case study on insomnia

Case study: assessing and counselling a patient with insomnia

Exploring questions to be considered when managing a patient with insomnia.

General Pharmaceutical Council (GPhC)

Case scenario

Mr AB, a 21-year-old pharmacy student, came to the local pharmacy last week with a seven-day prescription for diazepam 10mg tablets, one to be taken at night. The drug was prescribed to him by his GP because around five weeks ago Mr AB started suffering from insomnia. In fact, although he is typically supposed to wake up at 7:00am to attend his lectures, at 4:00am he is already fully awake. He does not find it difficult to fall asleep, nor does he wake up too frequently during the night. During the day, he feels very tired, anxious and tearful. It is now three days since the pharmacist dispensed his prescription and Mr AB has returned to the pharmacist because he claims he is still not able to sleep properly.

Source: Pharmaceutical Press

Pharmacy Case Studies by Soraya Dhillon and Rebekah Raymond. Pp 471 £29.99. London: Pharmaceutical Press; 2009. ISBN 978 0 85369 724 4

Case discussion

This discussion, adapted from Pharmacy Case Studies [1] , published by Pharmaceutical Press, highlights the main questions to be considered in managing Mr AB’s case. For more information on the diagnosis and treatment of insomnia, please refer to ‘Sleep disorders: diagnosis’ and ‘Sleep disorders: treatment’ .

How is insomnia defined?

Insomnia is characterised by the incapacity to sleep and/or to remain asleep for a reasonable period, which may vary from individual to individual. The sleep disturbance is observed at least three times per week and for at least one month.

What are the risk factors for the development of insomnia? Does Mr AB have any of the risk factors for developing insomnia?

Some of the most common risk factors for the development of insomnia are:

• Depression; typically, depressed individuals wake up earlier than usual (e.g. at least two hours before the scheduled time). For this reason, in the case presented, one might suspect the existence of an underlying depression.
• Excessive use of alcohol; excessive use of caffeine: Mr AB might have recently increased his alcohol intake. A possible recent increase in caffeine intake might be associated with the need to cope with his pending academic commitments.
• Stress, pain: Mr AB may be suffering from a short-term, exam-related, stressful situation.
• Hypomanic/manic episodes: in people with bipolar disorder.
• Circadian rhythm sleep disorders: jet lag; insomnia experienced by shift workers; and delayed sleep phase syndrome (sometimes seen in students who are enjoying their first experiences outside the family environment and who go to bed too late). This is something that should be discussed with the present client.
• Nocturnal polyuria, sometimes observed in conditions such as diabetes, kidney diseases, prostate enlargement, hormonal imbalances, use of diuretics.
• Sleep apnoea: interrupts the normal breathing stimulus of the central nervous system and the person must actually wake up to resume breathing.

What group of drugs does diazepam belong to? What are the main pharmacokinetic differences between the components of this class of drugs?

Diazepam is a benzodiazepine. Diazepam is more reliably absorbed following oral rather than intramuscular administration. This may be caused by precipitation in the muscle. Diazepam appears to undergo entero­hepatic recirculation with a second plasma peak occurring four to six hours after initial administration. This may be associated with re-sedation. Diazepam is oxidised in the liver to active metabolites including desmethyldi­azepam (nordiazepam), which has a half-life of over 100 hours. Benzodiazepine oxidation may be impaired in patients with liver disease and in some elderly patients. Metabolism of benzodiazepines, such as oxazepam and lorazepam, is not impaired in the elderly and in those with liver dysfunction.

Benzodiazepines have five major clinical indications:

• as anti-anxiety agents;
• as sedative hypnotics;
• as anticonvulsants;
• as muscle relaxants;
• as amnestic agents.

This five-fold clinical activity is possessed, to a greater or lesser extent, by all benzo­diazepines in current clinical use. The properties of benzodiazepines make them ideally useful for managing anxiety (e.g. diazepam, chlordiazepoxide, lorazepam); insomnia (e.g. diazepam, temazepam, nitrazepam, loprazolam, ­flurazepam, lormetazepam); epilepsy (e.g. clobazam, diazepam, lorazepam); sports injuries where muscle relaxation is required (e.g. diazepam) and as premedications prior to surgery (e.g. midazolam, lorazepam). The benzodiazepines have a number of other uses, including management of alcohol withdrawal ­syndrome (e.g. chlordiazepoxide, diazepam) and restless legs (clonazepam). Short duration of action may be useful (e.g. for falling asleep), although longer ­duration of action may be desired (e.g. in treatment of sleep-maintenance disturbances or for seizure control).

Among the different benzodiazepines, large variation exists in respect to their pharmacokinetic properties. Those benzodiazepines that have the long-acting metabolite N -desmethyldiazepam in common (e.g. diazepam, prazepam, clorazepate) are eliminated relatively slowly, others are metabolised rather rapidly (e. g. oxazepam, temazepam, triazolam). Pharmacokinetic parameters constitute the basis for a rational dosage regimen. In anticonvulsant and anti-anxiety treatment, stable blood levels of the drug are pursued so that compounds with long elimination half-lives of parent drug or active metabolites are of advantage. Conversely, if a benzodiazepine is taken as an hypnotic, the duration of action should be restricted to the night, hence a compound with a short elimination half-life is preferred.

What is the mechanism of action of diazepam in the treatment of insomnia?

Benzodiazepine agonists and other agonist ligands at the benzodiazepine site achieve their therapeutic effects by enhancing the actions of the inhibitory ­neurotransmitter gamma-aminobutyric acid (GABA) at its receptor. Benzo­diazepines have a binding site on the GABA-A receptor, which forms a channel through the membrane and opens and closes to control chloride flow into the cell. When benzodiazepine agonists act on their receptor site, GABA produces a more frequent opening of the channel, so that the flow of chloride is increased. As a result, the neuron will be less likely to go through depolarisation, which ultimately results in neuronal inhibition. For this reason, all GABAergic drugs produce sedation. Type I and type II GABA receptors have been identified; benzo­diazepines bind with relative non-selectivity to both types. There are several other drugs that are also ligands of the GABA–chloride ion receptor complex, notably barbiturates, chloral hydrate and the newer non-benzodiazepine hypnotics, zopiclone, zolpidem and zaleplon (‘Z’-drugs). The Z-drugs are likely to possess smaller residual next day ­sequelae than clinically equivalent doses of most benzodiazepines.

What are the side effects of diazepam?

Any prescription for benzodiazepines must be preceded by a careful risk–­benefit analysis considering the issues of an individual’s particular life situation, ­personality style and psychiatric diagnosis. Risks of both abuse and cognitive or psychomotor impairments have to be balanced against therapeutic benefits.

The most common side effects of benzodiazepines in routine clin­ical use are drowsiness, muscle weakness, lightheadedness, dizziness, ataxia, dysarthria, blurring of vision, confusion and apathy. Because of pharmacokinetic changes of pro-nordiazepam molecules (e.g. diazepam) associated with ageing, the elderly may be at increased risk. There may be an association between benzo­diazepine use and the risk of falls and/or hip fractures in the elderly. For those benzodiazepines given at bedtime for sleep induction and/or sleep maintenance in patients with insomnia, the problem arises when the clinically desired effect of nocturnal sedation carries over into the early part of the next day. Patients who work in any high accident risk environment (e.g. with heavy machinery), as well as those where cognitive failure could cause accident to themselves or others, should be warned about possible interactions of benzodiazepines with alcohol. Finally, increased hostility and aggression (‘paradoxical effects’) can sometimes be observed following ingestion of these drugs, especially in borderline personality disorders and in the elderly. Both benzodiazepines and newer non-benzodiazepine molecules possess a significant addiction liability; typical rebound and withdrawal symptoms may be observed if the drug is not carefully titrated down.

What formulations are available for diazepam?

Diazepam formulations include:

• Tablets: 2mg; 5mg; 10mg.
• Oral solution: 2mg/5ml.
• Strong oral solution: 5mg/5ml
• Injection (solution): diazepam 5mg/ml.
• Formulation for intravenous injection or infusion (emulsion): 5mg/ml.
• Rectal solution: 2mg/ml; 1.25ml (2.5mg); 2.5ml (5mg) tube; 4mg/ml, 2.5ml (10mg).
• Suppositories: 10mg.
• Dental prescribing on NHS: tablets or oral solution 2mg/5ml.

What alternative preparation(s) could the pharmacist recommend for Mr AB?

Diazepam is better indicated if insomnia is associated with daytime ­anxiety. Other benzodiazepines prescribed for insomnia include: nitrazepam, flur­azepam, loprazolam, lormetazepam and temazepam. The non-benzodiazepine hypnotics zaleplon, zolpidem and zopiclone are not licensed for long-term use. The sedative antipsychotic promethazine hydrochloride is sometimes used to facilitate sleep, with a 25–50mg ­recommended dose. Melatonin has proved effective for some clients, mostly in regulating the sleep/waking cycle. Although evidence of efficacy is limited, some clients use herbs such as valerian and chamomile. If Mr AB will finally be diagnosed with depression, a trial with an anti­depressant will be indicated.

What counselling could the pharmacist give Mr AB to help try and resolve the issue?

Relevant sleep hygiene issues may be discussed with the client. Some ­traditional remedies for insomnia have included drinking warm milk before bedtime, taking a warm bath in the evening, exercising vigorously for half an hour in the afternoon, having only a light evening meal, avoiding mentally stimulating activities in the evening hours, and making sure to get up early in the morning and to go to bed at a reasonable hour. Mr AB should seriously consider the ­possibility of tapering down gradually his caffeine intake and might want to avoid any excessive intake of alcohol. Distractions in the bedroom, including excessive light and noise (e.g. from television) should be avoided. Finally, Mr AB should be informed that with a continuous, long-term (e.g. more than 3–12 weeks), prescription of benzodiazepines, both tolerance and dependence have been described.

Fabrizio Schifano , MD, MRCPsych, Dip Clin Pharmacology is Chair in Clinical Pharmacology & Therapeutics, School of Pharmacy & Associate Dean, Postgraduate Medical School, University of Hertfordshire; Honorary Consultant Psychiatrist.

[1] Pharmacy Case Studies by Soraya Dhillon and Rebekah Raymond. Pp 471 £29.99. London: Pharmaceutical Press; 2009. ISBN 978 0 85369 724 4

General references

Breimer DD, Jochemsen R & von Albert HH. Pharmacokinetics of benzodiazepines. Short-acting versus long-acting.  Arzneimittel­forschung  1980;30:875–881.  PMID: 6106488

Curran HV, Schifano F & Lader MH. Models of memory dysfunctions? A comparison of the effects of lorazepam and scopolamine on memory, psychomotor performance and mood.  Psychopharmacology (Berlin)  1991;10:83–90.  PMID: 2006245

Hindmarch I. Medicines in the workplace: the effects of prescribed and OTC drugs on performance. In: Ghodse AH (ed.)  Addiction at Work: Tackling Drug Use and Misuse in the Workplace . London: Gower Publishing Ltd; 2015.

Joint Formulary Committee.  British National Formulary  55 .  London: British Medical Association and Royal Pharmaceutical Society of Great Britain, March 2008.

Leger D, Guilleminault C, Dreyfus JP  et al . Prevalence of insomnia in a survey of 12,778 adults in France.  Journal of Sleep Research  2000;9:35–42.  doi:10.1046/j.1365-2869.2000.00178.x

Schifano F. (1991) Ansiolitici benzodiazepinici (alprazolam, bromazepam, camazepam, clobazam, clorazepato dipotassico, clordiazepossido, clotiazepam, delorazepam, diazepam, estazolam, flunitrazepam, ­fluoresone, flurazepam, glaziovina, lorazepam, lormetazepam, me­butamato, medazepam, meprobamato, nitrazepam, nordiazepam, oxazepam, pinazepam, prazepam, temazepam, triazolam, valnottamide). In: Casiglia E and Gava R (eds)  L’Annuario dei Farmaci. Farmacologia Clinica e Terapia . Padova: Piccin Nuova Libraria, (I), pp. 111–129.

Schifano F. (2005) Substance misuse in the workplace. In: Ghodse AH (ed.)  Addiction at Work: Tackling Drug Use and Misuse in the Workplace . London: Gower Publishing Ltd.

Schifano F & Magni G. Panic attacks and major depression after discontinuation of long-term diazepam abuse.  Drug Intelligence and Clinical Pharmacy; the Annals of Pharmacotherapy  1989;23:989–990.  PMID: 2603456

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Insomnia: Prevalence, Impact, Pathogenesis, Differential Diagnosis, and Evaluation

Evelyn mai , m.d., daniel j buysse , m.d..

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Address correspondence to Daniel J. Buysse, M.D.: E-1127 WPIC, 3811 O’Hara St., Pittsburgh, PA 15213, USA. Telephone: (412) 246-6413. Fax: (412) 246-5300. E-mail: [email protected]

Introduction

Insomnia is the most common sleep disorder affecting millions of people as either a primary or comorbid condition. Insomnia has been defined as both a symptom and a disorder, and this distinction may affect its conceptualization from both research and clinical perspectives. However, whether insomnia is viewed as a symptom or a disorder, it nevertheless has a profound effect on the individual and society. The burden of medical, psychiatric, interpersonal, and societal consequences that can be attributed to insomnia underscores the importance of understanding, diagnosing, and treating the disorder.

Insomnia Prevalence

The prevalence of insomnia varies depending on the specific case definition. Broadly speaking, insomnia has been viewed as a symptom and as a disorder in its own right. Insomnia has also been defined by subtypes based on frequency, duration (acute versus chronic) and etiology. This picture is further complicated by considerations of insomnia as either a comorbid condition; as a symptom of a larger sleep, medical, or psychiatric disorder; or as a secondary disorder ( Harvey, 2001 ). An illustration of this idea is the overlap between insomnia and depression. Do insomnia and depression co-exist in an individual as separate disorders? Or is insomnia only one symptom in the larger context of depression? Or did insomnia secondarily developed as a distinct disorder from a primary depressive disorder?

The three main diagnostic manuals, International Classification of Sleep Disorders (ICSD-2) ( American Academy of Sleep Medicine, 2005 ), Diagnostic and Statistic Manual (DSM IV-TR) ( American Psychiatric Association, 2000 ), and International Classification of Disease (ICD-10) ( World Health Organization, 1992 ), vary in their approach to defining insomnia (see Table 1 ). ICSD-2 subdivides insomnia into descriptive, etiologic categories. Examples include Adjustment Insomnia (or, insomnia temporally related to an identifiable stressor) and Psychophysiological Insomnia (increased arousal and conditioned sleep difficulty) ( American Academy of Sleep Medicine, 2005 ; see Table 2 ). These categories also contain insomnia due to a mental disorder, substance, or medical condition. The DSM IV-TR, on the other hand, separates out Primary Insomnia (insomnia symptoms associated with distress or daytime impairment) from other “dyssomnias,” such as a breathing-related sleep disorder ( American Psychiatric Association, 2000 ). ICD-10 utilizes the broadest approach, categorizing insomnia based on underlying pathology: nonorganic insomnia and nonorganic disorder of the sleep-wake schedule ( World Health Organization, 1992 ) (see Table 2 ) [This version of table 2 contains only the ICSD definition of insomnia]. Duration of insomnia (at least 1 month of symptoms) is noted in ICSD-2 and DSM IV-TR; however frequency of symptoms is broached only in ICD-10 [please define insomnia according to ICD and DSM].

Insomnia Diagnostic Categories

Insomnia Definition

As a result of these differences in insomnia case definitions, estimates of insomnia prevalence have varied widely, from 10–40% ( Ford & Kamerow, 1989 ; Kuppermann et al., 1995 ; Ustun et al., 1996 ; Bixler et al., 1979 ; Simon & Von Korff, 1997 ; Mellinger et al., 1985 ; Ohayon, 2002 ; Ancoli-Israel & Roth, 1999 ). This problem is demonstrated by the findings of a prevalence study from South Korea. When insomnia was defined by frequency (symptoms occurring at least three nights per week), 17% of randomly selected subjects from the population qualified for the diagnosis. If the symptom of difficulty maintaining sleep was the defining factor, 11.5% of the sample was affected. However, using the more stringent criteria from DSM-IV, 5% of the sample qualified for the diagnosis ( Ohayon & Hong, 2002 ). Similar disparities were shown in a prevalence study from France ( Leger et al., 2000 ). According to a 2005 statement by the National Institutes of Health, insomnia has a prevalence of 10% if the definition necessitates daytime distress or impairment ( National Institutes of Health, 2005 ).

Given all the information available, the prevalence of insomnia symptoms may be estimated at 30% and specific insomnia disorders at 5–10% ( Roth, 2007 ).

Several risk factors for insomnia have been identified. Female sex, advanced age, depressed mood, snoring, low levels of physical activity, comorbid medical conditions, nocturnal micturation, regular hypnotic use, onset of menses, previous insomnia complaints, and high level of perceived stress have all been implicated as risk factors; the first three factors in particular, female sex, advanced age, and depressed mood, are consistent risk factors ( Morgan, 2003 ; Klink et al., 1992 ; Morgan & Clarke, 1997 ; Su et al., 2004 ; Johnson et al., 2006b ; Ford & Kamerow, 1989 ; Murata et al., 2007 ).

Precipitants of insomnia have also been studied. Bastien et al. ( Bastien et al., 2004 ) examined precipitating factors of insomnia and found that family, work or school, and health events proved to be the most common precipitants ( Bastien et al., 2004 ). Another study of psychosocial stressors in Japan demonstrated that employees with greater intragroup conflict and job dissatisfaction had greater risk for insomnia ( Nakata et al., 2004 ).

Knowledge of both risk factors and possible precipitants of insomnia can help to guide the evaluation and treatment of insomnia. Questions about psychosocial stressors at home and at work in high risk individuals, such as those experiencing depression or who are female or elderly, can help to shape and direct patient care.

Insomnia Impact

Insomnia and psychiatric conditions.

An estimated 40% of individuals with insomnia have a comorbid psychiatric condition ( Ford & Kamerow, 1989 ; McCall, 2001 ). In a review of epidemiological studies, Taylor et al. ( Taylor et al., 2003 ) found that insomnia predicted depression, anxiety, substance abuse or dependence, and suicide ( Taylor et al., 2003 ). In fact, the correlation between insomnia and later development of depression within 1–3 years is particularly strong ( Riemann & Voderholzer, 2003 ). Johnson et al. ( Johnson et al., 2006a ) found that in a community sample of adolescents that in 69% of cases, insomnia preceded comorbid depression, while an anxiety disorder preceded insomnia 73% of the time ( Johnson et al., 2006a ). In a large group of subjects aged 15 to 100 years, insomnia either appeared before (>40%) or at the same time (>22%) as mood disorders. This study also found that insomnia appeared at the same time (>38%) of the time or after (34%) as anxiety disorders ( Ohayon & Roth, 2003 ).

As further evidence of morbidity, individuals with insomnia complaints in the last year but without any previous psychiatric history were shown to have an increased risk of first onset major depression, panic disorder, and alcohol abuse the following year when compared to controls ( Weissman et al., 1997 ). Furthermore, adolescents who completed suicide were found to have higher rates of insomnia in the week preceding death than community control adolescents ( Goldstein et al., 2008 ).

Taken as a whole, these findings underscore the impact of insomnia on the individual while suggesting a possible relationship between insomnia and psychiatric disorders. The nature of this relationship has yet to be established. Insomnia could be an early symptom, part of a prodrome, of a depressive or anxiety disorder. Similarly, insomnia might also exist as a separate, comorbid disorder that either gave rise to or developed from a psychiatric condition. In either case the need to address insomnia and psychiatric disorders together remains important.

Insomnia and Medical Conditions

Associations between insomnia and a variety of medical conditions have also been established. Taylor et al. ( Taylor et al., 2007 ) found that in a community-based sample chronic insomniacs reported more heart disease, hypertension, chronic pain, as well as increased gastrointestinal, neurologic, urinary, and breathing difficulties. The converse was also shown to be true, in which subjects with hypertension, chronic pain, breathing, gastrointestinal, and urinary problems complained of insomnia more often than non-insomniacs ( Taylor et al., 2007 ). Others have also found increased odds ratios for insomnia in a variety of medical conditions, ranging from congestive heart failure to hip impairment ( Katz & McHorney, 1998 ).

Ancoli-Israel ( Ancoli-Israel, 2006 ) emphasized the different ways that insomnia and chronic medical conditions may relate to each other: sleep complaints may function as a symptom of a disorder, such as congestive heart failure and Cheyne-Stokes respiration gastroesophageal reflux disease and increased arousals. In other cases, insomnia may be a component of the etiology of a disorder, such as diabetes mellitus ( Ancoli-Israel, 2006 ).

The connection between cardiovascular disease and insomnia bears specific attention. After adjusting for age and coronary risk factors, a risk ratio of 1.5–3.9 between difficulty falling asleep and coronary heart disease has been demonstrated ( Schwartz et al., 1999 ). Men who experienced difficulty falling asleep were also shown to have a threefold risk of death secondary to coronary heart disease ( Mallon et al., 2002 ).

The relationship between chronic pain and insomnia is also of particular clinical relevance. In one study, more than 40% of insomniacs reported having at least one chronic painful physical condition. Moreover, chronic pain was in turn associated with shorter sleep duration and decreased ability to resume sleep following arousal ( Ohayon, 2005 ). Tang et al. ( Tang et al., 2007 ) found that 53% of chronic pain patients had scores suggestive on the Insomnia Severity Index of clinical insomnia versus 3% of subjects without pain ( Tang et al., 2007 ).

Socioeconomic Impact of Insomnia

In addition to psychiatric and medical comorbidities, insomnia is associated with substantial personal and societal consequences. One study that examined the effect of insomnia on primary care patients found insomniacs had double the number of days with restricted activity due to illness ( Simon & Von Korff, 1997 ). Another study showed that more insomniacs rated their quality of life as poor (22%) when compared to subjects without any sleep complaints (3%) ( Hajak et al., 2001 ). Insomnia has also been shown to have a detrimental effect on health-related quality of life to the same degree as chronic disorders such as depression and congestive heart failure ( Katz & McHorney, 2002 ). When the economic costs that encompass health care use, workplace effects of absenteeism, accidents, and increased alcohol consumption secondary to insomnia were considered, the annual cost was estimated to be between $35 to $107 billion a year ( Chilcott & Shapiro, 1996 ; Stoller, 1994 ). Insomnia has not been found to be associated with increased risk of death, however ( Phillips & Mannino, 2005 ).

Health care utilization, as defined by increased office visits and rates of hospitalization, is consistently higher in insomniacs than in subjects without sleep complaints ( Leger et al., 2002 ; Novak et al., 2004 ). In fact, the direct costs incurred through inpatient, outpatient, pharmacy, and emergency room usage is greater in insomniacs regardless of age ( Ozminkowski et al., 2007 ). An evaluation of the direct health care costs of insomnia in 1995 placed estimates at $13.9 billion in the United States and $2.1 billion in France ( Walsh & Engelhardt, 1999 ; Leger et al., 1999 ).

Function in the workplace is also negatively affected. Insomniacs miss work twice as often as good sleepers, with absenteeism particularly prominent in men and blue-collar workers ( Leger et al., 2006 ). The extra cost of work absenteeism secondary to insomnia, through decreased productivity and salary replacement, is then brought to bear on employers ( Godet-Cayre et al., 2006 ).

Insomnia Pathogenesis

Insomnia is often believed to arise from a state of “hyperarousal.” In the physiological hyperarousal model, an elevated level of alertness throughout the day and night makes it difficult to sleep. In support of this theory, insomniacs have been found to have an increased whole body metabolic rate when compared with normal sleepers ( Bonnet & Arand, 1997 ; Stepanski et al., 1988 ). They also score higher than normal sleepers on a Hyperarousal Scale, and, even during the day when complaining of fatigue, insomniacs still take a longer time to fall asleep ( Pavlova et al., 2001 ; Bonnet & Arand, 1995 ).

On functional neuroimaging, insomniacs show increased cerebral glucose metabolism both during sleep and wake states ( Nofzinger et al., 2004 ). On electroencephalography (EEG), insomniacs demonstrate increased beta activity and lower delta activity ( Krystal et al., 2002 ; Perlis et al., 2001 ). From an endocrine perspective, insomniacs, like patients with major depressive disorder, demonstrate corticotropin releasing factor hyperactivity, thus suggesting a role for hypothalamic-pituitary-adrenal axis dysfunction ( Roth et al., 2007 ).

Insomnia Evaluation

The cornerstone of the insomnia evaluation is a detailed history obtained during the patient interview. While the approach to the interview may vary depending on the practitioner, key points should be covered in order to ensure a thorough evaluation. Additional assessment tools, such as the sleep-wake diary, actigraphy, and in specific cases polysomnography, can supplement the information obtained in the interview. A list of diagnoses and comorbid conditions to consider during the insomnia evaluation can be found in Table 3 .

Insomnia Differential Diagnosis and Common Comorbidities

Patient interview

1. Detailed information about the nature of the complaint is necessary; if insomnia is related to sleep onset, sleep maintenance, early morning awakening, nonrestorative sleep quality, or a combination of these problems. Information obtained here may help to guide the diagnosis, such as a sleep onset complaint resulting from Restless Legs Syndrome as opposed to an early morning awakening presenting as part of a depressive disorder.

Additional information about the onset, course and duration, current presentation, frequency, severity, and precipitating or alleviating factors also helps to define the problem. In particular, a lifelong course with an onset in the absence of medical and psychiatric comorbidities may suggest a primary insomnia as opposed to a secondary insomnia that develops in late adulthood in the context of chronic pain.

2. Discussion of the sleep-wake routine. The sleep schedule, including bed time, sleep latency, number and length of nighttime awakenings, sleep reinitiation time, wake time, time spent in bed, and total sleep time should be reviewed. A patient’s preferred bedtime may not coincide with actual bedtime, as in a circadian rhythm disorder. Similarly, nighttime awakenings due to nightmares from PTSD as opposed to awakenings from nocturia due to prostate enlargement suggest different disorders.

The daytime routine with a review of work schedule, eating and exercise times, and duration and timing of naps is also important. Eating and exercise times that occur in close temporal relation to bedtimes may inhibit the patient’s ability to fall asleep. Moreover, naps of long duration that occur in the late afternoon or evening may have a similar negative effect on sleep latency and continuity.

3. Discussion of daytime functioning and associated symptoms. This category may include: daytime sleepiness, fatigue, difficulty with memory and concentration, depression, anxiety, irritability, impairment at work, school or home, and overall quality of life. A report of daytime impairment and patient distress may underscore the severity of symptoms, and thus highlight the need to aggressively treat insomnia. In this area, collateral report from family, teachers, or coworkers may prove helpful if the patient is unaware of the extent of his/her symptoms. Safety issues such as the negative effect on driving and work performance in potentially hazardous areas should be broached and may provide an opportunity for patient education.

4. Sleep conditions and routines. The conditions of the room used for sleep (example- effect of light, temperature, and noise); use of TV, computer, or radio both in the pre-bedtime routine and during periods of nighttime awakenings; the effect of anxiety during sleep latency and sleep reinitiation periods; and the presence of clock-watching before and during sleep times. Too much noise or light exposure in the sleeping room may inhibit sleep initiation. Similarly, clock-watching with each nighttime awakening may only further heighten an already raised level of anxiety. Specific difficulty falling asleep at home but not while out of town may suggest insomnia related to the bedroom environment.

5. Previous treatments tried and their effects and side effects. Treatments may include over the counter, homeopathic, herbal, or prescription medications as well as behavioral therapies. In addition to providing information on potential treatments that may not have been offered to the patient yet, information obtained in this area may provide a sense of the kind of treatment the patient is looking for.

6. Symptoms of other sleep disorders that could be affecting the complaint. Conditions such as restless legs syndrome, periodic limb movement disorder, sleep apnea, and sleep phase syndromes should be considered as possible contributors to insomnia.

7. Review of comorbid medical conditions that could play a role in the presentation. General categories to consider include: cardiovascular, pulmonary, neurologic, gastrointestinal, renal, endocrine, and rheumatologic.

8. Review of underlying psychiatric conditions and psychosocial stressors. Eliciting symptoms of depression, bipolar disorder, anxiety, panic – including nocturnal panic attacks, and psychosis can help to clarify the diagnostic picture while emphasizing the need to obtain or continue psychiatric care.

9. Review of substance use, including nicotine, alcohol, and caffeine. This discussion should cover amount, frequency, and time of day the substance is used as all of these substances may contribute to an insomnia complaint. Patient education about the effects of nicotine, alcohol, and caffeine on sleep should also be undertaken if it appears that substance use has a negative effect on sleep quality.

10. Review of family history of sleep, medical, and psychiatric disorders.

Physical and mental status exam

1. The physical exam may reveal signs consistent with sleep apnea (obesity, enlarged neck circumference, crowded orophaynx) as well as thyroid, cardiac, respiratory, and neurologic disorders.

2. The mental status exam may yield information about the patient’s mood, affect, level of alertness, and ability to attend.

Collateral sources interview

Interview of the patient’s bed partner or family members, if possible, to elicit symptoms of which the patient may be unaware. This part of the evaluation may also help to corroborate and expand upon the patient’s original description. Revelation about respiratory symptoms (snoring, apneas, or gasping) could suggest a sleep-disordered breathing etiology, while report of repeated limb movements may move the diagnosis towards RLS or PLMD.

Objective data

1. actigraphy.

Actigraphy helps to characterize rest-activity patterns and may have some utility as an objective measure when used in conjunction with a sleep-wake dairy and formal interview. For insomniacs actigraphy can provide information about circadian rhythms and sleep patterns ( Morgenthaler et al., 2007 ). Compared with polysomnography, however, actigraphy in insomniacs has had variable results: it has been found to both over and underestimate total sleep time ( Vallieres & Morin, 2003 ; Sivertsen et al., 2006 ; Sadeh & Acebo, 2002 ). Another study found that actigraphy was well validated by polysomnography with respect to number of awakenings, wake time after sleep onset, total sleep time, and sleep efficiency ( Lichstein et al., 2006 ). When using actigraphy increasing the duration of recording to more than 7 days may improve the reliability of sleep time estimates ( Van Someren, 2007 ).

2. Polysomnography

Polysomnography is not routinely used in the evaluation of insomnia; the onus of the diagnosis lies instead on the patient interview. According to 2003 practice parameters established by the American Academy of Sleep Medicine, specific cases may apply when polysomnography is warranted. These cases include suspicion of sleep-related breathing disorders or periodic limb movement disorders, uncertain initial diagnosis, treatment failure, and arousals leading to violent behavior ( Littner et al., 2003 ).

3. Sleep diaries

Sleep diaries recorded over 1–2 weeks can help track a patient’s sleep-wake patterns. Information including actual sleep-wake times, duration of time in bed, and day to day variability in sleep-wake times can be gathered from the diaries (see Figure 1 ).

Sleep Diary

Insomnia is thought to result from a state of “hyperarousal.” As a result of this elevated state of alertness, sleep may prove difficult. Formulating a clinical definition of insomnia has proven a challenge. Nevertheless, some enduring characteristics of insomnia include difficulty with sleep initiation or maintenance, early morning awakening, and nonrestorative sleep in the setting of daytime impairment or distress in the setting of adequate sleep opportunity. With these characteristics in mind the prevalence of insomnia is thought to be approximately 10%.

The evaluation of insomnia emphasizes the interview, during which information about the specific complaint, comorbid sleep, medical, or psychiatric conditions, family histories, medication, and substance use may be gathered. Additional information from collateral sources, sleep diaries, actigraphy, and polysomnography may also prove useful.

Insomnia is a disorder that has far-reaching effects: medical, psychiatric, personal, and societal consequences have all been linked with insomnia. The cost of insomnia can be measured not just in dollars, but also in impaired quality of life from comorbid conditions and impaired interpersonal relationships.

Acknowledgments

Supported by NIH grants MH24652 and AG20677

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Reference List

• American Academy of Sleep Medicine. The International Classification of Sleep Disorders, Second Edition (ICSD-2): Diagnostic and Coding Manual. Second Edition 2005. [ Google Scholar ]
• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000. [ Google Scholar ]
• Ancoli-Israel S. The impact and prevalence of chronic insomnia and other sleep disturbances associated with chronic illness. The American Journal of Managed Care. 2006;12:S221–S229. [ PubMed ] [ Google Scholar ]
• Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep. 1999;22 Suppl 2:S347–S353. [ PubMed ] [ Google Scholar ]
• Bastien CH, Vallieres A, Morin CM. Precipitating factors of insomnia. Behavioral Sleep Medicine. 2004;2:50–62. doi: 10.1207/s15402010bsm0201_5. [ DOI ] [ PubMed ] [ Google Scholar ]
• Bixler EO, Kales A, Soldatos CR, Kales JD, Healey S. Prevalence of sleep disorders in the Los Angeles metropolitan area. American Journal of Psychiatry. 1979;136:1257–1262. doi: 10.1176/ajp.136.10.1257. [ DOI ] [ PubMed ] [ Google Scholar ]
• Bonnet MH, Arand DL. 24-hour metabolic rate in insomniacs and matched normal sleepers. Sleep. 1995;18:581–588. doi: 10.1093/sleep/18.7.581. [ DOI ] [ PubMed ] [ Google Scholar ]
• Bonnet MH, Arand DL. Hyperarousal and insomnia. Sleep Medicine Reviews. 1997;1:97–108. doi: 10.1016/s1087-0792(97)90012-5. [ DOI ] [ PubMed ] [ Google Scholar ]
• Buysse DJ. Sleep Disorders and Psychiatry. Arlington, VA: American Psychiatric Publishing, Inc.: American Psychiatric Publishing Review of Psychiatry; 2005. [ Google Scholar ]
• Chilcott LA, Shapiro CM. The socioeconomic impact of insomnia. Pharmacoeconomics. 1996;10:1–14. doi: 10.2165/00019053-199600101-00003. [ DOI ] [ PubMed ] [ Google Scholar ]
• Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? Journal of the American Medical Association. 1989;262:1479–1484. doi: 10.1001/jama.262.11.1479. [ DOI ] [ PubMed ] [ Google Scholar ]
• Godet-Cayre V, Pelletier-Fleury N, Le Vaillant M, Dinet J, Massuel MA, Leger D. Insomnia and absenteeism at work. Who pays the cost? Sleep. 2006;29:179–184. doi: 10.1093/sleep/29.2.179. [ DOI ] [ PubMed ] [ Google Scholar ]
• Goldstein TR, Bridge JA, Brent DA. Sleep disturbance preceding completed suicide in adolescents. J.Consult Clin.Psychol. 2008;76:84–91. doi: 10.1037/0022-006X.76.1.84. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Hajak G SINE Study Group, & Study of Insomnia in Europe. Epidemiology of severe insomnia and its consequences in Germany. European Archives of Psychiatry and Clinical Neuroscience. 2001;251:49–56. doi: 10.1007/s004060170052. [ DOI ] [ PubMed ] [ Google Scholar ]
• Harvey AG. Insomnia: symptom or diagnosis? Clinical Psychology Review. 2001;21:1037–1059. doi: 10.1016/s0272-7358(00)00083-0. [ DOI ] [ PubMed ] [ Google Scholar ]
• Johnson EO, Roth T, Breslau N. The association of insomnia with anxiety disorders and depression: exploration of the direction of risk. Journal of Psychiatric Research. 2006a;40:700–708. doi: 10.1016/j.jpsychires.2006.07.008. [ DOI ] [ PubMed ] [ Google Scholar ]
• Johnson EO, Roth T, Schultz L, Breslau N. Epidemiology of DSM-IV insomnia in adolescence: lifetime prevalence, chronicity, and an emergent gender difference. Pediatrics. 2006b;117:e247–e256. doi: 10.1542/peds.2004-2629. [ DOI ] [ PubMed ] [ Google Scholar ]
• Katz DA, McHorney CA. Clinical correlates of insomnia in patients with chronic illness. Archives of Internal Medicine. 1998;158:1099–1107. doi: 10.1001/archinte.158.10.1099. [ DOI ] [ PubMed ] [ Google Scholar ]
• Katz DA, McHorney CA. The relationship between insomnia and health-related quality of life in patients with chronic illness. Journal of Family Practice. 2002;51:229–235. [ PubMed ] [ Google Scholar ]
• Klink ME, Quan SF, Kaltenborn WT, Lebowitz MD. Risk factors associated with complaints of insomnia in a general adult population. Archives of Internal Medicine. 1992;152:1634–1637. [ PubMed ] [ Google Scholar ]
• Krystal AD, Edinger JD, Wohlgemuth WK, Marsh GR. NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes. Sleep. 2002;25:630–640. [ PubMed ] [ Google Scholar ]
• Kuppermann M, Lubeck DP, Mazonson PD, Patrick DL, Stewart AL, Buesching DP, et al. Sleep problems and their correlates in a working population. Journal of General Internal Medicine. 1995;10:25–32. doi: 10.1007/BF02599573. [ DOI ] [ PubMed ] [ Google Scholar ]
• Leger D, Guilleminault C, Bader G, Levy E, Paillard M. Medical and socio-professional impact of insomnia. Sleep. 2002;25:625–629. [ PubMed ] [ Google Scholar ]
• Leger D, Guilleminault C, Dreyfus JP, Delahaye C, Paillard M. Prevalence of insomnia in a survey of 12,778 adults in France. Journal of Sleep Research. 2000;9:35–42. doi: 10.1046/j.1365-2869.2000.00178.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• Leger D, Levy E, Paillard M. The direct costs of insomnia in France. Sleep. 1999;22:S394–S401. [ PubMed ] [ Google Scholar ]
• Leger D, Massuel MA, Metlaine A. Professional correlates of insomnia. Sleep. 2006;29:171–178. [ PubMed ] [ Google Scholar ]
• Lichstein KL, Stone KC, Donaldson J, Nau SD, Soeffing JP, Murray D, et al. Actigraphy validation with insomnia. Sleep. 2006;29:232–239. [ PubMed ] [ Google Scholar ]
• Littner M, Hirshkowitz M, Kramer M, Kapen S, Anderson M, Bailey D, et al. Practice parameters for using polysomnography to evaluate insomnia. Sleep. 2003;26:754–757. doi: 10.1093/sleep/26.6.754. [ DOI ] [ PubMed ] [ Google Scholar ]
• Mallon L, Broman JE, Hetta J. Sleep complaints predict coronary artery disease mortality in males: a 12-year follow-up study of middle-aged Swedish population. Journal of Internal Medicine. 2002;251:207–216. doi: 10.1046/j.1365-2796.2002.00941.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• McCall WV. A psychiatric perspective on insomnia. Journal of Clinical Psychiatry. 2001;62 Suppl 10:27–32. [ PubMed ] [ Google Scholar ]
• Mellinger GD, Balter MB, Uhlenhuth EH. Insomnia and its treatment: Prevalence and correlates. Archives of General Psychiatry. 1985;42:225–232. doi: 10.1001/archpsyc.1985.01790260019002. [ DOI ] [ PubMed ] [ Google Scholar ]
• Morgan K. Daytime activity and risk factors for late-life insomnia. Journal of Sleep Research. 2003;12:231–238. doi: 10.1046/j.1365-2869.2003.00355.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• Morgan K, Clarke D. Risk factors for late-life insomnia in a representative general practice sample. Br.J.Gen.Pract. 1997;47:166–169. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Morgenthaler T, Alessi C, Friedman L, Owens J, Kapur V, Boehlecke B, et al. Practice parameters for the use of actigraphy in the assessment of sleep and sleep disorders: an update for 2007. Sleep. 2007;30:519–529. doi: 10.1093/sleep/30.4.519. [ DOI ] [ PubMed ] [ Google Scholar ]
• Murata C, Yatsuya H, Tamakoshi K, Otsuka R, Wada K, Toyoshima H. Psychological factors and insomnia among male civil servants in Japan. Sleep Medicine. 2007;8:209–214. doi: 10.1016/j.sleep.2007.01.008. [ DOI ] [ PubMed ] [ Google Scholar ]
• Nakata A, Haratani T, Takahashi M, Kawakami N, Arito H, Kobayashi F, et al. Job stress, social support, and prevalence of insomnia in a population of Japanese daytime workers. Social Science and Medicine. 2004;59:1719–1730. doi: 10.1016/j.socscimed.2004.02.002. [ DOI ] [ PubMed ] [ Google Scholar ]
• National Institutes of Health. Bethesda, MD: NIH State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults. 2005
• Nofzinger EA, Buysse DJ, Germain A, Price JC, Miewald JM, Kupfer DJ. Functional neuroimaging evidence for hyperarousal in insomnia. American Journal of Psychiatry. 2004;161:2126–2131. doi: 10.1176/appi.ajp.161.11.2126. [ DOI ] [ PubMed ] [ Google Scholar ]
• Novak M, Mucsi I, Shapiro CM, Rethelyi J, Kopp MS. Increased utilization of health services by insomniacs--an epidemiological perspective. Journal of Psychosomatic Research. 2004;56:527–536. doi: 10.1016/j.jpsychores.2004.02.007. [ DOI ] [ PubMed ] [ Google Scholar ]
• Ohayon MM. Epidemiology of insomnia: What we know and what we still need to learn. Sleep Medicine Reviews. 2002;6:97–111. doi: 10.1053/smrv.2002.0186. [ DOI ] [ PubMed ] [ Google Scholar ]
• Ohayon MM. Relationship between chronic painful physical condition and insomnia. Journal of Psychiatric Research. 2005;39:151–159. doi: 10.1016/j.jpsychires.2004.07.001. [ DOI ] [ PubMed ] [ Google Scholar ]
• Ohayon MM, Hong SC. Prevalence of insomnia and associated factors in South Korea. Journal of Psychosomatic Research. 2002;53:593–600. doi: 10.1016/s0022-3999(02)00449-x. [ DOI ] [ PubMed ] [ Google Scholar ]
• Ohayon MM, Roth T. Place of chronic insomnia in the course of depressive and anxiety disorders. Journal of Psychiatric Research. 2003;37:9–15. doi: 10.1016/s0022-3956(02)00052-3. [ DOI ] [ PubMed ] [ Google Scholar ]
• Ozminkowski RJ, Wang S, Walsh JK. The direct and indirect costs of untreated insomnia in adults in the United States. Sleep. 2007;30:263–273. doi: 10.1093/sleep/30.3.263. [ DOI ] [ PubMed ] [ Google Scholar ]
• Pavlova M, Berg O, Gleason R, Walker F, Roberts S, Regestein Q. Self-reported hyperarousal traits among insomnia patients. Journal of Psychosomatic Research. 2001;51:435–441. doi: 10.1016/s0022-3999(01)00189-1. [ DOI ] [ PubMed ] [ Google Scholar ]
• Perlis ML, Smith MT, Andrews PJ, Orff H, Giles DE. Beta/Gamma EEG activity in patients with primary and secondary insomnia and good sleeper controls. Sleep. 2001;24:110–117. doi: 10.1093/sleep/24.1.110. [ DOI ] [ PubMed ] [ Google Scholar ]
• Phillips B, Mannino DM. Does Insomnia Kill? Sleep. 2005;28:965–971. doi: 10.1093/sleep/28.8.965. [ DOI ] [ PubMed ] [ Google Scholar ]
• Riemann D, Voderholzer U. Primary insomnia: a risk factor to develop depression? Journal of Affective Disorders. 2003;76:255–259. doi: 10.1016/s0165-0327(02)00072-1. [ DOI ] [ PubMed ] [ Google Scholar ]
• Roth T. Insomnia: definition, prevalence, etiology, and consequences. J.Clin.Sleep Med. 2007;3:S7–S10. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Roth T, Roehrs T, Pies R. Insomnia: pathophysiology and implications for treatment. Sleep Medicine Reviews. 2007;11:71–79. doi: 10.1016/j.smrv.2006.06.002. [ DOI ] [ PubMed ] [ Google Scholar ]
• Sadeh A, Acebo C. The role of actigraphy in sleep medicine. Sleep Medicine Reviews. 2002;6:113–124. doi: 10.1053/smrv.2001.0182. [ DOI ] [ PubMed ] [ Google Scholar ]
• Sateia MJ, Doghramji K, Hauri PJ, Morin CM. Evaluation of chronic insomnia. An American Academy of Sleep Medicine review. Sleep. 2000;23:243–308. [ PubMed ] [ Google Scholar ]
• Schwartz S, McDowell AW, Cole SR, Cornoni-Huntley J, Hays JC, Blazer D. Insomnia and heart disease: a review of epidemiologic studies. Journal of Psychosomatic Research. 1999;47:313–333. doi: 10.1016/s0022-3999(99)00029-x. [ DOI ] [ PubMed ] [ Google Scholar ]
• Simon GE, Von Korff M. Prevalence, burden, and treatment of insomnia in primary care. American Journal of Psychiatry. 1997;154:1417–1423. doi: 10.1176/ajp.154.10.1417. [ DOI ] [ PubMed ] [ Google Scholar ]
• Sivertsen B, Omvik S, Havik OE, Pallesen S, Bjorvatn B, Nielsen GH, et al. A comparison of actigraphy and polysomnography in older adults treated for chronic primary insomnia. Sleep. 2006;29:1353–1358. doi: 10.1093/sleep/29.10.1353. [ DOI ] [ PubMed ] [ Google Scholar ]
• Stepanski E, Zorick F, Roehrs T, Young D, Roth T. Daytime alertness in patients with chronic insomnia compared with asymptomatic control subjects. Sleep. 1988;11:54–60. doi: 10.1093/sleep/11.1.54. [ DOI ] [ PubMed ] [ Google Scholar ]
• Stoller MK. Economic effects of insomnia. [Review] Clinical Therapeutics. 1994;16:873–897. discussion 854. [ PubMed ] [ Google Scholar ]
• Su TP, Huang SR, Chou P. Prevalence and risk factors of insomnia in community-dwelling Chinese elderly: a Taiwanese urban area survey. Aust.N.Z.J.Psychiatry. 2004;38:706–713. doi: 10.1080/j.1440-1614.2004.01444.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• Tang NK, Wright KJ, Salkovskis PM. Prevalence and correlates of clinical insomnia co-occurring with chronic back pain. Journal of Sleep Research. 2007;16:85–95. doi: 10.1111/j.1365-2869.2007.00571.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• Taylor DJ, Lichstein KL, Durrence HH. Insomnia as a health risk factor. Behavioral Sleep Medicine. 2003;1:227–247. doi: 10.1207/S15402010BSM0104_5. [ DOI ] [ PubMed ] [ Google Scholar ]
• Taylor DJ, Mallory LJ, Lichstein KL, Durrence HH, Riedel BW, Bush AJ. Comorbidity of chronic insomnia with medical problems. Sleep. 2007;30:213–218. doi: 10.1093/sleep/30.2.213. [ DOI ] [ PubMed ] [ Google Scholar ]
• Ustun TB, Privett M, Lecrubier Y, Weiller E, Simon G, Korten A, et al. Form, frequency and burden of sleep problems in general health care: a report from the WHO Collaborative Study on Psychological Problems in General Health Care. European Psychiatry. 1996;11:S5–S10. [ Google Scholar ]
• Vallieres A, Morin CM. Actigraphy in the assessment of insomnia. Sleep. 2003;26:902–906. doi: 10.1093/sleep/26.7.902. [ DOI ] [ PubMed ] [ Google Scholar ]
• Van Someren EJ. Improving actigraphic sleep estimates in insomnia and dementia: how many nights? Journal of Sleep Research. 2007;16:269–275. doi: 10.1111/j.1365-2869.2007.00592.x. [ DOI ] [ PubMed ] [ Google Scholar ]
• Walsh JK, Engelhardt CL. The direct economic costs of insomnia in the United States for 1995. Sleep. 1999;22:S386–S393. [ PubMed ] [ Google Scholar ]
• Weissman MM, Greenwald S, Nino-Murcia G, Dement WC. The morbidity of insomnia uncomplicated by psychiatric disorders. General Hospital Psychiatry. 1997;19:245–250. doi: 10.1016/s0163-8343(97)00056-x. [ DOI ] [ PubMed ] [ Google Scholar ]
• World Health Organization. Geneva: World Health Organization; The ICD-10 classification of mental and behavioural disorders. Clinical descriptions and diagnostic guidelines. 1992
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Morin CM , Chen S , Ivers H, et al. Effect of Psychological and Medication Therapies for Insomnia on Daytime Functions : A Randomized Clinical Trial . JAMA Netw Open. 2023;6(12):e2349638. doi:10.1001/jamanetworkopen.2023.49638

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Effect of Psychological and Medication Therapies for Insomnia on Daytime Functions : A Randomized Clinical Trial

• 1 Centre de Recherche CERVO/Brain Research Center, École de Psychologie, Université Laval, Quebec City, Quebec, Canada
• 2 Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
• 3 Department of Psychiatry and Behavioral Services, University of California, San Francisco
• 4 University of Colorado, Denver
• 5 National Jewish Health, Denver, Colorado
• 6 Duke University Medical Center, Durham, North Carolina

Question   Which first-stage treatment is optimal for improving daytime functions among patients with insomnia, and which second-stage treatment offers the best added value for patients whose insomnia has not remitted?

Findings   In a randomized clinical trial of 211 adults with insomnia disorder, first-stage treatment with behavioral therapy (BT) or zolpidem produced significant improvements for various daytime outcomes, including depressive symptoms, fatigue, functional impairments, and mental health, that were no different between groups. Adding a second-stage therapy offered an added value for further improving daytime functions with immediate and delayed effects observed for treatment sequences starting with zolpidem and BT, respectively.

Meaning   These findings support the comparable efficacy between sequential treatments starting with BT and zolpidem for addressing the daytime consequences of insomnia.

Importance   Daytime functional impairments are the primary reasons for patients with insomnia to seek treatment, yet little is known about what the optimal treatment is for improving daytime functions and how best to proceed with treatment for patients whose insomnia has not remitted.

Objectives   To compare the efficacy of behavioral therapy (BT) and zolpidem as initial therapies for improving daytime functions among patients with insomnia and evaluate the added value of a second treatment for patients whose insomnia has not remitted.

Design, Setting, and Participants   In this sequential multiple-assignment randomized clinical trial conducted at institutions in Canada and the US, 211 adults with chronic insomnia disorder were enrolled between May 1, 2012, and December 31, 2015, and followed up for 12 months. Statistical analyses were performed on an intention-to-treat basis in April and October 2023.

Interventions   Participants were randomly assigned to either BT or zolpidem as first-stage therapy, and those whose insomnia had not remitted received a second-stage psychological therapy (BT or cognitive therapy) or medication therapy (zolpidem or trazodone).

Main Outcomes and Measures   Study outcomes were daytime symptoms of insomnia, including mood disturbances, fatigue, functional impairments of insomnia, and scores on the 36-item Short-Form Health Survey (SF-36) physical and mental health components.

Results   Among 211 adults with insomnia (132 women [63%]; mean [SD] age, 45.6 [14.9] years), 104 were allocated to BT and 107 to zolpidem at the first stage. First-stage treatment with BT or zolpidem yielded significant and equivalent benefits for most of the daytime outcomes, including depressive symptoms (Beck Depression Inventory-II mean score change, −3.5 [95% CI, −4.7 to −2.3] vs −4.3 [95% CI, −5.7 to −2.9]), fatigue (Multidimensional Fatigue Inventory mean score change, −4.7 [95% CI, −7.3 to −2.2] vs −5.2 [95% CI, −7.9 to −2.5]), functional impairments (Work and Social Adjustment Scale mean score change, −5.0 [95% CI, −6.7 to −3.3] vs −5.1 [95% CI, −7.2 to −2.9]), and mental health (SF-36 mental health subscale mean score change, 3.5 [95% CI, 1.9-5.1] vs 2.5 [95% CI, 0.4-4.5]), while BT produced larger improvements for anxiety symptoms relative to zolpidem (State-Trait Anxiety Inventory mean score change, −4.1 [95% CI, –5.8 to –2.4] vs −1.2 [95% CI, −3.0 to 0.5]; P  = .02; Cohen d  = 0.55). Second-stage therapy produced additional improvements for the 2 conditions starting with zolpidem at posttreatment in fatigue (Multidimensional Fatigue Inventory mean score change: zolpidem plus BT, −3.8 [95% CI, −7.1 to −0.4]; zolpidem plus trazodone, −3.7 [95% CI, −6.3 to −1.1]), functional impairments (Work and Social Adjustment Scale mean score change: zolpidem plus BT, −3.7 [95% CI, −6.4 to −1.0]; zolpidem plus trazodone, −3.3 [95% CI, −5.9 to −0.7]) and mental health (SF-36 mental health subscale mean score change: zolpidem plus BT, 5.3 [95% CI, 2.7-7.9]; zolpidem plus trazodone, 2.0 [95% CI, 0.1-4.0]). Treatment benefits achieved at posttreatment were well maintained throughout the 12-month follow-up, and additional improvements were noted for patients receiving the BT treatment sequences.

Conclusions and Relevance   In this randomized clinical trial of adults with insomnia disorder, BT and zolpidem produced improvements for various daytime symptoms of insomnia that were no different between treatments. Adding a second treatment offered an added value with further improvements of daytime functions.

Trial Registration   ClinicalTrials.gov Identifier: NCT01651442

Insomnia is a highly prevalent sleep disorder that tends to be persistent or recurrent 1 - 4 and can produce a significant burden on the individual and society. 5 - 7 Insomnia is a 24-hour disorder that consists not only of nocturnal symptoms (ie, difficulty initiating and/or maintaining sleep) but also daytime symptoms. 8 - 10 As one of the key components for insomnia diagnosis, daytime functional impairments such as fatigue and mood disturbances are often the primary reasons for patients with insomnia to seek treatment, 11 , 12 indicating the necessity of addressing daytime consequences of insomnia.

Current recommended treatments for insomnia in clinical practice guidelines include 2 major approaches: psychological therapies (ie, cognitive behavioral therapy [CBT]) and medications (eg, benzodiazepine-receptor agonists and sedating antidepressants). 13 - 15 Although medications are more frequently used in clinical practice mostly because they are more easily accessible, few data exist about the efficacy of sleep-promoting medications for improving daytime functions. With regard to CBT, the main outcomes are related to improving sleep continuity and insomnia severity, yet some evidence also suggests that it may be effective in improving various daytime symptoms, such as depressive and anxiety symptoms, daytime sleepiness, fatigue, and quality of life, among insomnia patients and those with comorbid depressive disorder. 16 - 19 However, the effects of CBT on daytime symptoms are predominantly small to moderate, as revealed by a recent meta-analysis. 16

Only a few studies have directly compared the efficacy of CBT and medications for daytime symptoms in insomnia, with mixed findings. In a randomized clinical trial (RCT) of young and middle-aged patients with chronic sleep-onset insomnia, no significant differences were found among CBT, medications, and combination therapy on mood-related changes after intervention. 20 Another RCT of older patients with chronic insomnia found that CBT was more effective than zopiclone in reducing anxiety symptoms in the long term, and equally effective in reducing depressive symptoms in the short term. 21 Furthermore, in an exploratory study of sequential treatments involving both medication and CBT, only CBT provided alone led to significant improvements in depressive symptoms from baseline to postintervention. 22 These inconsistent results preclude definite conclusions about optimal therapy for improving daytime symptoms among patients with insomnia disorder. 23 Although previous insomnia treatment studies have focused primarily on improving nocturnal symptoms of sleep continuity, greater attention to residual daytime impairments is important to optimize long-term outcomes. In addition, it is common for patients with insomnia who had suboptimal treatment responses to switch from one therapy to another in clinical practice. However, to our knowledge, no study has explored which first-stage treatment is optimal for improving daytime functions among patients with insomnia and which second-stage treatment offers the best added value for patients whose insomnia has not remitted with psychological or medication first-stage therapy.

The main objectives of this study were to compare short-term and long-term changes in daytime functions of 4 treatment sequences using psychological (behavioral and cognitive) and pharmacologic therapies (zolpidem and trazodone) for insomnia. In particular, the study aimed to compare the efficacy of behavioral therapy (BT) and zolpidem as first-stage therapies for improvement of daytime functions. For those whose insomnia did not remit after first-stage therapy, the added value of a second treatment was evaluated. Daytime functions investigated in the current study were among the predefined secondary outcomes of a previously published trial. 24 Previous publications regarding the primary outcome related to sleep have suggested the benefits of sequential treatment paradigms on improving nocturnal symptoms of insomnia. 25 , 26 We hypothesized that (1) participants receiving BT would show greater improvements in daytime functions after first-stage treatment than those receiving zolpidem and (2) of all patients receiving second-stage treatment, those who switched modalities (from BT to zolpidem, or vice versa) would report greater improvements at the end of second-stage treatment and at follow-ups than those continuing with the same treatment modality.

This study is part of an RCT that aimed to examine the comparative efficacy of 4 treatment sequences involving psychological and medication therapies for insomnia with and without comorbid psychiatric disorder (trial protocol in Supplement 1 ). Details of the study design, methods, and primary results can be found elsewhere. 24 - 26 The study was conducted at 2 sites: Institut Universitaire en Santé Mentale de Québec, Université Laval, Québec City, Québec, Canada, and National Jewish Health, Denver, Colorado. Participants were enrolled between May 1, 2012, and December 31, 2015. Ethical approval for the study was granted by the local ethics committees of both sites and all participants provided written informed consent. This study followed the Consolidated Standards of Reporting Trials ( CONSORT ) reporting guideline.

This project adopted a sequential multiple assignment randomized trial (SMART) design with 2 treatment stages and 2 treatment modalities for each stage ( Figure ). 25 Eligible participants were randomly assigned to BT or zolpidem at a 1:1 ratio. The first randomization was conducted at each site and stratified by sex, age (<55 vs ≥55 years), and presence of a comorbid psychiatric disorder. After the initial 6 weeks of therapy, patients who met insomnia remission criteria were followed up for the next 12 months while receiving maintenance therapy. Participants were regarded as meeting insomnia remission criteria if their Insomnia Severity Index (ISI) score was less than 8 at the end of first treatment stage. 27 Patients whose insomnia did not remit were randomized (stratified by first randomization and comorbidity) to a second-stage psychological therapy (BT or cognitive therapy [CT]) or medication therapy (zolpidem or trazodone). Measurements were conducted at baseline, end of first-stage therapy (post1) and second-stage therapy (post2), and at 3- and 12-month follow-ups. A complete description of the study protocol is available in Supplement 1 . 24

A total of 211 adults with chronic insomnia were recruited from the community through media advertisements and physician referrals. All participants included in the study met the following criteria: (1) aged 21 years or older, (2) persistent (>1 month) difficulties initiating or maintaining sleep despite adequate opportunity for sleep, (3) sleep onset latency or wake time after sleep onset of 30 minutes or more for 3 or more nights per week during 2 weeks of sleep diary monitoring, (4) ISI total score more than 10, (5) score of 2 or more on either the interference or distress item of the screening ISI. Participants were excluded if they had untreated psychiatric disorders or uncontrolled medical conditions or had conditions that interfered with sleep quality and sleep continuity. Additional details about exclusion criteria can be found in a previous publication. 25 Self-reported race and ethnicity were collected to determine if the study population accurately represents the disease population. 28

The current study focused on changes in daytime functional outcomes, including mood disturbances, fatigue, functional impairments of insomnia, and the 36-item Short-Form Health Survey (SF-36) physical and mental health components. 29 Changes in mood status were assessed with the Beck Depression Inventory–II (BDI-II) 30 and the Trait part of the State-Trait Anxiety Inventory (STAI-Trait). 31 Different dimensions of fatigue (eg, physical and mental) were measured by the Multidimensional Fatigue Inventory (MFI). 32 The Work and Social Adjustment Scale (WSAS) was used to assesses the functional effect of insomnia on 5 domains: ability to work, home management, social leisure activities, private leisure activities, and relationships. 33 Physical and mental health were evaluated by the SF-36, 29 a quality-of-life measure, with a higher score representing a more favorable health state.

The first-stage psychological therapy consisted of BT, which included sleep restriction 34 and stimulus control procedures. 35 The second-stage psychological treatment consisted of CT, which targeted some perpetuating mechanisms (eg, ruminations and worries) that are implicated in the association between insomnia and mood disturbances (eg, anxiety and depression). 36

The first-stage medication treatment involved sublingual zolpidem, 5 mg to 10 mg, taken nightly at bedtime. The second-stage pharmacotherapy consisted of trazodone, 50 to 150 mg, taken 30 minutes before bedtime. As a serotonin receptor antagonist and reuptake inhibitor antidepressant, trazodone can alleviate a wide range of depressive symptoms with an additional sedative effect of sleep, 37 and it has shown efficacy for both patients with insomnia and those with comorbid major depression. 38 Additional information about treatment implementation can be found in a previous publication. 25

The intention-to-treat analyses were performed in April and October 2023. To evaluate each treatment sequence while taking into account the nature of the SMART design (ie, 2 randomizations, where the second is conditional on the response to the first), the analytic strategy was based on recommendations from Nahum-Shani et al. 39 Daytime functional outcomes according to 4 treatment sequences and 5 times (assessment after first-stage treatment [post1] to follow-up at 12 months) were analyzed using weighted generalized estimating equations models with identity link function. 40 Weights were computed as the product of a missing model weight (to attenuate the effect of missing at random data) and a randomization weight (to correct for the inclusion of data from the patients whose insomnia remitted in stage 1 in the 2 sequences at stage 2 and beyond). Strata variables (site, age, sex, and comorbidity status) and outcome value at baseline were included as covariates. 41 A priori contrasts within the weighted generalized estimating equations models were used to estimate temporal changes (baseline to post1, post1 to post2, and post2 to 12-month follow-up) and their 95% CIs and to test significance for comparisons between and within sequences. Data analyses were performed using the SAS, version 9.4, statistical software (SAS Institute Inc) with standard 2-tailed P  < .05 considered statistically significant ( P values for comparisons between sequences were adjusted for multiplicity using the simultaneous test procedure 42 ).

A total of 211 adults (132 women [63%]; mean [SD] age, 45.6 [14.9] years; 14 Black participants [7%], 11 Hispanic participants [5%], 182 White participants [86%], and 4 participants [2%] of other race or ethnicity [Asian (n = 2), Middle Eastern origin (n = 1), and not specified (n = 1)]) who met criteria for insomnia disorder (mean [SD] duration, 13.2 [12.5] years) were randomly allocated to BT (n = 104) or zolpidem treatment (n = 107) ( Table 1 ). 25 Seventy-four participants (35%) had a comorbid psychiatric disorder (eg, anxiety and depression). Use of psychotropic medication (other than sleep-promoting) was reported by 35 participants (17%) at baseline.

Of the 211 randomized participants, 168 completed first-stage therapy ( Figure ), 25 including 88 in the BT group and 80 in the zolpidem group. There were no significant differences in attrition rates between the 2 groups (BT, 16 [15%] vs zolpidem, 27 [25%]; P  = .15). After first-stage therapy, 36 participants in the BT group and 29 in the zolpidem group reached insomnia remission criteria (ISI score <8). Of the available participants whose insomnia did not remit, 108 accepted randomization to second-stage treatment (27 per condition). At baseline, the mean (SE) scores of the STAI-Trait and BDI-II for the included participants in both groups (STAI-Trait: BT group, 39.2 [0.4]; zolpidem group, 38.5 [0.4]; and BDI-II: BT group, 9.0 [0.4]; zolpidem group, 9.7 [0.4]) were below the cutoff scores for clinical mood impairments.

Table 2 shows adjusted mean (SE) values for psychological and daytime functional outcomes. Significant reduction in anxiety symptoms (STAI-Trait) was made with BT after first-stage treatment (mean change, −4.1 [95% CI, −5.8 to −2.4]; Cohen d  = 0.79), but not with zolpidem therapy (−1.2 [95% CI, −3.0 to 0.5]; d  = 0.24), and the difference between changes was significant ( P  = .02; d  = 0.55) (eTable in Supplement 2 ). At post2, a further reduction of anxiety was observed in both conditions starting with zolpidem (mean change: zolpidem plus BT, −4.4 [95% CI, –7.5 to –1.2]; d  = 0.85; zolpidem plus trazodone, −1.8 [95% CI, –3.4 to −0.3]; d  = 0.36), while no change was observed in the sequences starting with BT. Comparisons for post1 to post2 changes of the 4 sequences at post2 was significant for STAI-Trait score (eTable in Supplement 2 ).

Both first-stage therapies produced significant improvements for depressive symptoms (mean change in BDI-II score: BT, −3.5 [95% CI, −4.7 to −2.3]; d  = 0.90; zolpidem, −4.3 [95% CI, −5.7 to −2.9]; d  = 1.10), fatigue (mean change in MFI score: BT, −4.7 [−7.3 to −2.2]; d  = 0.47; zolpidem, −5.2 [95% CI, −7.9 to −2.5]; d  = 0.64), functional impairments (mean change in WSAS score: BT, −5.0 [95% CI, −6.7 to −3.3]; d  = 0.78; zolpidem, −5.1 [95% CI, −7.2 to −2.9]; d  = 0.80), and the SF-36 mental health subscale (mean change: BT, 3.5 [95% CI, 1.9-5.1]; d  = 0.52; zolpidem, 2.5 [95% CI, 0.4-4.5]; d = 0.38); significant improvements for the SF-36 physical health subscale were made only with zolpidem as first-stage treatment (mean change, 1.8 [95% CI, 0.1-3.6]; d  = 0.35; Table 2 ). There were no significant group differences for any of those measures (eTable in Supplement 2 ).

At post2, further improvements were observed for fatigue (mean MFI score change: zolpidem plus BT, −3.8 [95% CI, −7.1 to −0.4]; d  = 0.36; zolpidem plus trazodone, −3.7 [95% CI, −6.3 to −1.1]; d  = 0.46), functional impairments (mean WSAS score change: zolpidem plus BT, −3.7 [95% CI, −6.4 to −1.0]; d  = 0.62; zolpidem plus trazodone, −3.3 [95% CI, −5.9 to −0.7]; d  = 0.55) and the SF-36 mental health subscale (mean score change: zolpidem plus BT, 5.3 [95% CI, 2.7-7.9]; d  = 0.91; zolpidem plus trazodone, 2.0 [95% CI, 0.1-4.0]; d  = 0.35) in treatment sequences starting with zolpidem, while for depression symptoms, only the zolpidem plus BT sequence showed significant improvements (mean BDI-II score change, −2.8 [95% CI, −4.9 to −0.6]; d  = 0.71) ( Table 2 ). No additional changes were observed in the 2 sequences starting with BT at post2, except for functional impairments (mean WSAS score change: BT plus CT, −2.6 [95% CI, −4.4 to −0.7]; d  = 43). The comparisons of the 4 sequences yielded a significant overall effect only for the SF-36 mental health subscale at post 2 (eTable in Supplement 2 ), with both conditions starting with zolpidem showing higher scores on the SF-36 mental health subscale.

Both conditions starting with BT showed significant improvements from post2 to 12-month follow-up for anxiety symptoms (mean change in STAI-Trait score: BT plus zolpidem, −4.6 [95% CI, −7.7 to −1.5]; d  = 0.90; BT plus CT, −3.1 [95% CI, −4.6 to −1.7]; d  = 0.61), fatigue (mean change in MFI score: BT plus zolpidem, −4.9 [95% CI, −7.9 to −1.9]; d  = 0.60; BT plus CT, −4.1 [95% CI, −6.9 to −1.2]; d  = 0.50), and functional impairments (mean change in WSAS score: BT plus zolpidem, −2.8 [95% CI, −5.3 to −0.2]; d  = 0.46; BT plus CT, −2.2 [95% CI, −3.9 to −0.5]; d  = 0.37) ( Table 2 ). For depressive symptoms, only the BT plus CT sequence showed a significant improvement from post2 to 12-month follow-up (mean change in BDI-II score: −1.5 [95% CI, −2.8 to –0.2]; d  = 0.39). No group differences were obtained at follow-ups for any of the outcomes (eTable in Supplement 2 ).

The findings in the subgroup analysis by psychiatric comorbidity (absent vs present) were similar to those from the main analysis for most of the outcomes. However, they are not reported in detail here due to the small sample sizes and reduced power for those analyses.

The current study showed that first-stage treatment with BT or zolpidem was effective in reducing daytime symptoms of insomnia, with no significant differences between groups. The addition of a second-stage therapy resulted in an added value in enhancing daytime functions. In particular, immediate effects of second-stage therapies were observed for sequences that used zolpidem as the initial treatment, while delayed effects were made with sequences starting with BT at 12-month follow-up. Overall, these findings provide further support for the efficacy of CBT and sleep-promoting medication for improving daytime functions among patients with insomnia.

Although some studies have previously reported benefits of CBT on daytime outcomes, 16 - 19 reports of daytime functional improvements with medication therapy are relatively novel, to our knowledge. 43 A significant reduction in anxiety symptoms was seen with BT after first-stage treatment, but not with zolpidem, which is similar to the findings of a previous study conducted among patients with insomnia without psychiatric comorbidity. 21 The relative superiority of BT compared with zolpidem for reducing anxiety symptoms may be partly explained by the significant reduction in sleep latency and time awake after sleep onset made with BT, which could lead to reduced anxiety and worry when initiating sleep and during midnight awakenings. 25 In addition, BT may also reduce sleep-related anxiety or distress through modifying participants’ perception of sleep. 44 However, this finding should be interpreted with caution, as the threshold for clinically significant anxiolysis should be a 50% or greater reduction in baseline total score. 45 , 46

At the end of second-stage therapy, although patients in the 2 groups starting with zolpidem showed further improvements for most daytime outcomes, only patients who switched from pharmacotherapy to psychological treatment (from zolpidem to BT) reported greater reductions in depressive severity. This finding aligned with our hypothesis that switching treatment modalities would lead to greater treatment benefits, although it needs to be interpreted cautiously given the smaller sample size for the treatment sequence involving 2 medications and the mild range of depressive symptoms. In the treatment sequences starting with BT, patients who received 2 treatments within the same modality (from BT to CT) had slightly better outcomes than those who switched modality (from BT to zolpidem) at 12-month follow-up, which may be partially attributed to the broader action of CT by targeting psychological and mood symptoms compared with zolpidem. 36 , 47

Some of the findings need to be interpreted cautiously given some methodological limitations. First, the lack of a control condition and the relatively small sample sizes for each treatment sequence may reduce the statistical power to detect more significant group differences. Second, only patients whose insomnia did not remit received second-stage therapy, while patients with insomnia who achieve remission can still have residual daytime impairments (eg, fatigue and mood disturbances) that are associated with future relapse 48 and may be adequately addressed only by maintenance therapy. Additional studies should consider including daytime outcomes as one of the measures to guide treatment decisions. Third, the study population may not accurately represent the target disease population due to its underrepresentation of racial and ethnic minority groups, 28 which could potentially affect the generalizability of the findings to the broader population of individuals.

The present study documented the efficacy of BT and zolpidem for improving daytime functional outcomes among patients with insomnia and the effect of BT on reducing anxiety symptoms. Adding a second treatment offered an added value for further improvements of daytime functions. Future developments of insomnia treatment strategies should take into account the daytime consequences of insomnia. Additional studies are needed to further investigate the potential benefits of switching treatment modalities and incorporating a therapeutic component that can address psychological and mood disturbances.

Accepted for Publication: October 23, 2023.

Published: December 28, 2023. doi:10.1001/jamanetworkopen.2023.49638

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2023 Morin CM et al. JAMA Network Open .

Corresponding Author: Charles M. Morin, PhD, École de Psychologie, Université Laval, 2325, rue des Bibliothèques, QC G1V 0A6, Canada ( [email protected] ).

Author Contributions: Drs Morin and Edinger had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Morin and Edinger were co–principal investigators.

Concept and design: Morin, Beaulieu-Bonneau, Krystal, Bélanger, Edinger.

Acquisition, analysis, or interpretation of data: Morin, Chen, Ivers, Beaulieu-Bonneau, Krystal, Guay, Cartwright, Simmons, Lamy, Busby, Edinger.

Drafting of the manuscript: Morin, Chen, Ivers.

Critical review of the manuscript for important intellectual content: Morin, Chen, Beaulieu-Bonneau, Krystal, Guay, Bélanger, Cartwright, Simmons, Lamy, Busby, Edinger.

Statistical analysis: Morin, Ivers.

Obtained funding: Morin, Krystal, Edinger.

Administrative, technical, or material support: Morin, Beaulieu-Bonneau, Krystal, Cartwright, Simmons, Lamy, Busby, Edinger.

Supervision: Morin, Guay, Bélanger, Simmons, Lamy, Edinger.

Conflict of Interest Disclosures: Dr Morin reported receiving grants and personal fees from Eisai and Idorsia; grants from Lallemand Health; and royalties from Mapi Research Trust outside the submitted work. Dr Krystal reported receiving grants from Janssen Pharmaceuticals, Axsome Pharmaceutics, Attune, Harmony, Neurocrine Biosciences, Reveal Biosensors, The Ray and Dagmar Dolby Family Fund, and the National Institutes of Health; personal fees from Axsome Therapeutics, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage, and Takeda; and stock options from Big Health and Neurawell outside the submitted work. No other disclosures were reported.

Funding/Support: This study was funded by grant MH091053 from the National Institute of Mental Health.

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 3 .

Additional Information: The Data and Safety Monitoring Board (DSMB) was composed of 3 members including Daniel Almirall, PhD, University of Michigan (Chair), Vaughn McCall, MD, Medical College of Georgia, and Richard Bootzin, PhD, deceased. Members of the DSMB received honoraria at the standard National Institutes of Health rate. The DSMB committee was responsible for safeguarding the interests of study participants, assessing the safety and efficacy of study procedures, and monitoring the overall conduct of the study. The DSMB completed an annual review of the trial conduct. This committee was independent from the sponsor and declared no competing interests.

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