WASHINGTON, Sept. 9 -- When hot flashes keep breast cancer patients awake, antidepressants augmented by zolpidem (Ambien) may bring more sleep time, suggested a small randomized trial reported here.
More than twice as many patients treated with zolpidem had improvement in objective measures of sleep time and quality, Hadine Joffe, M.D., of Massachusetts General Hospital in Boston, reported at the 2008 ASCO Breast Cancer Symposium.
Quality of life also improved significantly in the zolpidem versus placebo groups. Measures of hot flashes and mood did not differ between the treatment groups.
"Targeting sleep disturbance in breast cancer survivors with hot flashes may be an important strategy to optimize well-being," said Dr. Joffe. "Current approaches to treatment are only partially effective, which can lead to persistent sleep disturbance."
"Use of an agent like zolpidem is convenient in that it can be implemented at the same time as therapy for hot flashes without interrupting it," she added.
Selective serotonin reuptake inhibitors (SSRIs) and the dual reuptake inhibitor venlafaxine (Effexor) are widely used to treat hot flashes but provide only partial relief in a majority of patients, said Dr. Joffe.
To test the hypothesis that augmentation of antidepressant therapy with a hypnotic agent might improve hot flash management and improve sleep and quality of life, she and co-investigators randomized 53 breast cancer patients. Eligible patients had reported a minimum of 14 hot flashes over the previous two weeks and insomnia for at least one month, including three or more awakenings per night associated with hot flashes.
Patients already taking an SSRI or venlafaxine continued therapy, and those not taking one of the neurotransmitter reuptake inhibitors started treatment with venlafaxine XR at 75 mg/day. The patients were randomized to zolpidem at 10 mg/day or placebo and followed for five weeks.
Sleep quality was assessed by the Pittsburgh Sleep Quality Index and a wrist actigraph. Hot flashes were monitored by means of a patient diary and an electronic monitor worn at night.
The primary outcome was the proportion of patients who completed the study and had improvement in sleep quality (defined as at least a three-point decrease in the index) or a reduction in awake time after sleep onset (defined as at least a 15-minute improvement by the actigraph).
The principal secondary outcome was change in quality of life as assessed by a standardized instrument.
The patients' mean age was 51 and ranged from 30 to 65. Dr. Joffe reported that 89% of patients were postmenopausal (either natural or treatment-induced). In a third of cases, hot flashes were attributed to endocrine therapy, followed by natural menopause (28%), oophorectomy (23%), and chemotherapy (15%).
The patients averaged eight hot flashes per day, including two per night by the electronic monitor. At baseline their sleep quality score averaged 9, and awake time after sleep onset averaged 34 minutes.
Dr. Joffe reported that 23 of 25 (88%) patients randomized to zolpidem completed the study compared with 16 of 28 (57%) in the placebo group. Overall, 40% of the zolpidem patients versus 14% of placebo patients had sleep improvement by the end of the study (P=0.035).
Additionally, 60% of zolpidem patients who completed the study reported a reduction in awake time, as did all of 16 placebo patients who completed the study. However, objective assessment by actigraphy showed awake time decreased in 40% of the zolpidem group and none of the placebo patients.
An overall improvement in quality of life was documented in the zolpidem group, whereas the placebo group had an overall decline (P=0.01).