The missing warning on a drug for desperate people - The Guardian May 17, 2001

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The missing warning on a drug for desperate people
http://www.guardian.co.uk/comment/story/0,3604,492305,00.html

Users of an antidepressant are not yet being alerted to a possible suicide risk

Ed Harriman
Thursday May 17, 2001
The Guardian

It may seem hard to believe that a big drug company would drag its feet over an official request to provide depressed people with warnings that might save their lives. But that is what appears to be happening.
The government's watchdog, the medicines control agency, decided almost a year ago to ask drug companies including GlaxoSmithKline the world's biggest, to warn patients of a possible risk of suicide associated with Prozac-style drugs. Glaxo's Seroxat is one of the most prescribed.



In August, the agency wrote asking the firm to include the following straightforward words on the patient information leaflets stuffed into drug packets:

"Occasionally thoughts of suicide or self harm may occur or may increase in the first few weeks of treatment with Seroxat, until the antidepressant effect becomes apparent. Tell your doctor immediately if you have any distressing thoughts or experiences."

Dr Keith Jones, director of the agency, said at the time: "The committee on the safety of medicines ... considered it was important that patients and the families of patients were made aware of a possible risk of an increase in suicidal behaviour." He added: "We are taking this issue very seriously."

However, patients prescribed GlaxoSmithKline's wonder drug will today look in vain for this warning. It seems the firm does not like the wording.

A director, Ian Hudson, was asked about this last December during US legal proceedings by lawyer Andy Vickery: (The drug is called Paxil in the US):

Vickery: "Incidentally, is SmithKline going to implement the new suicide warning that the medicines control agency in the UK recommended back in August of this year?"

Hudson: "Could you refer to ... tell me exactly what the warning is?"

Vickery: "The warning concerning suicide, suicide and Paxil. Have you seen it?"

Hudson: "Well SmithKline Beecham and the MCA have been in discussion in relation to ... including some wording within the UK data sheet. Exactly what the final wording will be, I don't know, I haven't seen it. I would have to consult my colleagues on that..."

Vickery: "But is SmithKline Beecham going to implement a wording change with respect to the issue of suicide on the Paxil label some time in the near future?"

Hudson: "We've certainly been in discussions with the MCA about that. I'm not sure whether that's finally resolved and when that's going to happen..."

(Shortly afterwards, Hudson left Glaxo and joined the medicines control agency in a senior position, although it is not suggested he personally handled this issue thereafter.)

Glaxo's public relations staff say their own, different wording was proposed to the agency in March and is now lying on the table. But they say it is "confidential".

So, to date, depressed patients continue to go without any warning at all.

Behind this bewildering and somewhat unsavoury delay, lie bigger issues. There is looming litigation, and large sums may be at stake for manufacturers of what has been hailed for years as a miracle drug.

Seroxat is an SSRI - a selective serotonin reuptake inhibitor - an antidepressant that works by changing the chemistry in the brain. SSRIs are being marketed for an ever-widening range of complaints, including premenstrual tension.

The chemical is GlaxoSmithKline's biggest selling drug, raising some £1.5bn last year, nearly £100m in the UK. Only Eli Lilly's Prozac, of all the SSRI's, outsells it. Many depression victims say it has helped them greatly.

But Seroxat has had special problems almost from the day it was licensed some 10 years ago. In 1993, the committee on safety of medicines - which advises the MCA - warned doctors that in light of "symptoms occurring on withdrawal ... including dizziness, sweating, nausea, insomnia, tremor and confusion ... [it] should not normally be discontinued abruptly."

Since then more adverse re action reports have been filed about Seroxat for problems associated with withdrawal symptoms than for all the other antidepressants, including Prozac, combined.

Suicide risk is another matter where GlaxoSmithKline faces challenges. This Monday, the firm goes on trial in Wyoming sued by the survivors after Donald Schell ran amok, shot family members and turned the gun on himself, two days after he was prescribed the drug in 1998. The family and Vickery, their no-nonsense Texas lawyer, hope to convince a jury that the drug triggered Mr Schell to go berserk. The firm deny this.

"What I intend to prove is that SmithKline knew about this potential risk for violence and suicide," says Vickery. It was he who recorded the deposition from Dr Hudson, then SmithKline's vice-president for clinical safety based in Harlow, Essex.

One of the big selling points of all SSRIs has been that they are less risky than older antidepressants, so-called tricyclic drugs. Promotion literature states boldly that Seroxat is "safe-in-overdose": if a patient swallows a bottle that in itself is unlikely to kill them.

But this is no longer the whole story, due to a crucial new study. Before Christmas an article appeared in the British Journal of Psychiatry by Dr Stuart Donovan and colleagues. It's their report of 2,776 patients taking SSRIs who turned up at Derbyshire Royal Infirmary over two years. They found that if you look for a statistically significant relationship between taking SSRIs and suicide by overdosing on them, you won't find much.

But they did find a relationship between taking SSRIs and all forms of deliberate self-harm - including overdose, attempted overdose, hanging, gassing, laceration, deliberate road traffic accidents, head banging, swallowing non-medicines - much higher for SSRIs than for the older tricyclics. (This applies whether the cause is SSRIs themselves or merely the delay in their effect.)

The relationship is so strong, Dr Donovan says, that he firmly believes promotional material for SSRIs including Seroxat should be changed immediately so doctors no longer prescribe them to potentially suicidal patients thinking, mistakenly, that by doing so they are protecting their lives.

Dr Donovan sent the manuscript to SmithKline Beecham (who partly financed the study with Eli Lilly) before it was published asking for comments. They never replied.

This history of controversy is hardly calculated to make depressed patients on Seroxat feel more comfortable. If they're worried - and indeed, as the warning with their pills would have told them had it been included by now - they should see their doctors for advice.

Ed Harriman is an investigative film-maker

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