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Press releases Saturday 19 February 2005
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(1) SUICIDAL BEHAVIOUR CAUSED BY ANTIDEPRESSANTS "CANNOT BE RULED OUT"
(2) DRUGS USED TO TREAT ALZHEIMER'S IN NURSING HOMES ARE WORSENING SUFFERERS' ILLNESS
(3) WOMEN SHOULD BE ADVISED NOT TO DRINK ALCOHOL IN PREGNANCY
(4) FOLIC ACID RECOMMENDATIONS
HAVE HAD LITTLE IMPACT ON BIRTH DEFECTS
(1) SUICIDAL BEHAVIOUR CAUSED BY ANTIDEPRESSANTS "CANNOT
BE RULED OUT"
(Selective serotonin reuptake
inhibitors (SSRIs) and suicide in adults)
http://bmj.com/cgi/content/full/330/7488/385
(Antidepressant treatment
and the risk of fatal and non-fatal self harm in first episode depression)
http://bmj.com/cgi/content/full/330/7488/389
(Association between suicide
attempts and selective serotonin reuptake inhibitors)
http://bmj.com/cgi/content/full/330/7488/396
(Editorial: Suicide, depression, and antidepressants)
http://bmj.com/cgi/content/full/330/7488/373
Antidepressant drugs may be associated with an increased risk of suicidal behaviour, particularly in the early stages of treatment, shows new evidence in this week's BMJ.
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressant, yet concerns have arisen that these drugs may induce or worsen suicidal feelings in vulnerable patients.
Three studies published in this issue shed new light on the benefits and harms of these drugs.
In the first study, researchers analysed 702 trials involving over 87,000 patients with depression and other clinical conditions to establish whether a link exists between use of SSRIs and suicide attempts.
They found that patients taking SSRIs were twice as likely to attempt suicide compared with patients taking placebo. However, no increase in risk was seen when only fatal suicidal attempts were compared between SSRIs and placebo. Finally, they found no difference between patients taking SSRIs and those taking other drugs, known as tricyclic antidepressants.
The authors point out that, while the absolute risk of suicide is low, the widespread use of SSRIs makes this a population health concern. They also warn that major limitations in the published trials may have led to underestimates of the risk of suicide attempts.
The second study reviewed 477 trials submitted by drug companies to the safety review of the Medicines and Healthcare products Regulatory Agency (MHRA). These trials compared SSRIs with placebo in adults with depression and other clinical conditions.
The research team found no evidence that SSRIs increased the risk of suicide. They found weak evidence of an increased risk of self harm, but no evidence of an increased risk of suicidal thoughts.
Increased risks of suicide and self harm caused by SSRIs cannot be ruled out, say the authors, but larger trials with longer monitoring periods are needed to assess the balance of risks and benefits fully. They recommend that patients should be warned of the potential hazard and monitored closely in the early weeks of treatment.
The final study was based on information from the General Practice Research Database and analysed the risk of self harm and suicide in over 146,000 patients taking SSRIs and tricyclic antidepressants for the first time.
Risks of self harm and suicide were no different in patients prescribed SSRIs compared with those prescribe tricyclics. However, under 18s prescribed SSRIs seemed to be at increased risk of self harm.
The finding that SSRIs and tricyclic antidepressants have a similar risk profile with respect to suicide and self harm is reassuring, say the authors. They call for further research to assess the short and long term risks and benefits of antidepressants.
Despite several limitations, these studies provide some useful insights for clinical practice, write experts in an accompanying editorial. For instance, they should make doctors aware that SSRIs and tricyclics may induce or worsen suicidal behaviour during the early phases of treatment and encourage them to monitor patients closely. They should also discourage the routine prescribing of antidepressant drugs in children and adolescents.
"The debate is not yet done, but these papers crystallise arguments that have been drifting in the ether these past months," says Kamran Abbasi, BMJ Acting Editor. "How many people who turned to 'happy pills' would not have done so if they had been fully aware of the potential harms?"
Contacts:
Paper 1: Dean Fergusson, Scientist,
Ottawa Health Research Institute, Clinical Epidemiology Program, Ontario,
Canada
Email: dafergusson@ohri.ca
Paper 2: Dr Cherry Lewis, Research
Communications Manager, Public Relations Office University of Bristol, UK
Email: cherry.lewis@bristol.ac.uk
Paper 3: Carlos Martinez, Epidemiologist,
General Practice Research Database Division, Medicines and Healthcare products
Regulatory Agency, London, UK
Email: carlos.martinez@gprd.de
Editorial: Andrea Cipriani, Research
Fellow in Psychiatry, Department of Medicine and Public Health, Section of
Psychiatry and Clinical Psychology, University of Verona, Italy
Email: andrea.cipriani@medicina.univr.it
or
John Geddes, Professor of Epidemiological
Psychiatry , Department of Psychiatry, University of Oxford, Warneford Hospital,
Oxford, UK
Email: john.geddes@psychiatry.oxford.ac.uk
(2) DRUGS USED TO TREAT ALZHEIMER'S IN NURSING HOMES ARE WORSENING SUFFERERS' ILLNESS
Online First
(Quetiapine and rivastigmine and cognitive decline in Azheimer's
disease: randomised double blind placebo controlled trial)
http://bmj.bmjjournals.com/cgi/rapidpdf/bmj.38369.459988.8F
Quetiapine, a drug commonly used in nursing homes to treat agitation and related symptoms in people with Alzheimers' disease actually worsens patients' illness, speeding up their rate of decline significantly, says a paper published on bmj.com today.
Antipsychotic drugs are used in up to 45% of nursing homes to treat agitation, a common and distressing symptom of dementia (a catch-all term for diseases such as Alzhimer's.)
Researchers found that, when given a placebo as treatment for these symptoms, patients showed little change. But those patients given the commonly used antipsychotic drug quetiapine showed a marked worsening in the condition with marked deterioration of memory and other higher brain functions (cognitive decline).
This is particularly significant as quetiapine had been regarded as one of the safer of the antipsychotic drugs available, say the authors.
The study looked at 93 patients with dementia across the north east of England over six months. Those in the study taking quetiapine experienced a doubling in cognitive decline compared with the control group who had been given placebo. Those taking another antipsychotic in the trial, rivatigmine, showed little or no worsening of their illness - but no improvement in symptoms above the placebo group.
There have been concerns about the safety of the two most commonly used antipsychotic drugs in people with dementia, risperidone and olanzapine, because of increased risk of stroke, say the authors. The current study highlights considerable concern regarding the safety of quetiapine, and suggest that quetipaine is not a viable alternative to these medications.
This study has vital implications for the treatment of patients with dementia, argue the authors. Quetiapine should not be used instead of other drugs for alleviating their symptoms, and these findings highlight concerns over long term use of antipsychotics in these patients.
Contact:
Professor Clive Ballard, Institute
of Psychiatry, King's College London, UK
Email: clive.ballard@kcl.ac.uk
(3) WOMEN SHOULD BE ADVISED NOT TO DRINK ALCOHOL IN PREGNANCY
(Editorial: Low level alcohol
consumption and the fetus)
http://bmj.com/cgi/content/full/330/7488/375
Expectant mothers should be advised not to drink alcohol, as this may pose health risks to the foetus, argues an editorial in this week's BMJ.
While the UK Department of Health advises that women can safely drink one or two units of alcohol per week, a team of psychiatrists in London highlight several studies which cast doubt on the guidance.
The authors looked at reports into foetal alcohol syndrome, a condition developed by some babies exposed to alcohol in the womb, resulting in stunted growth, facial abnormalities and neurocognitive deficits (brain disorders). An overarching foetal alcohol spectrum disorder - traceable to the pregnant mother's alcohol consumption say the authors - has also been identified.
Both the syndrome and disorder cause a wide range of behavioural disorders, they argue, including hyperactivity, problems with mental organisation, and difficulties in understanding the consequences of one's behaviour. Symptoms may also overlap with conditions such as autism and attention deficit hyperactivity disorder (ADHD).
Previously the syndrome was thought to be caused by mothers drinking heavily in pregnancy. But the authors argue that recent studies suggest that far less exposure to alcohol in the womb may put babies at risk—as little as one drink per week in one study. Individual differences in alcohol metabolism may protect most women when drinking small quantities, add the team, but it is currently impossible to predict who is at risk and who is not.
More research is needed to find out just how much alcohol may be damaging to a foetus, argue the authors. In the interim, the only safe message for expectant mothers is to abstain from alcohol, they conclude.
Contact:
Raja Mukherjee, Honorary Lecturer,
Learning Disability Psychiatry, St George's Hospital Medical School, London,
UK
Email: rmukherj@sghms.ac.uk
(4) FOLIC ACID RECOMMENDATIONS HAVE HAD LITTLE IMPACT ON BIRTH DEFECTS
Online First
(International retrospective cohort study of neural tube defects in
relation to folic acid recommendations: are the recommendations working?)
http://bmj.bmjjournals.com/cgi/rapidpdf/bmj.38336.664352.82
Recommendations on use of folic acid consumption have had no detectable impact on the incidence of neural tube defects, according to an international study published on bmj.com today.
These results support a move towards food fortification in addition to recommending use of supplements.
Trials showed, more than a decade ago, that folic acid can reduce the occurrence of neural tube defects, such as spina bifida, by half or more. Since then, many countries have tried to promote use of folic acid, either by fortifying foods or, more often, by recommending the use of supplements.
Although studies have shown that fortification of flour is effective, the impact of recommendations alone is not known.
Researchers examined data from over 13 million births in Europe and Israel from 1988 to 1998. For each country, cases of neural tube defects were identified, and policies and recommendations regarding folic acid were ascertained.
Recommendations alone did not seem to influence trends in neural tube defects, despite the proved effectiveness of folic acid. The authors estimate that thousands of pregnancies that would otherwise have been healthy were affected by neural tube defects in the study area alone since 1992.
The most likely explanation for these results is that recommendations were not implemented widely enough to produce a sustained change in behaviour in a sufficiently large proportion of women to cause measurable effects, say the authors.
These findings underscore the ongoing missed opportunities for prevention. In addition to recommending use of supplements, public health agencies and medical professionals should strongly consider implementing food fortification programmes, they conclude.
Contact:
Natasha Singh, Public Affairs Specialist,
National Center on Birth Defects and Developmental Disabilities, Centers
for Disease Control and Prevention, Atlanta, USA
Email: nsingh1@cdc.gov
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