Opinion
VIEWPOINT
Clinical Management of Insomnia Disorder
Daniel J. Buysse, MD The central feature of insomnia disorder is dissatisfac-
Department of tion with sleep quantity or quality, associated with dif-
Psychiatry, School of ficulty falling asleep, maintaining sleep, or early morn-
Medicine, University of
ing awakening.1 Insomnia disorder causes clinically
Pittsburgh, Pittsburgh,
Pennsylvania. significant distress or impairment in important areas
of functioning. Sleep difficulties occur at least 3 nights
A. John Rush, MD per week for at least 3 months, and are not better
Duke-National explained by use of substances, medications, or by an-
University of
Singapore, Singapore;
other disorder. Insomnia is diagnosed only when an in-
and Department of dividual has adequate opportunity for sleep; this distin-
Psychiatry, Duke guishes insomnia from sleep deprivation, which has
University Medical different causes and consequences. Insomnia disorder
School, Durham,
North Carolina. is often comorbid with other sleep-wake, mental, or
medical disorders that require separate management.
Charles F. Reynolds III, Increased neural, physiological, and psychological
MD arousal, together with perpetuating behavioral factors
Department of
(such as excessive time in bed) are thought to underlie
Psychiatry, School of
Medicine, University of most cases of chronic insomnia. Acute insomnia, which
Pittsburgh, Pittsburgh, meets all diagnostic criteria as chronic insomnia except
Pennsylvania. in duration, may have different causes and specific treat-
ment implications.
Individuals with insomnia disorder typically experi-
ence multiple sleep symptoms over time. Nevertheless,
specific sleep symptoms may aid differential diagnosis.
Difficulty falling asleep may signal delayed sleep phase
syndrome, restless legs syndrome, or anxiety. Difficulty
maintaining sleep can result from sleep apnea, nocturia,
or pain. Early morning awakening is associated with ad-
vanced sleep phase syndrome and depression.
Measurement-Based Assessment
The diagnosis of insomnia relies on patient history from
both the patient and bed partner. Self-report question-
naires and sleep diaries are often useful to assess insom-
nia severity, identify behaviors contributing to persis-
tent insomnia, and monitor treatment effects. The
Insomnia Severity Index2 and Consensus Sleep Diary3 are
examples of clinically practical, sensitive outcome mea-
sures. Both questionnaires can be completed quickly,
within 2 to 3 minutes, at home or in the clinician’s office
and provide useful self-report and behavioral informa-
tion facilitating clinical management.
Cognitive Behavioral Treatment
The American College of Physicians (ACP) recommends
cognitive behavioral therapy for insomnia (CBT-I) as the
initial treatment for chronic insomnia disorder.4 The ACP
also recommends that clinicians and patients use a shared
Corresponding decision-making approach, including a discussion of the
Author: Charles F.
Reynolds III, MD,
benefits,harms,andcosts,todecidewhethertousemedi-
University of Pittsburgh cations when CBT-I alone is unsuccessful.
School of Medicine, CBT-I is a multimodal treatment that combines sev-
3811 O’Hara St,
eral behavioral and cognitive interventions. Specific com-
Pittsburgh, PA 15213
(reynoldscf@upmc ponents include education (eg, healthy sleep practices
.edu). and expectations), stimulus control instructions, time-
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in-bed restriction, and relaxation training. CBT-I pro-
duces reliable, durable benefits in 70% to 80% of pa-
tients and may reduce the use of sedatives.5 CBT-I can
be delivered by trained therapists and by self-guided,
fully automated online programs (eg, SHUTi, Sleepio, and
others). Overall CBT-I shows moderate to large effect
sizes on outcomes of interest, including time to fall
asleep, continuity, restfulness, and duration of sleep.5
Brief behavioral treatment for insomnia (BBTI),6 an
evidence-based, easily administered approach derived
from CBT-I, can also be used in a variety of treatment set-
tings. BBTI is delivered in a single initial session with 2 to
3 brief follow-up visits in person or by telephone. BBTI in-
cludes 4 behavioral interventions that improve sleep con-
solidation by increasing sleep “drive,” reinforcing sleep
regularity, reducing arousal, and increasing associations
between bed and sleep: (1) reduce time in bed to match
actual sleep duration, (2) get up at the same time every
day, regardless of sleep duration, (3) do not go to bed un-
less sleepy, and (4) do not stay in bed unless asleep.
The patient’s progress should be monitored through
daily sleep diaries and weekly telephone calls or elec-
tronic communications. As sleep becomes more con-
solidated, the patient can gradually increase time in bed
to find the optimal balance between sleep continuity and
sleep duration.
Pharmacological Treatment
Pharmacological treatment is most appropriate for pa-
tients with acute insomnia (<3 months) and should be
considered as an adjunct to cognitive behavioral treat-
ment for patients with chronic insomnia disorder. The
level of evidence for all drugs in the management of in-
somnia disorder is weak, with almost all studies rated as
having a lower level of evidence because of industry
sponsorship and other risks of bias related to issues such
as small sample sizes, limited duration of follow-up, and
limited clinical relevance (eg, comparison with placebo
rather than an active pharmacologic or intervention).
Changes in numerical indicators of efficacy (eg, changes
in sleep latency) are consistent but not large.7
US Food and Drug Administration (FDA)–approved
prescription medications for insomnia include benzodi-
azepines and benzodiazepine receptor agonists (BzRAs),
the melatonin receptor agonist ramelteon, the tricyclic
drug doxepin, and the orexin receptor antagonist
suvorexant. Even though the margin of safety for ben-
zodiazepines and BzRAs is relatively wide, adverse ef-
fects may include anterograde amnesia, complex sleep-
related behaviors, falls, cognitive impairment, respiratory
depression, and rebound insomnia. Agents with short
elimination half-lives are preferred to longer-acting drugs
to avoid daytime sedation. Intermittent dosing 3 to 4
times per week may reduce exposure and long-term use.
Doxepin (3-6 mg) is appropriate for sleep maintenance
(Reprinted) JAMA Published online October 23, 2017 E1
 Opinion Viewpoint

insomnia and may be particularly helpful in patients with contrain-

dications to benzodiazepine and BzRA drugs, such as substance use
disorders. Suvorexant improves sleep maintenance insomnia symp-
toms with little evidence of tolerance and has a distinct mechanism
of action. Ramelteon is most appropriate for sleep onset insomnia
symptoms. Although antihistamines (eg, diphenhydramine, doxyl-
amine) are FDA-approved for insomnia, evidence regarding their ef-
ficacy and safety is not robust.
A variety of other drugs commonly used to treat insomnia have
not been rigorously evaluated for efficacy and safety and are not FDA-
approved for this indication. These include low doses of sedating an-
tidepressantdrugs(eg,trazodone,mirtazapine).Sedatingantipsychotic
drugs (eg, olanzapine, quetiapine) are recommended only for patients
withappropriatepsychiatricdiagnosesbecauseoftheirpotentialmeta-
bolic, neurologic, and cardiovascular effects. Complementary and al-
ternativeagents,includingmelatoninandvalerian,alsolacksufficiently
rigorous efficacy and safety data to recommend their use.
Treatment Approach
Published clinical practice guidelines suggest a pragmatic ap-
proach to the treatment of insomnia disorder,7 such as the steps pre-
sented in the Box, and also emphasize that the data supporting drug
therapy are limited. Although the pragmatic approach suggests se-
quential steps, the clinician may modify the order to address a par-
ticular patient’s needs and preferences.
Conclusions
Insomnia disorder is frequently presented in general medical prac-
tice. Evaluation involves a careful history with the patient and bed
partner, if available, and use of brief instruments to gauge severity
and behaviors that destroy sleep. Use of cognitive behavioral therapy
for insomnia is recommended as the first-line treatment. Pharma-
cotherapy of insomnia disorder, if used, should be on a short-term
basis, and in shared decision making with the patient.
Box. Steps in a Pragmatic Approach to the Treatment
of Insomnia Disorder
Step 1: Evaluation
Evaluate sleep and daytime symptoms and comorbid conditions.
Optimize treatment of comorbid conditions.
Step 2: Initial Treatment
Acute insomnia diagnosis: consider short-acting hypnotic
(eg, temazepam or zolpidem 3-4 nights weekly for 3-4 weeks),
then taper and discontinue.
Chronic insomnia disorder diagnosis: implement cognitive
behavioral intervention.
Step 3: Evaluate Response and Treatment
Evaluate sleep and daytime symptom response.
Continued symptoms with cognitive behavioral intervention:
consider combined treatment using a drug appropriate for sleep
onset or sleep maintenance symptoms.
Continued symptoms with pharmacotherapy: consider switching
class of hypnotic (eg, benzodiazepine or benzodiazepine receptor
agonist to doxepin, ramelteon, or suvorexant).
Step 4: Evaluate Response and, if Symptoms Continue,
Reevaluate Diagnosis
Reevaluate and treat comorbid disorders.
Evaluate other contributing factors (eg, life events, new medical
or psychiatric disorder) and address with psychosocial,
behavioral, or medical treatment.
Step 5: Treatment-Resistant Insomnia Disorder Diagnosis
Refer to sleep specialist for evaluation of other sleep-wake
disorders, including sleep apnea.
Step 6: Monitor
Monitor for long-term treatment response and sequelae such
as depressive or anxiety disorder, substance use disorder,
or neurodegenerative disorder.

ARTICLE INFORMATION
Published Online: October 23, 2017.
doi:10.1001/jama.2017.15683
Conflict of Interest Disclosures: All authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest.
Dr Buysse reported receiving consulting fees
from Bayer, BeHealth Solutions, CME Institute,
Ebb Therapeutics, Merck, and Emmi Solutions.
Dr Rush reported receiving consulting fees from
Akili, American Psychiatric Association, Brain
Resource Company, Compass, Curbstone
Consultant, Eli Lilly, Emmes, Holmusk, LivaNova,
Lundbeck A/S, MindLinc, Montana State University,
National Institute on Drug Abuse, Santium,
Sunovion, Taj Medical, Texas Tech, and Takeda USA;
speaking fees from LivaNova, John Peter Smith
Health Network, University of Montana, Montana
State University, SingHealth, Stanford University,
and Global Medical Education; and royalties from
Guilford Press and the University of Texas
Southwestern Medical Center. Dr Reynolds
reported receiving pharmaceutical drug supplies for
National Institutes of Health (NIH)–sponsored
research studies from Bristol-Myers Squibb, Forest,
Pfizer, and Lilly; grant funding from the National
Institute of Mental Health, National Heart, Lung,
and Blood Institute, Centers for Medicare &
Medicaid Services, Patient-Centered Outcomes
Research Institute, Brain and Behavior Research
Foundation, Commonwealth of Pennsylvania,
John A. Hartford Foundation, National Palliative
Care Research Center, Clinical and Translational
Science Institute, and American Foundation for
Suicide Prevention; speaker fees from MedScape
and WebMD; being co-inventor and receiving
royalties from the psychometric analysis of the
Pittsburgh Sleep Quality Index; and serving on the
American Association for Geriatric Psychiatry
editorial review board. As of 2016, Dr Reynolds
assumed the role of editor-in-chief for the American
Journal of Geriatric Psychiatry, for which he receives
an honorarium.
Funding/Support: This work was supported by
grants P60 MD000207, P30 MH090333,
UL1RR024153, and UL1TR000005 from the NIH
and the University of Pittsburgh Medical Center
Endowment in Geriatric Psychiatry.
Role of the Funder/Sponsor: The funders had no
role in the preparation, review, or approval of the
manuscript; and decision to submit the manuscript
for publication.
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