
Morin, Case-control 100 Age M = 45, 8-10 Optional GDR Age/sex-matched 54% of patients using sedative-hypnotics ceased
1994[86] 36% Male sessions component following CBTi.
Morin, Single arm case 5 Age M = 62, 11 sessions Psychiatrist- NA By 8 weeks, 4 patients ceased, and 1 patient reduced
1995[87] series 80% Male planned GDR use by 90%. 3 patients remained medication-free at
3-months.
Schramm, Non- 32 Age M = 48, 11 sessions Physician GDR Waitlist ‘Regular sedative-hypnotic use’* was reported by
1995[88] randomised 39% Male 46% of patients at baseline, 14% at post-treatment,

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waitlist group 21% at 3-months, and 30% at 12-months.

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Jacobs, Single arm 113 Age M = 39, 7 sessions Physician GDR NA 38% of patients on sedative-hypnotics ceased by

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1995[89] 36% Male post-treatment.
Backhaus, Single arm 20 Age M = 43, 6 sessions NA NA Of the 12 patients using sedative-hypnotics at

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2001[125] 35% Male baseline, 42% ceased post-treatment, 50% ceased at

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12-month follow-up, and 88% at ≥24-month follow-
up.

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Rybarczyk, 3-arm RCT 38 Age M = 68, 8 sessions NA Audio-relaxation, Among the 15 patients using sedative-hypnotics at
2002[126] 42% Male Waitlist baseline, there was no between-group difference in

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cessation following treatment.
Baillargeon, RCT of CBTi 65 Age M = 67,
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9 sessions Physician GDR GDR-alone Compared to GDR-alone, combined GDR + CBTi
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2003[18] vs. CBTi + 59% Male (without CBTi) group showed greater rate of sedative-hypnotic
GDR cessation by post-treatment (38 vs. 77%), and 12-
months (24 vs. 70%).
Morin, 3-arm RCT 76 Age M = 63, 10 sessions Physician GDR, Combined CBTi Greater cessation in combined group (85%) than
2004[68] (CBTi vs. GDR 50% Male 10 sessions and GDR CBTi (54%), or GDR (48%) groups by post-
vs. treatment. No between-group differences in sedative-
combination) hypnotic cessation at 12-months (42-70%).
Dolan, Chart review 48 Age M = 43, 8 sessions NA NA 38% of patients on sedative-hypnotics ceased by
2010[127] 42% Male post-treatment. Patients were not actively encouraged
to discontinue sedative-hypnotics, however met with
physicians after each CBTi session to discuss
treatment progress and medication use.
Yi, case series 5 Age M = 55, 5 sessions GDR NA By post-treatment, 1 patient ceased, 3 reduced, and 1

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2012[128] 40% Male showed no change in sedative-hypnotic use.
Lichstein, 3-arm RCT 70 Age M = 64, 8 sessions 6 sessions with Placebo RCT of CBTi + GDR, placebo + GDR, and GDR-
2013[129] 29% Male Physician biofeedback + alone. No between-group differences in cessation.
GDR 66% of patients ceased by post-treatment, and 49%
by 12-months.
Park, Chart review 41 Age M = 52, 5 sessions NA Case-matched By post-treatment, 30% of CBTi group ceased,
2018[130] 24% Male (n = 41) TAU (n = 100) versus 2% of TAU controls.
Fung, Case series 5 Age M = 55, 6 sessions Blind tapering NA All patients ceased sedative-hypnotic use by post-
2019[131] 20% Male treatment.

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CBTi = cognitive behavioural therapy for insomnia, GDR = gradual dose reduction, TAU = treatment as usual. The term ‘sedative hypnotics’ is used to encompass any
medications consumed for sleep. *Researcher-defined ‘sedative-hypnotic reduction’ outcome.

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Figure 1. Theoretical ‘stepped care’ model of cognitive and behavioural therapy and sedative-hypnotic withdrawal interventions, effectiveness,

and resource requirements. CBTi = cognitive and behavioural therapy for insomnia.
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Figure 2. Cycle of sedative-hypnotic dependence (black-text), and potential mechanisms by which tailored CBTi interventions may facilitate

reduction at different stages (blue-text).