Treating Insomnia Improves Mood State, Sleep, and Functioning in Bipolar Disorder: A Pilot Randomized Controlled Trial

Bipolar disorder is a common, severe, and chronic disorder (Angst & Sellaro, 2000; Judd et al., 2002). Despite important advances in treatments, new treatment options are urgently needed, particularly for subsyndromal interepisode mood symptoms that impair functioning and increase the risk of relapse (Judd et al., 2002). Sleep disturbance is among the most prominent correlates of mood episodes and inadequate recovery. Reduced need for sleep is a symptom of mania. During episodes of depression, insomnia or hypersomnia are common (American Psychiatric Association, 2013). Even during the interepisode period, sleep is disturbed; up to 70% of bipolar disorder patients report a clinically significant sleep disturbance (Harvey, Schmidt, Scarna, Semler, & Goodwin, 2005), which is associated with relapse and suicide attempts (Sylvia et al., 2012). Sleep disturbance escalates just before and worsens during episodes (Jackson, Cavanagh, & Scott, 2003) and does not always resolve with medication (Gruber et al., 2009, 2011). In addition, poor sleep efficiency, night-to-night variability, long sleep onset latency (Eidelman, Talbot, Gruber, & Harvey, 2010), and delayed phase (Giglio et al., 2010; Mansour et al., 2005) are also common problems for individuals with bipolar disorder. The heterogeneity of sleep problems in bipolar disorder raise significant management and research challenges. Multiple lines of evidence suggest that sleep disturbances, such as insomnia, contribute to mood symptoms in bipolar disorder. First, bipolar disorder patients with short compared with longer sleep exhibit more symptoms of mania, depression, anxiety, and irritability (Gruber et al., 2009). Moreover, shorter total sleep time is associated with increased mania and depression severity over 12 months (Gruber et al., 2011). Second, in a 7-day diary study, total wake time was associated with next morning negative mood in bipolar disorder, and evening negative mood was associated with longer total wake time the following night in both bipolar disorder and insomnia (Talbot et al., 2012). Moreover, in an 8-week diary study, there was a tight coupling across days and nights between sleep and negative affect (Gershon et al., 2012). Third, sleep disturbance is a common prodrome, or early warning signal, of relapse (Jackson et al., 2003). Fourth, experimentally induced sleep deprivation is associated with the onset of hypomania or mania in bipolar disorder (e.g., Wehr, Sack, & Rosenthal, 1987). Together, these data raise the possibility that treating sleep disturbance among patients who meet diagnostic criteria for bipolar disorder could improve mood and functioning and alter the course of the disorder. Despite the clear importance of sleep disturbance in bipolar disorder, very few empirical data specifically address its treatment. We are unaware of any controlled clinical trials for insomnia in bipolar disorder. Zolpidem was the most commonly prescribed medication for insomnia in bipolar disorder in one chart review (Schaffer, Schaffer, Miller, Hang, & Nordahl, 2011), but case reports on benzodiazepines for insomnia in bipolar disorder have not been encouraging (Sattar, Ramaswamy, Bhatia, & Petty, 2003; Weilburg, Sachs, & Falk, 1987). Indeed, drawing from the large sample that participated in the Systematic Treatment Enhancement Program for Bipolar Disorder, Perlis et al. (2010) reported that benzodiazepines were associated with worse outcome. A case report on gabapentin (Egashira et al., 2011) and open trials of medications targeting circadian rhythms (Bersani & Garavini, 2000; Calabrese, Guelfi, Perdrizet-Chevallier, & the Agomelatine Bipolar Study Group, 2007) are more promising but preliminary. Quetiapine was associated with not only relief of bipolar depression but also improved sleep in several studies (e.g., Calabrese et al., 2005; Thase et al., 2006). Existing evidence-based nonpharmacologic interventions for bipolar disorder include psychoeducation (Colom, Vieta, & Scott, 2006), prodrome monitoring (Lam et al., 2003), interpersonal and social rhythm therapy (IPSRT; Frank, 2005), family therapy (Miklowitz & Goldstein, 1997), and cognitive behavior therapy (CBT) administered individually (Lam et al., 2003) or in groups (Patelis-Siotis et al., 2001) as well as combination approaches (Craighead & Craighead, 2001). These treatments, several of which include some attention to sleep disturbances, reduce relapse among adults with bipolar disorder. However, to the best of our knowledge, most of these trials have not had sleep as a primary emphasis or included sleep outcome measures, nor have these treatments incorporated specific insomnia treatment techniques. In light of the ongoing need for novel, effective, well-tolerated treatments for bipolar disorder, we developed a bipolar disorder– specific modification of CBT for insomnia (CBTI-BP). The modifications were focused on improving safety and targeting the unique features of sleep in bipolar disorder by integrating elements from IPSRT, chronotherapy, and motivational interviewing. CBT for insomnia (CBT-I) was selected as the basis for the treatment because (a) substantial evidence demonstrates the efficacy of CBT-I (Morin et al., 2006), even for insomnia comorbid with psychiatric disorders (Taylor & Pruiksma, 2014), including depression (Manber et al., 2008), posttraumatic stress disorder (Ger-main, Shear, Hall, & Buysse, 2007; Talbot et al., 2014), and schizophrenia (Myers, Startup, & Freeman, 2011); (b) when insomnia is comorbid with another psychiatric disorder, the symptoms associated with the other psychiatric disorder can also improve following CBT-I (Manber et al., 2008; Myers et al., 2011; Talbot et al., 2014); (c) previous treatments for bipolar disorder have not been informed by the principles underlying CBT-I (Eidelman et al., 2010; Harvey, 2008); and (d) CBT-I improves sleep efficiency, reduces night-to-night variability, and improves sleep onset latency, all of which are problematic for patients with bipolar disorder (Eidelman et al., 2010). Elements were added from IPSRT (Frank, 2005) to regularize daily social rhythms, building on regular bed and wake-up times. Promising data on chronotherapy, such as dark therapy and light therapy (Wirz-Justice, Benedetti, & Terman, 2009), were integrated by adding a 30–60 min wind-down period in dim light and exposure to bright light on waking within an individualized brisk wake up. Motivational interviewing (Miller & Rollnick, 2002) was incorporated in every session given the challenges inherent to behavior change and recognizing the rewarding nature of many sleep-incompatible behaviors. The aim of the present pilot study was to evaluate the efficacy of CBTI-BP to determine initial feasibility and generate effect size estimates. Interepisode adults with insomnia and bipolar disorder Type I were randomly allocated to receive eight sessions of CBTI-BP or eight sessions of psychoeducation (PE). PE controlled for therapeutic attention and expectation of improvement. We hypothesized that CBTI-BP, relative to PE, would be more efficacious for improving mood state, sleep symptoms, and functioning.