Licence to kill

After Harold Shipman was convicted in 2000 of murdering 15 of his patients with an overdose of morphine, a two-year inquiry recommended big changes to the legal framework governing healthcare and medicine. Yet when, in November 2009, a report revealed that certain legally prescribed drugs were killing 1,800 elderly people with dementia annually and causing 1,600 strokes, the response was very different. The drugs in question are powerful tranquilisers known as antipsychotics, designed to treat schizophrenia and bipolar disorder. They are also used on dementia patients to control difficult behaviour such as agitation, aggression and sleep disturbance. Their side effects can include rapid weight gain, involuntary movements, very low blood pressure, lethargy, seizures and intense dreams or nightmares. The report, commissioned by the department of health due to mounting concern by groups working with the elderly, was led by Sube Banerjee, a professor at the Institute of Psychiatry. It found that repeated warnings by the medical authorities about the drugs had been ignored by doctors. Yet it did not recommend trying to discover how this could have happened, or what needs to be done to prevent it. Nor did it call for any sanctions against the doctors involved. No GP should have been surprised that the dangers these drugs posed to dementia patients outweighed the benefits. In 2002, there were warnings about a raised risk of brain haemorrhages with antipsychotics in the elderly in Canada. In 2004, both the European and British drug regulatory agencies warned that the drugs tripled the risk of stroke. In 2005, the US regulator (the FDA) warned of a higher death rate in dementia patients given antipsychotics. In 2006, a trial by Robert Rosenheck in Connecticut found that antipsychotics were no better than a placebo in improving dementia patients’ behaviour or quality of life. In 2007, a top FDA scientist estimated the annual number of deaths from antipsychotics in US nursing homes at 15,000. So why prescribe them at all—and how were doctors able to? Promotion, sometimes illegally, by pharmaceuticals companies is a factor. In Britain, the drugs were prescribed without a licence from the medicines and healthcare products regulatory agency (MHRA). A licence means that clinical trials show that drugs are safe and effective. But antipsychotics, such as olanzapine and quetiapine, are only licensed for conditions such as schizophrenia and bipolar disorder. The doctors who prescribed them for dementia did so “off-label”—that is, based on their own judgement. This is a well-established practice and makes clinical sense: doctors may sometimes judge an unlicensed drug to work for a patient, such as antidepressants for bipolar disorder. But as the General Medical Council’s guidelines state, doctors must “be satisfied that there is a sufficient evidence base and/or experience of using the medicine to demonstrate its safety and efficacy.” While it’s impractical to investigate thousands of GPs for failing to do this, it does seem that British regulators were failing to monitor the situation—and ignoring evidence coming from US court cases. In January 2009, Eli Lilly, manufacturer of the antipsychotic Zyprexa, used in Britain under the name olanzapine, was fined $1.4bn—at the time the largest individual corporate criminal fine in US history—for illegally marketing it. Court documents show the company had run a campaign recommending the drug for children and the elderly. Known side effects such as drowsiness were promoted as benefits in the elderly, who often suffer from insomnia. That case, and similar ones, had been working their way through the US legal system for six years. Was there really no one in the British regulatory agencies who thought they might have lessons for patients here? Banerjee’s report talked of “a general cumulative failure… to develop an effective response to the challenges posed by dementia.” As an Oxford University report published in February revealed, while 820,000 people are affected by the condition, at a cost to Britain’s economy of £23bn per year, funding for dementia research is 12 times lower than that for cancer research. The GPs prescribing these drugs may have done so simply as a last resort. Underfunding also means that other options which have been shown to help, such as cognitive behavioural therapy, encouraging patients to exercise and better training for nurses and carers, have not been adequately researched. Proper, evidence-based medicine doesn’t just involve running large, expensive trials of new drugs. And if dangerous, unlicensed drugs have been used despite extensive warnings, a full inquiry is surely the least the victims deserve.