“Efficacy and Safety of Non-Benzodiazepine Hypnotics for Chronic Insomnia in Patients With Bipolar Disorder”, 2011-02 (; backlinks):
Background: Insomnia in patients with bipolar disorder (BD) can cause distress, daytime dysfunction, cognitive impairment, worsening of hypomanic/manic symptoms and increased suicide risk. Physicians often prescribe hypnotics for BD patients with insomnia although no hypnotic has a specific FDA indication for this use. In this study, the patterns of use, efficacy and safety of 5 non-benzodiazepine hypnotics (NBZHs) were assessed in a large group of outpatients with BD.
Method: A chart review was performed for all older adolescents and adult BD outpatients in a private outpatient clinic. Clinical data was collected for any patient who had ever been prescribed a NBZH for insomnia and included successful current use, past unsuccessful treatments, side effects, duration of use, concurrent psychiatric medications, and absence or presence of untoward events often associated with chronic use of hypnotics.
Results: A large number of BD patients take NBZHs as needed or on a daily basis. 4 NBZHs had adequate success rates; ramelteon was limited in efficacy. Some patients experienced satisfactory results from a NBZH after unsuccessful trials with one or more other NBZHs. About half of the current NBZH users are taking them on a daily long-term basis, and none of these patients have experienced unacceptable untoward events. About 3 quarters of the chronic NBZH users are taking antimanic medications concurrently, and less than half of the chronic users are taking antidepressants.
Limitations: The results may not be generalizable to other BD populations. A control group was not included in the design. Chronic users of NBZHs were not asked to discontinue their NBZH in order to confirm indication for long-term use.
Conclusion: Most NBZHs can be effective and safe agents for selected BD outpatients with episodic or chronic insomnia. Failure to respond to one or more NBZH does not preclude a satisfactory response to a different NBZH. Some BD patients who take maintenance antimanic agents also require NBZH treatment. Overactivation from antidepressant treatment does not contribute to chronic NBZH use in most BD patients.
…Results: Data was collected from a total of 361 consecutive BD patients; 550 (69%) were female. 173 (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 (8%) and ramelteon: 3 (4%).
The treatment success rate for all past trials of each NBZH was zolpidem: 87⁄145 (60%), zolpidem CR: 15⁄26 (58%), eszopiclone: 34⁄74 (46%), zaleplon: 12⁄33 (36%) and ramelteon: 4⁄27 (15%). The most common causes of treatment failure for all of the NBZHs were lack of efficacy (44%) and intolerable side effects (26%). The most common side effects which resulted in discontinuation of each NBZH are listed in Table 1 and for all NBZHs combined are listed in Table 2: 29 (34%) of the current NBZH users did not respond to one previous NBZH trial, 16 (19%) failed two previous NBZH trials, and two (2%) were not successful with 3 previous NBZH trials.
The NBZHs taken by the 40 current chronic daily users include zolpidem (18), eszopiclone (13), zolpidem CR (5), ramelteon (3) and zaleplon (1). The average duration of use for the chronic users is 30 months ± 30 SD (range 1–132 months). 28 (74%) of the chronic users are also taking maintenance antimanic medications (lithium, valproic acid, carbamazepine, and antipsychotics), and 17 (45%) are taking maintenance antidepressants (medications which have FDA approval for an acute major depressive episode or lamotrigine). 7 (18%) of the chronic users have a prior history of substance abuse. Only one of the chronic users was taking over the maximum recommended dose (15 mg of zolpidem), and this dose was with the concurrence of the treating psychiatrist. None of the chronic users reported any of the following known negative consequences of long-term use of hypnotics: misuse/abuse, tolerance, fractures from a fall, motor vehicle accidents or parasomnias.