A 22-year-old female presents and complains of difficulty with sleeping. She also endorses sadness, decreased interest in social activities, intrusive thoughts about her role in her mother’s death, trouble concentrating, and passive suicidal ideation. The patient attributes these symptoms to her inability to obtain adequate sleep. She reports staying in bed for 12–14 hours each night but estimates only 4 hours total sleep time. This has affected her job performance; she is unable to complete tasks efficiently and is irritable when relating to colleagues. She often ruminates during the day about how bad the night will be and has migrated her bedtime progressively earlier to attempt to achieve adequate sleep.
Insomnia disorder is defined in the International Classification of Sleep Disorders, third edition (ICSD-3) as: 1) the patient reports difficulty initiating or maintaining sleep, or waking up too early; 2) sleep difficulties occur despite adequate opportunity and circumstances for sleep; and 3) the patient describes daytime impairment that is attributable to the sleep difficulties.
Patients must meet all three criteria in order to be diagnosed with insomnia. This first criterion represents a slight shift from the ICSD-2, which included “unrefreshing sleep” in addition to difficulty initiating or maintaining sleep. Although clinically important, “unrefreshing” or “nonrestorative” sleep has been notoriously difficult to consistently define and validate.
Another change in the newer classification is the elimination of subtypes (eg, psycho-physiological, paradoxical, idiopathic, insomnia due to a medical condition, insomnia due to a mental condition, inadequate sleep hygiene) included in the ICSD-2. The validity of these categories has been questioned, due to considerable overlap between groups and poor inter-rater reliability.1 In clinical practice, these distinctions are rarely useful because they are either nearly impossible to identify (eg, paradoxical insomnia, in which the patient markedly misreports total sleep time) or practically interchangeable (eg, psycho-physiological insomnia and insomnia due to poor sleep hygiene, both of which warrant similar behavioral interventions).
The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM- 5)2 (Table 1) criteria for insomnia disorder are similar to the ICSD. Changes between the DSM-IV and DSM-5 reflect the same research advances that motivated the changes in ICSD. First, nonrestorative sleep is no longer by itself a complaint warranting a diagnosis of insomnia disorder. Instead, dissatisfaction with sleep quality also requires 1 of the 3 cardinal symptoms of insomnia. Second, the DSM-5 removes the distinction between primary and comorbid insomnia. As researchers have learned more about the relationship between insomnia and psychiatric disorders, it has become increasingly clear that the relationship is often bidirectional. It is seldom clear that insomnia is merely secondary to another disorder. Furthermore, various research studies suggest that insomnia itself should be addressed regardless of its comorbidity—a practice that may be facilitated by the shift in terminology introduced in the DSM-5.
DSM-52 Criteria for Insomnia Disorder
Although it is considered a sleep disorder, research has shown that the physiologic abnormalities characteristic of the disorder are present 24 hours per day. The crucial pathophysiologic feature of insomnia is hyperarousal.3 This is evidenced in a variety of physiologic domains including autonomic activation (increased heart rate, decreased heart rate variability); elevated stress hormones (eg, cortisol and norepinephrine); higher metabolic rate (increased VO2 max [maximum rate of oxygen consumption] and brain metabolism); electroencephalographic arousal (increased high-frequency beta activity); and behavioral evidence of decreased sleep propensity (increased latency to sleep during daytime nap opportunities).
In parallel to these neurobiological alterations, a common set of pathological cognitive-behavioral elements underlie insomnia in most patients. Frequently, insomnia is triggered in a susceptible individual by a stressful life event—the precipitant. This could be a social, medical, or psychological stressor that temporarily disrupts the normal sleep pattern. Acute insomnia is common in this setting and frequently resolves without treatment. However, a subset of patients will go on to develop chronic insomnia despite resolution of the initial precipitant. In this group, there are frequently both predisposing and perpetuating factors that maintain the unsatisfactory sleep pattern despite resolution of the precipitating circumstances. Predisposing conditions may include a tendency toward rumination, poor coping skills, older age, or medical illness. Perpetuating factors are often behaviors undertaken by the patient as compensatory responses to the insomnia such as going to bed earlier, napping, and excessive thoughts about the need for sleep. These cognitive and behavioral patterns become counter-productive because they increase time in bed while alert and anxious, thereby creating a state of conditioned arousal in the bedroom that serves to further perpetuate insomnia.
Tools for Diagnosis
The primary tools for diagnosis of insomnia are clinical history and sleep diaries. Clinical history should focus on identifying precipitants of insomnia as well as behavioral and cognitive features that may be perpetuating the disorder. A full psychiatric and medical history is an essential component of the workup of insomnia as comorbid disorders may be additional sources of sleep disruption and targets of therapy. In addition to history, sleep diaries are another important tool in the diagnosis of insomnia. Although insomniacs have a tendency to underestimate total sleep time, diaries can provide useful information about an erratic sleep schedule or excessive time in bed that may prove to be useful targets for behavioral intervention.
Polysomnography is rarely required for the diagnosis of insomnia. The primary utility of this test is to exclude other sleep disorders that may be causing (or co-occurring with) the insomnia. Patients who report loud snoring, choking/gasping, or witnessed apneas should be studied to rule out sleep-disordered breathing. Those reporting abnormal movements during sleep or dream-enactment behavior should be studied to rule out rapid eye movement behavior disorder. Actigraphy is also seldom helpful clinically and has not been well validated in insomnia patients who may spend considerable time lying still in bed while awake.
Relationship with Other Psychiatric Disorders
Insomnia is over-represented in a wide spectrum of psychiatric disorders. The most well described association is with mood disorders. This relationship is complex and bidirectional, as insomnia is not only a symptom of depression but also a predictor of it. In one meta-analysis study, the odds of new onset depression in patients with insomnia compared to those without insomnia was 2.60 (confidence interval: 1.98–3.42).4
The comorbidity of depression and insomnia likely influences the presentation and the course of both disorders. For instance, depressed patients with insomnia tend to have a more severe form of depression compared to those without.5 This group is also at a higher risk for adverse outcomes related to major depressive disorder (MDD), particularly suicidal thoughts and behaviors. This association persists after adjustment for depression severity and other psychiatric comorbidity.3 With regard to characteristics of insomnia, it has commonly been held that patients with MDD tend to have a propensity toward early morning awakenings as opposed to other types of insomnia. This association, however, has not been substantiated in research studies. Instead, the distribution of insomnia symptoms throughout the night seems to be similar to insomniacs without depression.6 It is true, however, that insomniacs with depression tend to have shorter total sleep time compared to those without depression7—likely indicating a more severe form of insomnia.
In bipolar depression, decreased sleep during the manic phase rarely meets criteria for insomnia due to perceived lack of need for sleep. However, recent research has shown that inter-episode bipolar patients also sleep worse than normal controls, displaying impairment in clinical sleep variables and associated distress that frequently meets criteria for the diagnosis of insomnia.8
Insomnia is also a frequent accompaniment of other psychiatric disorders. In schizophrenic patients, the onset of psychosis is often associated with profound insomnia. Similarly, sleep difficulties may be a prodrome marking the imminent relapse of psychosis among treated patients.9 The association between sleep disturbance and suicidal behaviors seen in depressed patients is also true in patients with schizophrenia, with an odds ratio = 12.7 noted in one study.10
Because anxiety is a common predisposing factor in insomnia, it is not surprising that patients with anxiety disorders suffer disproportionately from insomnia. Posttraumatic stress disorder (PTSD), in particular, is frequently characterized by the same hypervigilance that underlies insomnia disorder. Furthermore, nightmares are common in this group and may be a trigger to sleep disturbance. It is likely that the relationship between insomnia and PTSD is bidirectional—sleep disturbance is not only a characteristic of PTSD but also a marker of increased vulnerability to a maladaptive stress response that generates PTSD.11
Panic disorder is another anxiety disorder that is frequently comorbid with insomnia. This association may be due in part to nocturnal panic attacks, which have been reported in 58% of those with panic disorder and may constitute a more severe form of the illness.12 Although it is clear that nocturnal panic attacks disrupt sleep and perpetuate insomnia, there is also evidence that sleep deprivation lowers the threshold for a panic response to a carbon dioxide challenges.13 As in other psychiatric disorders, there is likely a bidirectional causative relationship whereby nocturnal panic symptoms provoke insomnia and lack of sleep in turn exacerbates panic disorder.
In the past, insomnia was often viewed as a symptom of psychiatric disorders likely to resolve with treatment. However, as reflected in the new definitions detailed above, recent research has focused on insomnia and psychiatric disorders as distinct diagnostic entities with separate (albeit inter-related) characteristics and courses. Thus, in most cases, it is appropriate to undertake treatment for both disorders simultaneously.
There are two primary approaches to treatment of insomnia: cognitive behavioral therapy (CBT) and hypnotic medications. Selection of a treatment approach should be made in collaboration with the patient. Some patients have a preference to avoid medications, while others aren’t able to make the time commitment or tolerate the temporarily increased fatigue required for CBT. In those who are willing and able, a combination of the two approaches is probably the most effective for long-term management.
Cognitive Behavioral Therapy
Cognitive behavioral therapy for insomnia (CBT-i) generally consists of 6–8 weekly sessions in which patients are taught to identify and rectify the unhelpful behaviors and cognitive patterns that perpetuate insomnia. A variety of strategies are taught in CBT-i, including sleep hygiene, relaxation techniques, and cognitive restructuring; however, the two components with proven efficacy are sleep restriction and stimulus control.
Stimulus control is based on principles of classical conditioning. In this model, the bedroom and the process of attempting to sleep become stimuli that produce anxiety and physiological arousal, thereby interfering with sleep and perpetuating insomnia. Accordingly, in CBT-i, the patient is directed to get out of bed when awake and unable to sleep in order to preserve the bed as a place for drowsiness/sleep.
Sleep restriction is the other well-validated intervention in CBT-i. Sleep diaries are crucial for successful implementation of this technique (Figure 1). Initially, baseline diaries are used to determine the estimated total sleep time. The patient is given instructions to limit the total time in bed to the actual amount of time slept. Initially, total sleep time will decrease relative to baseline, but the increased sleep drive that ensues will over time facilitate faster sleep onset and better sleep maintenance. Such improvements help to reduce anxiety regarding sleeplessness, increase confidence in the ability to fall and stay asleep, and lead to the reestablishment of a pattern of regular sleep. Time in bed is then gradually increased as long as difficulties with sleep initiation or maintenance do not return.
Sleep diary example.
In patients with psychiatric disorders, there are theoretical barriers that may interfere with successful implementation of CBT-i. For instance, lack of motivation in patients with mood disorders may interfere with adherence to the strict sleep schedule required in sleep restriction. Patients with PTSD or panic disorder may be unable to suppress the arousal response using stimulus control due to persistent negative stimuli in the bedroom. In patients with bipolar disorder, sleep restriction should be pursued with great caution due to risks of precipitating a manic episode. However, several studies have shown that the efficacy of CBT-i for insomnia symptoms is not different between patients with and without depression, and may also produce therapeutic benefit for the mood disorder.14 In those with nightmares or nocturnal panic attacks, these symptoms should be concurrently addressed because, when they are, CBT-i is also likely to be effective.15
The most well-researched and commonly used hypnotics bind to the benzodiazepine site on gamma-aminobutyric acid-A (GABA-A) receptors (Table 2). These include both the benzodiazepines and the newer benzodiazepine receptor agonists (BZRA). Although the newer agents are somewhat more selective for a subtype of the GABA-A receptor, practically this makes little difference. The choice of hypnotic should be made based on the patient’s tolerance and preference as well as pharmacokinetic considerations. For instance, patients with exclusively sleep onset difficulties may benefit from shorter-acting agents (eg, zolpidem, triazolam), whereas longer-acting agents (eg, lorazepam, eszopiclone) would be more appropriate for those with impaired-sleep maintenance. If benzodiazepine agonists are ineffective, poorly tolerated, or contraindicated, alternative treatment options include sedating antidepressants, melatonin agonists, atypical antipsychotics, and antiepileptics.
US Food and Drug Administration-approved Drugs for Treatment of Insomnia
Several of the newer BZRA hypnotic medications have been studied specifically for use in patients with both insomnia and depression. Although evidence is conflicting regarding their efficacy to improve mood outcomes, it is clear that sleep and quality of life can be markedly improved by the use of hypnotic medications as adjuncts to antidepressants for the initial therapy of MDD with depression.16 Furthermore, follow-up studies have shown no evidence of withdrawal or rebound insomnia in such patients after the hypnotic is stopped.17