Suicide, depression, and antidepressants
BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7488.373 (Published 17 February 2005) Cite this as: BMJ 2005;330:373
All rapid responses
I think the title "No indication for increased rate of suicide
attempts by
SSRIs in the Netherlands" may give a false impression to the reader;
perhaps "No indication for an increased rate of suicide attempts by
SSRIs as
compared to TCAs in the Netherlands" would be more appropriate as it is
suggested that certain SSRIs may cause an overall increase in the
suicide attempts
rate in any population into which they are introduced.
Richard L. Marquet states, "In conclusion: our data, based on suicide
and suicide attempts presented to Dutch GPs participating in the Dutch
Sentinel Network, do not support the notion that SSRIs trigger more
suicide attempts than TCAs".
Regards
John H.
Competing interests:
None declared
Competing interests: No competing interests
Repeat suicide attempts inspite of drug medications should suggest
another approach is needed, for example, a detailed biochemical analysis
of essential nutrient levels.
Zinc deficiency causes depression and other mental illnesses, but
this important fact is usually ignored by psychiatrists.1-4 Zinc
supplements taken alone can lower copper stores and result in reduced
superoxide dismutase activities. This can cause severe depression which
responds dramatically to alternating copper and zinc supplements. Vitamin
B and EFA deficiencies are also common in depression and need to be
treated.
1 Maes M, D'Haese PC, Scharpe S, D'Hondt P, Cosyns P, De Broe ME.
Hypozincemia in depression. J Affect Disord. 1994 Jun;31(2):135-40.
2 Grant ECG. Re: Depression, Antidepressants, and Breast Cancer:
Considering Only the "Facts" that Fit?
http://bmj.com/cgi/eletters/329/7465/529#76040, 28 Sep 2004
3 Grant ECG. Schizophrenics need zinc and not DHEA or testosterone
supplements. http://bmj.com/cgi/eletters/330/7484/158#95066, 1 Feb 2005
4 Grant ECG. Psychiatrists ignore science
http://bmj.com/cgi/eletters/330/7485/260#94858, 30 Jan 2005
Competing interests:
None declared
Competing interests: No competing interests
Editor- The ongoing debate on the possible association between
suicide attempts and the use
of selective serotonin reuptake inhibitors (SSRIs), especially in younger
patients, prompted us to look for such an association in the data
collected by Dutch general practitioners (GPs). The data were derived from
GPs participating in the Dutch Sentinel Network which covers about 1% of
the Dutch population and is representative of the total population with
regard to age, sex, geographical distribution and level of urbanization.
On a regular basis GPs from the Network report to our Institute on the
incidence of various diseases and events including suicide and suicide
attempts. For every case of suicide and suicide attempt additional
information is provided such as age, sex, previous attempts, previous
contact with the GP, the presence of depression and its treatment.
We analyzed the database of the years 1997-2003 focusing on the
proportion of repeated suicide attempts in relation to the prescription by
GPs of two different types of antidepressants: SSRIs and tricyclic
antidepressants (TCAs). We argued that an increase in suicide attempts
triggered by either of the two types of drugs should be paralleled by a
higher proportion of repetitive attempts. To investigate a possible
relation with age, the study population was divided in younger and older
patients on the basis of the median age (younger and older than 35
years). Because of the relatively small numbers a more refined
stratification was not useful.
A total of 364 suicide and suicide attempts were analyzed, 151 in
patients not being diagnosed as depressed and 213 by depressed patients.
SSRIs and TCAs were given to 44% and 18% of the depressed patients,
respectively, starting before the first attempt. Eight percent was treated
with other drugs and 30% was not given any medication.
The proportions of repeated attempts (2->10) in relation to age
and the prescription of SSRIs (n=93) were as follows: total group: 30%,
< 35 years: 22%, >35 years: 35%. The corresponding percentages for
TCA (n=38) were: 37%, 44% and 30%, respectively.
It is clear that the proportion of repeated attempts in the total group
of patients using SSRIs is not higher than in patients using TCAs (30%
versus 37%). If anything, the results suggest that the opposite might be
the case. However, the difference is not statistically significant.
Especially for the younger patients the data seem to imply that TCAs might
even be more harmful than SSRIs, (44% versus 22% repetitive attempts), but
again, the difference is not significant (p= 0.10).
In conclusion: our data, based on suicide and suicide attempts
presented to Dutch GPs participating in the Dutch Sentinel Network, do
not support the notion that SSRIs trigger more suicide attempts than TCAs.
Competing interests:
None declared
Competing interests: No competing interests
When I was training in Psychiatry (1993-98) it was well recognised
that there was an increased risk of suicide among patients when treatment
for "depression" was started. Depression was viewed as a syndrome with a
number of features, two of which were believed to be particularly
important in its initial treatment:
1) the degree of sadness which the patient felt and
2) their energy level.
These two components of depression seemed to respond at different
rates to antidepressant treatment, and energy levels often seemed to
improve more quickly than mood. When patients were low in mood and had
little motivation they appeared sad and hopeless, but too dejected to do
anything about it. When they were a little better they still seemed sad
and hopeless, but might have enough energy to try and change things (which
might mean trying to kill themselves).
The increased numbers of depressed patients attempting suicide when
some antidepressants are started may simply be an indication of those
drugs' efficacy at treating some of the components of depression more
rapidly - but it does highlight the need to monitor some patients closely.
It is good that this problem with antidepressant treatment has been
emphasised, but viewing it as a drug side-effect may not be entirely
helpful: while the ideal antidepressant would lift mood significantly
before it had any other effects, such a drug is not yet available and the
place of other interventions such as psychotherapy (and even
hospitalisation) should not be forgotten.
Competing interests:
None declared
Competing interests: No competing interests
If we take "depression" as having a prevalence of 5%, that yields
3,000,000 cases in the UK. If, then 15% kill themselves that means 450,000
deaths by suicide. If one assumes they are at risk for 45 years to make
the maths easier it yields 10,000 deaths per annum as deaths by suicide
through depression alone. This is about 3x the total suicide rate for the
UK. They don't add up.
I can see the argument for old-fashioned melancholic depression with
somatic symptoms and delusions of guilt or morbid themes. To suggest that
mild forms of 'depression' are related to this doesn't make much sense.
Competing interests:
None declared
Competing interests: No competing interests
I would be interested to learn if the research carried out by
Cipriani et al included any screening for alcohol or other substance
misuse. Whether any such misuse was established, or considered to have any
influence.
With thanks.
Competing interests:
None declared
Competing interests: No competing interests
EDITOR – The decline in routine antidepressant prescribing in
children and adolescents that Cipriani et al expect has already begun.[1]
We analysed antidepressant prescribing by general practitioners between 1
January 2000 and 31 December 2004. Our aim was to examine the effects of
the UK Committee on Safety of Medicines (CSM) advice.[2]
We used the IMS Disease Analyzer-Mediplus database, which contains
anonymised primary care records for about 3 million UK patients.[3] The
prevalences in 2000, 2002 and 2004 were calculated and compared for
significance.
25,552 prescriptions were issued to 5728 children and adolescents.
Antidepressant use increased between 2000 and 2002 (5.4 to 6.6 per 1,000,
p<0.001), with a rise in the number of patients prescribed selective
serotonin reuptake inhibitors (SSRIs) and venlafaxine. Conversely, between
2002 and 2004, there was a decrease in antidepressant prevalence (6.6 to
5.7 per 1,000, p<0.001). The use of CSM-withdrawn antidepressants
(citalopram, escitalopram, fluvoxamine, paroxetine, sertraline and
venlafaxine) dropped by a third (3.06 vs 2.04 per 1,000, p<0.001).
However, there was no change in fluoxetine prevalence (2.06 vs 2.29 per
1,000, p=0.09). The use of tricyclic antidepressants decreased, although
this was only marginally significant (1.98 vs 1.72 per 1,000, p=0.03).
Since 2003, fewer children and adolescents have been prescribed
antidepressants in primary care, particularly the CSM-withdrawn drugs.
However, the use of fluoxetine and non-SSRI antidepressants has not risen,
suggesting that they are not used as alternatives to the CSM-withdrawn
drugs.
Fewer prescriptions may be issued for mild depression, or patients
and their parents are more aware, and therefore more cautious, about
antidepressant treatment. Also, clinicians may choose psychotherapies,
such as cognitive-behavioural therapy, over antidepressants. More
referrals to Child and Adolescent Mental Health Services will have
implications on existing NHS capacity. This needs to be quantified to help
with health service planning and provision. Further research to understand
the integrated management of depression in childhood and adolescence since
the CSM advice is required, so that adequate infrastructure and resources
can be provided.
Competing interests:
ICKW has received research and educational grants from different pharmaceutical companies including GSK, Eli Lilly and Pfizer (manufacturers of different SSRIs) but none was related to antidepressants or this study. MLM and MT have no competing interests.
Competing interests: No competing interests
It is unfortunate that Cipriani et al.'s editorial, which makes a lot
of sound points about the risks and benefits of antidepressants, states
that 'Up to 15% of patients with unipolar depression eventually commit
suicide'. This suggests that 15% is a reasonable estimate, rather than a
gross overestimate based on very unrepresentative samples. Furthermore,
the link to the cited reference (which explains what is wrong with the 15%
statistic) is wrong (a different editorial in the 23 June 2001 issue).
How many casual readers will be misled by this statement, which reinforces
a stubbornly persistent myth?
Competing interests:
None declared
Competing interests: No competing interests
Selective Serotonin Reuptake Inhibitors (SSRIs) and Suicide Fatalities
Selective Serotonin Reuptake Inhibitors (SSRIs) and Suicide
Fatalities
Cipriani et al1 provide a balanced review of the trio of reports on
antidepressants and suicide that appeared in the february 19 issue of BMJ,
but they do not address the most dreaded outcome—suicide fatalities. It
is instuctive to compare the findings on these drugs with those for Cox-2
inhibitors. In the latter case, randomized trials have demonstrated a
clear and consistent, dose-dependent association between drug and
outcome: serious cardiovascular events. In the case of antidepressants,
suicide occurs so infrequently that clinical trials lack the statistical
power convincingly to draw or exclude an association. Thus, surrogate
outcomes of suicidal ideation and suicide attempts have been used instead.
That these outcomes are important clinically cannot be denied, but their
connection to suicide fatalities remains unproven. With the publication
of the above three of papers we now have suicide fatality data on adults
from four large studies, and it is time for these findings to be given
their due, as few as the numbers may be.
Jick et al2 reported the distribution of antidepressant prescriptions
within 90 days of death in 17 suicides occurring in the base population of
their study, and matched these cases with 157 controls prescribed one of
the same antidepressants. Using dothiepin as the reference group, there
was no association between any of the other antidepressants and suicide.
Using their raw numbers the odds ratio for SSRIs (fluoxetine and
paroxetine) vs. tricyclics (amitriptyline and dothiepin) was 0.92 (0.33-
2.53). The three papers in the February 19 issue reported the following
O.R.s (95% C.I.) on suicide fatalities for SSRI vs placebo: 0.57 (0.26-
1.25)3, 0.74 (0.25-2.21)4, and 0.95 (0.24-3.78)5.
The confidence intervals are wide and are consistent with either a
sizeable protective effect or a disturbing harmful effect. At the same
time, the point estimates consistently have failed to demonstrate even a
nominal trend toward increased risk of suicide fatality for SSRIs in four
independent studies.
1. Cipriani A, Barbui C, Geddes JR: Suicide, depression, and
antidepressants: patients and clinicians need to balance benefits and
harms. BMJ 2005;330:373-374.
2. Jick H, Kaye JA, Jick SS: Antidepressants and the risk of suicidal
behaviors. JAMA 2004;292:338-343.
3. Martinez C, Rietbrock S, Wise L, Ashby D, Chick J, Moseley J, Evans S,
Gunnell D: Antidepressant treatment and the risk of fatal and non-fatal
self harm in first episode depression: nested case-control study. BMJ
2005;330:389-395.
4. Gunnell D, Saperia J, Ashby D: Selective serotonin reuptake inhibitors
(SSRIs) and suicide in adults: meta-analysis of drug company data from
placebo controlled, randomised controlled trials submitted to the MHRA’s
safety review. BMJ 2005;330:385-389.
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 2995;330:396-402.
Competing interests:
Have consulted with a law firm on the defense of a manufacturer of one of the SSRIs.
Competing interests: No competing interests