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Right to a fair trial: St John’s wort

29 Oct, 09 | by Steven Reid, Evidence-Based Mental Health

The updated NICE guideline for depression is just out. Here is what it has to say about St John’s wort:

Although there is evidence that St John’s wort may be of benefit in mild or moderate depression, practitioners should:
• not prescribe or advise its use by people with depression because of uncertainty about appropriate doses, persistence of effect, variation in the nature of preparations and potential serious interactions with other drugs (including oral contraceptives, anticoagulants and anticonvulsants)
• advise people with depression of the different potencies of the preparations available and of the potential serious interactions of St John’s wort with other drugs.

Funny that. In the last issue of EBMH, Edzard Ernst, the professor of complementary medicine who has become the bête noire of the alternative medicine crowd was less dismissive. Reviewing the latest Cochrane update he concludes that there is now plenty of evidence demonstrating that SJW is an effective antidepressant and if you can avoid herb-drug interactions, it may be safer than conventional drugs. So why don’t we recommend SJW for depression?

I have written about SJW here before and was less than complimentary (ouch!). My scepticism was similar to the NICE position: you can’t be sure what you are getting, and patients thinking that it’s not really a drug mix it with prescription medication and run into trouble. Perhaps, however, there is more to it than that. Given the rather murky history of clinical trials and marketing with conventional antidepressants and the often marginal benefit over placebo it does seem as though when it comes to evidence we hold St John’s wort to a higher standard. Trawl through the rapid responses of a trial involving SJW and you will find a degree of nit-picking that is rarely seen with the SSRIs. This type of reader or reviewer bias is not much discussed and competing interest statements rarely include declarations of inherent prejudice. In this editorial for Clinical Evidence, Professor Ernst criticises the knee-jerk assumption that if a clinical trial of a complementary medicine shows efficacy it must be a flawed trial. So is St John’s wort being treated unfairly? The answer, I think, has to be yes.

Schizophrenia and the Art of War

2 Sep, 09 | by Steven Reid, Evidence-Based Mental Health

We have had a War on Terror, a War on Drugs, a War on Cancer, and a War on Poverty. We do have a mental health czar – it seems a czar is essential when forces need to be mobilized – but no War on Mental Illness as yet. Maybe we should…Mark Salter sees parallels in our responses to war and schizophrenia in his trenchant critique of the updated NICE guidance on the management of schizophrenia. You can find it on the EBMH homepage. The parallels are not especially favourable although he doesn’t mention lions or donkeys. Maybe he should…

Clozapine: first-line treatment for schizophrenia?

24 Jul, 09 | by Steven Reid, Evidence-Based Mental Health

Long considered the Heineken of antipsychotic drugs (refreshing the parts of the brain other drugs cannot reach…sorry), clozapine also comes with more restrictions and health warnings than a pack of cigarettes in California. That might change following this study from the Lancet showing that people with schizophrenia prescribed clozapine had a lower mortality rate than those taking any other antipsychotic or on no treatment at all.

Clozapine has been around since the 1960s and when it was introduced offered the distinct advantage of an extremely low incidence of the motor side effects – stiffness, abnormal movements – that beset other antipsychotics at the time. That was until 1975 when it was withdrawn after a case series was reported of 16 patients on clozapine developing agranulocytosis (a severe deficiency of white blood cells), half of them going on to die.

The drug disappeared for 10 years or so until in 1988 it was rehabilitated following a classic study that demonstrated its superior efficacy in treatment-resistant schizophrenia, where other drugs had little or no effect. It was invited back into the formulary but this time with compulsory blood count monitoring and the proviso that at least two other antipsychotics should be tried first

For this new study Jari Tiihonen and colleagues were looking at the gap in mortality between people with schizophrenia and the general population in Finland over 11 years. They had access to data on 67000 individuals with schizophrenia – that’s right 67000. You can do research like that when you have ‘socialized’ medicine. First, they found that over the duration of the study the 25 year gap in life expectancy remained unchanged, despite the introduction of newer treatments. In what may come as a surprise to some, given the notoriety of antipsychotics and their side effects, those taking antipsychotics over the course of the study had a lower mortality rate than those who were drug-free. But by far the drug with the lowest risk of death (due to any cause) was clozapine. Quetiapine, haloperidol and risperidone increased that risk by 41 per cent, 37 per cent and 34 per cent respectively when compared to an older drug, perphenazine. In contrast use of clozapine was associated with a 26 per cent reduction in mortality. Clozapine was also associated with a lower risk of suicide than any other drug.

The NICE guidance for schizophrenia (in England and Wales) updated in March this year had this to say about clozapine: Offer clozapine to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least two different antipsychotic drugs. At least one of the drugs should be a non-clozapine second-generation antipsychotic.

Time for a rethink perhaps as not only is clozapine the most effective antipsychotic we have; it may also be the safest.

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