Combining depot antipsychotic medications with novel antipsychotics in forensic patients: a practice in search of a principle

OBJECTIVE

We observed a pattern of combining depot antipsychotic medicationwith the newer ‘atypical’ antipsychotics in forensicpatients. We aimed to determine the prevalence and rationalefor such ‘combination therapy’.

METHOD

The medical records of forensic patients in 3 forensic hospitalsin New South Wales, Australia, were reviewed and the responsiblepsychiatrists asked to explain the rationale for treatmentof those patients on combination therapy.

RESULTS

Twenty-two per cent of the forensic patient population werereceiving combination therapy. The reasons given for combinationtherapy were the presence of treatment-resistant illness, toensure adherence to at least part of the treatment and to assisttransfer to lower security units.

CONCLUSIONS

Such a high prevalence of a practice that is discouraged andwithout theoretical justification is a cause for concern. Itappeared to reflect the practical difficulties of managingforensic patients.

Introduction

TOP

Introduction

Forensic patients in New South Wales are either unfit to betried, have been found not guilty of a serious offence on thegrounds of mental illness or have been transferred to hospitalbecause their illness could not be adequately managed in themainstream prison setting. Most have schizophrenia, often complicatedby substance abuse and antisocial conduct.

The authors observed that each of the five psychiatrists attendingthe maximum-security prison hospital had independently prescribedcombinations of the more recently available atypical medications,olanzapine and risperidone, in combination with the conventionalantipsychotic medications available in slow-release preparationsgiven by injection. The treatment decisions were independent,and there was little review of each other's prescribing practices.Other centres have reported similar patterns of prescribingin treatment-resistant patients (Norrie & Hustig, 1998).

Several reasons were proposed for the decisions to prescribea combination treatment. First, forensic patients are oftenprescribed medication against their will, and thus the useof atypical antipsychotics may be seen as a way of minimisingdistressing side-effects and also reducing the risk of developingtardive dyskinesia (by allowing the use of lower net doses ofdepot antipsychotic) (Umbricht & Kane, 1996; Brecher, 1996).Second, forensic patients are more often treatment-resistant(Beck et al, 1997), and a combination of medications may havebeen prescribed in the hope that this would provide a widerspectrum of efficacy. Third, many forensic patients have ahistory of poor compliance with treatment (Young et al, 1986). It has been observed that some patients do not take oral medicationin tablet form even in the strictly-supervised setting of amaximum-security hospital. Fourth, in the community, mentallydisordered offenders are often non-compliant with oral antipsychotics (Duncan & Rogers, 1998), and this (in combination withsubstance abuse) has been associated with prediction of seriousviolent acts in this population (Swartz et al, 1998). Thesefactors may help to explain the considerable resistance to thetransfer of forensic patients to lower-security settings inNew South Wales. Treatment with depot medication has been seenas a secure form of treatment, more likely to result in a patientbeing accepted and approved for transfer to such a setting.

Method

TOP

Method

Long Bay Hospital is a 90-bed maximum-security psychiatric hospitalbuilt in 1985 in the grounds of the largest prison complexin New South Wales. The forensic wards of Cumberland and MorissetPsychiatric Hospitals have 24 beds each, described as medium-security,and they usually accept forensic patients from the more securesetting.

The medical records of patients in all three hospitals werereviewed, with particular note being taken of diagnosis, durationof illness and the antipsychotic medication prescribed. Foreach patient receiving a combination therapy, the responsiblepsychiatrist was asked to complete a brief questionnaire toexplain the reasons for giving this medication. For comparison,data were also collected from a group of 40 treatment-resistant patients living in three supervised group homes in the community.

Results

TOP

Results

There were 60 forensic patients in Long Bay Prison Hospitalat the time of the survey, all of whom were male, as femaleforensic patients are located elsewhere. There was a totalof 45 forensic patients in the lower-security units of Cumberlandand Morisset Hospitals (including 4 female patients). The totalsample size was therefore 105. The mean age was 36 years (range20-77 years, s.d. 11.3). Schizophrenia was the most commondiagnosis (n=96, 91.4%). Other diagnoses were schizoaffectivedisorder (n=3, 2.9%), delusional disorder (n=1, 1%), bipolarmood disorder (n=1, 1%), depression (n=1, 1%), severe personalitydisorder (n=1, 1%), epilepsy (n=1, 1%) and post-head injurysyndrome (n=1, 1%). The diagnosis of substance abuse usuallyrelated to behaviour prior to admission, and was not oftencited as a current diagnosis because the length of time spentin custody usually precluded recent drug use. The mean duration of illness, taken from the first recorded contact with psychiatricservices where known, was 12.28 years (range 1-42 years, s.d.9.37). There was little difference in length of diagnosis inpatients receiving combinations of oral atypical antipsychoticsand conventional depot antipsychotics (mean 10.21 years. s.d.6.39), and patients not receiving such a combination (mean 12.33 years, s.d. 10.15).

Fifty-two per cent of patients (n=55) were receiving atypical antipsychotics, of which 35 (63.6%) were receiving olanzapine,13 (23.6%) were receiving risperidone and 7 (12.7%) were receivingclozapine (Table 1). The mean doses were: olanzapine 17.6mg per day, risperidone 4.7 mg per day and clozapine 387 mg per day, respectively. Far fewer patients were receiving oralforms of other antipsychotic medications (n=19, 18.1%).

View this table:
[in this window]
[in a new window]
Table 1. Atypical antipsychotics prescribed (n=55)

Half the patients (n=52) were receiving depot antipsychotics,of whom 30 (57.7%) were receiving zuclopenthixol (mean dose225 mg 2-weekly, range 50-600 mg every 2 weeks), 14 (26.9%)were receiving halo-peridol (mean dose 68 mg 2-weekly, range12.5-200 mg every 2 weeks), 6 (11.5%) were receiving flupenthixol(mean dose 60 mg 2-weekly, range 40-100 mg every 2 weeks) and2 (3.8%) patients were receiving fluphenazine (mean dose 37.5mg 2-weekly, ranges 25-50 mg every 2 weeks) (Table 2).

View this table:
[in this window]
[in a new window]
Table 2. Depot antipsychotics prescribed (n=52)

Twenty-three patients (22%) were receiving a combination oforal atypical and depot conventional antipsychotics. This comparedwith only 10 (9.5%) patients receiving oral conventional anddepot conventional antipsychotics. Of those patients on combinationtherapy, only one was receiving a maximum (or as in this case,greater than maximum) dose of depot conventional antipsychotic, as defined by the British National Formulary (British MedicalAssociation & Royal Pharmaceutical Society of Great Britain,2001).

The reasons cited for the use of depot preparations in additionto atypical antipsychotics (more than one could be given) were:treatment-resistance (n=20, 87%), a history of non-compliancewith medication (n=14, 61%) and to assist in transfer to alower-security unit (n=7, 30%). Only consultants at the maximum-securityunit cited the reason as assisting the transfer to a lower-securityunit. The objective of reducing the potential side-effectsof treatment, with depot medications through seeking a lowernet dose of depot by giving part of the treatment as an oralatypical antipsychotic, was not cited as a reason for combination therapy.

The reasons given for not prescribing clozapine to patientsreceiving combinations of other drugs were the resistance ofpatients to taking clozapine and the likelihood that they wouldnot persist with oral medication or comply with the requirementof regular blood counts. Several of the patients had been treatedwith clozapine without success or had treatment withdrawn becauseof a haematological complication.

Eight (20%) of the community sample (n=40) were receiving a combination of depot medication and atypical antipsychotics.Thirteen (32.5%) were receiving depot antipsychotic medicationand five (12.5%) were receiving clozapine. Treatment-resistancewas cited as the reason for prescribing combination therapyfor all of the patients in the community sample, with unreliableadherence to treatment cited as a reason for combination therapyin only two of those patients.

Discussion and conclusion

TOP

Discussion and conclusion

A review of the scientific literature revealed that combinationtherapy with atypical and conventional antipsychotics is notencouraged. The American Psychiatric Association's guidelinesfor the treatment of schizophrenia encourage monotherapy (American Psychiatric Association, 1997).The Royal College of Psychiatrists'Consensus Statement (Thompson, 1994) describes the practiceof combining more than one antipsychotic as undesirable, althoughit may be occasionally acceptable in patients for whom it hasbeen shown to be necessary from the experience of dealing withthem for many years. Similarly, reviews of the management oftreatment-resistant schizophrenia have usually recommendedadequate trials of treatment with single antipsychotic medications,rather than combinations of antipsychotics (Pantelis & Barnes, 1996).

We found no publications reporting clinical trials of treatmentwith combinations of antipsychotic medication, although thereare references to the practice as a strategy for managing treatment-resistantschizophrenia (Frankenburg, 1999; Norrie & Hustig, 1998; Daniel & Whitcomb, 1998). Weiden et al (1998) discusscombination therapy for patients with a high risk of non-compliance should depot medication be withdrawn, and who have only partiallyresponded to treatment. In such a group, combination with atypicalswas described as ‘a practical way to augment the depotresponse’.

A possible benefit of combination therapy is that it may increase compliance with oral antipsychotic medication, as patients aremore likely to become compliant with medication after theirsymptoms abate and insight develops. Moreover, the routineof taking regular medication may have developed through theuse of combination therapy. Given these factors, it is possiblethat compliance with the oral antipsychotic may continue afterthe depot antipsychotic has been withdrawn. However, as faras we are aware, this assertion is not supported in the literature.The data did not support the assertion that combination therapywas used to reduce the distressing side-effects associatedwith typical antipsychotics in that none of the treating psychiatristsoffered this as a rationale for treatment. Given this, andthat only one of the patients on combination therapy was ona maximum dose of depot conventional antipsychotic, it maybe that patients on combination therapy had not received anadequate trial of maximum-tolerated doses of depot antipsychotic.

The observation of widespread treatment with combinations ofantipsychotic medication may reflect poor practice, as monotherapyis an agreed treatment goal for schizophrenia (American Psychiatric Association, 1997;Thompson, 1994). This is of particularconcern as forensic patients are a vulnerable patient population. However, it is also recognised that forensic patients are moredifficult to treat because of more severe, treatment-resistantillnesses, multiple diagnoses and a history of serious offendingwhile psychotic. The survey reveals that in this group, compliancewith treatment, severity of illness, treatment-resistance andtransfer to lower-security settings are of particular concernto the treating psychiatrists. Although the community samplesof severely treatment-resistant patients were not strictlycomparable with the forensic patients, combination therapywas found to be as common in the community sample, and reflectedan attempt to overcome treatment-resistance, rather than becauseof concern over non-compliance or dangerousness when untreated.This was supported by the finding that only a third of the community sample were receiving depot medication, compared withhalf of the forensic patients. A more representative estimateof Australian community practice is provided by a 1998 surveyof 1034 patients prescribed antipsychotic medication withinone area health service (Lambert & Singh, 2000). Thissurvey found that 42% were receiving a depot preparation, butonly 18% of those (7.6% of the total sample) were receivinga combination of depot and oral medication. The type of oralmedication was not recorded.

Our survey has found that the prescription of oral atypicalantipsychotic medications in combination with depot antipsychoticpreparations is common, both in forensic patients and in acommunity sample, although for different reasons. The practiceis discouraged and there is no published research to supportsuch a combination on theoretical or practical grounds. However,this practice appears to be widespread because of the desireto attempt to overcome treatment-resistance and to assist managementin lower-security settings. More generally, the practice probablyreflects a deficiency in the range of treatment options currentlyavailable and the lack of a depot atypical antipsychotic.

Acknowledgments

We wish to thank Dr Peter Shea and Dr Andrew Walker at MorissetHospital, and Dr Martin Patfield at Cumberland Hospital fortheir assistance in collecting the data.

References

TOP