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health inequalities

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 That was until 1975 when it was withdrawn after a case series was reported of 16 patients on clozapine developing agranulocytosis (a severe deficiency of white blood cells), half of them going on to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.

Some are more equal than others

26 Mar, 09 | by Steven Reid, Evidence-Based Mental Health

With free market capitalism seemingly spinning off into oblivion, despite the best efforts of our Supreme Leader and his G20 disciples, the benefits of globalisation for the world economy are looking a little shaky at the moment. Whilst it has brought an unprecedented increase in prosperity for some, for others low wages and an economy underpinned by massive debt mean that the world seems a more unequal place than ever before. These inequalities are of course not just international but intranational: countries are made up of classes.

In 2004 Michael Marmot charted the impact of inequality on health in The Status Syndrome. This month his text is joined on the shelf by The Spirit Level (Richard Wilkinson and Kate Pickett). Both books marshal an array of epidemiological studies to present a robust bottom line: there is a strong correlation between a country’s level of economic inequality and its social and environmental problems. What’s more, it isn’t just the poorest in the most unequal societies that suffer but the richest too. So according to Wilkinson, “countries such as the US, the UK and Portugal, where the top 20% earn seven, eight or nine times more than the lowest 20%, scored noticeably higher on all social problems at every level of society than in countries such as Sweden and Japan, where the differential is only two or three times higher at the top.” And those social problems range from obesity to big prison populations, from teenage pregnancy rates to, of course, mental illness.

That an unequal society leads to more mental distress may seem self-evident but a study recently published by the World Health Organisation – Mental health, resilience and inequalities – amasses a broad range of evidence to show that mental health problems are not only more pronounced in unequal societies, but that mental health is also key to understanding the impact of inequality on a range of other health outcomes. Dr Lynne Friedli, the report’s author, maintains that the chronic stress of struggling with material disadvantage is intensified by doing so in more unequal societies. In turn chronic stress has a deleterious effect on the neuroendocrine, cardiovascular and immune systems increasing the risk of disorders such as coronary heart disease and metabolic syndrome. Maybe so, although the strength of the evidence is contestable. But what’s to be done? Dr Friedli’s wish list seems rather optimistic:

• social, cultural and economic conditions that support family and community life
• education that equips children to flourish both economically and emotionally
• employment opportunities and workplace pay and conditions that promote and protect mental health
• partnerships between health and other sectors to address social and economic problems that are a catalyst for psychological distress
• reducing policy and environmental barriers to social contact

This sounds too much like ‘motherhood and apple pie’ to me, although a strident call for wealth redistribution would probably be asking a lot of WHO. Of course, the UK government would claim that they have made considerable progress in all of these areas over the last decade. If that is the case, why is there a need to convene a new National Equality Panel to show how your chances in life are influenced by, among other things, ‘how much money you earn’? We are also awaiting another review of Health Inequalities in England to show us the way.

Gordon Brown is busy trumpeting the need for economic and financial reforms ahead of the G20 meeting, or as it has now been rebranded: the London Summit. An opportunity to redress global imbalances? Not bloody likely. I’m more inclined to believe this pithy observation from the Financial Times: “A crisis-torn world is in no mood for the heavy lifting of global rebalancing. Policies are being framed with an aim towards recreating the boom. Washington wants to get credit flowing again to indebted US consumers. And exporters – especially in Asia – would like nothing better than a renewal of demand led by the world’s biggest consumer. It is a recipe for disaster.”

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