A deadly prescription to combat depression
Andrew Jack reports on fresh concerns over the controversial antidepressant Seroxat and other selective serotonin reuptake inhibitors, which have been linked with suicides among patients
Just two days after Jonathan Woods was prescribed Seroxat in February last year to treat mild anxiety brought on by work, he complained of breathlessness and extreme fear. His doctor asked him if he felt suicidal, but he said he loved his wife too much to kill himself.
On the morning that he had his seventh daily pill, his wife took the day off to accompany him to the doctor. But during the 20 minutes that she was out taking their children to school, he took his own life.
“I think Seroxat is a very dangerous, mind-altering drug,” says his mother, Stella. “I understand that it may help some people, but it should not be prescribed for mild depression or social phobia, or even major depression without strict supervision. It makes me angry that no-one seems to be taking any responsibility for this.”
Mr Woods's case is one of 1,700 being brought in the UK by Mark Harvey, a Cardiff lawyer, against GlaxoSmithKline (GSK), the pharmaceutical group that manufactures Seroxat, also known as paroxetine. Last week, he wrote to the company seeking compensation under consumer protection legislation.
“I was sceptical at first, but there is a shedful of stories of suicides, aggression and withdrawal problems,” Mr Harvey says.
“I have never said the drug should not be prescribed, but the science is not sufficiently up to speed to be able to identify why one individual benefits and another does not.
“It should be restricted to the most serious cases, and then monitored,” he adds.
His legal action follows a number of undisclosed settlements made by GSK in the US, and a continuing internal investigation by the Medicines and Healthcare products Regulatory Agency, the UK government watchdog, which could lead to it taking criminal action against GSK.
The moves come at a time of renewed discussion surrounding the category of antidepressant drugs known as selective serotonin reuptake inhibitors (SSRIs) introduced from the late 1980s, of which Seroxat is one and Prozac is the best known alternative.
They work by increasing the functional amounts in the brain of serotonin, a neurotransmitter involved in determining mood. Unlike tricyclic antidepressants, the previous class, they do not affect two other neurotransmitters, noradrenaline and dopamine, interference with which can cause side-effects, especially in overdose.
SSRIs are recommended by professional bodies including the UK's Royal College of Psychiatry and the National Health Service's National Institute for Clinical Excellence, and are widely used, with 18m prescriptions to about 3.5m patients in England alone last year.
But in October the US Food and Drug Administration launched a review of antidepressants and their risks in provoking adult suicides, and yesterday the European Medicines Agency also expressed concerns.
And last Monday, the MHRA issued the findings of its own 18-month study triggered by negative media reports and complaints from patients. The conclusions went some way to conceding there had been weaknesses in past use of SSRIs. Kent Woods, the MHRA chief executive, said that the drugs had “likely been over-prescribed” in treating milder forms of depression, and that public information was not adequate. He called for careful monitoring, and particular caution with one drug, venlafaxine or effexor.
The findings reflected a series of modifications to the information supplied with SSRIs, which have highlighted both a growing number of side-effects as well as increased risk of side-effects; warned of the dangers of rapid withdrawal; and advised against prescription to adolescents, in whom there have been indications that they can induce strong suicidal feelings.
An online survey for the FT this week of 200 GPs by
www.doctors.net.uk, a professional network, showed 23 per cent prescribed SSRIs at least 10 times per week, but 26 per cent said they would prescribe fewer in future. While arguing that “a modest increase in the risk of suicidal thoughts and self-harm . . . cannot be ruled out” with the use of SSRIs when compared with a placebo, the MHRA inquiry concluded that there was no clear increased risk of suicide compared with other antidepressants.
It stresses that suicides have been falling in the UK while prescriptions of antidepressants were rising, and that it is questionable to blame the drugs when suicide is most likely at the start of patients' treatment.
But critics of the regulators, such as Charles Medawar, head of Social Audit (
www.socialaudit.org.uk), say the MHRA findings are flawed and reflect problems with the methodology employed.
He suggests that the working group should have taken time to study individual cases of patients taking SSRIs, rather than relying on aggregated data. That could have helped highlight how the drug may differentially affect various kinds of people.
Mr Medawar questions the “cosy” link between regulators and the pharmaceutical industry, and suggests antidepressants are part of a broader trend of “over-medicalisation” of society. “This study again gives the benefit of the doubt to the drug industry and not to the patient,” he says.
Katie Greenfield, a member of Mr Harvey's action against GSK, who took more than seven years to wean herself off Seroxat, argues: “The drug companies are there to provide a bigger return to their shareholders. They don't have consumers' interests at heart.”
But the consensus in the medical establishment today may be best summed up by Professor Louis Appleby, the government's national director for mental health, who argues that the benefits of drugs including SSRIs for millions of depressive patients far outweigh the risks of non-treatment. What is needed at least is their more selective use.
抑郁症的致命处方
去年2月医生给乔纳森?伍兹（Jonathan Woods）开出处方，用赛乐特（Seroxat）治疗由于工作造成的轻度焦虑症，仅仅两天之后，他又抱怨说，自己呼吸急促并拌有极度恐惧。医生问他是否有自杀念头，但他说，他太爱他的妻子了，所以不会自杀。
在他服用第7粒药丸的那天早上，他的妻子请假陪他去看医生。就在她暂时离开医院送孩子上学的20分钟里，他结束了自己的生命。
“我认为赛乐特是一种非常危险的药物，能引起心理变化，”他的妈妈斯泰拉（Stella）说。“我明白它可能帮助某些人，但不应该开方用它治疗轻度抑郁症或社交恐惧症，在没有严格监护的情况下甚至连重度抑郁症都不应服用。我很气愤，因为好像没有人为此承担任何责任。”
在英国，伍兹先生案是卡迪夫（Cardiff）律师马克?哈维（Mark Harvey）上诉葛兰素史克（GSK ，即GlaxoSmithKline）的1700宗案件之一。制药集团葛兰素史克是生产赛乐特的厂商，该药物又名帕罗西汀（paroxetine）。
“一开始我还有点犹疑不定，可是不断地有消息说到自杀、攻击和逃避现实等问题，”哈维先生说。
“我从来没说这种药不应该开，但是科学发展得还不够快，目前尚不能鉴定为什么某一个人可以受益、而另一个人却不受益。”
“它应该限用于最严重的病例，而且应该监控使用，”他补充道。
在哈维先生提出诉讼之前，GSK集团已经在美国进行过一些未经披露的和解，而英国政府的监察机构，即医药和保健产品管理委员会（Medicines and Healthcare products Regulatory Agency），也在进行一项内部调查，这项调查有可能导致对GSK集团的刑事诉讼。
这些行动的采取，正值人们重新讨论有关抗抑郁类药物的问题之时。抗抑郁类药物是20世纪80年代末开发的一类选择性5-羟色胺再摄取抑制剂（SSRIs，即selective serotonin reuptake inhibitors），赛乐特是其中之一，百忧解（Prozac）则是人们熟知的另一种。
这类药物的作用是由于增加了5-羟色胺在大脑中的功能量，5-羟色胺是一种可决定情绪的神经传递素。与以前的三环抗抑郁药类（tricyclic antidepressants）不同，它们不影响另外两种神经传递素，即去甲肾上腺素和多巴胺，对这两者的干预会导致一些副作用，尤其是超剂量服用时。
SSRIs得到一些专业机构的推荐，其中包括英国皇家精神病学院（Royal College of Psychiatry）和英国国家健康中心（National Health Service）下属的国家临床卓越研究院（National Institute for Clinical Excellence）。这类药物应用得非常广泛，去年仅在英格兰地区，就对350万名病人开出了1800万份处方。
但是10月份，美国食品药物管理局（Food and Drug Administration）开始了一次调研，考察抗抑郁类药物及其导致成年人自杀的风险。近日欧洲药品局（European Medicines Agency）也对此表示了关切。
最近，英国医药和保健产品管理委员会发布了该委员会自己进行的18个月的调研结果。导致这项调研的是一些负面媒体报道以及病人的投诉。调研结论在一定程度上承认，以往在SSRIs的使用上存在不足之处。该机构首席执行官肯特?伍兹（Kent Woods）说，这类药物“可能被滥用”于治疗较轻形式的抑郁症了，且公众信息也不适当。他呼吁严格监控，并格外当心一种叫作文拉法新（venlafaxine）、又名effexor的药物。
研究结果反映出，对有关SSRIs的信息进行了一系列的修正。这些修正强调了数量正在增加的副作用和更大的副作用风险，警告了骤然停药的危险，并建议不对青少年开方，因为有迹象表明这类药物引起青少年产生强烈的自杀念头。
本周《金融时报》通过专业网站
www.doctors.net.uk，对200名普通医师开展了一次网上调查。结果表明23%的调查对象每周至少10次开方使用SSRIs，不过26%的调查对象说他们今后会少开这类药。虽然医药和保健产品管理委员会的调研结果提出，在与一种安慰剂进行比较研究时，使用SSRIs 后“自杀念头和自伤倾向的风险有一定增长……是不能排除的”，但同时它也得出结论说，与其它抗抑郁药物进行比较研究时，自杀风险并未增长。
研究结果强调指出，在抗抑郁类药物处方增长的同时，英国的自杀人数却一直在下降，而且，自杀最容易发生在病人的治疗初期，所以如果都归咎于这类药物是有问题的。
但是管理机构的批评者们，如社会审计（Social Audit，
www.socialaudit.org.uk ）总裁查尔斯?梅达沃（Charles Medawar）说，医药和保健产品管理委员会的调研结果不正确，它们反映了其采用的调研方法有问题。
他主张，调研组本应花时间对服用SSRIs的病人进行个案研究，而不是依赖总计数据。那样才能有助于鉴别药物是怎样对各种人发生不同作用的。
梅达沃先生质疑管理机构与制药业之间的“安逸的”关系，并提出，抗抑郁类药物乃是社会“过分医药化”大潮的一个组成部分。“这项调研又一次令制药业而不是病人，在这种疑问中受益，”他说。
凯蒂?格林菲尔德（Katie Greenfield）是哈维先生上诉葛兰素史克案的成员之一，她花费7年多的时间才断掉了赛乐特。她论说道：“制药公司一心只想给股东们提供更大回报。它们才不把消费者的利益放在心里呢。”
不过，对于目前有关医药机构的舆论，概括得最好的莫过于刘易斯?艾泼尔比（Louis Appleby）教授了。刘易斯?艾泼尔比教授是英国政府的国家精神健康主管，他提出，包括SSRIs在内的药物，为千百万抑郁病患者带来的好处，远远超过了不治疗的风险。需要做到的最起码的事情，是更有选择地使用它们
