Risperidone

This drug has high affinity for the 5-HT2A receptor, with a similar affinity at the D2 receptor to most typical antipsychotics. In the acute phase of treatment, risperidone appears as effective as haloperidol in terms of improvement in positive and secondary negative symptom scores53.

The optimal dose of risperidone appears to be between 4 and 6 mg/day. At doses higher than 8–12mg/day risperidone can cause extrapyramidal side-effects of tremor, rigidity and restlessness, with a similar frequency to typical antipsychotics. Risperidone can increase serum prolactin which may lead to sexual dysfunction.

Risperidone has been assessed for long-term efficacy and safety in a number of long-term openlabel studies. Earlier data suggested that long-term therapy with risperidone was associated with a meaningful reduction in psychopathology, amelioration of extrapyrimidal side-effects (EPS) and improved social functioning from baseline measures or against placebo.

More recently a meta-analysis of eleven of the risperidone/conventional antipsychotic comparator randomized controlled trials was performed54. The author reported that slightly but significantly more patients on risperidone showed clinical improvement than with comparison antipsychotics (57% vs. 52%) and used significantly less medication for EPS (29.1% vs. 33.9%).

Olanzapine

A more broad-spectrum atypical antipsychotic, olanzapine has a side-effect profile similar to that of clozapine but with a higher incidence of extrapyrimidal side-effects at doses above 20 mg/day. Olanzapine also demonstrates antagonistic effects at a wide range of receptors, but has a higher affinity for D2 and 5-HT2A receptors than clozapine and a lower affinity at the D1 receptor subtype. In acute-phase studies, olanzapine is efficacious for positive and secondary negative symptoms and was superior to haloperidol on overall

improvement according to the Brief Psychiatric Rating Scale (BPRS)55 and every other secondary measure.

Standard-dose olanzapine (5–15 mg/day) has been shown to be an effective maintenance treatment for schizophrenia in comparison with placebo56. The estimated 1-year risk of relapse with olanzapine was 19.6–28.6% for standarddose olanzapine in comparison with a 69.9% risk of relapse with placebo. Initial data from a metaanalysis of three studies using haloperidol-treated patients as a test group, indicated that 80.3% of patients receiving olanzapine maintained their response at 1 year in comparison with 72% for haloperidol-treated patients57.

Quetiapine

Another broader-spectrum atypical, quetiapine has a similar receptor binding profile to clozapine, but with relatively lower affinity for all receptors and virtually no affinity for muscarinic receptors. Quetiapine is effective in acute phase studies for the treatment of positive and secondary negative symptoms. Initial randomized controlled trials indicated that quetiapine (250–750mg, n=96) was more effective than placebo (n = 96) and that this efficacy was not seen at doses of less than 250 mg/day of quetiapine58. In comparison with chlorpromazine, response rates to quetiapine were similar across all symptom domains59. Response rates between haloperidoland quetiapine-treated groups are also similar60.

In all of these studies, the rates of EPS with quetiapine were similar to those seen in placebotreated groups and significantly lower than in conventional antipsychotic comparator groups. Most common side-effects are somnolence and dry mouth. Quetiapine demonstrates a lower potential to cause weight gain than clozapine and olanzapine, and does not increase serum prolactin61.

In long-term studies, quetiapine was well tolerated with up to 75% of respondents to a questionnaire denying any side-effects from quetiapine62.