Rapid Responses to:

EDITORIALS: Andrea Cipriani, Corrado Barbui, and John R Geddes Suicide, depression, and antidepressants BMJ 2005; 330: 373-374 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Misleading statement re 15% suicide

Melissa K Raven   (18 February 2005)

Decline in antidepressant prescribing to children and adolescents in primary care since UK CSM advice

Macey L Murray, Mary Thompson (IMS Health) and Ian CK Wong (Centre for Paediatric Pharmacy Research).   (18 February 2005)

Suicide, depression & antidepressants

Peter O'Loughlin   (19 February 2005)

15%! The figures don't add up.

Andrew J Smith   (19 February 2005)

Antidepressants and Increased Risk of Suicide

Peter J T Balfour   (22 February 2005)

No indication for increased rate of suicide attempts by SSRIs in the Netherlands

Richard L Marquet, Aad Bartelds, Francois Schellevis   (3 March 2005)

Suicide attempts on drug medications

Ellen C G Grant   (4 March 2005)

Re: No indication for increased rate of suicide attempts by SSRIs in the Netherlands

John P Heptonstall   (4 March 2005)

Selective Serotonin Reuptake Inhibitors (SSRIs) and Suicide Fatalities

Raymond Crowe   (24 March 2005)

Misleading statement re 15% suicide 18 February 2005
Melissa K Raven, Lecturer, Public Health Flinders University, Bedford Park SA 5042, Australia Send response to journal: Re: Misleading statement re 15% suicide	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
Decline in antidepressant prescribing to children and adolescents in primary care since UK CSM advice 18 February 2005
Macey L Murray, research fellow Centre for Paediatric Pharmacy Research, the School of Pharmacy, University of London, WC1N 1AX, Mary Thompson (IMS Health) and Ian CK Wong (Centre for Paediatric Pharmacy Research). Send response to journal: Re: Decline in antidepressant prescribing to children and adolescents in primary care since UK CSM advice	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.
Suicide, depression & antidepressants 19 February 2005
Peter O'Loughlin, Addictions Counsellor Eden Lodge Practice, Beckenham BR3 3AT Send response to journal: Re: Suicide, depression & antidepressants	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
15%! The figures don't add up. 19 February 2005
Andrew J Smith, Consultant Psychiatrist Sealock Centre, Cardiff Send response to journal: Re: 15%! The figures don't add up.	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
Antidepressants and Increased Risk of Suicide 22 February 2005
Peter J T Balfour, Career Grade Trainee Conwy & Denbighshire NHS Trust Send response to journal: Re: Antidepressants and Increased Risk of Suicide	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
No indication for increased rate of suicide attempts by SSRIs in the Netherlands 3 March 2005
Richard L Marquet, Senior investigator Netherlands Institute for Health Services Research (Nivel), 3500BN, Utrecht, the Netherlands, Aad Bartelds, Francois Schellevis Send response to journal: Re: No indication for increased rate of suicide attempts by SSRIs in the Netherlands	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
Suicide attempts on drug medications 4 March 2005
Ellen C G Grant, physician and medical gynaecologist Kingston-upon-Thames, KT2 7JU,UK Send response to journal: Re: Suicide attempts on drug medications	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
Re: No indication for increased rate of suicide attempts by SSRIs in the Netherlands 4 March 2005
John P Heptonstall, Director of The Morley Acupuncture Clinic and Complementary Therapy Centre. Practitioner of TCM -acu LS27 8EG Send response to journal: Re: Re: No indication for increased rate of suicide attempts by SSRIs in the Netherlands	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
Selective Serotonin Reuptake Inhibitors (SSRIs) and Suicide Fatalities 24 March 2005
Raymond Crowe, The George Winokur Professor of Psychiatry Psychiatry Research MEB, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1000 Send response to journal: Re: 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.