Abstract
Antipsychosis medications remain the cornerstone of treatment of schizophrenia [1]. With the introduction of new generation antipsychosis medications (clozapine in 1992, risperidone in 1995, and olanzapine in 1997), the drug treatment of psychoses has been undergoing rapid change as clinicians have started using the new medications. Clozapine is widely recommended for use in patients with schizophrenia, which has proved resistant to other antipsychotic therapy given the superior efficacy as well as low risk of extrapyramidal side effects [2,3]. Risperidone and olanzapine have been established as effective antipsychotics, more effective than conventional medications particularly with respect to negative symptoms, at doses where there is a low risk of extrapyramidal side effects [4,7].
Although new generation antipsychosis medications are being used extensively, little is known about how clinicians actually use these drugs. A paper in the Journal presented survey evidence from Australian psychiatrists which was an interesting reflection of clinician opinion [8]. A recent survey of 28 patients in an inpatient unit found that 17 were being prescribed atypicals [9]. However, there is little information available about clinical practice in outpatient/community settings.
This paper presents the results of a detailed survey of antipsychotic medication use within a public community psychiatry service, together with data concerning adjunctive therapies, focusing particularly on the new generation drugs. The reasons clinicians gave for making certain specific therapeutic choices are also reported.
Method
The Alfred Hospital Psychiatric Service consists of a 50-bed inpatient unit and extensive community psychiatric services. It is a comprehensive area psychiatric service for a population of approximately 220 000 people in an inner urban community which has a high prevalence of residents suffering from psychotic illnesses. The community services include an emergency mobile outreach team, outpatient services at two clinics, intensive case management services and highly supported residential services. This survey was conducted within the community services which record all clinical contacts, retaining files and data at the two community clinic sites.
In order to conduct a cross-sectional assessment of drug use patterns, all prescriptions for antipsychotic medications and all patients using antipsychotic medications within the community services in May 1998 were identified from pharmacy records. Clinic records and clinical case notes were then used to establish demographic data for the patients, diagnosis according to DSM-IV criteria [10], types of atypical and conventional medication utilised, mean and modal doses, and types of concomitant or adjunctive medication prescribed in additional to the antipsychotics. Written questions were directed to the relevant prescribers concerning indications for new generation antipsychotics, indications for depot conventional antipsychotics, and reasons for using combinations of antipsychotic therapies in particular patients. If further information was needed, the prescribers were contacted by the first author.
The data were tabulated and, where applicable, statistical comparisons were carried out using Chi squared, Student's t- and Mann-Whitney U-tests. In this paper, the terms ‘novel’, ‘new generation’ and ‘atypical’ are used interchangeably to refer to clozapine, risperidone and olanzapine.
Results
In May 1998, community psychiatric services treated 859 patients, 507 men and 352 women with a mean age of 41 ± 11.5 years. It was found that of these, 662 patients (77%) were receiving antipsychotic medications. Of the total prescriptions, 53% were for novel medications and 47% for conventional medication.
Details concerning atypical medications are given in Table 1. Risperidone was the most commonly used drug, followed by olanzapine and clozapine. Mean doses were 4.15 ± 2.51 mg, 14.26 ± 8.24 mg and 377.49 ± 178.94 mg, respectively. There were no significant gender differences in dose. At these doses, the cost of risperidone was about half the cost of olanzapine and clozapine.
Number of patients taking atypical antipsychotics with doses and estimated costs
The diagnoses of patients receiving novel antipsychotic medication are given in Table 2. While most of the patients were suffering from schizophrenia or schizoaffective disorder, 8% of the patients had bipolar illness while a small number of patients were receiving atypical antipsychotics for major depression and borderline personality disorder.
DSM-IV diagnoses of patients taking atypical medication
Only 12% of patients had received novel medications as their first antipsychotic: 88% of patients had been on conventional antipsychotic medications before changing to atypical drugs. The most common reason (in 78% of cases) given for change to an atypical was the lack of efficacy of conventional therapy. In 40% of cases clinicians suggested that occurrence of extrapyramidal side effects on conventional therapy was also a reason for change (more than one reason could be given). Other unrelated reasons were given in only 5% of cases.
Among the 333 patients on conventional antipsy-choses medications, 144 (43%) were on oral medication, while 220 (66%) were on depot medication. Details of oral conventional antipsychotics are given in Table 3. While thioridazine was the most commonly used drug (given to 28% of patients), in only 16 patients (11%) was it the sole antipsychotic. Mean dose of thioridazine was 146.8 ± 103.3 mg overall and 345.3 ± 38.1 mg for patients on thioridazine alone. Haloperidol was the next the most commonly prescribed drug, closely followed by trifluoperazine. The mean dose of haloperidol was 8.7 ± 7.9 mg. Another 17% of these outpatients were receiving chlorpromazine.
Numbers of patients prescribed particular oral conventional antipsychotic medications
The most commonly prescribed depot medication was flupenthixol decanoate (35%), closely followed by fluphenazine decanoate which was administered to 33% of patients on depot. Only 12% of patients received haloperidol decanoate (Table 4). The indications for giving depot medications are given in Table 5, by far the most common indication was non-compliance.
Numbers of patients receiving particular depot antipsychotic
Clinicians nominated the following as the main reason for using depot medication
Eighty-four patients (13%) were receiving two antipsychotics (Table 6). Eight percent were receiving a combination of atypical and conventional drugs, while 5% were receiving atypical plus depot medications. Of the 29 patients (4%) on depot plus oral conventional, the most common combination (n = 18) was depot plus thioridazine. The reasons for using the combination of atypical and depot were ascertained. The likelihood of non-compliance, poor response to atypical drug and gradual change from depot to oral medication each accounted for 32% of responses. Patient preference for the atypical and depot combination was nominated by the clinician as the reason in 8% of cases.
Numbers of patients receiving different combinations of antipsychosis drugs
Use of anticholinergics, mood stabilisers, anti-depressants and benzodiazepines in relation to haloperidol and the three novel antipsychotics are given in Table 7. Anticholinergics were either benztropine (68%) or procyclidine (31%). Forty-six percent of patients on haloperidol required anticholinergics. Significantly fewer patients on risperidone than haloperidol required anticholinergics (p < 0.05). Patients on clozapine and olanzapine were less likely to be on anticholinergics than those on risperidone and haloperidol.
Percentage of patients taking nominated antipsychotic also taking each of four adjunctive medications
Significantly more patients on haloperidol than the three atypicals were using mood stabilisers (p < 0.05). The most common used mood stabiliser was valproate (70%), followed by lithium (23%) and carbamazepine (6%). Patients on clozapine were less likely to be receiving benzodiazepines than those on risperidone and olanzapine. While the percentage of patients on olanzapine receiving benzodiazepines was numerically smaller than the percentage with risperidone and haloperidol, this was not significant. Adjunctive antidepressants consisted of sertraline (37%), venlafaxine (22%), paroxetine (14%), fluoxetine 7% and amitriptyline (7%). The use of clozapine was associated with less frequent use of anti-depressants than that seen with the other three drugs.
Of the 16 patients taking thioridazine as the sole antipsychotic, 33% were also taking a mood stabiliser, 16% were on benzodiazepines, 8% were on anti-depressants and 8% were prescribed anticholinergics.
Discussion
The majority of antipsychotics prescribed by community services in May 1998 at the Alfred Hospital were the new generation drugs, risperidone, olanzapine or clozapine. Research evidence concerning the advantages of these drugs with respect to the low risk of extrapyramidal side effects and clinical efficacy [5,6] thus appears to be reflected in the increasing use of these drugs by clinicians. Significant numbers of patients remain on depot conventional medications; atypical medications are not available in depot form. The use of depot is clearly linked to clinician perceptions of likely non-compliance. Arguably a greater proportion of patients may be able to benefit from novel antipsychotic medication if compliance is addressed through strategies such as intensive community supports rather than the use of depot medication. Depot antipsychotics are associated with higher morbidity from side effects including tardive dyskinesia [11,12].
Earlier recommendations in relation to risperidone doses suggested a modal dose of 6 mg [2]. It is now clear that the doses of risperidone being used by clinicians are falling [9,13]. The mean and modal doses of risperidone used in The Alfred service are entirely consistent with these international trends. An interesting observation is that the cost of risperidone appears to be substantially less than that of olanzapine and clozapine. Whether these differences will be reflected in overall cost effectiveness requires further investigation of outcomes.
More patients on risperidone were using anti-cholinergic medications than those on clozapine and olanzapine. Whether this is indicative of greater propensity of risperidone to cause extrapyramidal side effects, or whether clinicians are inadvertently continuing anticholinergics which are usually required when patients are being switched from conventional drugs to risperidone [14] merits further investigation. Maximal clinical efficacy with risperidone probably occurs at doses below those inducing extrapyramidal side effects [4].
The findings of this survey confirm that clinicians are using new generation antipsychosis medications for illnesses other than schizophrenia. It has long been established that antipsychosis medications treat the symptoms of psychosis rather than specifically those of schizophrenia [14]. Limitations on use of atypical drugs imposed by regulatory authorities due to lack of diagnosis-specific studies in particular illnesses is inconsistent with clinical realities and is deleterious to patient care.
The treatment of schizophrenia and related psychoses is clearly characterised by extensive use of adjunctive medications according to the findings of this survey. Mood stabilisers, antidepressants and benzodiazepines were frequently coprescribed. It was notable that in each instance patients on clozapine were less likely to be receiving adjunctive therapy. Whether this reflects particular therapeutic and other pharmacological characteristics of clozapine or clinician concern about increased side effects burden from drug combinations with clozapine, merits further investigation. It is not known how clozapine monotherapy compares with other antipsychotic plus adjunctive medication combinations.
The use of combinations of antipsychotics in a significant proportion of patients was also observed. While there are justifiable clinical indications for combinations such as transient oral supplementation and the transition period from one drug to another, it would appear that a proportion of patients are receiving combinations of antipsychotic drugs for reasons which do not conform with either empirical evidence or clinical recommendations such as those of the American Psychiatric Association [15]. Some patients with schizophrenia in the community are so unwell that clinicians may feel forced to opt for extraordinary measures. Greater peer review and support at the clinical level may assist with optimisation of prescribing practices, particularly in the most difficult cases.
This survey provides informative data on patterns of antipsychotic drug use in community psychiatry at a particular period of time characterised by rapid change in the treatment of psychoses. The authors intend to repeat this survey in the near future. The information obtained is unusual as it emanates from mostly stable patients with psychoses living in the community, most previous surveys have been hospital-centred [9].
This study did not attempt to ascertain data concerning efficacy or tolerability, which if available would have enabled far more interpretation of the significance of the findings. However, information concerning naturalistic clinical practice is essential to inform debate concerning improvement in standards of care for patients suffering from psychoses.