Classical Versus Atypical Antipsychotics

As atypical antipsychotics have become established as alternatives to classical agents, clinicians are presented with the dilemma as to which should be their first choice in patients with schizophrenia and psychotic illnesses, and indeed whether there is sufficient justification to transfer a patient stabilised on a classical agent over to an atypical.

Atypical antipsychotics may have advantages in three areas. First, they appear to be better tolerated,2 in particular being less likely than classical agents to induce extrapyramidal effects and hyperprolac-

2 Whilst the advantages of atypicals over classical antipsychotics may seem clear cut, one analysis using only trials where doses of classical antipsychotics were at or below a dose of haloperidol 12 mg/day or equivalent (now regarded as the upper limit for optimised use of these agents) produced rather different results. Although the atypicals retained their advantage in causing extrapyramidal side effects less frequently, overall tolerability and efficacy appeared to be similar. Geddes J et al 2000 Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. British Medical Journal 321:1371-1376.

tinaemia (with gynaecomastia and galactorrhoea), although these latter remain common with risperidone and amisulpride. Improved tolerance is reflected in better compliance with taking atypical agents, so lessening the chance of psychosis being untreated with the likelihood of relapse once remission has been achieved. Secondly, atypical antipsychotics are more efficacious against the negative symptoms of schizophrenia which are particularly debilitating in chronic illness.

Thirdly, clozapine (but not the newer atypicals) is more effective than classical agents for resistant schizophrenia.

Atypical antipsychotics are significantly more expensive than classical drugs. In some countries this will be the overriding argument for retaining classical agents as first choice drugs in schizophrenia. Additionally, if a patient is successfully maintained on a classical antipsychotic, transfer to an atypical agent is difficult to justify. Where a classical antipsychotic is not achieving optimal results or causes unwanted effects, a more persuasive case for change to an atypical can be made.

But economic analysis must take into account factors beyond the crude cost of drugs. If atypical antipsychotics truly cause fewer distressing extrapyramidal symptoms and improve compliance, they may prevent relapse of psychotic illness and protect patients against lasting damage from periods of untreated psychosis. Greater effectiveness in treating negative symptoms would afford patients with schizophrenia more opportunity of re-integrating into the community and to make positive contributions to society rather than the alternative of long-term institutionalisation. Such factors alleviate the cost burden of psychotic illness on society, and must form part of the overall accounting between classical and atypical drugs as first line treatment.

Mood stabilisers

In bipolar affective disorder patients suffer episodes of mania, hypomania and depression, classically with periods of normal mood in between. Manic episodes involve greatly elevated mood, often interspersed with periods of irritability or undue

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