PEP Topic 
Sleep-Wake Disturbances

Paroxetine is a selective serotonin-reuptake inhibitor (SSRI) type of antidepressant. Paroxetine tablets, suspension, and extended-release tablets are used to treat depression, panic disorder, and social anxiety disorder. Paroxetine tablets and suspension are also used to treat obsessive-compulsive disorder, generalized anxiety disorder, and posttraumatic stress disorder. SSRIs and antidepressants in general have been evaluated for use for pain and peripheral neuropathy. Paroxetine specifically has been studied in patients with cancer for hot flashes, sleep-wake disturbance, and fatigue.

Paroxetine is a strong inhibitor of the CYP2D6 enzyme system that acts to metabolize tamoxifen to its active form, endoxifen. A retrospective study of women with breast cancer taking tamoxifen and paroxetine showed a significantly increased risk of death from breast cancer with overlapping use of both agents. Caution is recommended in the use of paroxetine for women experiencing tamoxifen-induced hot flashes.


Effectiveness Not Established

Research Evidence Summaries

Palesh, O. G., Mustian, K. M., Peppone, L. J., Janelsins, M., Sprod, L. K., Kesler, S., . . . Morrow, G. R. (2012). Impact of paroxetine on sleep problems in 426 cancer patients receiving chemotherapy: a trial from the University of Rochester Cancer Center Community Clinical Oncology Program. Sleep Medicine, 13, 1184–1190.

doi: 10.1016/j.sleep.2012.06.001

Study Purpose:

To compare the effects of paroxetine to placebo on sleep problems in patients with cancer.

Intervention Characteristics/Basic Study Process:

This study was a post hoc analysis of data from a randomized, controlled trial (RCT) previously implemented to examine the effects of paroxetine on fatigue. Patients seen between 1997 and 1999 with any type of cancer receiving chemotherapy were recruited and randomized to either 20 mg of paroxetine daily or placebo. Data were collected seven days after each chemotherapy cycle. Patients received follow-up and reminder telephone calls from the study nurse. For analysis purposes, patients were classified as those with sleep problems or good sleepers based on depression inventory scores. Those who reported sleep difficulties of any type at least one to two nights a week were classified as having sleep problems. Responses to single items regarding sleep on rating scales used in the study were used as primary outcome measures.

Sample Characteristics:

  • The sample was comprised of 426 patients (23.9% male, 66.1% female).
  • Mean age was 56.4 years.
  • Multiple tumor types were included; the highest volumes were breast, lung, and hematologic cancers.
  • Of the patients, 72% were married.
  • At baseline, 80.8% of patients had sleep problems as defined in the study.


  • Single site 
  • Outpatient 
  • University of Rochester

Phase of Care and Clinical Applications:

Patients were undergoing the active antitumor treatment phase of care.

Study Design:

The study was a secondary analysis of a double-blind, placebo-controlled RCT.

Measurement Instruments/Methods:

  • Hamilton Depression Inventory (HDI)
  • Hamilton Depression Rating Scale (HDRS)
  • Center for Epidemiologic Studies Depression Scale (CESD)


At the end of cycle 4 of chemotherapy, there was a significant difference in the prevalence of patients with sleep problems between those on paroxetine (79.3%) versus placebo (88%) (p = 0.01; d = 0.23). Rates of severity of sleep problems were not significantly different between the groups.


The findings provide relatively weak evidence that paroxetine may help patients with cancer undergoing treatment to reduce the prevalence of mild sleep problems. Validated sleep quality measures were not used.


  • Unintended interventions or applicable interventions not described would influence the results.
  • Measurement validity/reliability was questionable.
  • No other relevant interventions, or lack of these that could impact sleep, were described. 
  • The method of measurement of sleep disturbance is questionable; selected items within depression scales were used, rather than validated measures designed to measure sleep. 
  • The criterion for the definition of sleep problems sets a very low standard to represent sleep problems.

Nursing Implications:

Further research on the effects of selective serotonin reuptake inhibitors (SSRIs) to improve sleep in patients with cancer who have sleep problems is needed. The positive findings are limited by the measurement of sleep problems and the fact that this analysis was performed from a study that was not designed to measure the outcome of sleep.