Paroxetine

Paroxetine

PEP Topic 
Hot Flashes
Description 

Paroxetine is a selective serotonin-reuptake inhibitor (SSRI) 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 post-traumatic 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 disturbances, and fatigue. 

Paroxetine is an SSRI antidepressant that 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.

Benefits Balanced With Harm

Research Evidence Summaries

Kelly, C., Juurlink, D., Gomes, T., Duong-Hua, M., Pritchard, K., Austin, P., & Paszat, L. (2010). Selective serotonin reuptake inhibitors and breast cancer mortality in women. BMJ, 340, c693.

doi:10.1136/bmj.c693
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Study Purpose:

Researchers sought to show that  some SSRI antidepressants reduce tamoxifen’s effectiveness by inhibiting its bioactivation by cytochrome P450 2D6 (CYP2D6).

Intervention Characteristics/Basic Study Process:

The study enrolled postmenopausal women with breast cancer using tamoxifen therapy and a single SSRI antidepressant (paroxetine fluoxetine, sertraline, citalopram, fluvoxamine, or venlafaxine.)

Sample Characteristics:

The study included women living in Ontariowho were 66 years or olderand treated with tamoxifen for breast cancer between 1993 and 2005 and with a single SSRI. (24,430 women were identified; 2,430 entered into study; mean age was 74 years).

Inclusion criteria: Postmenopausal women with breast cancer newly treated with tamoxifen (defined as no tamoxifen prescription in the preceding year) and a single SSRI antidepressant (paroxetine fluoxetine, sertraline, citalopram, fluvoxamine, or venlafaxine)

Exclusion criteria: Antidepressant use of duloxetine or escitalopram

Setting:

Ontario Cancer Registry provided the data.

Study Design:

This was a retrospective cohort study.

Measurement Instruments/Methods:

The study examines the total duration of tamoxifen therapy (index date: date tamoxifen was last dispensed plus an additional 60 days) and the extent to which co-prescription of potentially interacting medications occurred during the course of treatment. The primary outcome was death from breast cancer

Results:

Of 2,430 women treated with tamoxifen and single SSRI, 374 (15%) died of breast cancer during follow up. Absolute increases of 25%, 50%, and 75% in the proportion of time on tamoxifen overlappingthe  use of paroxetine were associated with 24%, 54%, & 91% increases in the risk of death from breast cancer. (p < 0.05) No such risk was seen with other antidepressants

Limitations:

Reported study limitations included lack of information on breast cancer stage and lack of information on indication for antidepressant use.

Stearns, V., Slack, R., Greep, N., Henry-Tilman, R., Osborne, M., Bunnell, C., … Isaacs, C. (2005). Paroxetine is an effective treatment for hot flashes: Results from a prospective randomized clinical trial. Journal of Clinical Oncology, 23, 6919–6930.

doi:10.1200/JCO.2005.10.081
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Study Purpose:

The study assessed the  efficacy of paroxetine compared to placebo in reducing hot flashes in women with or without history of breast cancer.

Intervention Characteristics/Basic Study Process:

There were four study arms:

  • Arm A: four weeks of paroxetine 10 mg/day followed by four weeks of placebo 
  • Arm B: four weeks of paroxetine 20 mg/day followed by four weeks of placebo
  • Arm C: four weeks of placebo followed by four weeks of paroxetine 10 mg/day
  • Arm D: four weeks of placebo followed by four weeks of paroxetine 20 mg/day

Sample Characteristics:

Women with or without history of breast cancer having at least 14 hot flashes per week were eligible, of whom 279 women were screened, and 151 were randomly assigned. 107 patients completed study. Mean age was 53 years. More than 80% had prior history of breast cancer, and 60% were taking an antiestrogen.

Inclusion criteria:

  • Adult women with and without a prior history of breast cancer who could not or did not wish to take hormone therapy
  • History of troublesome hot flashes occurring at least 14 times per week lasting 1 month or longe
  • ECOG performance status of 0–2
  • Creatinine and bilirubin less than two times normal level
  • Vitamin E use for at least one month prior to study entry and continued through study period 
  • Antiestrogen use for at least one month prior to study entry and continued through study period

Exclusion criteria: Concomitant use of cytotoxic chemotherapy, radiation therapy, estrogen or progesterone use, antidepressants, monoamine oxidase inhibitors, or treatments for hot flashes

Setting:

The study was conducted in multi-institutional out-patient oncology clinics.

Study Design:

The trial was stratified, randomized, double-blind, cross-over, and placebo-controlled . Participants were stratified by age group (younger than 60 or older than 60) and antiestrogen use (yes or no).

Measurement Instruments/Methods:

Measures included:

  • Hot flash daily diary
  • QOL tools:
    • The Center for Epidemiologic Studies Depression Scale
    • Hospital Anxiety and Depression Scale (seven anxiety items)
    • Medical Outcomes Study (MOS)
      • Sleep Problems Index
      • Sexual Problems Index 
      • Overall health-related QOL questionnaire

Results:

Paroxetine 10 mg significantly reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively compared to 13.7% and 13.7% for placebo (p = .0006 and p = .0008, respectively). Paroxetine 20 mg significantly reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively compared to 26.6% and 28.8% for placebo (p = .002 and p = .004, respectively). Efficacy was similar between the two doses but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared to placebo (p = .01).

Conclusions:

Study attrition was a limitation: 39 women did not complete 9 weeks of therapy; 26 women did not return diaries.


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