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Oxleas NHS Trust, Pinewood House, Pinewood Place, Dartford, Kent DA27WG (tel: 01322625762; fax:01322552999; e-mail: Carol.Paton{at}oxleas.nhs.uk)
Oxleas NHS Trust, Queen Elizabeth Hospital, London
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Abstract |
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Risperidone long-acting injection (RLAI) is the first atypical antipsychotic drug to be available in a ‘depot’ formulation. The evidence base underpinning its use is small. We sought to evaluate its early use in clinical practice by a naturalistic follow-up study of the first 50 patients to be prescribed RLAI in one National Health Service Trust.
RESULTS
At 6 months, 54% of patients had achieved at least minimal improvement, 4% were unchanged, 24% failed to comply, and 18% fared poorly and were switched to alternative antipsychotics. The attrition rate at 6 months was 42%. Supplementation with oral antipsychotics was often required for longer than 3 weeks. Only half of those who had a good clinical outcome at 6 months had achieved this by 3 months.
CLINICAL IMPLICATIONS
Some patients responded well to RLAI, but the overall attrition rate was high. Although RLAI provides additional choice in the range of treatments available for people with schizophrenia, we have much to learn about how to optimise its use in practice.
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Introduction |
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Method |
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As the study was naturalistic, patients whose mental state deteriorated were switched to alternative treatments at the prescribers’ discretion. Such patients were grouped together and rated as ‘treatment failures’, indicating that the prescriber had taken the decision to change treatment. Patients who actively refused medication or failed to keep appointments so that administration was too erratic to be effective were rated as ‘refused’.
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Results |
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Who received it?
One patient was cared for by elderly services, two by learning disabilities
services, and one by forensic services. The remaining 46 were in the care of
adult services, ranging from intensive care through rehabilitation and
assertive outreach to clinically stable out-patients. All had a psychotic
illness, although not always schizophrenia; this is in line with the licensed
indications for risperidone.
Dosage and clinical outcomes at 3 and 6 months
The mean dosage prescribed was 32 mg every 2 weeks at 3 months and 35 mg
every 2 weeks at 6 months. Fourteen patients who completed 6 months of
treatment were receiving 25 mg, six patients 37.5 mg and nine patients 50 mg.
Patient outcomes at 3 and 6 months are shown in
Table 1. There was no
difference in mean dosage between responders and non-responders. Patients who
were very much or much improved at 3 months maintained this improvement at 6
months. Half of those rated as minimally improved at 3 months were very much
or much improved at 6 months. The attrition rate at 6 months was 42%.
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Other findings
Although data were not collected systematically, many patients remained on
(and seemed to require) oral medication for longer than the 3-week lead-in
period recommended by the manufacturer. By 6 months, all patients were
receiving RLAI as antipsychotic monotherapy.
Providing supplies of RLAI to both in-patient units and community psychiatric nurse (CPN) bases in a large specialist mental health trust has been challenging. Systems for dealing with ‘cold chain’ products had not previously been in place: community mental health centres (CMHCs) did not routinely have a drug refrigerator or cool bags. Wastage was caused by RLAI being left unrefrigerated in CMHCs, leaking needles (packs do not contain a spare needle) and patients refusing their injection after the dose had been reconstituted. At a cost of £148 for each 37.5 mg dose (the mean dose used), the total wastage cost can be considerable.
The inflexibility of fixed doses and dosage intervals caused problems for some prescribers and patients.
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Discussion |
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Response
Risperidone long-acting injection has been shown to be superior to placebo
in a 12-week randomised controlled trial
(Kane et al, 2003), equivalent to oral risperidone in a 12-week randomised controlled trial
(APC/DTC Briefing, 2002), and
effective and relatively well tolerated in a 1-year open study. This is a
fairly slim evidence base. Nothing is known about the efficacy of RLAI in
comparison with conventional depots or how patients switched from conventional
depot therapy fare. Just over half our cohort had made at least minimal
clinical gains by 6 months, although the proportion achieving very good or
good clinical outcomes was just 40%. Given the way that response was
quantified, in that an improvement in neurological side-effects rather than an
improvement in psychotic symptoms may have been the desired goal, this seems
low.
Only half of those who achieved a very good or good clinical outcome at 6 months had done so by 3 months. If RLAI is to be prescribed, then at least 6 months treatment might be required to identify all responders. A fifth of patients were switched to another antipsychotic because the prescribing doctor judged that their mental state was either deteriorating (if previously stable) or failing to improve (if acutely unwell). The period of greatest risk seemed to be the first few months of treatment. This may be due to the pharmacokinetics of RLAI in that it takes at least 3 weeks after the first injection to achieve ‘therapeutic’ plasma levels of risperidone. The recommended 3-week period for supplementing RLAI with oral risperidone might not be adequate for all patients. Although data were not collected systematically, many patients in our cohort received (and seemed to require) additional oral treatment for up to 8 weeks after their first injection of RLAI. It is possible that our response rate might have been higher if prescribers had provided patients with oral antipsychotic cover for longer and continued RLAI for at least 6 months before switching to alternative antipsychotic agents.
Dose
The modal dose prescribed was 32 mg at 3 months and 35 mg at 6 months. Some
patients did not like the inflexibility of both doses and dosage intervals. No
negotiation is possible about ‘small’ dosage decreases as the
whole contents of a vial have to be administered. Likewise, the frequency of
administration cannot be decreased to every 3 or 4 weeks as an aid to
maintaining a therapeutic alliance with the patient.
Attrition rate
A systematic review has failed to find a difference in attrition rates
between patients prescribed oral antipsychotic drugs and those prescribed
depot formulations (Adams et al,
2001), although it is known that a quarter of those who are
prescribed conventional depots are dissatisfied with their treatment
(Walburn et al,
2001). It is possible that compliance rates are superior for depot
preparations in the real world where compliance rates in general are likely to
be lower than in clinical trials. At the very least, covert non-compliance is
avoided. Falloon (1984)
reported an 80% compliance rate with depots compared with 60% with oral
antipsychotics. O'Ceallaigh & Fahy
(2001) suggest that compliance
rates with atypical depots may be superior.
By 6 months, over a fifth of our cohort had withdrawn from treatment after either actively refusing their injection or more passively failing to turn up for appointments or be accessible to their CPN. When added to the 20% of patients whose treatment was changed by the prescriber, 42% were no longer receiving RLAI 6 months after treatment was started. This is a higher attrition rate than the 35% seen during the 1-year open label licensing study conducted by the manufacturers (APC/DTC Briefing, 2002).
Use by forensic services
Forensic psychiatrists are frequent prescribers of conventional depot
antipsychotics and, in a previous survey, indicated that they would use more
atypical drugs if a depot preparation became available
(Paton et al, 2002).
However, only one patient from forensic services was prescribed RLAI. The
reasons for this low local uptake rate are unknown.
Conclusions
In one mental health trust, 40% of patients who were prescribed RLAI had
achieved good or very good clinical outcomes at 6 months, 18% fared poorly and
were switched to alternative treatments, and 24% failed to comply. The
remainder made minimal clinical gains. Supplementation with oral antipsychotic
agents may be required for longer than the 3-week period recommended by the
manufacturer and at least 6 months treatment with RLAI may be required to
identify all responders. Although a welcome addition to the range of
antipsychotic preparations available, RLAI is unlikely to replace conventional
depot antipsychotic drugs in all patients. We have much to learn about how to
optimise its use in clinical practice.
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References |
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TopAbstractIntroductionMethodResultsDiscussionReferences |
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APC/DTC BRIEFING (2002) Long acting risperidone injection (Risperdal Consta). www.druginfozone.org
FALLOON, R. H. (1984) Developing and maintaining adherence to long-term drug-taking regimens. Schizophrenia Bulletin, 10, 412 -417.
GEDDES, J., FREEMANTLE, N., HARRISON, P., et al
(2000) Atypical antipsychotics in the treatment of schizophrenia:
systematic overview and meta-regression analysis. BMJ,
321, 1371
-1376.
GUY, W. (1976) ECDEU Assessment Manual for Psychopharmacology (revised), p. 534. Rockville, MD: National Institute of Mental Health.
KANE, J. M., EERDEKENS, M., LINDENMAYER, J. P., et al
(2003) Long-acting injectable risperidone: efficacy and safety of
the first long-acting atypical antipsychotic. American Journal of
Psychiatry, 160, 1125
-1132.
NATIONAL INSTITUTE OF CLINICAL EXCELLENCE (2002) Guicance on the Use of Newer (Atypical) Antipsychotic Drugs for the Treatment of Schizophrenia. Health Technology Appraisal 43. London: NICE.
NATIONAL SCHIZOPHRENIA FELLOWSHIP (2001) A Question of Choice. London: NSF.
O'CEALLAIGH, S. & FAHY, T. A. (2001) Is there a
role for the depot clinic in the modern management of schizophrenia?
Psychiatric Bulletin,
25, 481
-484.
PATON, C., GARCIA, J. A. & BROOKE, D. (2002) Use
of atypical antipsychotics by consultant psychiatrists working in forensic
settings. Psychiatric Bulletin,
26, 172
-174.
WALBURN, J., GRAY, R., GOURNAY, K., et al
(2001) Systematic review of patient and nurse attitudes to depot
antipsychotic medication. British Journal of
Psychiatry, 179, 300
-307.
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