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Medication for schizophrenia

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VOL: 97, ISSUE: 31, PAGE NO: 38

Richard Gray, PhD, RN, is Medical Research Council fellow in health services research, Institute of Psychiatry, London

Since antipsychotic drugs were introduced more than 50 years ago, mental health nurses have had an important role in helping patients to manage their medication. They administer drugs, educate patients on the likely effects - positive and negative - monitor side-effects and evaluate treatment responses.

Since antipsychotic drugs were introduced more than 50 years ago, mental health nurses have had an important role in helping patients to manage their medication. They administer drugs, educate patients on the likely effects - positive and negative - monitor side-effects and evaluate treatment responses.

Mental health nurses also often advise psychiatrists on which medication may suit a particular patient. In the past few years there has been growing recognition that formalising this practice, for example by giving mental health nurses some form of prescriptive authority, could have considerable benefits for patients.

The government is committed to extending nurse prescribing and issued a consultation document last year (Department of Health, 2000) proposing that mental health might be an area in which nurse prescribing should take place.

It is vital for mental health nurses to keep up to date with research on the use of antipsychotic medications, not only to help them in their ongoing management of medication but also to enable them to take part in the debate on the development of mental health nurse prescribing.

Facts about schizophrenia
Before considering the problems and challenges of drug treatment for people with schizophrenia, we should remind ourselves what a serious and debilitating illness it is.

The condition is characterised by a range of symptoms, the most common being hallucinations, delusions, thought disorder, impaired cognitive functioning, social isolation and lack of motivation. About 200,000 people in the UK have schizophrenia and the lifetime risk is about one in 100 (Gray and Smedley, 1997). It is usually a chronic relapsing condition: people tend to get it when they are fairly young, typically in their twenties, and 80% of those who have one episode have repeated relapses (Gray and Smedley, 1997).

People with schizophrenia have high mortality rates: life expectancy is about 10 years less than the general population, primarily because some will commit suicide. A third will have a co-morbid substance misuse problem, typically alcohol and/or cannabis (Wright et al, 2000), and almost half will experience depression (Baynes et al, 2000).

Although schizophrenia is a relatively rare condition, it places a great economic burden on society. People with the condition consume 5% of the total NHS inpatient budget and the estimated annual direct economic cost in England and Wales is at least £2.8bn (Knapp, 1997).

Typical (conventional) antipsychotic drugs
Although it is very effective in treating symptoms, antipsychotic medication, particularly conventional drugs such as haloperidol and chlorpromazine, have always been known to have a number of serious and unpleasant side-effects. These often result in people stopping their medication, increasing the risk of relapse.

Perhaps the most widely known symptoms are extrapyramidal symptoms (EPS). Acute EPS - parkinsonism, akathisia and dystonia - are seen in about 50% of patients treated with conventional antipsychotic drugs. These do not normally go away unless treated but are difficult to treat effectively. For example, anticholinergic medication can alleviate some parkinsonian symptoms, such as stiffness and tremor, but has its own side-effects, including dry mouth, blurred vision and cognitive deficits, and may exacerbate the symptoms of schizophrenia.

Late onset movement disorders, such as tardive dyskinesia, are also often observed in patients taking conventional antipsychotic medication. Tardive dyskinesia can be particularly debilitating, and once it has developed it is almost impossible to treat effectively (Gray, 1999).

A long list of other potential and relatively common side-effects can be seen in patients taking antipsychotic medication. This includes sexual dysfunction, weight gain and sedation, all of which patients find distressing.

It has long been known that antipsychotic drugs can cause cardiac arrhythmias, leading in rare cases to death. Last year the Committee on Safety of Medicines announced significant restrictions on the prescription of thioridazine after concerns over rare but serious cardiotoxicity.

Although conventional antipsychotic drugs are effective for most patients, they are poorly tolerated and, as a result, many patients refuse to take them.

Atypical (modern) antipsychotic drugs
There is a clear need for modern treatments that are at least as effective as conventional antipsychotic drugs but are safer and have fewer side-effects. Over the past decade a number of new, so-called atypical, antipsychotics have been introduced in the UK. The first was clozapine in 1990, next came risperidone in 1993, followed by sertindole in 1996, olanzapine in 1997 and most recently quetiapine in 1998.

By definition atypical antipsychotics cause fewer EPS. Importantly, risperidone, olanzapine and quetiapine do not have the cardiac side-effects reported with sertindole, thioradazine or droperidol (Gray, 2001). In particular, risperidone has been shown to be effective and well tolerated in older people, who make up a large proportion of those being reviewed for possible switches from thioridazine.

Risperidone is effective in treating patients with psychotic symptoms such as aggression, suspicion, hallucinations and delusions (Marder and Meibach, 1994), but without the severe side-effects associated with many older treatments.

However, atypical antipsychotic drugs are not free of side-effects. In fact, sertindole was voluntarily withdrawn by its manufacturer in 1998 because of fears over cardiac safety: nine patients treated with it in the UK had died. And the side-effects of clozapine, specifically the risk of neutropenia, are potentially so serious that the drug is licensed for use only with patients who are treatment resistant and where the benefits of treatment are considered to outweigh the risks.

In contrast, clinical experience with risperidone, olanzapine and quetiapine has shown them to be exceptionally well tolerated (Gray, 1999). The problems caused by raised prolactin levels, such as sexual dysfunction and menstrual problems, are rare, although they have been seen in some patients on higher doses of risperidone (Gray, 1999).

Clozapine and risperidone can both cause postural hypotension, especially early in treatment. Clozapine, olanzapine and quetiapine are sedative, and anticholinergic effects such as dry mouth and blurred vision are fairly common in patients taking clozapine and are occasionally seen in patients taking olanzapine (Gray, 1999).

Overall, however, treatment with atypical antipsychotic drugs produces a dramatic reduction in side-effects compared with conventional drugs.

A reduction in side-effects is not the only benefit of atypical antipsychotic medication. Clinical trials show that risperidone (Kennedy et al, 2000), olanzapine (Duggan et al, 2001) and quetiapine (Srisurapanont et al, 2001) are effective in treating schizophrenia, result in clinical improvements in symptoms and prevent relapse.

A review of 31 studies evaluating clozapine shows that the drug is more effective than typical antipsychotic medications but cannot be widely used owing to its side-effects. There is also evidence that atypical antipsychotic drugs may be effective in treating negative symptoms, such as social isolation and withdrawal (Tollefson et al, 1997), but further long-term trials are needed to confirm this.

Preliminary work suggests that atypical drugs may be useful in treating cognitive symptoms (Fujii et al, 1997), reducing violence, aggression (Rabinowitz et al, 1996) and suicidal impulses (Munro, 1999) and, perhaps most importantly, improving patients' quality of life. Based on this compelling evidence, the latest Maudsley prescribing guidelines (Taylor et al, 2001) recommend that atypical antipsychotic drugs should be the treatment of choice for people with schizophrenia.

Prescribing practices
Despite the benefits of atypical antipsychotic medication, many psychiatrists and GPs continue to rely on traditional drugs. In fact, only 25% of UK patients are prescribed atypical drugs (Frangou and Lewis, 2000).

Alarmingly, those who are prescribed these drugs are also likely to be taking conventional drugs, so-called antipsychotic polypharmacy (Taylor et al, 2001). It is not uncommon for patients to be prescribed risperidone, plus zuclopenthixol decanoate (depot Clopixol), plus droperidol, and procyclidine as required.

Such prescribing practice makes little sense because the positive effects of a lack of EPS from the atypical antipsychotic drug are counteracted by the addition of a conventional therapy that causes EPS. In addition, this method of prescribing is not grounded in any evidence and, most importantly, will not bring the patient any therapeutic benefits.

Many clinicians continue to use conventional drugs because they have more experience with them and are concerned that there is not enough evidence about the safety of atypical drugs. However, in the case of risperidone, there is almost a decade of clinical experience and, as Welch and Chue (2000) observe, it is a fallacy to say the older drugs are safer when, primarily because of issues surrounding cardiac safety, it is highly unlikely they would be approved for clinical use today.

Another reason why clinicians do not prescribe modern treatments could be cost. Traditional drugs such as haloperidol or chlorpromazine cost a few pounds for a month's supply. Atypical antipsychotic drugs are much more expensive. For example, prices ranges from £117 a month for risperidone to £241 a month for clozapine (Taylor, 2001). Some NHS trusts consider that risperidone should be used as a first-line treatment, primarily on economic grounds.

Another possible explanation of why atypical antipsychotics are not more widely used is because of the formulations available. Many clinicians prefer to use medications that can be given as a long-acting depot preparation (Kane et al, 1998), because they believe this method of administration improves compliance and, therefore, outcomes.

Whether this is the case and whether patients find this route of administration acceptable is not clear. However, most atypical drugs are available only in tablet form. Some, such as risperidone, are also available as a syrup. Depot versions of atypical antipsychotic drugs and a long-acting injectable version of risperidone are being developed.

Conclusion
Schizophrenia is a serious and debilitating mental illness. Although antipsychotic drugs such as chlorpromazine were revolutionary in their time, they cause distressing side-effects. There is now considerable clinical experience and research to establish that modern atypical antipsychotic drugs are safe and effective and should be the standard treatment for people with schizophrenia.

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