Correspondence
5 Speer CP, Gefeller O, Groneck P, et al. Finally, many men with low-risk
Randomised clinical trial of two treatment
regimes of natural surfactant preparations in
neonatal respiratory distress syndrome.
Arch Dis Child 1995; 72: F8–13.
Dutasteride and active
surveillance of low-risk
prostate cancer
We thank Chris Parker for his
Comment (March 24, p 1078)1 on our
Science Photo Library
REDEEM trial.2 We agree that most
men with very low-risk prostate cancer
do not require radical treatment and
that a longer study would have been
ideal. Nevertheless, we disagree with
his recommendation against the use
of 5α-reductase inhibitors (5ARIs) in
this setting.
Many men with low-risk cancers
receive treatment, especially in the USA
where more than 90% receive radical or
even hormonal therapy.3 Furthermore,
many men on active surveillance
discontinue expectant therapy owing
to anxiety over worsening biopsy
results or increasing prostate-specific
antigen (PSA) concentrations. Parker
is correct in that we did not correct
PSA as in other studies. This point was
carefully considered and deemed to
limit our ability to assess real-world
benefits of these drugs.
We disagree with Parker’s interpret-
ation of the pathological progression
data. The REDEEM study was not
powered to assess pathological pro-
gression independently. Nonetheless,
we found a trend towards a benefit on
the basis of pathological progression
only (p=0·079), and one cannot refute
that, clinically and statistically signifi-
cantly, more dutasteride-treated men
had no cancer at final biopsy than did
men on placebo.2
Whether 5ARIs increase rates of
high-grade disease remains a matter
of debate;4,5 however, in the active
surveillance setting, patients are
carefully monitored, which increases
the likelihood of early identification of
adverse changes.
1590
there is no clinical or scientific basis for
tumours have enlarged prostates
and significant lower urinary tract
symptoms. There is credible level 1
evidence to support use of 5ARIs not
only to alleviate such symptoms but
to prevent urological catastrophe.
We declare that we have no conflicts of interest
other than those stated in the original paper.
Neil E Fleshner, on behalf of the
REDEEM trial investigators
neil.fleshner@uhn.ca
Princess Margaret Hospital, University of Toronto,
Toronto, ON M5G 2M9, Canada
1 Parker C. What (if anything) to do about low-risk
prostate cancer. Lancet 2012; 378: 1078–80.
2 Fleshner NE, Lucia MS, Egerdie B, et al.
Dutasteride in localised prostate cancer
management: the REDEEM randomised,
double-blind, placebo-controlled trial. Lancet
2012; 378: 1103–11.
3 Barocas DA, Cowan JE, Smith JA Jr, Carroll PR.
What percentage of patients with newly
diagnosed carcinoma of the prostate are
candidates for surveillance? An analysis of
the CaPSURE database. J Urol 2008;
180: 1330–34.
4 Andriole GL, Bostwick DG, Brawley OW, et al.
Effect of dutasteride on the risk of prostate
cancer. N Engl J Med 2010; 362: 1192–202.
5 Thompson IM, Chi C, Ankerst DP, et al. Effect of
finasteride on the sensitivity of PSA for
detecting prostate cancer. J Natl Cancer Inst
2006; 98: 1128–33.
When is grief a disease?
The Lancet asks, “When should grief be
classified as a mental illness?” (Feb 18,
p 589).1 Our reply is, “never”. But some
recently bereaved individuals are not
simply grieving. They are also experi-
encing a full-blown major depressive
episode. How can physicians help
in such cases? That is the crux of the
“bereavement exclusion” debate sur-
rounding the forthcoming fifth edition
of the Diagnostic and Statistical
Manual of Mental Disorders (DSM-5).
Bereavement-related grief does not
immunise against a major depressive
episode; indeed, bereavement can
precipitate such episodes.2 But when
a major depressive episode develops
in the context of bereavement, it
does not differ substantially from any
other instance with respect to course,
severity, or treatment response.3 Hence,
singling out bereavement-related major
depressive episodes for exclusion.
Some who favour the bereavement
exclusion focus on certain overlapping
features of grief and major depressive
episodes, such as intense sadness and
withdrawal from customary activities.
But grief and major depressive
episodes also differ in important
respects. Thus, in grief, painful feelings
come in waves, often mixed with
positive memories of the deceased;
in major depressive episodes, mood
and ideation are almost constantly
negative. In grief, self-esteem is
usually preserved; in major depressive
episodes, feelings of worthlessness
and self-loathing are common.4
As Thomas à Kempis noted,5 grief
is one of the “proper sorrows of the
soul” and must be allowed to run its
course. But when a major depressive
episode intercedes, professional at-
tention is warranted. We must not
medicalise grief—but neither can we
afford to normalise major depressive
episodes. Removing the bereavement
exclusion helps prevent them from
being overlooked, and facilitates the
possibility of appropriate treatment.
We declare that we have no conflicts of interest.
*Sidney Zisook, Ronald Pies,
Emmanuelle Corruble
szisook@ucsd.edu
Department of Psychiatry, University of California—
San Diego and San Diego VA Healthcare System,
La Jolla, CA 92093, USA (SZ); Department of
Psychiatry, Tufts University School of Medicine,
Boston, MA, USA (RP); and Department of Psychiatry,
INSERM U669, Bicêtre University Hospital, Assistance
Publique–Hôpitaux de Paris, Paris, France (EC)
1 The Lancet. Living with grief. Lancet 2012;
379: 589.
2 Kendler KS, Thornton LM, Gardner CO. Genetic
risk, number of previous depressive episodes,
and stressful life events in predicting onset of
major depression. Am J Psychiatry 2001;
158: 582–86.
3 Zisook S, Kendler KS. Is bereavement-related
depression different than non-bereavement-
related depression? Psychol Med 2007;
37: 779–94.
4 Zisook S, Reynolds CF, III, Pies R, et al.
Bereavement, complicated grief, and DSM—part
1: depression. J Clin Psychiatry 2010; 71: 955–56.
5 à Kempis T. Counsels on the spiritual life.
London: Penguin Books, 1995.
www.thelancet.com Vol 379 April 28, 2012