Antipsychotic medication (or neuroleptics) are an effective treatment for people with schizophrenia. In 1952, Henri Laborit, a surgeon in Paris, was looking for a way to reduce surgical shock in his patients. Much of the shock came from the anaesthesia, and if he could find a way to use less, his patients could recover quicker. He knew that shock was a result of certain brain chemicals so he looked for a chemical to counteract these.
His administration of a drug called Chlorpromazine had a marked effect on his patients. Previously restrained and often violent patients could now make contact with others and be left without supervision. It seemed to have a calming effect without sedating his patients. It was then trialled for a number of psychiatric disorders. Some being successful, however there were side effects and drawbacks to the drug which were revealed in the passing years.
Following the introduction of first-generation (typical) antipsychotics (FGAs) in the early 1950s, there was a radical change in the therapeutic regimens for schizophrenia.
But, as noted, it soon became apparent that these antipsychotics produced serious side effects including extrapyramidal symptoms (EPS) - a distressing and debilitating movement disorder. The extrapyramidal system itself is a neural network that is part of the motor system.
Along with extrapyramidal symptoms, other side effects of FGAs included;
- Neuroleptic Malignant Syndrome (NMS), a rare, but life-threatening idiosyncratic reaction to the medication. The syndrome is characterised by muscle rigidity, fever and a sudden raised body temperature which can be fatal. Incidence rates range from 0.02 to 3%.
- Drowsiness, dry mouth, weight gain, constipation, depression.
To prevent EPS, second-generation (a-typical) antipsychotics were developed. These newer medications differed from FGAs primarily on the basis of their reduced risk of inducing EPS (Yamamoto & Inada, 2012).
Second-generation antipsychotics are effective against psychosis and, at therapeutic doses, seldom cause EPS. Their therapeutic effects are attributable to central antagonism of both serotonin and dopamine receptors, and also possibly to relatively loose binding to D2 receptors (Lehan, 2004).
Controversy still lingers over the efficacy of first and second generation antipsychotics. Second generation antipsychotics were seen as an advance in drug treatment 20 years ago when they were developed, as they had additional benefits and fewer adverse effects. However, the invention of second-generation drugs have been regarded by some as invention only, a clever manipulation by the drug industry for marketing purposes, and there is often selective publication of trials that can skew the evidence in favour of a drug preferred by the investigators. Leucht and colleagues (2008) compiled a meta-analysis titled, 'Second-generation versus first-generation antipsychotic drugs for schizophrenia'. There were 150 trials examined. In 95 of them, the second-generation antipsychotic was compared with the high-potency first-generation antipsychotic Haloperidol. The use of Haloperidol showed a bias in favour of the second-generation drugs. Because this first-generation drug is likely to be associated with a high rate of EPS. They also avoided comparison with a medium-potency FGA, because these drugs are just as efficacious as the second-generation drug.
Antipsychotic drugs differ in their potencies and have a wide range of adverse effects, with nothing that clearly distinguishes the two groups. The only second-generation antipsychotic that is better than other drugs in resisting schizophrenia is clozapine. Nevertheless, it is argued that second-generation drugs have no special a-typical characteristics, that they are no more effective, do not improve specific symptoms, are less cost effective, and have no clearly different side effects than first-generation drugs (The Lancet, 2009).
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