A Meta-Analysis of Sleep Disturbances in Panic Disorder

*Geneviève Belleville and Alenka Potočnik*

## **Abstract**

The nature and prevalence of sleep disturbances in panic disorder (PD) have been often discussed but remain unclear. The objective of this systematic review and meta-analysis is to document sleep disturbances in PD. Systematic database search and standardized extraction were conducted. Meta-analysis was computed on self-report (subjective) and polysomnographic (PSG) (objective) data and on prevalence rates of nocturnal panic attacks (NPA). Of the 1262 publications retrieved, 31 were included. PD patients were compared to healthy controls on subjective and objective measures. Patients had higher Pittsburgh sleep quality index (PSQI) global scores (hedges' g = 1.306, 95% CI [0.532, 2.081]), longer PSG sleep latency (hedges' g = 0.81, 95% CI [0.576, 1.035]), poorer PSG sleep efficiency (hedges' g = −0.79, 95% CI [−1.124, −0.432]), and shorter stage 2 (hedges' g = 0.70, 95% CI [−1.231, −0.120]) and total sleep time (hedges' g = −0.739, 95% CI [−1.127, −0.351]). Among patients, 52.1% (95% CI [0.464, 0.577]) reported NPA (≥1/lifetime). Patients with PD demonstrate subjective and objective sleep alterations. More than half have experienced NPA. These sleep disturbances could have a significant role in maintaining PD symptoms.

**Keywords:** panic disorder, nocturnal panic attacks, insomnia, sleep, sleep disturbances, meta-analysis

#### **1. Introduction**

Panic disorder (PD) is a common anxiety disorder, with a prevalence rate of 3.7% in the general population [1]. It is characterized by sudden and recurrent surges of anxiety known as panic attacks, apprehensiveness about panic, and avoidance of potential future panic attacks [2]. In PD, as in many anxiety disorders [3], sleep may be affected. The existing literature describes two primary types of sleep problems in patients with PD: insomnia and nocturnal panic attacks (NPA).

#### **1.1 Insomnia in patients with PD**

DSM-IV-TR defines insomnia as difficulty initiating or maintaining sleep, early awakening, or non-restorative sleep [4]. Symptoms must be present at least three times per week for at least 1 month and must be the source of significant distress or dysfunction [4]. Compared to DSM-IV-TR, DSM-5 added new criteria for insomnia, including early awakening and dissatisfaction with sleep quality [2]. Furthermore, the minimum duration of symptoms was increased to 3 months [2]. Insomnia is assessed using a wide variety of measures that can be generally classified as subjective or objective. The former uses self-report questionnaires and diaries or

clinician-rated assessments; the latter uses physiological measures such as polysomnography or actigraphy [5].

## **1.2 Nocturnal panic attacks**

NPA are paroxysmal events characterized by abrupt awakening in a state of intense anxiety and discomfort [6]. In contrast with panic attacks that begin after waking, individuals experiencing NPA wake up in a state of panic [2]. Nocturnal panic attacks generally occur between stage 2 and stage 3 sleep and are not associated with the content of a nightmare [6]. In the majority of cases, daytime panic attacks are more frequent than NPA. However, a minority of patients primarily experience nocturnal panic attacks [7], and cases of individuals with exclusively nocturnal panic attacks have been reported [8]. Nocturnal panic attacks can be assessed using the NPA appendix from the anxiety disorders interview schedule for DSM-IV. This clinicianadministered interview thoroughly assesses NPA and includes questions relating to NPA frequency, apprehensiveness about future NPA, and avoidance behaviors.

### **1.3 Why study sleep in panic disorder?**

Disturbed sleep in patients with PD is associated with greater PD severity [9]. In a recent study, researchers found that there was a significantly higher prevalence of insomnia (insomnia severity index > 8) in patients with severe or moderate PD symptoms than in patients with mild symptoms [9]. In addition to being associated with symptom severity, sleep disturbances, specifically NPA, are associated with suicidal behavior [10].

Not only are sleep disturbances (insomnia and NPA) associated with greater PD severity and with suicidal behavior, they are also hypothesized to perpetuate panic symptoms. Researchers have proposed that insomnia, NPA, and panic interact and reinforce one another in a vicious cycle [11]. Studies of individuals from the general population revealed that one night of sleep deprivation increases general anxiety and physiological activation [12]. In a similar experiment with patients with PD, researchers observed panic attacks in 40% of patients after one night of sleep deprivation, although none of the participants had experienced a panic attack in the prior week [13]. In the same study, none of the control participants (healthy controls or patients with obsessive-compulsive disorder) reported a panic attack the following day [13]. Although the experience of insomnia is distinct from the experience of sleep deprivation, patients with chronic insomnia can develop a sleep deficit [14]. Some researchers have therefore hypothesized that the effect of chronic insomnia could be comparable (although less intense) to the effect of sleep deprivation, resulting in increased general activation and triggering panic attacks [11]. When an individual also experiences NPA, they may develop apprehensiveness about going to sleep [15]. Apprehensiveness can result in a delayed bedtime, thereby compounding lack of sleep, increasing general activation, and potentially triggering panic [11]. Furthermore, some patients with PD tend to experience distress and even panic attacks in states of relaxation or states of decreased vigilance [16, 17]. It is hypothesized that such a reaction may occur immediately prior to sleep in some patients and may disturb sleep onset.

### **1.4 Unresolved issues related to insomnia in patients with PD**

#### *1.4.1 Subjective sleep data*

Numerous studies have reported subjective sleep data from patients with PD, collected using a wide variety of psychometric tools. For example, many studies

**97**

*A Meta-Analysis of Sleep Disturbances in Panic Disorder DOI: http://dx.doi.org/10.5772/intechopen.86306*

sleep alterations in PD.

*1.4.2 Objective sleep data*

due to their costly and complex nature.

clarity on the rate of NPA in patients with PD.

of the current literature on the subject.

have used the Pittsburgh sleep quality index and report a general sleep quality index [18–21]. The Hamilton depression scale (HAM-D) is another frequently used scale that assesses difficulty initiating and maintaining sleep, as well as early awakenings [22–25]. Moreover, some studies measure variables that are not included in the definition of insomnia, such as sleep duration [23]. This diversity of variables and measures complexifies comparison between studies and precludes a clear portrait of

In contrast to subjective sleep data, objective data is collected in a standardized fashion, generating results that are comparable across studies. However, despite greater uniformity in assessment, the literature on objective sleep data has yielded contradictory results. For example, some authors have reported poorer sleep efficiency in patients with PD in comparison to healthy controls [19, 26], whereas others report no difference between groups [27]. Similarly, inconsistent results have been published about slow-wave sleep (stages 3 and 4) and REM sleep latency [6, 22, 26–31]. The wealth of conflicting data is confusing and can lead to erroneous conclusions. For example, if two studies report a difference between PD and control groups in a given variable and two others report no difference, readers tend to conclude that no substantial difference exists, which may not be the case [32]. Among possible explanations, inconsistencies may be partly attributable to a lack of statistical power: indeed, polysomnographic studies tend to have small sample sizes

**1.5 Unresolved issues concerning the prevalence of NPA in patients with PD**

et al. [33] reported an NPA prevalence rate of 37%, whereas Stein et al. [20] reported a figure almost twice as high (68%). Moreover, different authors use different frequency criteria, ranging from "at least one lifetime NPA" [34–36], to "two to four NPA per year" [33], to "a minimum of four NPA per month" [37], or to "many times per week" [33]. A summary of the data is indicated in order to gain

**1.6 The need for a systematic literature review and meta-analysis**

would be significantly different from that of healthy controls.

The results of NPA prevalence studies vary significantly. For example, Schredl

The unanswered questions described above indicate a clear need for a more precise portrait of sleep disturbances in PD. A systematic review of the existing literature is warranted. Some authors have undertaken the effort in recent decades [38–41], but contradictory results from objective data and variations in the reporting of subjective data resulted in questions remaining about sleep alterations in the population. Lack of uniformity in NPA prevalence measurement and reporting yielded significant variability in prevalence rate estimates. Meta-analytic methodology involves pooling all samples into one group to conduct a quantitative analysis of data from previous research, with greater statistical power than when analyzing each study's data alone. This method would likely allow for a clearer interpretation

The present study was designed to systematically review the existing literature on sleep disturbances in PD. More precisely, the objectives were (1) to compare sleep in patients with PD to sleep in healthy controls and (2) to assess the prevalence rate of NPA in patients with PD. We hypothesized that the sleep of patients with PD

#### *A Meta-Analysis of Sleep Disturbances in Panic Disorder DOI: http://dx.doi.org/10.5772/intechopen.86306*

have used the Pittsburgh sleep quality index and report a general sleep quality index [18–21]. The Hamilton depression scale (HAM-D) is another frequently used scale that assesses difficulty initiating and maintaining sleep, as well as early awakenings [22–25]. Moreover, some studies measure variables that are not included in the definition of insomnia, such as sleep duration [23]. This diversity of variables and measures complexifies comparison between studies and precludes a clear portrait of sleep alterations in PD.
