In the present study we investigated the prescription pattern of antipsychotic drugs for inpatients with schizophrenia in Japan.
According to a standardized protocol of the Research on East Asia Psychotropic Prescription Pattern-Antipsychotics first-time study,1 patients diagnosed with schizophrenia who were inpatients between 1 July and 31 July 2004 was examined at seven hospitals from four regions in Japan (one hospital in Hokkaido, two hospitals in Iwate prefecture, one hospital in Tokyo, and three hospitals in Fukuoka prefecture). Patients selected for inclusion fulfilled the diagnostic criteria for schizophrenia of the International Classification of Disease, 10th revision (ICD-10) or the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The design was a cross-sectional survey. Data collected included personal and clinical characteristics, physical condition, durations of illness and significant symptoms for the past month, prescription of all medications and their doses, and adverse effects. The data were collected by the attending psychiatrist at the time of study in compliance with the protocol set forth. Antipsychotic drugs were divided into first- and second-generation antipsychotic drugs, the former included chlorpromazine and all other conventional drugs while the latter consisted of the atypical agents such as risperidone, olanzapine, quetiapine, and perospirone. All antipsychotic drugs were converted into chlorpromazine equivalents (CPZeq) according to the suggestions by Inagaki et al.2,3 and Bezchlibnyk-Butler and Jeffries.4
A total of 323 patients were surveyed. There were more male (57.3%) than female (42.7%) patients. The age distribution was wide (17–86 years), with a mean age of 50.1 ± 16.5 years. Most patients had a long duration of illness: 77.4% had an illness duration of ≥10 years. In other words, most patients in the present study were considered to be chronic cases. The most frequent psychiatric symptoms in the whole sample for the previous 1 month were delusions (70.3%), social dysfunction (68.7%), negative symptoms (64.7%), hallucinations (56.3%), disorganized speech (39.3%), disorganized/catatonic behavior (13.9%), aggression/verbal (12.4%), aggression/physical (6.5%), and other symptoms (1.5%).
The number of psychotropic drugs and antipsychotic drugs prescribed were 4.06 ± 2.48 and 1.76 ± 0.86, respectively. Sedative/hypnotic drugs (61.3%) and antiparkinsonian drugs (60.7%) were prescribed in most cases. In contrast, mood stabilizers were prescribed in only under one-third of cases. Of all antipsychotic drugs, risperidone (47.4%) was the most frequently prescribed drug, followed by olanzapine (22.0%), haloperidol (21.7%) chlorpromazine (21.4%), zotepine (12.4%), quetiapine (11.8%), perospirone (6.8%), and sulpiride (5.9%). The mean dose for the whole sample was 798.3 ± 653.6 mg CPZeq.
The major finding was that prescribing of second-generation antipsychotic drugs is becoming popular in Japan, but prescription rates for first-generation antipsychotic drugs is still high, which is compatible with the fact that many clinicians in Japan administer oral and i.m. preparations of first-generation antipsychotic drugs such as haloperidol, chlorpromazine, or levomepromazine to patients in the acute phase of schizophrenia for the purpose of relieving excitement or hallucinatory behaviors. Recently, Currier and Simpson compared the short-term effects of a combination of oral risperidone liquid and oral lorazepam with a combination of i.m. haloperidol and i.m. lorazepam for psychotic agitation, and they found that both treatment groups showed similar improvements on different measures of agitation.5 We also demonstrated that risperidone liquid is effective and well tolerated for the treatment of acute-phase schizophrenia, and that efficacy is related to its effects on dopaminergic activity, but not noradrenergic activity.6 Another choice for ameliorating excitement and impulsiveness in schizophrenia patients is adjunctive mood stabilizers such as valproic acid and lithium.7 Expert consensus guidelines suggest the use of adjunctive valproate for patients with schizophrenia who exhibit agitation, excitement, aggression, or violence.8 Taken together, atypical antipsychotic drugs and mood stabilizers may be a useful alternative for the treatment of psychotic agitation in schizophrenia patients. In the present study, we also found that polypharmacy still goes on in Japan. Polypharmacy of antipsychotic drugs, even atypical ones, increases the total dose of antipsychotic drugs and adverse side-effects, and causes drug interactions.9
In conclusion, although prescribing of the second-generation antipsychotic drugs is becoming popular, the prescription rate in first-generation antipsychotic drugs and anticholinergic agents still remains high, and clinicians also prescribe two or more antipsychotic drugs for treating schizophrenia inpatients.