Preliminary communicationEfficacy and safety of nonbenzodiazepine hypnotics for chronic insomnia in patients with bipolar disorder
Introduction
A recent NIH conference on the manifestations and management of chronic insomnia in adults concluded that “chronic insomnia is a major public health problem affecting millions of individuals, and that little is known about the mechanisms, causes, clinical course, comorbidities and consequences of chronic insomnia.” Moreover, the same panel was concerned about the lack of research data on the long-term use of medication treatment for chronic insomnia (National Institutes of Health state of the science conference statement, 2005).
Chronic insomnia is a prevalent problem in patients with bipolar disorder (BD) (Harvey, 2008). Recent studies indicate that BD patients can experience chronic insomnia even when their daytime mood symptoms are under control between affective episodes (Harvey et al., 2005). Successful treatment of chronic insomnia for any patient is important because persistent insomnia can cause considerable subjective distress, metabolic disorders, impairment in cognition and daytime dysfunction. Moreover, results from a recently published study indicate that chronic insomnia may be associated with a reduction of gray matter in the left orbitofrontal cortex (Altena et al., 2010). The control of chronic insomnia in patients with BD is now considered a therapeutic priority because chronic insomnia can cause or exacerbate manic-related symptoms in bipolar patients (Colombo et al., 1999, Wehr et al., 1987, Wehr et al., 1982) and can also increase the risk of suicide (Wojnar et al., 2009).
Many physicians who treat BD prescribe hypnotics for selected patients on both a short and long-term basis despite the lack of clinical trials supporting this intervention in BD patients (Plante and Winkelman, 2008). Moreover, there is no specific FDA indication for the use of any hypnotic in the treatment of insomnia associated with BD.
Benzodiazepines have been the most commonly prescribed hypnotics in general until the recent introduction of several nonbenzodiazepine hypnotics (NBZHs), beginning with zolpidem in 1993. NBZHs are promoted as having several advantages over the benzodiazepines (Schatzberg and Nemeroff, 2009). Several studies have addressed the safety and efficacy of NBZHs for patients with chronic primary insomnia (Schatzberg and Nemeroff, 2009). However, no studies have addressed patterns of use, safety and efficacy of NBZHs specifically for insomnia in BD patients, especially the extended daily use for chronic insomnia in this patient population (Plante and Winkelman, 2008). In this preliminary study, not subsidized by the pharmaceutical industry, the patterns of use, efficacy and safety of NBZHs were addressed in a large group of BD outpatients.
Section snippets
Methods
A review was performed on all the treatment charts of all older adolescent (ages 15–17) and adult outpatients with any type of DSM-IV-TR BD diagnosis (American Psychiatric Association, 2000) currently treated in a private practice staffed by two board certified psychiatrists (CBS and LCS), each with 30 years of clinical experience, who specialize in the treatment of BD. Patients were considered a candidate for a hypnotic if they were experiencing a sleep disturbance characterized by difficulty
Results
Data was collected from a total of 361 consecutive BD patients; two hundred fifty (69%) were female. One hundred and seventy-three (48%) of the 361 total had taken at least one NBZH. Of these 173 patients, 87 (49%) are currently taking a NBZH. Of the current NBZH users, 47 (55%) are taking them as needed and 40 (46%) are taking them chronically. The distribution of the combined current chronic and as needed NBZH use is zolpidem: 50 (59%), zolpidem CR: 9 (11%), eszopiclone: 17 (20%), zaleplon: 7
Discussion
The results of this preliminary study provide several important findings regarding the use of NBZHs for insomnia in outpatients with BD. About one half of the subjects have been prescribed a NBZH, indicating that NBZHs are frequently indicated for this patient population in a clinical treatment setting. Zolpidem, zolpidem CR and eszopiclone were relatively efficacious for both as needed and chronic use (46% to 60%). Zaleplon was effective for as needed use in a few patients (36%), but there was
Role of funding source
No grants, individual or industry support were provided to any of the authors related to this study.
Conflict of interest
All authors declare that they have no actual or potential conflicts of interest.
Acknowledgement
No acknowledgements.
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