Psychosis
Consensus on antipsychotic doses
Interpreting evidence would be easier if the clinically equivalent doses of antipsychotics were known. There are not enough data from clinical trials to provide a rigorous comparison so an international clinical panel convened to develop a consensus (Am J Psychiatry 2010;167:686‐93).
Using olanzapine 20mg daily as a standard and chlorpromazine as a historical reference, they agreed equivalent doses for 37 oral anti psychotics, and 14 short‐acting and 10 long‐acting injectable antipsychotics. Haloperidol lactate was the standard for the short‐acting injectable antipsychotics. A full list of dosing equivalents is provided in the paper.
The authors found a high level of agreement. Based on the participants' clinical experience, the median starting dose of antipsychotic therapy is equivalent to 4.8mg daily olanzapine; the target dose range is approximately 1025mg daily olanzapine; and the median maximal dose is 30.9mg daily olanzapine. Overall, doses were reduced by 25 per cent for the treatment of bipolar disorder, mild symptoms and first‐episode psychosis; they were increased by a similar proportion for acute psychotic illness and unsatisfactory response. Doses for short‐acting injectable agents were 20 per cent lower than for oral preparations.
Aripiprazole
The relationship between blood levels and effectiveness of aripiprazole has not been well studied, say London investigators, whose literature review has evaluated the potential role of therapeutic drug monitoring (J Clin Psychiatry 2010; doi:10.4088/JCP.09yr05060gre).
Their analysis of eight trials including 164 patients with schizophrenia found a clear linear relationship between dose and the plasma levels of aripiprazole and its active metabolite. A range of plasma concentrations of 150300ng per ml was associated with a 68 per cent response rate, though D2/D3 receptor occupancy was saturated at peak plasma levels above 100‐200ng per ml, or doses of 10mg daily. Adverse effects were more likely with increasing plasma levels, becoming moderate to severe in the range 210‐335ng per ml. The authors therefore propose a target plasma level of 150210ng per ml.
Treatment outcomes in first‐episode schizophrenia
A study of all 13 600 first episodes of schizophrenia occurring in Denmark between 1996 and 2005 has described significant year‐onyear changes in clinical practice (Acta Psychiatr Scand 2010; doi:10.1111/j.1600‐0447.01576.x).
Mean age at diagnosis decreased from 35 to 31 years. Hospital stay, inpatient treatment and psychiatric admissions all declined and this was associated with more intensive treatment in the community. Prescribing of antipsychotics within one year of diagnosis increased from 67 to 81 per cent of patients whereas the use of second‐generation antipsychotics rose from 15 to 89 per cent and the proportion of patients receiving long‐term polypharmacy increased from 17 to 37 per cent. There were also increases in mean dose, the number of antipsychotics prescribed in the first year and in the use of antidepressants.
Preventing relapse with risperidone
How soon can the dose of an antipsychotic be reduced for maintenance therapy? Not too soon, according to a recent trial from China (Am J Psychiatry 2010; 167:676‐85).
After stabilisation of an acute episode of schizophrenia with risperidone 4‐8mg daily, 404 patients were randomised to continue their dose (mean 4.3mg daily) up to one year, or to reduce the dose by half after four weeks or after 26 weeks.
Relapse rates were 8, 24 and 16 per cent in the no dose reduction, four‐week and 26‐week dose reduction groups respectively. Predicted mean time to relapse increased from 571 days with four‐week dose reduction to 615 days with 26‐week dose reduction and 683 days with full maintenance dosing. This was associated with significant changes in positive and negative syndrome scale (PANSS) scores in the three groups, and more patients who continued the full dose were rated as stable and improved at the end of the study. There were no differences in adverse events or concomitant medication. Copyright © 2010 Wiley Interface Ltd