Intended for healthcare professionals

Rapid response to:

Practice ABC of breast diseases

Medical treatment of early breast cancer. I: adjuvant treatment

BMJ 2006; 332 doi: (Published 05 January 2006) Cite this as: BMJ 2006;332:34

Rapid Response:

Use of venlafaxine for hot flushes

Hot flushes are a significant side effect in patients undergoing
adjuvant treatment for breast cancer. Reasons include patients being peri-
or post-menopausal at diagnosis, having to stop hormone replacement
therapy (HRT) after diagnosis, treatment such as adjuvant chemotherapy
precipitating menopause and side effects of endocrine therapies
themselves. Changes in circulating oestrogen levels or increased
concentration of gonadotrophins lead to alteration in neurotransmitters
and instability of the thermoregulatory set point in the hypothalamus.
This is probably via 5-HT1a and 5-HT2a receptors, although the exact
pathophysiology is unclear(1).In the review by Smith and Chua(2) a number
of treatments are suggested for this problem, including venlafaxine.

The use of venlafaxine for hot flushes is based on double-blind
randomised controlled trial of 191 patients with a previous breast cancer
or at high risk of developing it(3). They were randomised to placebo or a
dose of 37.5mg, 75mg or 150mg venlafaxine for 4 weeks. The response rates
as measured by median reduction in hot flush scores from baseline were
27%, 37%, 61% and 61% respectively. The authors concluded that for
treatment of hot flushes the starting dose should be 37.5mg. If there was
no response after 1 week the dose could be increased to 75mg, but no
higher due to increased side effects e.g. dry mouth and nausea.

Venlafaxine (Efexor) is a selective serotonin reuptake inhibitor
(SSRI) with noradrenergic properties, and was included in the report of
the Committee on Safety of Medicines (CSM) expert working group on the
safety of SSRI antidepressants published in December 2004(4).This report
was produced due to concerns about the safety of these drugs, in
particular with respect to an increased risk of self-harm(5). Venlafaxine
was mentioned separately due to particular concerns about cardiotoxicity,
toxicity in overdose and increased risk of withdrawal reactions. The CSM
recommended that venlafaxine “should only be initiated by specialist
mental health practitioners, including GPs with a specialist interest, and
there should be arrangements in place for continuing supervision of the
patient.” In addition the report also stated that venlafaxine should not
be used in patients with heart disease (including ECG abnormalities),
hypertension or electrolyte abnormalities. Although the dosage commonly
used for treating hot flushes is low (37.5mg to 75mg daily) compared with
standard doses for depression of 75mg to 375mg daily, the CSM
recommendation is applicable too.

In view of the above report, venlafaxine should not be used in the
treatment of therapy induced hot flushes in breast cancer patients. Trials
have not yet shown an effective treatment for this problem apart from HRT,
which increases breast cancer recurrence and therefore should be
avoided(6) . In addition, most trials show a response rate to placebo of
20 to 30%. Possible alternatives as outlined by Smith and Chua include
switching to an alternative adjuvant therapy, clonidine, evening primrose
oil or acupuncture. Care should be taken with natural remedies which may
have oestrogenic properties. However these symptoms often remain difficult
to manage in this group of patients.

Specialist Registrar in Clinical Oncology
Norfolk and Norwich University Hospital NHS Trust

1. Stearns V, Ullmer L, Lopez JF, Smith Y, Isaacs C, Hayes DF. Hot
flushes. The Lancet 2002;360:1851-1861

2. Smith I, Chua S. ABC of breast diseases: Medical treatment of
early breast cancer. I: adjuvant treatment. BMJ 2006;332:34-37

3. Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI,
Barton DL et al. Venlafaxine in management of hot flashes in survivors of
breast cancer: a randomised controlled trial. The Lancet 2000;356:2059-

4. Report of the CSM expert working group on the safety of selective
serotonin reuptake inhibitor antidepressants. 6 December 2004.

5. Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Herbert P,
Hutton B. Association between suicide attempts and selective serotonin
reuptake inhibitors: systematic review of randomised controlled trials.
BMJ 2005; 330: 396

6. Holmberg L, Anderson H, HABITS steering and data monitoring
committees. HABITS (hormonal replacement therapy after breast cancer – is
it safe?), a randomised comparison: trial stopped. The Lancet 2004;

Competing interests:
None declared

Competing interests: No competing interests

18 January 2006
Abigail E Hollingdale
specialist registrar in clinical oncology
Norfolk and Norwich University Hospital NHS Trust, Colney Lane, Norwich, NR4 7UY