Suicide A drug side effect?

The US Food and Drug Administration stresses that it has established no direct link between these medications and suicidal thoughts. But regulators admit they have had one of two indicators of potential trouble.

In some, a review of a drug8217;s early clinical trials turned up increased rates of suicidal thinking among subjects taking the medicine. In others, the FDA observed an upswing of reports that patients taking a medication developed symptoms of depression.

As a result, FDA officials and medical researchers are scouring data for clear signs that these drugs increase the risk of dangerous psychiatric symptoms. The agency will require developers of many new drugs to test for psychiatric side effects.

8220;We8217;re trying to develop systematic strategies for looking8230; in a more rigorous way,8221; said Dr Thomas Laughren, director of the FDA8217;s division of psychiatry products.

The recent rash of advisories comes four years after the FDA first suggested a connection. Prompted by reports that suggested children taking antidepressants were more likely to commit suicide, the agency in 2004 warned that antidepressants may increase the risk of suicidal fantasies and behaviours among children.

Scientists long have known that many drugs used to treat symptoms below the neck enter the brain also and that the receptors and chemicals on which they work in organs like the heart, blood vessels or liver are present in the brain as well, although they may have different functions there.That these drugs might have an incidental effect on mood, then, 8220;shouldn8217;t be terribly surprising,8221; Laughren said.

One of the first drugs that will require testing for psychiatric side effects before it can be approved in the US is Rimonabant, an anti-obesity drug used in 20 other countries. After early clinical trials suggested patients had increased rates of depression and anxiety, an FDA advisory panel voted last June to recommend a delay in market approval pending further study. The FDA has asked Rimonabant8217;s maker, Sanofi-Aventis, to detect and measure suicidal side effects.

Some of the reports prompting advisories were wholly unexpected. In Japan, where antiviral medicines such as Tamiflu and Relenza are widely used to shorten the duration and ease the symptoms of influenza, raised serious alarms.

In the span of several months, two 14-year-old patients taking Tamiflu 8212; a boy and a girl 8212; fell to their death from high-rise apartment buildings in suspected suicides, and two 12-year-olds on the medication were injured after falling from buildings. Delirium, hallucinations and psychotic behaviour caused one child to bolt into traffic to his death.

An FDA advisory panel was told last November that there have been 25 deaths and 365 cases of abnormal behaviour in people younger than 21, who have taken Tamiflu since it was approved in 1999. Although regulators underscored that hallucinations and bizarre behaviour can be a consequence of the high fevers and brain inflammation that can come with influenza, they acknowledged that they could not, without further scrutiny, rule out a link to Tamiflu.

Last month, the FDA notified physicians of the Japanese incidents and urged close monitoring of young patients. In early April, GlaxoSmithKline, maker of the antiviral medication Relenza, voluntarily issued a similar notification to physicians.

On March 27, the FDA went on to announce that it was investigating a 8220;possible association between the use of Singulair,8221; a pill used to treat asthma and allergies, and changes in mood and behaviour, including suicidal thinking and suicide attempts. That warning came after the FDA saw an uptick in reports of patients taking Singulair and experiencing symptoms of depression, including thoughts of self-destruction.

Reports to the FDA also prompted a warning to healthcare professionals February 1 about Chantix, an anti-smoking drug approved in May 2006. As the medication gained a foothold among US smokers, patients began telling physicians and the FDA of peculiar behaviour, agitation, depressed mood and suicidal thoughts and actions.

By January, the FDA had concluded, 8220;it appears increasingly likely that there may be an association between Chantix and serious neuropsychiatric symptoms8221; and urged physicians to weigh that possibility when prescribing the drug and to carefully monitor patients who take it.

One recent warning emerged not from spontaneous reports by patients and doctors but from an internal FDA effort.

Last year, after studies had shown an increase in suicidal thoughts and behaviour among people taking certain drugs for epilepsy, the FDA conducted a broad review of clinical trials for 11 anti-convulsive drugs.

Although such reports of psychiatric side effects defy prediction, researchers said understanding the connection between mind and body should lead the way to better guesses at which drugs might unexpectedly darken a patient8217;s mood, and why.

8220;With every passing day, we8217;ve learned so much that there8217;s a strong connection8221; between physical and mental health, said Dr Husseini Manji, director of the Anxiety and Mood Disorders Program at the National Institute of Mental Health. 8220;When you8217;re depressed, a lot of things in your body don8217;t work well. But conversely, both medical illnesses and certain medications can markedly make you depressed.8221;