The new antipsychotics

The so-called ‘atypical antipsychotic drugs’ have been hailed as a pharmaceutical breakthrough and have, by now, largely replaced the old guard of neuroleptics. However, a recent overview of these modern medicines questions the claim that this new class of antipsychotics is broadly superior to conventional ones.

So, what is the evidence for this claim? The first neuroleptic medications were developed in the 1950s to relieve the hallucinogenic and paranoid symptoms of schizophrenia and other psychoses. Unfortunately, these drugs brought with them unwanted extrapyramidal (brain motor system) side-effects such as tardive dyskinesia, characterised by muscle stiffness, tics, tremors and other awkward movements.

Led by the introduction of clozapine (Clozaril), the umbrella name of ‘atypical antipsychotics’ became the calling card for this next generation of drugs – which also includes olanzapine (Zyprexa), quetiapine (Seroquel) and risperidone (Risperdal). They have shown promise in suppressing the depressive and antisocial aspects of mental illness that had evaded the earlier drug treatments. And although these atypical antipsychotics each came with its own set of side-effects, the studies suggested that none were as serious as the antipyramidal effects described above (World J Biol Psychiatry, 2000; 1: 204-14).

However, this doesn’t mean that they are necessarily safer.

On reviewing the literature for both the modern and older antipsychotics, researchers noted dubious methodology in some cases – such as basing findings on non-matching dosages across several clinical trials. Overall, no marked advantages of atypical antipsychotics could be found in terms of efficacy, tolerability or mental function. Indeed, researchers warned that “the much promoted advantage of reduced risk of extrapyramidal symptoms with modern antipsychotic drugs needs to be balanced against other adverse effects” (CNS Drugs, 2005; 19 [Suppl 1]: 1-93).

The list of damaging – and sometimes life-threatening – side-effects seen with atypical antipsychotics is lengthy:

* Agranulocystosis (a low white cell count) – which increases susceptibility to infection. It is so commonly seen with clozapine that the drug is only prescribed as a last resort – and even then, only under strict (and expensive) monitoring (Int J Neuropsychopharmacol, 2005; 8: 311-3)

* Akathisia (extreme restless movements of the arms and legs) – an extrapyramidal symptom. In one recent case study, two patients developed this symptom after taking quetiapine (Psychosomatics, 2005; 46: 291-301)

* Cognitive problems – which, again, have been seen with quetiapine (BMJ, 2005; 330: 874)

* Depression – seen, according to one recent case report, in a schizophrenic patient taking quetiapine, suggesting that these atypical antipsychotics may contribute to or worsen the condition for which they are prescribed (Clin Neuropharmacol, 2005; 28: 133-5)

* Diabetes and weight gain (see box above)

* Hyperprolactinaemia (abnormally high levels of the hormone prolactin) – frequently seen (in 60 per cent of women and 40 per cent of men) with the older antipsychotics and prolactin-raising versions of the new breed (risperidone and amisulpride). Symptoms include the development of breasts in men, abnormal secretion of breastmilk, sexual dysfunction, infertility and menstrual disorders (Drugs, 2004; 64: 2291-314)

* Neuroleptic malignant syndrome (NMS) – a rare and potentially fatal condition, characterised by altered consciousness, fever, unstable blood pressure and muscular rigidity. NMS has been reported with clozapine, risperidone, olanzapine and quetiapine (Expert Opin Drug Saf, 2003; 2: 21-35)

* Pancreatitis – the findings for which suggest that clozapine, olanzapine and risperidone, in that order, can cause this potentially fatal disease (Pharmacotherapy, 2003; 23: 1123-30)

* Sexual dysfunction – found in a major Spanish study of 636 patients taking olanzapine (in 35.3 per cent), quetiapine (in 18.2 per cent) and risperidone (in 43.2 per cent). Risperidone also was shown to have the highest risk of reproductive side-effects (J Sex Marital Ther, 2003; 29: 125-47).

For alternatives to this dangerous family of drugs, consult WDDTY’s The Guide to Mental Health (UK price £6.95, including p&p). This book can be purchased through our website at: or by calling us on 0870 444 9886.

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Written by What Doctors Don't Tell You

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