Choice of drug

The newer drugs appear to offer an advance in the treatment of schizophrenia, at least in expanding the range of choice of available drugs. They are recommended by NICE ( to be 'considered in the choice of first-line treatments for individuals with newly diagnosed schizophrenia'. In other words, the evidence reviewed did not allow NICE to recommend that the newer drugs should generally be used as first-line treatment, or that they should be reserved for use when a typical drug has failed.

Some psychiatrists still regard chlorpromazine as their first-line antipsychotic; however, they are now in a minority. Clinical experience is that the majority of UK psychiatrists do now regard atypical antipsychotics as first-line drugs, and most will reserve the older drugs for when atypical drugs have not worked.

Overall, the advantage lies with the prescriber becoming familiar with two or three key drugs, which he can prescribe with confidence and which work in his hands.

In my own practice, I find olanzepine be a satisfactory initial treatment for acute psychotic episodes. Often a suitable starting dose is 5 mg at night. There are liquid and quick-dissolving tablets, formulations that are helpful if there is doubt about whether the patient can be trusted to swallow conventional pills. It is a sedative drug, and this is helpful to patients (and nurses) in the acute stages. It does not, however, seem to be the most powerful drug against the core symptoms of psychosis, delusions, and hallucinations. I find that a combination of olanzepine with a small dose of haloperidol (1.5-5 mg, for example) can be helpful if there are residual psychotic symptoms. Such doses of haloperidol are well tolerated, and the combination may be better in the long run than the alternative of persisting with maximum doses of olanzepine, with the attendant risk of weight gain.

The main disadvantage of olanzepine is its association with weight gain and even with diabetes; if it is used as a maintenance treatment, therefore, the dose should be reduced to a minimum, and monitoring of weight is important.

Risperidone can produce extrapyramidal effects, more so than olanzepine, but less so than the typical antipsychotics. It is less associated with weight gain and olanzepine. There is an injectable preparation, which offers an alternative to the traditional depot antipsychotics; some patients do well on it. However, it seems not to be as strong a drug as the 'typical' antipsychotics for the most severely affected.

Aripiprazole and quetiapine are other atypicals available; they are felt to have benign profiles of unwanted effects, but to be of limited effectiveness in severely ill patients.

If the first drug chosen does not work, it is logical to change to one of a different chemical group. If two drugs have failed, clozapine should be considered.

Clozapine is a highly effective antipsychotic but is licensed only for use in resistant cases that have failed to respond to first-line drugs. Because of its risk of agranulocytosis, it is only available on a named-patient basis on condition that regular blood counts are satisfactory. The full benefit of clozapine may not be seen for at least a year.

Thioridazine causes few Parkinsonian effects, and is sedative, but is more likely to cause confusion - all these because of its strong anticholinergic properties. It has been described as 'the first atypical'. Unfortunately, because of cardiovascular side-effects, it is no longer regarded as suitable for routine use.

Haloperidol is pharmacologically 'cleaner', with fewer actions outside the dopaminergic system; it has a reputation of being prone to cause extrapyramidal effects. This may be due to its previous use in very high doses, perhaps in an effort to produce the sedation that its mainly dopamine-focused actions mean is inherently unlikely.

However, even small doses of haloperidol (1.5-5 mg) are profoundly antipsy-chotic, and at this dose, haloperidol is well tolerated. It can be supplemented with benzodiazepines (or olanzepine) if additional sedation is required. Such regimens offer an alternative, probably underused, to automatic prescription of the very much more expensive atypicals.

Amisulpiride was thought to have specific effectiveness against negative symptoms, but unfortunately, this has not generally been borne out in use. It appears to be a fairly gentle, although not especially strong, antipsychotic.

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