Recent advances in antipsychotic treatment of schizophrenia have offered several new compounds which avoid many of the limitations of the classical antipsychotics. These so-called ‘atypical’ antipsychotics have fewer extrapyramidal side effects, greater efficacy against negative symptoms and greater efficacy in otherwise treatment-resistant patients. However, the mechanism of action of these atypical antipsychotics is still unclear. The several receptors currently implicated in the pharmacological profile of these atypical antipsychotics include subtypes of those for dopamine, serotonin, noradrenaline, and acetylcholine among others. The current hypotheses for possible mechanisms of action of atypical antipsychotics are discussed along with the experimental correlates of antipsychotic efficacy in animal models.

Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. Since psychopharmacological treatment is thought tc act on the underlying biological basis of the disease, brain imaging techniques enable us to understand the mechanism of action of such compounds. One important tool used to determine patterns of brain dysfunction and how psychopharmacological agents such as antipsychotic compounds work is single-photon emission computerised tomography (SPECT). This technique allows determination of striatal D2 receptor occupancy rates, which are associated with the extrapyramidal side effects (EPS) of antipsychotic drugs. Studies have confirmed that atypical antipsychotic agents have lower occupancy rates than typical agents. No association has been found between D2 receptor occupancy rates n the striatum and antipsychotic efficacy, and it therefore appears that striatal D2 receptor occupancy rates are not necessary for the antipsychotic effect of such agents in schizophrenia. The availability of more refined radioligands will help us not only to understand the action of antipsychotics but also the pathophysiology of schizophrenia.

The data on efficacy and tolerance from four (phase II and III) trials of quetiapine (Seroquel® or ICI 204,636) in a total of 1,461 patients with acute exacerbations of chronic or sub-chronic schizophrenia are briefly reviewed. Together, the results of these trials have demonstrated antipsychotic efficacy in comparison with placebo and equivalent efficacy to haloperidol. In spite of its short plasma elimination half-life, quetiapine is equally effective when given in twice-daily and three-time daily doses. The optimum dose is between 300 mg and 400 mg per day, and the main and most consistent adverse effect is sedation. It has a low extrapyramidal side effect liability and does not produce sustained elevations in plasma prolactin levels.

Although only a few studies have been performed and published data are scarce, it seems clear that sexual dysfunctions frequently occur during treatment with antipsychotics in 30–60% of patients with schizophrenia. It is important to evaluate the occurrence of sexual dysfunction and its relation to antipsychotic treatment.

The assessment of new treatment strategies such as the atypical antipsychotic agents goes far beyond the assessment of psychopathology, and includes evaluation of their effects on a variety of needs associated with living in the community. This article provides some empirical data for such a multidimensional perspective in analysing drug treatment with conventional antipsychotics. We focus on two groups of schizophrenic patients discharged from a psychiatric hospital, who were followed up for one year. One group was treated with oral and the other with depot medication. The two groups were assessed on their needs for care, quality of life, and rehospitalisation rates. We found few significant differences between depot- and orally-medicated patients. However, patients treated with depot antipsychotics were receiving higher mean daily doses. Patients taking oral medication had a lower rate of adverse effects but were more non-compliant, which resulted in a higher rehospitalisation rate, confirming our assumpt on that patients take different risk-to-benefit decisions. Orally-medicated patients did not have a better functional status than depot-medicated patients.

Schizophrenia has a major impact on the quality of life of sufferers, and its broader impact on families and on society are well known, although less thoroughly documented. The majority of sufferers require long-term treatment and support, and there are depressingly frequent media stories about violent incidents involving people with the illness. Consequently the costs of schizophrenia, broadly defined, loom large, not just from the perspective of health care decision-makers and governments, but also from that of sufferers and their families, to many other people with only indirect experience of the disease.