Q My wife and daughter were both put onto olanzapine (Zyprexa) last year, having been prescribed other antipsychotic drugs for 30 and 10 years, respectively. I am alarmed at how my family has been prescribed these powerful medicines without their ‘informed consent’ or with reference to me as their carer. Any information on olanzapine would be most welcome. - Anthony R. Burton, Nailsworth, Glos
A Antipsychotic drugs are primarily prescribed for schizophrenia, but may also be given for mania and bipolar disorder (manic depression). When first developed in the 1960s, antipsychotics were hailed as a breakthrough in the treatment of schizophrenia. Their major mode of action is as ‘dopamine antagonists’ - they neutralise the brain cells that respond to dopamine.
Dopamine is a naturally occurring brain chemical with several important functions. It plays a critical role in the way the brain controls body movements, and is also important in our emotional responses - especially feelings of pleasure.
When these dopamine-antagonist drugs were first given to schizophrenics, chaotic psychiatric wards suddenly became havens of calm, with patients miraculously transformed into models of good behaviour. At last, said the psychiatrists, we have proof that schizophrenia is a disorder of brain chemistry - and of dopamine in particular.
However, although these new antipsychotic drugs had an immediate effect on brain chemistry, the patients took weeks to respond - and frequently, the drugs simply did not work. They did reduce the delusional, paranoid and hallucinatory symptoms of schizophrenia, but failed to deal with the underlying depressive aspects of the condition, such as a lack of interest in the outside world, social withdrawal, and impaired speech and communication.
The other major problem was the side-effects. Patients began to develop what looked like the classic symptoms of Parkinson’s disease - drooling, a shuffling gait, muscle stiffness and tremor. Strictly speaking, however, these were not side-effects, but direct effects of the drug.
Indeed, we now know that parkinsonism itself is caused by a lack of dopamine, which is why L-dopa is given as a treatment for the disease. So, antipsychotics, which deliberately ‘antagonise’ or block dopamine, inevitably cause parkinsonian-type symptoms.
US investigative journalist Robert Whitaker recently discovered that psychiatrists used to recommend that, in order to achieve a 'good dose' of antipsychotics, the patient should actually be made to develop symptoms of parkinsonism (Whitaker R, Mad in America, Perseus Publishing, 2002).
Partly to help prevent these adverse events (but also because the patents on the old drugs had expired), in the 1990s, a new class of drugs was developed. These were called ‘atypical antipsychotics’, where the adjective only meant that these new drugs were not intended to cause parkinsonism.
However, the ‘atypicals’ are still typical in that they knock out dopamine receptors in the brain. Their major difference is a molecular add-on that is designed to increase serotonin (the lack of which is believed to cause depression).
When first marketed, the atypicals were sold to doctors as 'breakthrough' drugs that 'balance the chemistry' of the brain, with 'a favourable side-effect profile'.
The best-selling atypical is the drug olanzapine that your wife and daughter have been prescribed. It is manufactured by US drug giant Eli Lilly under the trade name ‘Zyprexa’, and has been a runaway success. Since its launch in 1996, it has become Lilly’s top money-earner, with sales of $2.6 billion in 2002.