Volume 166 Issue 3

Hepatitis B and C in New South Wales prisons: prevalence and risk factors Tony G Butler, Kate A Dolan, Mark J Ferson, Linda M McGuinness, Phillip R Brown and Peter W Robertson MJA 1997; 166: 127 For comment see Crofts Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Laboratory methods - Statistical methods - Results - Participants - Serology and risk factors - Discussion - Acknowledgements - References - Authors' details - ©MJA1997 Abstract Objectives: To determine the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among inmates entering the New South Wales correctional system and to examine risk factors for infection. Design: Cross-sectional survey. Setting: Reception Centre at Long Bay Correctional Centre, Sydney, New South Wales, June to December 1994. Participants: 408 adult male inmates received at the reception centre (28% of the 1450 new inmates eligible for compulsory HIV testing). Outcome measures: Presence of HBV core and surface antibody and surface antigen; HCV antibody; risk factors; inmates' knowledge about risk factors. Results: 37% of inmates tested positive for HCV antibody, 31% for HBV core antibody and 3.2% for HBV surface antigen (indicating recent infection or carrier status). Among those who reported a history of injecting illegal drugs, rates rose to 66% for HCV antibody and 43% for HBV core antibody. Prevalence of HBV and HCV antibodies was similar in Aboriginal and non-Aboriginal inmates, but HBV antigen carrier rate was significantly higher among Aboriginals (12% versus 2.2%). Knowledge about hepatitis risk factors was poor (only 20% named injecting drug use), although recidivists were significantly better informed than those new to the correctional system. Multivariate analysis identified injecting drug use, past exposure to hepatitis B virus and previous imprisonments as significant predictors for HCV infection, and age over 25 years and HCV antibodies for HBV infection. Conclusions: Results suggest that about a third of adult male prisoners entering the NSW correctional system may have been infected with HBV or HCV. Measures such as education about hepatitis risk factors and HBV vaccination are needed to reduce hepatitis transmission in this population. MJA 1997; 166: 127-130 Introduction The reported high prevalence of hepatitis B and C in prison populations is attributed to the disproportionate number of people in prisons who engage in risk behaviours, particularly injecting illegal drugs.1-8 It is estimated that up to 60% of inmates are committed for drug-related offences.9 Further, an Australian study estimated that during their incarceration 25%-44% of inmates occasionally injected illegal drugs, 14%-34% engaged in occasional anal intercourse and 5%-18% did both.10 Among inmates entering the Victorian prison system in 1991 and 1992, 39% were positive for hepatitis C antibody (including 64% of those reporting a history of injecting illegal drugs), 33% were positive for hepatitis B antibody and 2.5% for hepatitis B surface antigen.11 There are no recent studies of the prevalence of infection with hepatitis B and C viruses (HBV and HCV) in New South Wales prisons. Our study aimed to determine the prevalence of HBV and HCV infection among inmates entering the NSW correctional system and to examine the risk factors associated with these infections. Methods The study was performed at the Reception Centre at Long Bay Correctional Centre, Sydney, NSW, from June to December 1994. The Reception Centre receives about 51% of adult males entering the NSW correctional system, most of whom are then transferred to other prisons. At the time of our survey, all inmates entering NSW prisons were routinely screened for the human immunodeficiency virus (HIV) by public health nurses of the Corrections Health Service. Inmates were also invited to participate in the hepatitis survey. Recruitment depended on the nurses' availability to enrol inmates during HIV screening, and in busy periods it was not always possible to enrol all new inmates. No information was sought from those who did not agree to participate. Inmates who agreed to participate were briefed on the project and informed that a consent form had to be signed, a blood specimen was needed, and a risk factor questionnaire would be administered by the nurse. Nurses also asked inmates to describe ways in which hepatitis can be transmitted. All inmates who tested positive for HBV and HCV antibodies were counselled by public health nurses. HCV-positive inmates routinely receive follow-up liver function tests. Inmates who reported having had HBV vaccination were given booster vaccination if antibody tests indicated they were not immune. All other inmates who tested negative for HBV core antibody were offered hepatitis B vaccination. Ethics approval for the study was granted by the Eastern Sydney Area Health Service Ethics Committee and the NSW Department of Corrective Services. Laboratory methods HBV core antibody (indicating past exposure) was tested with an anti-HBc enzyme immunoassay kit (General Biologicals, Taiwan). Samples positive for HBV core antibody were tested for HBV surface antigen (indicating carrier status) with the HBsAg-enzyme immunoassay (Murex, Dartford); positive results were confirmed by HBs reverse passive haemagglutination assay (Serodia, Tokyo). Inmates who reported having been vaccinated against hepatitis B were tested for HBV surface antibody with the HBsAb-enzyme immunoassay (General Biologicals, Taiwan). A level of 30 IU/mL was considered the minimum necessary for immunity. HCV antibody was detected with the Innotest HCVAbIII assay (Innogenetics, Belgium). Reactive samples were retested in duplicate and, if again reactive, were tested with anti-HCV (Murex, Dartford). Samples that were reactive in each of the two types of assay were classified as positive, and those with discrepant results as equivocal. Statistical methods Relative risks were calculated with the statistical software Epi Info-6,12 and logistic regression was performed with the software SPSS-6. 13 The c 2 test was used to test for association between Aboriginality and serostatus. Results Participants About 1450 inmates were tested for HIV at the Long Bay Reception Centre between June and December 1994. Of these, 410 adult males (28%) consented to be screened for HBV and HCV antibodies. It is not known how many of the remainder were not invited to participate and how many refused. Two inmates were counted twice as they were released and reincarcerated during the study period. Results of their second tests were excluded from the analysis. The 408 subjects were aged 17-73 years (mean, 30.6 years; standard deviation, 10.1), and 296 (73%) had been imprisoned previously. Country of origin was: Australia, 80%; Europe, 8.6%; New Zealand and the Pacific Islands, 3.5%; Asia, 2.7%; the Middle East, 2.7%; and elsewhere or unknown, 2.5%. Forty-one inmates (10%) identified themselves as Aboriginal. Serology and risk factors Prevalence of HBV and HCV antibodies and HBV antigens is shown in Box 1 (below). About a third of inmates were positive for HBV core antibody (31%) or for HCV antibody (37%), with 21% positive for both. Among those who reported having received HBV vaccination, only 34% had HBV surface antibody levels (indicating immunity). No significant differences were found between Aboriginal and non-Aboriginal inmates in prevalence of HBV core and HCV antibodies. However, the HBV carrier rate was significantly higher among Aboriginals (12% versus 2.2%; c2 =11.8; P < 0.001). Among those reporting hepatitis B vaccination, more Aboriginals (50%) than non-Aboriginals (32%) had developed immunity, but the difference was not significant. The association between risk behaviours and HBV and HCV infection is shown in Box 2. The risk of each infection was significantly increased by a history of injecting drug use, previous imprisonment, sharing of injecting equipment, age over 25 years, injecting drug use during previous imprisonment, and tattooing (P< 0.05 or less). Risk also increased significantly with increasing numbers of previous imprisonments (P< 0.01 or less). Risk of HCV infection was also significantly increased by tattooing, sex with an injecting drug user and presence of HBV antibodies (P< 0.001). Among the 67 inmates who reported injecting drug use during a previous imprisonment, 77% were positive for HCV antibody and 56% for HBV antibody. In addition, among the 150 inmates positive for HCV antibody, only 14 (9%) did not report a history of injecting drug use. The following independent variables were entered into a logistic regression model, with HBV and HCV infection as separate outcome variables: injecting drug use, sex with an injecting drug user, tattoos, Aboriginality, age group (over 25 years versus 25 years and under), previous imprisonment, and HBV or HCV infection. For HCV infection, significant predictors were injecting drug use (odds ratio [OR], 19.9; P< 0.001), presence of HBV antibody (OR, 5.6; P< 0.001), and previous imprisonment (OR, 3.9; P< 0.001). For HBV infection, significant predictors were presence of HCV antibody (OR, 6.2; P< 0.001), and age over 25 years (OR, 3.4; P< 0.001). Among the 85 inmates positive for both HBV and HCV antibodies, 83 (98%) reported previous imprisonment, 78 (92%) reported injecting drug use, 40 (47%) reported sharing injecting equipment, 64 (75%) had tattoos, and 31 (36%) reported being tattooed in prison. Inmates' knowledge of risk factors for hepatitis B and C transmission is shown in Box 3 (below). Few inmates were knowledgeable about risk factors, with injecting drug use nominated by only 20% and tattooing by only 2%. However, those who had been imprisoned previously were significantly more likely to identify injecting drug use as a risk factor than those new to the correctional system, and significantly less likely to answer "no idea" about risk factors. Discussion Our results agree with those of a 1991-1992 study of Victorian prison inmates.11 We found that 37% of inmates were positive for HCV antibodies (39% in Victoria), 31% for HBV antibodies (33% in Victoria), and 3.2% for HBV surface antigen B (2.5% in Victoria). Our results also agree with those of two Victorian studies, which found rates of 62% and 68%, respectively, for HCV infection among injecting drug users.8,14 Extrapolating our results to the current NSW male prison population of over 6000 implies that almost 2000 inmates are likely to have been exposed to HBV, about 200 are HBV carriers, and over 2000 are HCV-antibody-positive. In contrast, there were 25 HIV-positive inmates in NSW correctional centres at the time of the study (0.4%; 23 male and 2 female) (unpublished data). NSW prison inmates are offered hepatitis B vaccination if their sentences exceed six months and they are considered "at risk". However, inmates with shorter sentences may also be at risk. We believe that all inmates have the right to be protected from possible infection and that all should start a course of hepatitis B vaccination on entry to the correctional system. It may be appropriate to use recently described accelerated vaccination schedules, which provide protective levels of anti-hepatitis B surface antibody relatively quickly.15 In addition, if hepatitis B vaccination courses are not completed in prison, inmates should be educated about the need to complete them after release. We found that among the 108 inmates (26%) who reported having had hepatitis B vaccination only a third were immune, possibly because of failure to complete the recommended vaccination schedule. Vaccination history could not be verified. We found that previous imprisonment was a significant risk factor for HCV infection, suggesting that measures to minimise the spread of hepatitis within prisons are essential. In addition, as many injecting drug users spend time in prison, it is an appropriate point for intervention to break the cycle of infection by educating them about risks for hepatitis transmission and providing vaccination. Prison education programs seem to have improved awareness about transmission of hepatitis, as inmates with a prison history were more likely to know the role of injecting drug use and less likely to have "no idea" about hepatitis transmission. However, knowledge was still poor, and only 2% of inmates identified tattooing as a risk factor for hepatitis transmission, which is of concern given the popularity of tattooing in this population. The link between tattooing and HCV infection has been identified elsewhere,16,17 and should receive more emphasis in hepatitis education programs. The recent decision by the NSW Department of Corrective Services to make condoms available in prisons may reduce hepatitis transmission. Other measures, such as removing obstacles for accessing bleach, and needle exchange, should also be considered in the fight to curb the spread of hepatitis. Our findings suggest that chronic hepatitis may become one of the prison system's major health concerns over the next two decades. Acknowledgements The study was funded in part by a grant from the NSW Health Department AIDS/Infectious Diseases Branch. We wish to thank the nursing staff at the NSW Corrections Health Service for assistance in data collection (Amanda Christensen, Sheryl Frewin, Marion Grey, Cherylyn Jesson, Linda Kemp, Jodie Lee, and Sandra Parsons). References Acedo A, Campos A, Bauza J, et al. HIV Infection, hepatitis, and syphilis in Spanish prison [letter]. Lancet 1989; 2: 226. Hull HF, Lyons LH, Mann JM, et al. Incidence of hepatitis B in the penitentiary of New Mexico. Am J Public Health 1985; 75: 1213-1214. Koplan JP, Walker JA, Bryan JA. Prevalence of hepatitis B surface antigen and antibody at a state prison in Kansas. J Infect Dis 1978; 137: 505-506. Melico-Silvestre A, Pombo V, Pereira A, et al. Seroepidemiological survey of transmissible infections in Portuguese prisoners [letter]. AIDS 1991; 5: 780-781. Decker M, Vaughn W, Brodie J, et al. Seroepidemiology of hepatitis B in Tennessee prisoners. J Infect Dis 1984; 150: 450-458. Chiaramonte M, Trivello R, Renzulli G, et al. Hepatitis B virus infection in prisons. J Hyg Camb 1982; 89: 53-58. Vlahov D, Nelson K, Quinn T, Kendig N. Prevalence and incidence of hepatitis C virus infection among male prison inmates in Maryland. Eur J Epidemiol 1993; 9: 566-569. Fairley CK, Leslie DE, Nicholson S, et al. Epidemiology and hepatitis C virus in Victoria. Med J Aust 1990; 153: 271-273. Corrections Health Service. Strategic Plan 1993-1998. Sydney: NSW Health Department, 1994. Douglas RM, Gaughwin MD, Ali RL, et al. Risk of transmission of the human immunodeficiency virus in the prison setting [letter]. Med J Aust 1989; 150: 722. Crofts N, Stewart T, Hearne P, et al. Spread of blood borne viruses among Australian prison entrants. BMJ 1995; 310: 285-288. Epi Info [computer program], version 6.0. Atlanta, Ga: Centers for Disease Control, 1994. SPSS-6: Statistical package for the social sciences [computer program], version 6. Chicago, Ill: SPSS Inc, 1994. Crofts N, Hopper J, Bowden S, et al. Hepatitis C virus infection among a cohort of Victorian injecting drug users. Med J Aust 1993; 159: 237-241. Bayas J, Bruguera M, Martin V, et al. Hepatitis B vaccination in prisons: the Catalonian experience. Vaccine 1993; 11: 1441-1444. Kaldor J, Archer, G, Buring M, et al. Risk factors for hepatitis C virus infection in blood donors: a case-control study. Med J Aust 1992; 157: 227-230. Holsen DS. Prevalence of antibodies to hepatitis C virus and association with intravenous drug abuse and tattooing in a national prison in Norway. Eur J Clin Microbiol Infect Dis 1993; 12: 673-676. (Received 10 Jan, accepted 21 Oct, 1996) Authors' details New South Wales Health Department, AIDS/Infectious Diseases Branch, Sydney, NSW. Tony G Butler, MSc, Public Health Officer. National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW. Kate A Dolan, BSc, Research Officer. South Eastern Sydney Area Health Service, Sydney, NSW. Mark J Ferson, FRACP, FAFPHM, Director of Public Health. NSW Corrections Health Service, Long Bay Correctional Centre, Sydney, NSW. Linda M McGuinness, Grad Dip HSc, RN, Assistant Director of Nursing; Phillip R Brown, MBA, FAFPHM, Chief Executive Officer. Microbiology Department, Prince of Wales Hospital, Sydney, NSW. Peter W Robertson, PhD, Serologist. No reprints will be available. Correspondence: Mr T G Butler, NSW Health Department, AIDS/Infectious Diseases Branch, Locked Bag 961, North Sydney, NSW 2059. - To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Tony G Butler · Kate A Dolan · Mark J Ferson · Linda M McGuinness · Phillip R Brown · Peter W Robertson

Hyponatraemia and death after "ecstasy" ingestion Michael J A Parr, Heather M Low and Paull Botterill A 15-year-old girl collapsed with respiratory arrest after taking "ecstasy" at a "dance party". She presented to hospital with hyponatraemia and cerebral oedema and later died. We postulate that ingestion of large amounts of water contributed to the hyponatraemia. Advice to those using ecstasy at dance parties should be modified to suggest moderate fluid intake only and to emphasise the need to seek prompt medical attention for non-resolving symptoms. MJA 1997; 166: 136 For comment see White et al. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Introduction - Clinical record - Discussion - Acknowledgements - References - Authors' details - ©MJA1997 Introduction Recent deaths associated with ingestion of the illicit drug "ecstasy" have attracted widespread publicity and debate about the cause of death. Ecstasy (3,4-methylenedioxymethamphetamine; MDMA) is an ampheta mine derivative which has short-term hallucinogenic and stimulant effects, but in the long term may deplete brain serotonin by reducing numbers of serotonergic nerve terminals.1 Previous ecstasy-related deaths have involved hyperthermia, rhabdomyolysis, coagulopathy and cardiac toxicity.2 We report a death after ecstasy ingestion associated with hyponatraemia, a less well known complication. Clinical record A previously healthy 15-year-old girl was admitted to the Intensive Care Department in coma after a respiratory arrest. The evening before admission, she had been at a "dance party", where she had taken MDMA at about midnight. She was also believed to have drunk large quantities of water at the party, as then advised by health authorities (e.g., United Kingdom Health Education Authority, and National Poisons Unit), to counteract the hyperthermic effects of MDMA. About 0500, while still at the dance party, she began to vomit. After leaving the party she rested at a friend's house, where she had episodes of dry retching, impaired consciousness, confusion and some abnormal twitching movements. At 1000, about ten hours after ingestion of the MDMA, she was still drowsy and confused, and then collapsed with respiratory arrest while being walked downstairs. There was an estimated 12 minutes of hypoventilation and apnoea, with no cardiopulmonary resuscitation until an ambulance crew arrived. At 1023, on arrival of the ambulance crew, she was found to be in sinus tachycardia with palpable pulses, and she was intubated and ventilated by the crew. Spontaneous cardiac output was maintained throughout. She received naloxone, Hartmann's solution (1000 mL) and polygeline (Haemaccel, Hoechst) (500 mL) before arrival at hospital. At 1118, in the Emergency Department she was found to have: Glasgow Coma Scale score, 3; heart rate, 110 bpm; blood pressure, 80/50 mmHg; temperature, 32.8oC. She had bilateral papilloedema, fixed dilated pupils, no eye movements, no corneal, gag or cough reflexes and no reactions to pain. The hypotension did not respond to a further 1000 mL of 0.9% saline, and a noradrenaline infusion was started. This corrected the hypotension but did not improve the neurological status. At 1145, results of biochemical tests of blood taken before treatment in the Emergency Department showed reduced concentrations of serum electrolytes, suggesting haemodilution (see Box [below]). The haemodilution was corrected within six hours with infusion of 0.9% saline, moderate fluid restriction (total fluids, 60 mL/hour) and diuresis with frusemide and mannitol. At 1205, a chest x-ray revealed changes consistent with pulmonary oedema, and at 1245 computed tomography of the brain showed cerebral oedema with marked effacement of basal cisterns and inferior displacement of the brainstem. An electrocardiogram at 1400 was normal. Blood-gas analysis at 1500 showed respiratory alkalosis. Maximum serum creatine kinase level was raised, and there was no sign of coagulopathy (see Box [above]). On the second day of admission, the patient was making spontaneous efforts to breathe (on the ventilator) but otherwise her neurological status had not changed. She required noradrenaline to maintain blood pressure but had no cardiac arrhythmias. A nuclear magnetic resonance scan confirmed diffuse cerebral oedema, with decreased blood flow within the major cerebral vessels. Overnight, the patient deteriorated, developing diabetes insipidus and ceasing to breathe spontaneously. On the third day of admission, results of clinical examination were consistent with a diagnosis of brain death, and a cerebral angiogram confirmed this diagnosis. Postmortem findings showed diffuse brain swelling, with cerebellar tonsillar herniation and pituitary necrosis. Analysis of antemortem urine and blood revealed MDMA at levels of 430 ng/mL and 0.05 mg/L, respectively. No other drugs were detected. Discussion We report the death of a previously well young girl after ingestion of MDMA. The cause of death was thought to be hypoxic encephalopathy after respiratory arrest following acute water intoxication secondary to ingestion of MDMA. It would seem likely that hyponatraemia and cerebral oedema before the respiratory arrest were major factors in her death. The cerebral oedema is unlikely to have resulted from hypoxia after the respiratory arrest, as it would then usually be accompanied by bradycardia or asystole, neither of which was present. In addition, there was no evidence that the patient suffered cardiac arrhythmia, toxicity or infarction, which have caused other amphetamine-related deaths.3 The contribution of intravenous therapy to the hyponatraemia, fluid overload and cerebral and pulmonary oedema is unclear. Given the volumes (1500 mL) and osmotic concentrations (hypertonic or isotonic) of the solutions administered, any contribution is likely to have been small. The effects of MDMA are numerous and complex, and severe reactions are unpredictable.1 There have been many reports of MDMA-associated deaths caused by fulminant hyperthermia, coagulopathy and rhabdomyolysis,1 and clinical awareness of these problems seems high. However, many other complications of MDMA ingestion, such as hyponatraemia, may result in death or serious morbidity and have received less publicity. Instances of hyponatraemia after MDMA ingestion have been reported, with postulated causes that include ingestion of large quantities of water, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and contamination of the MDMA with other chemicals.4-9 Hyponatraemia raises a diagnostic dilemma, as its signs may be indistinguishable from those of MDMA intoxication. 10 There is evidence that morbidity associated with hyponatraemia is highest in children and women and is not related to either the magnitude or duration of the hyponatraemia.11 To our knowledge, this is the first Australian report of a fatality associated with ecstasy in which hyponatraemia and cerebral oedema appeared to be the main pathological processes. However, dissecting out the various factors involved in the death is extremely difficult. The roles of MDMA, the dance party environment, water ingestion, hyponatraemia, cerebral oedema, hypoxia, hypotension and SIADH are intertwined. The dance party environment encourages heavy exercise in a hot environment, with the advice to drink plenty of water. In the presence of high salt losses, this may produce hyponatraemia. Water ingestion may become uncontrolled as the individual attempts to treat symptoms or as the MDMA impairs rational judgement or possibly stimulates compulsive repetitive behaviour.12 Cerebral oedema as a result of hyponatraemia is well recognised and may result in tentorial herniation, respiratory arrest and cerebral hypoxia.11 SIADH has also been implicated in ecstasy-associated hyponatraemia.9 Although the mechanism is unclear, animal research suggests that serotonin increases secretion of antidiuretic hormone.13 Given the many people who take ecstasy without apparent ill-effect, it has acquired a safe reputation. Among the many adverse reactions, we must now include life-threatening hyponatraemia, which may have the same symptoms and signs as MDMA intoxication. To avoid adverse reactions, individuals using MDMA at dance parties are often advised to rest, avoid overheating, wear loose clothing and drink plenty of cool drinks.14 However, there is no evidence that this prevents adverse reactions. Furthermore, because of the possibility of hyponatraemia, this advice should be modified to suggest ingesting only moderate amounts of liquids. The importance of seeking medical attention promptly for non-resolving symptoms should also be emphasised. Acknowledgements The authors would like to thank the NSW Senior Deputy State Coroner, Mr John Abernethy, for releasing this information for publication, and Dr John A Henry of the National Poisons Unit, Guy's Hospital, London (UK), for assistance with this case. References Green AR, Goodwin GM. Ecstasy and neurodegeneration. BMJ 1996; 312: 149-150. Henry JA. Ecstasy and the dance of death. BMJ 1992; 305: 5-6. Dowling GP, McDonough E, Bost RO. Eve and ecstasy. A report of five deaths associated with the use of MDEA and MDMA. JAMA 1987; 257: 1615-1617. Henry JA, Jeffreys KJ, Dawling S. Toxicity and deaths from 3,4 methylenedioxymethamphetamine ("ecstasy"). Lancet 1992; 340: 284-287. Maxwell DL, Polkey MI, Henry JA. Hyponatraemia and catatonic stupor after taking "ecstasy". BMJ 1993; 307: 1399. Kessel B. Hyponatraemia after ingestion of "ecstasy" [letter]. BMJ 1994; 308: 414. Lehmann ED, Thom CH, Croft DN. Delayed severe rhabdomyolysis after taking "ecstasy". Postgrad Med J 1995; 71: 186-188. Milroy CM, Clark JC, Forrest AR. Pathology of deaths associated with "ecstasy" and "eve" misuse. J Clin Pathol 1996; 49: 149-153. Holden R, Jackson MA. Near fatal hyponatraemic coma due to vasopressin over-secretion after "ecstasy" (3,4-MDMA) [letter]. Lancet 1996; 347: 1052. Matthai SM, Davidson DC, Sills JA, Alexandrou D. Cerebral oedema after ingestion of MDMA ("ecstasy") and unrestricted intake of water [letter]. BMJ 1996; 312: 1359. Arieff AI. Management of hyponatraemia. BMJ 1993; 307: 305-308. Finch E, Sell L, Arnold D. Drug workers emphasise that water is not an antidote to drug [letter]. BMJ 1996; 313: 690. Brownfield MS, Greathouse J, Lorens SA, et al. Neuropharmacological characterization of serotoninergic stimulation of vasopressin secretion in conscious rats. Neuroendocrinology 1988; 47: 277-283. Shapiro H. Information for drug workers from ISDD. Ecstasy update. Druglink 1996; 11: 1. (Received 26 July, accepted 21 Nov, 1996) Authors' details Intensive Therapy Unit, Royal North Shore Hospital, Sydney, NSW. Michael J A Parr, MRCP, FRCA, Senior Registrar; currently, Consultant in Anaesthesia and Intensive Care, Frenchay Hospital, Bristol, UK; Heather M Low, FRACP, Senior Staff Specialist. NSW Institute of Forensic Medicine, Sydney, NSW. Paull Botterill, FRCPA, Pathologist. No reprints will be available. Correspondence: Dr H M Low, Intensive Therapy Unit, Royal North Shore Hospital, St Leonards, NSW 2065. - To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Heather M Low · Paull Botterill

Clinical Practice The role of the general practitioner in the treatment of schizophrenia: specific issues This article provides practical guidelines for general practitioners in treating schizophrenia. Specific areas include pharmacological treatment, supportive therapy, depression and suicide, alcohol and drug abuse, sexuality, and physical health. Vaughan J Carr MJA 1997; 166: 143-146 Introduction - Drug therapy - Supportive therapy - Depression and suicide - Alcohol and drug abuse - Sexuality - Physical health - Conclusion - Acknowledgements - References - Authors' details - - More articles on Psychiatry This is the second in a two-part series. The first article was published in the MJA 20 January 1997 issue. Introduction This second paper in this series deals with more specific issues in the primary care treatment of patients with schizophrenia, and attempts to clarify the roles of general practitioners (GPs) and specialist services, highlighting the areas which may be especially well provided by GPs. Practical guidelines are provided in the Box. Drug therapy Systematic accounts of the drug treatment of schizophrenia are available,1,2 and only matters particularly relevant to GPs will be covered here. Antipsychotic drugs are still chosen mostly on the basis of side effects. Low potency drugs (e.g., chlorpromazine, thioridazine) are more likely to produce sedation, postural hypotension and anticholinergic side effects, while higher potency drugs (e.g., haloperidol, fluphenazine) tend to cause more extrapyramidal side effects, such as parkinsonism, acute dystonia and akathisia. Some newer drugs (e.g., risperidone) are said to be more benign in their side effect profile; further use and investigation may bear this out. Clozapine seems unique in having marked benefits for about one-third of otherwise "treatment resistant" patients; this drug is subject to stringent controls because of the associated risk of agranulocytosis. Antipsychotic drugs are only partially effective in controlling psychotic symptoms. Up to 30% of patients on maintenance drug treatment relapse within two years3 -- this is not entirely explained by poor compliance. A third or more of schizophrenic patients taking antipsychotic drugs continue to experience delusions and/or hallucinations, usually in attenuated form.4,5 Therefore, when psychotic symptoms persist after two or more antipsychotic drugs have been taken (separately), in adequate doses, for a cumulative total of 12 months, measures other than drug treatment are necessary. Firstly, factors that may be contributing to persistent symptoms (e.g., drug or alcohol abuse, relationship problems) should be identified and dealt with if possible, usually by a specialist. Secondly, where appropriate, effective non-pharmacological treatment strategies should be added to a suitable drug regimen. Several individual psychological (e.g., cognitive behaviour therapies) and family-oriented (e.g., training in problem-solving skills) interventions are available. These require specialist expertise, and GPs can be instrumental in locating appropriate providers of these treatments. With very few exceptions, only one antipsychotic drug should be used at a time. The dose should be the minimum required to maintain remission, and side effects should be absent or minimal. Excessive doses of antipsychotic drugs augment negative symptoms, impair cognitive function, mimic depression, undermine compliance by causing dysphoria and discomfort, produce higher rates of side effects that contribute to stigmatisation by rendering the patient more conspicuous, and can cause irreversible complications (e.g., tardive dyskinesia). Overmedication also interferes with rehabilitation. GPs can monitor antipsychotic drug use to ensure that doses are not unnecessarily high. Doses of haloperidol greater than 10 mg per day (or the equivalent) are not currently justified and approximately half this amount is now recommended, even less for first psychotic episodes. Adjunctive medication (e.g., lithium, carbamazepine) should only be used on specialist advice. There is no role for long term use of benzodiazepines, although they can be useful adjuncts in acute episodes, particularly when sedating a patient in an emergency. Long term use of anticholinergic drugs for the treatment of drug-induced parkinsonism should be avoided as they may mask the signs of tardive dyskinesia and impair cognitive function. The relapse signature: Patients and their families should be encouraged to monitor the patient's symptoms in association with GPs and specialist services. Each patient is said to have a unique relapse "signature"6 -- a sequential emergence of symptoms and signs which herald an impending relapse. There is often a "window" of 2-4 weeks in which such early warning signs appear,6 signalling the need to increase doses of antipsychotic drugs to prevent relapse. GPs should review with patients their typical sequence of warning signs so that they can correctly interpret them and make timely adjustments to the drug regimen. Non-compliance with medication is inevitable at some stage in most patients' treatment. It is said that 80% of patients are non-compliant with medication 40%-80% of the time.7 Reasons for this include medication side effects, complex dosing schedules, stigma, lack of knowledge or false beliefs about medication, and poor insight or denial of illness.7,8 Some patients reason that stopping medication will signify they are not ill.8 Some patients may prefer the psychotic state, either because of certain rewards from being ill (secondary gain) or difficulties in coping with normal expectations and responsibilities.8 Non-compliance may occasionally be an attempt to assert control or a manifestation of rebellion. Dealing with non-compliance requires a good working relationship, incorporating sound education about the illness and its management. Keeping dosing schedules simple and eliminating side effects are important strategies. Asking about medication and reasons for non-compliance in a non-judgemental way will encourage disclosure. One useful strategy is to assume episodic non-compliance and openly regard each occasion as a learning opportunity for the patient. Involving the patient in drug management, including allowing limited self-regulation of doses,8 together with self-monitoring of symptoms, will benefit the patient. Simply resorting to depot medications undermines the patient's collaborative role in health care. Arranging for medication to be taken under supervision, which is fraught with potential conflict, or seeking legal means of enforcing drug administration (e.g., community treatment orders), should only be a last resort. Supportive therapy GPs, preferably in conjunction with specialist services, can provide supportive therapeutic relationships which predict good outcomes in schizophrenia.9 In general, realistic goals should be set, which include protecting vulnerabilities, minimising stress and strengthening adaptive capabilities.8 Initial supportive techniques of reassurance, explanation and the opportunity for airing emotion can progressively incorporate education about the illness and its management, clarification of patients' "relapse signatures", the role of medication, and attention to daily living skills, social and occupational functioning. Counselling by GPs can help patients learn simple stress management techniques, anxiety control strategies and problem-solving skills for coping with non-psychotic (e.g., social) anxiety and depression linked to relationship problems or stressful life events. GPs should supplement self-monitoring of symptoms by examining patients' mental state at each appointment. This includes assessment of the status of psychotic symptoms and, although it is important not to dwell excessively on these, GPs should not avoid asking such questions as: Do your beliefs about . . . continue to trouble you?; or Have you been hearing voices in the past few weeks? Are you able to ignore them? What have you found helpful when they occur? Patients with schizophrenia learn three kinds of palliative coping techniques to deal with psychotic and other symptoms:10 cognitive control (e.g., reappraisal, self-instruction, acceptance, manipulation of attention); behavioural control or the generation and implementation of action alternatives (e.g., increased or decreased activity, diversion, withdrawal from stimulation, altered arousal); and social support recruitment. They can be helped to identify their usual coping techniques, modify and extend them. GPs can encourage patients to practise these by imagining they have a particular symptom and then implementing an identified coping strategy. Such rehearsal of coping skills may facilitate their successful transfer to everyday settings. Families of schizophrenic patients need support and GPs can provide education, aided by various leaflets and other publications on schizophrenia which are now readily available. GPs can also provide explanation, reassurance, advice and the opportunity to air emotional distress (especially anger, shame, sadness and guilt). Specialist services can provide various forms of more specific family counselling and education on schizophrenia. Schizophrenia is usually a prolonged illness of relapses and remissions, but the eventual outcome is better than was previously thought -- most patients make a good long-term social recovery (i.e., improved social relationships and self-care abilities).11 The early years are crucial in determining the patient's ultimate level of function and substantial gains may take years to become apparent. Depression and suicide Depressive symptoms are common in schizophrenia, especially during recovery after an acute psychotic episode (postpsychotic depressive disorder). However, it can be difficult to distinguish between the almost ubiquitous low level depressive symptoms in schizophrenia and a major depressive syndrome that will require specific treatment. The negative symptoms of schizophrenia and the effects of antipsychotic drugs can both mimic depression. Nevertheless, discerning clinicians can diagnose a major depressive episode. A specialist referral to help confirm the diagnosis may be required. Depressive disorders in schizophrenic patients can be treated as for similar conditions in other patients, including the use of antidepressant medication. The risk of such drugs triggering relapse of schizophrenic symptoms is small. Major risks include the risk of suicide by overdose, and appropriate precautions should be taken to guard against this. A course of antidepressant drugs at recommended daily doses can be added to the antipsychotic drug regimen for 6-12 months, together with whatever psychotherapeutic assistance is indicated. Between 10% and 13% of schizophrenic patients commit suicide,12 mostly during the first 10 years of the illness. There are no reliable guidelines for predicting and preventing suicide in these patients. The schizophrenic patient more likely to commit suicide is a young, single, unemployed, socially isolated man whose illness is marked by numerous exacerbations and hospital admissions for psychosis.12 He often has a past history of depression and/or attempted suicide, and perhaps a non-delusional, demoralising awareness of his deterioration, which is particularly acute if he has previously had some higher education and realises that his family's expectations and his own ambitions are unlikely to be fulfilled. Sensitive enquiry may reveal considerable underlying emotional distress with depressive symptoms, accompanied by feelings of hopelessness and inadequacy. If a GP recognises something like this pattern in a patient, then a thorough assessment should be undertaken and an urgent specialist referral should be made if the GP is concerned about the patient's risk of suicide. Alcohol and drug abuse In an Australian sample of 194 patients, we estimated that the six-month prevalence of alcohol or drug abuse or dependence in schizophrenic patients treated by community mental health services was 26.8% and the lifetime rate was 59.8% (unpublished data). Apart from tobacco and caffeine, the commonest substance abused was alcohol, followed by cannabis and amphetamines. Up to 74% smoked cigarettes and 40% smoked more than 40 cigarettes daily; 17% consumed more than 600 g of caffeine daily. Substance abuse in schizophrenia is increasing,13 is more common in young men with antisocial characteristics, and has been linked to poor compliance with treatment, increased hospital admissions, depression, suicide, assaultive behaviour, instability of accommodation and homelessness. In addition, alcohol and cannabis have both been associated with increased positive symptoms of schizophrenia.14,15Detecting substance abuse in schizophrenia is the first priority. GPs should use non-judgemental enquiry to become thoroughly familiar with the patient's current and past pattern of drug use, including tobacco, caffeine and alcohol, gauging the quantity, frequency and context of use. An undetected alcohol or drug problem should be suspected in patients who respond poorly to treatment. If necessary, a referral can be made to mental health services with special therapeutic programs for psychiatric and substance abuse comorbidity. If alcohol or drug abuse is detected in patients during remission, even when no immediate adverse consequences are apparent, the GP should first attempt to determine the patient's reasons for using those substances. The patient can then be informed in a matter-of-fact way about their detrimental effects on schizophrenia and general health, highlighting the extent to which alcohol, cannabis and amphetamines worsen psychotic symptoms and lead to relapse. The difficulty is that this information may not match the selective recollection of patients, who may even report certain benefits from using drugs. It is preferable not to argue, but to point out that all substances, including therapeutic agents, have a certain "margin of safety" between desired effects and adverse consequences, but that the "margin of safety" for some drugs is much narrower than others. Having indicated that complete abstinence is the safest course of action, a harm minimisation approach can be negotiated as a satisfactory compromise. A series of short-term achievable goals can be identified in sequence, including aiming to control levels of consumption (including issues of safe needle use, where relevant), then moving on to goals for reducing consumption, incorporating strategies for preventing relapse and parting from the alcohol and drug culture. Simultaneously, the GP can attend to factors that may be contributing to the patient's substance use, including resolution of interpersonal and practical problems (e.g., money, accommodation), with the help of other agencies if necessary, and encourage the development of additional coping skills and the pursuit of other interests. Sexuality There are very few systematically collected data about sexual functioning of schizophrenic patients. Their fertility rates are increasing,16 and schizophrenic women can be at increased risk of sexual exploitation and abuse.17 For patients with schizophrenia, sexual fulfilment contributes to self-esteem and well-being, and psychosexual function and capacity for intimacy are important prognostic factors. However, antipsychotic drugs can interfere with sexual activity and inappropriate sexual behaviours caused by the illness can lead to ostracism and loneliness. GPs should enquire about patients' relationships, sexual behaviours, sexual orientation, knowledge of sexuality and reproduction, need for contraception, and understanding of safe-sex practices. It can also be helpful to ascertain whether the patient experiences any sexual dysfunction, which is common,18 but not always due to medication, and ensure that the patient is informed about sexually transmitted diseases where necessary. Specific interventions may be appropriate. Physical health Patients with schizophrenia often have high rates of concurrent physical illness,19,20 especially cardiovascular and respiratory diseases.21 Among the risk factors for physical ill-health are smoking, alcohol and drug use, antipsychotic drugs, poor nutrition and hygiene, obesity, sedentary lifestyle, poverty and social isolation. Schizophrenic patients should be examined six-monthly for side effects and complications of antipsychotic drug use. Akathisia can be detected by observing the patient at rest, both seated and standing, and asking whether there are any subjective feelings of restlessness (especially in the legs)22 which may be present in the absence of objective signs. Observations of gait and posture will enable the characteristic tremor and bradykinesia of parkinsonism to be detected, while passive flexion and extension of the upper limbs will reveal cog-wheel rigidity.23 Examination for tardive dyskinesia can be conducted using the readily available Abnormal Involuntary Movement Scale (AIMS), which facilitates detection and quantification of the variety of orobuccal and choreoathetoid limb movements possible in this condition.24 Parkinsonism and akathisia should be dealt with by a reduction in the dose of antipsychotic drugs or by changing to a lower-potency drug. Anticholinergic agents should only be used in the short term for parkinsonism and are ineffective for akathisia; the latter can sometimes be controlled with propranolol. There is no effective treatment for tardive dyskinesia and decisions about its management should be made in consultation with a psychiatrist or other specialist. Patients over the age of 40 require an annual physical (and dental) examination, including measurement of blood pressure, examination of the cardiovascular and respiratory systems and skin, assessment of drug side effects, and urinalysis.25 This can also provide an opportunity for a systems review to help detect symptoms which patients may not report spontaneously. Thyroid function, full blood count and erythrocyte sedimentation rate should be determined. Vision and hearing can be checked, and a chest x-ray and electrocardiogram ordered25 if there is any indication of cardiovascular or respiratory disease. Breast examination and Pap smear in women should be performed as indicated for the general female population. Conclusion Although the long-term treatment of schizophrenia is multimodal and multidisciplinary, GPs are in a position to take an active, even central, role in the care of patients with this illness. Models of "shared care" for schizophrenia involving GPs as integral members of the treatment team are just beginning to be established. If they live up to their promise they will provide significant improvements in the comprehensive care of schizophrenic patients. To function effectively in this context most GPs will require some initial training and continuing education. Acknowledgements I am grateful to Associate Professor Patrick McGorry and Drs Peter Hopkins, Brian Masters, Steve Robinson and Tony Ryan for their comments on earlier drafts of this paper. References Keks NA, Kulkarni J, Copolov DL. Treatment of schizophrenia. Med J Aust 1989; 151: 462-467. Kane JM. Schizophrenia. N Engl J Med 1996; 334: 34-41. Davis J. Overview: maintenance therapy in psychiatry: I. Schizophrenia. Am J Psychiatry 1975; 132: 1237-1245. Silverstein ML, Harrow M. First-rank symptoms in the postacute schizophrenic: a follow-up study. Am J Psychiatry 1978; 135: 1481-1486. Johnstone EC, Owens DGC, Gold A, et al. Schizophrenic patients discharged from hospital: a follow-up study. Br J Psychiatry 1984; 145: 586-590. Birchwood M, Macmillan F, Smith J. Early intervention. In: Birchwood M, Tarrier N, editors. Innovations in the psychological management of schizophrenia. Assessment, treatment and services. Chichester: John Wiley & Sons, 1992: 115-145. Van Kammen DP, Marder SR. Dopamine receptor antagonists. In: Kaplan HI, Sadock BJ, editors. Comprehensive textbook of psychiatry. 6th ed. Baltimore: Williams & Wilkins, 1995: 1987-2022. Fenton WS, McGlashan TH. Schizophrenia: individual psychotherapy. In: Kaplan HI, Sadock BJ, editors. Comprehensive textbook of psychiatry. 6th ed. Baltimore: Williams & Wilkins, 1995: 1007-1018. Frank AF, Gunderson JG. The role of the therapeutic alliance in the treatment of schizophrenia: relationship to course and outcome. Arch Gen Psychiatry 1990; 47: 228-236. Carr V. Patients' techniques for coping with schizophrenia: an exploratory study. Br J Med Psychol 1988; 61: 339-352. Harding CM, Zubin J, Strauss JS. Chronicity in schizophrenia: fact, partial fact, or artifact? Hosp Community Psychiatry 1987; 38: 477-485. Caldwell CB, Gottesman II. Schizophrenics kill themselves too: a review of risk factors for suicide. Schizophr Bull 1990; 16: 571-589. Cuffel BJ. Prevalence estimates of substance abuse in schizophrenia and their correlates. J Nerv Ment Dis 1992; 180: 589-592. Duke PJ, Pantelis C, Barnes TRE. South Westminster Schizophrenia Survey: alcohol use and its relation to symptoms, tardive dyskinesia and illness onset. Br J Psychiatry 1994; 164: 630-636. Linszen DH, Dingemans PM, Lentor ME. Cannabis abuse and the course of recent-onset schizophrenic disorders. Arch Gen Psychiatry 1994; 51: 273-279. Lane A, Byrne M, Mulvany F, et al. Reproductive behaviour in schizophrenia relative to other mental disorders: evidence for increased fertility in men despite decreased marital rate. Acta Psychiatr Scand 1995; 91: 222-228. Darves-Bornoz JM, Lemperiere T, Degiovanni A, Gaillard P. Sexual victimization in women with schizophrenia and bipolar disorder. Soc Psychiatry Psychiatr Epidemiol 1995; 30: 78-84. Bhui K, Puffet A, Herriot P. A survey of sexual problems amongst psychiatric inpatients. Soc Psychiatry Psychiatr Epidemiol 1995; 30: 73-77. Brugha TS, Wing JK, Smith BL. Physical health of the long-term mentally ill in the community. Is there unmet need? Br J Psychiatry 1989; 155: 777-781. Honig A, Pop P, Tan ES, et al. Physical illness in chronic psychiatric patients from a community psychiatric unit. The implications for daily practice. Br J Psychiatry 1989; 155: 58-64. Vieweg V, Pandurangi A, Levenson J, Silverman J. Medical disorders in the schizophrenic patient. Int J Psychiatry Med 1995; 25: 137-172. Barnes TRE. A rating scale for drug-induced akathisia. Br J Psychiatry 1989; 154: 672-676. Simpson GM, Angus JWS. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 1970; 212 Suppl: 11-19. Kaplan HI, Sadock BJ, Grebb JA, editors. Kaplan and Sadock's synopsis of psychiatry: behavioural science, clinical psychiatry. 7th ed. Baltimore: Williams & Wilkins, 1994: 952. Burns T, Kendrick T. Schizophrenia. In: Pullen I, Wilkinson G, Gray DP, editors. Psychiatry in general practice today. London: The Royal College of Psychiatrists and the Royal College of General Practitioners, 1994: 194-208. Authors' details Discipline of Psychiatry, Faculty of Medicine and Health Sciences, The University of Newcastle, Newcastle, NSW. Vaughan J Carr, MD, FRANZCP, Professor of Psychiatry. Reprints: Professor V J Carr, Discipline of Psychiatry, Faculty of Medicine and Health Sciences, The University of Newcastle, Callaghan, NSW 2308. 1: Practical guidelines for specific aspects of primary care for patients with schizophrenia Pharmacological treatment Antipsychotic drugs should be chosen after considering their relative side effects. Use only one antipsychotic drug at a time When symptoms persist despite compliance, consider non-pharmacological strategies Use minimum dose required for maintaining remission and avoiding side effects Monitor symptoms: identify relapse signature Explore reasons for non-compliance and regard as a learning opportunity Encourage patient's role as a collaborator Supportive therapy Develop a supportive therapeutic relationship within which you: Set realistic goals Educate both patient and family Encourage symptom self-monitoring and coping skills Depression and suicide Depressive symptoms are common in schizophrenia. Treat as in other patients, with antidepressant drugs if necessary Consider risk of suicide Refer to specialist if necessary Alcohol and drug abuse Substance abuse is highly prevalent in schizophrenia, and has adverse effects on the course of the illness. Routinely enquire about substance use Strongly suspect if treatment response is poor Inform patient of adverse effects, and negotiate harm minimisation through short-term goals Refer to specialist if necessary Sexuality Normal sexual functioning can be affected by the illness and by antipsychotic medication. Discuss contraception Discuss safe sexual practices Try to ascertain any sexual dysfunction Physical health Schizophrenic patients have many risk factors for and high rates of concurrent physical disease. Examine six-monthly for side effects and complications of antipsychotic drugs Do a physical check annually for patients over 40 Back to text

Vaughan J Carr