ORIGINAL PAPERS Investigation of depot neuroleptic injection site reactions

Julie C. Jones, Jennifer C. Day, John R. Taylor and Christophers. Thomas

Aims and method A cross-sectional survey was ship between reactions and other related vari performed on 318 patients receiving depot ables such as dose, volume, concentration and medication. The presence or absence of a depot site frequency of injection, age, gender and body reaction was recorded by psychiatric nursing staff on a mass index. All patients prescribed depot standardised form. neuroleptic medication attending the depot clinic Results Seventeen per cent of patients were found to at Withington Hospital in south Manchester and have clinically significant depot site reactions. Such from a defined catchment area of south Liverpool reactions were associated with increased frequency of were included in the study. All patients who injection and increased total volume of depot participated gave informed consent, and the administered in the previous 12 months. The severity of study was approved by the local ethics commit a depot site reaction was unrelated to the tees. The following demographic and clinical concentration of depot preparation administered. details were recorded: age, gender, case note Clinical implications Depot site reactions may be diagnosis, date of first episode, dose and reduced by maximising the interval between frequency of depot and all other current medic injections and using low volume (highly concentrated) ation. Details relating to depot administration preparations of depot neuroleptic medication. were systematically collected on a standard form (available from the author upon request), includ ing the volume of depot administered at the time The use of depot neuroleptics in patients suffer of survey, total volume of depot administered in ing from schizophrenia has been associated with the previous year, total number of injections improved compliance and reduced rates of administered in the previous year and any relapse (Hirsch et al 1973; Gottfries & Green. difficulty with injection. 1974: Glazer & Kane, 1992). However, depot The nurses in Liverpool and Manchester who administration has been associated with a normally administered the depot injections were number of complications at the site of injection asked to participate in the study and were shown including nodules and indurations, muscle how to rate the presence or absence of a depot- granulomas, fibrosis, abscess formation and site reaction on the standardised form. They the accumulation of oil after repeated injections were asked to rate the site of the injection for (Starmark et al. 1980: McCreadie et al, 1979; skin thickening, infection/erythema, nodules/ Belanger-Annable. 1985: Hamann et al, 1990). lumps, bleeding, pain and tenderness experi Such adverse events are distressing to the enced as a result of the injection. All of these patient and may lead to non-compliance. items were rated on a four-point Likert scale Hay (1995) found that 19% of patients receiv from zero (none) to four (severe). Because of ing depots experienced significant problems at the distance between the two centres no the site of injection over a 22-week period. These formal assessment of interrater reliability was reactions were more likely to be associated with conducted. concentrated depot preparations, higher doses, In order to investigate the possible contribu larger volumes, weekly injections, prolonged tion of obesity to depot site complications, body treatment, older age and with the prescription mass and height were noted in Manchester only of haloperidol decanoate or zuclopenthixol (weight and height were not routinely recorded in decanoate. Liverpool) and the body mass index was calcu lated. Depot doses were converted to flupenthixol twice weekly equivalent doses using the equiv alence table in the British National Formulary The study (Number 31, March 1996). Chlorpromazine The present study aimed to determine the equivalents were then calculated using standard prevalence of depot reactions and the relation methods (Davis, 1974: Foster, 1989). Clinically

Psychiatric Bulletin (1998), 22. 605-607 605 ORIGINAL PAPERS significant depot reactions were judged as any Relationship between depot site reactions and reaction which scored at least two on the Likert other variables scale. The data were entered into a database and analysed on SPSS for Windows. Clinically significant depot site reactions were associated with greater volumes of depot and greater numbers of injections administered dur ing the previous 12 months (Mantel-Haenszel (for linear association) /2=6.10. d.f.= l, P=0.01 Findings and 7.24, d.f.=l, P<0.01, respectively). There was Subject details a highly significant relationship between total volume of depot administered in the past 12 One hundred and fourteen (36%) patients from months and frequency of injection (Spearman Liverpool and 204 (64%) from south Manchester R=0.56. P<0.001). Ordinary concentrations of took part in the study. Two patients in south depot injection were less likely to be associated Manchester declined to take part. There were with depot site reactions when compared with 196 male and 122 female patients with a mean concentrated and low volume preparations age of 43 years (s.d.= 12. range=18 to 76 years). (Mantel-Haenszel (for linear association) Two hundred and sixty-two (83%) had a case X2=5.36, d.f.= l, P=0.02). However, patients pre note diagnosis of schizophrenia: 24 (7.5%) had scribed highly concentrated depot preparations an affective disorder; 20 (6.3%) had a schizo- were prescribed a significantly higher number of affective disorder; and a further eight (2.5%) had injections (ordinary concentration= 17.1, concen- diagnoses varying from organic psychosis, ob trated=20.8 and highly concentrated=29.7 injec sessive-compulsive disorder and temporal lobe tions per year) than the other two groups (ANOVA epilepsy. The diagnosis was not ascertained for F(2, 304)=22.9, P<0.001) and also received a four patients due to missing case notes. The significantly higher volume of depot preparation mean age at first episode of illness was 28 years in the previous year (ordinary concentration= (s.d.=9.1, range=12 to 68 years). 27.6, concentrated=24.4 and highly concen- trated=43.4 ml per year) than the other groups (ANOVAF(2. 308)=10.2. P<0.001). Prevalence of depot site reactions When the severity (sum of Likert scores) of a Side-effects such as bleeding and pain after depot site reaction was analysed after controlling injection, rated one on the Likert scale, were for the volume of depot received in the past 12 common and thus the following results refer only months, no significant difference was found to depot site reactions which scored at least two, between low and higher concentrations of depot. as this was viewed as a clinically significant As flupenthixol decanoate was the most fre depot site reaction. Table 1 shows the number of quently prescribed depot and was available in patients prescribed each depot who experienced three concentration types (20mg/ml. 100mg/ a clinically significant depot site reaction. ml, 200mg/ml) the analysis was repeated and Haloperidol decanoate was associated with the restricted to flupenthixol decanoate. As with the highest proportion of depot site reactions, but whole group there was a trend for more severe this proportion was not significantly different depot site reactions to occur with increasing from the other four depot preparations. The concentration of preparation (Mantel-Haenszel overall prevalence of clinically significant depot /2=3.2, P=0.07): however, when the volume of site reaction was 17%. depot received in the past 12 months was Clinically significant depot site reactions were controlled, there was no significant difference caused by pain (8.2%). bleeding (6.9%), nodules between the three preparations of flupenthixol (4.4%) and skin thickening (3.5%). Clinically decanoate. significant erythema was not present in any of There was no relationship between depot site the patients investigated. reactions, and the dosage of depot (as measured

Table 1. Prevalence of clinically significant depot site reactions

Clinically significant decanoate, decanoate, palmitate, decanoate, decanoate, reactionAbsent n(%)160(83) n(%)41 n(%)21 n(%)18(82) n(%)21

(85) (88) (75) Present 34(17) 7(15) 3(12) 4(18) 7(25) TotalFlupenthixol 194(100)Fluphanzine48(100)Pipothiazine24(100)Zuclopenthixol22(100)Haloperidol 28(100)

606 Jones et al ORIGINAL PAPERS

by chlorpromazine equivalents), concurrent medi Acknowledgements cation, body mass index, gender or age of subject. Thanks are due to Professor A. Burns for helpful comments on an earlier draft of this paper and to Comment Mrs Julie Morris for statistical advice. Some care should be exercised in interpreting our results as the numbers of patients receiving depot preparations other than flupenthixol de- References canoate were small and the interrater reliability BELANGER-ANNABLE.M. (1985) Long acting neuroleptics: of the nursing staff who rated the presence or technique for intramuscular injection. Canadian Nurse. absence of a clinically significant depot site 81. 1-3. DAVIS.J. M. (1974) Dose equivalence of the anti-psychotic reaction was not formally assessed. There was drugs. Journal of Psychiatric Research. 11. 66-69. also some uncertainty about whether the sub FOSTER.P. (1989) Neuroleptic equivalence. Pharmaceutical jects from Manchester and Liverpool were repre Journal. 243. 431-432. sentative of patients receiving depot medication GLAZER.W. M. & KANE.J. M. (1992) Depot neuroleptic elsewhere in the UK. treatment: an underutilised treatment option. Journal If these caveats are put to one side then this of Clinical Psycluatry. 53. 426-533. GOTTFRIES.C. G. &GREEN.L. (1974) Flupenthixol decanoate study found the prevalence of localised adverse in treatment of out-patients. Acia Psychiatrica reactions to depot neuroleptics to be 17%, which Scandinauica. 255 (suppl.). 15-23. is similar to the 19% found by Hay (1995). Such HAMANN.G. L.. EGAN,T. M.. WELLS.B. G.. et al (1990) reactions were associated with increased fre Injection site reactions after intramuscular quency of injections and increased total volume administration of haloperidol decanoate 100mg/ml. of depot administered in the previous 12 months. Journal of Clinical Psychiatry. 51. 502-504. HAY,J. (1995) Complications at site of injection of depot Flupenthixol and fluphenazine decanoate were neuroleptics. British Medical Journal. 311. 421. the most commonly prescribed depots. As in Hay's (1995) study haloperidol and zuclo- HIRSCH.S. R. GAIND.R. ROHDE.P. D., et al (1973) Out patient maintenance of chronic schizophrenic patients penthixol decanoate were associated with a with long-acting fluphenazine: Double blind placebo slightly higher proportion of depot-site reactions, trial. British Medical Journal, i. 633-637. McCREADlE.R. G.. KIERNAN.W. E. S., VENNER,R. M., et al but this increase was not statistically significant. (1979) Probable toxic necrosis after prolonged Hay (1995) and Svendsen (1989) observed fluspirilene administration. British Medical Journal. 1. more depot site reactions when concentrated 523-524. preparations were used, but they did not control STARMARK.J.. FOREMAN.A. & WAHLSTROM,J. (1980) for the volume of depot administered in the Abscesses following prolonged intramuscular administration of perphenazine enantate. Aria previous 12 months. In this study we found a Psychiatrica Scandinauica. 62. 154-157. significant increase in clinically significant SVENDSEN.O. (1989) Siudies of Tissue Injuries Caused by depot-site reactions with higher concentrations Intramuscular Injection of Drugs and Vehicles. Metlwds of depot, but also found that those patients for Quantification and Effects of Concentration. Volume. receiving concentrated preparations had more Vehicle. Injection Speed and Intralipomatous Injection. frequent injections and a significantly higher Copenhagen: Medicinsk-historisk Museum. volume of depot administered in the previous 12 months. When the analysis was repeated Julie C. Jones, Department of Psychiatry. adjusting for the volume of depot administered in University Hospital of South Manchester. the past 12 months, there was no significant Manchester: Jennifer C. Day, Department of relationship between the severity of depot site Pharmaceutical Sciences. University of reaction and concentration of depot. Nottingham. Nottingham: John R. Taylor. North If our findings are replicated, then there may Mersey Community Trust, Sefton General be a case for increasing the interval between Hospital. Liverpool and "Christopher S. depot neuroleptic injections and using low Thomas. Department of Psychiatry. University volume (highly concentrated) preparations in Hospital of South Manchester. Nell Lane. order to reduce the administration of high Manchester M20 8LR volumes which appear to increase the risk of clinically significant depot-site reactions. "Correspondence

Investigation of depot site reactions 607