PEP Topic 
Sleep-Wake Disturbances

Classified as a sedative-hypnotic drug, zolpidem slows brain activity to allow sleep and is used to treat insomnia. It is taken once per day at bedtime. The drug is available as a generic and can be administered as a tablet by mouth, a sublingual tablet, an oral spray, and an extended-release tablet taken by mouth.

Effectiveness Not Established

Research Evidence Summaries

Joffe, H., Partridge, A., Giobbie-Hurder, A., Li, X., Habin, K., Goss, P., . . . Garber, J. (2010). Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes: a randomized, double-blind, placebo-controlled trial. Menopause, 17, 908–916.

doi: 10.1097/gme.0b013e3181dbee1b

Study Purpose:

To evaluate the efficacy of optimizing hot flash (HF) treatment, as determined by sleep and quality of life (QOL) measurements, by combining the hypnotic agent zolpidem with a selective-serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) in a randomized, placebo-controlled, double-blind clinical trial.

Intervention Characteristics/Basic Study Process:

All women were evaluated for current use of SSRIs/SNRIs for the treatment of HFs. If currently on an SSRI/SNRI for HFs, they were instructed to continue use. If they were nonusers, they were started on venlafaxine 75 mg per day. They were then randomized to receive zolpidem 10 mg each evening or placebo each evening for five weeks. Patients were evaluated at baseline and at the end of the study.

Sample Characteristics:

  • The study enrolled 53 women with a mean age of 51.1 years (range 29.6–65.3 years).
  • The women were being treated for breast cancer or were being managed for increased risk of breast cancer. 
  • Adjuvant endocrine therapies were used by 71% of the women, with 29 taking tamoxifen.
  • The level of perceived sleep disturbance was high.
  • Patients reported HFs and awakenings, part of a clinical insomnia syndrome that was attributed to the HFs.
  • Median time since diagnosis was 27.2 months (interquartile range 13.7–49.9 months).
  • Patients must have completed therapy more than three months prior to enrollment.
  • Menopause status varied.
  • Women with primary sleep disorders or psychiatric disorders were excluded.


  • Multisite
  • Outpatient clinics
  • Boston, Massachusetts

Phase of Care and Clinical Applications:

Patients were undergoing the long-term follow-up phase of care.

Study Design:

The study was a randomized, placebo-controlled, double-blind clinical trial. 

Measurement Instruments/Methods:

  • Objective and subjective sleep HF measures:  sleep questionnaire, sleep diary, actigraphy using an actigraphic watch (Actiwatch-Score, Mini Mitter  Co, Inc. Bend, Oregon), skin temperature using the sterna lskin-conductance monitor (Biolog ambulatory recorder, UFI, Morro Bay, California), 7-day North Central Cancer Treatment Group Daily Vasomotor Symptom Diary    
  • Beck Depression Inventory (BDI)
  • Period of time awake after sleep onset (WASO) as determined by the actigraphic watch
  • Pittsburgh Sleep Quality Index (PSQI)
  • Quality of Life Inventory (QOLI)


Due to the high percentage of drop-outs in the placebo arm, the investigators changed the way they evaluated the results.  First, they identified the number of people who completed the study and showed improvement in sleep scores. The proportion of women completing the study varied by treatment assignment; 88% (22/25) of those who received zolpidem completed the therapy, whereas 57% (16/28) of those receiving placebo did so. Responders were those who completed the study AND showed improvement in their sleep scores. Forty percent (10) of the women taking zolpidem responded, whereas 14% (4) of the placebo group responded. Sleep improved in more women in the zolpidem arm than the placebo arm. The investigators looked at the differences in outcome measures between the two groups that completed the therapy. Measurements of PSQI scores and WASO time were significantly worse in the placebo arm. PSQI scores improved by 15% in the zolpidem arm and worsened by 26% in the placebo arm. The same was true with WASO time, which improved by 9% in the zolpidem arm and worsened by 2% in the placebo arm. In addition, patients in the zolpidem arm showed improvement in their QOL scores, whereas those on placebo showed a decrease in QOL scores. No change occurred in depressive symptoms in either group.


Zolpidem appears to improve a patient’s perception of nighttime HFs, perhaps by allowing her to sleep through the HF. Sleep scores improved, as did QOL in patients who augmented SSRIs with zolpidem for HFs. No change occurred in objective measurements of the number of HFs. Treatments targeting sleep may be an important supplemental strategy to optimize well-being.


  • The study had a small sample size.
  • The study had a high drop-out rate.
  • The study had a heterogeneous sample.

Nursing Implications:

Sleep disturbances due to HFs are among the most commonly reported symptoms in patients with breast cancer.  Augmenting SSRIs/SNRIs with zolpidem may improve perception of nighttime HFs and, in turn, improve sleep and QOL. Further study is required.