3 Siguardson ER, Ridge JA, Kemeny N, Daly JM. Tumor and liver drug uptake following hepatic melanoma metastatic to the liver after chemoembolisation with cisplatinum and polyvinyl artery and portal vein infusion. J Clin Oncol 1987;5:1836-9. sponge. Proceedings ofthe Amenecan Societyfor Clinical Oncology 1987;6:210. 4 Chen HSG, Gross JF. Intra-arterial infusion of anti-cancer drug: theoretic aspects of drug delivery 12 Ensminger N, Niederhuber J, Gyves J. Effective control ofliver metastases from colon cancer with and review of responses. Cancer Treat Rep 1980;64:31-40. an implanted system for hepatic arterial chemotherapy. Proceedings of the American Society for 5 Lokich J, Eisenmerger W. Ambulatory pump infusion devices for hepatic artery infusion. Semin Clinical Oncology 1982;1:94. Oncol 1983;10:183-90. 13 Grage TB, Vassillopoulos PP, Shingleton WW. Results of a prospective randomised study of 6 Dakhil S, Eisenmenger W, Cho K, Niederhuber J, Doan K, Wheeler R. Improved regional hepatic artery infusion with 5-fluorouracil versus intravenous 5-fluorouracil in patients with selectivity of hepatic arterial bischlorethylnitrosourea with degradable microspheres. Cancer hepatic metastases. A Central Oncology Group study. Surgery 1979;86:550-5. 1982;50:63 1-5. 14 Kemeny N, Daly J, Reichman B, Geller N, Botet J, Oderman P. Intrahepatic or systemic infusion 7 Konno T, Meada H, Iwai K, Maki S, Tashiro S, Uchida M, Migauchi Y. Selective targeting of anti- of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma: a randomised cancer drug and simultaneous image enhancement of solid tumors by arterially administered trial. Ann Intern Med 1987;107:459-65. BMJ: first published as 10.1136/bmj.297.6646.435 on 13 August 1988. Downloaded from lipid contrast medium. Cancer 1984;54:2367-74. 15 Hohn D, Stagg R, Friedman M, et al. The NCOG randomised trial of intravenous versus 8 Klopp CT, Bateman J, Berry N, Alford C, Winship T. Fractionated regional cancer chemotherapy. intrahepatic FUDR for colorectal cancer metastatic to the liver. Proceedings of the American Cancer Res 1950;10:229. Society for Clinical Oncology 1987;6:85. 9 Bierman HR, Byron RL, Miller ER, Shimkin MB. Effects of intra-arterial administration of 16 Oberfield RA. Intra-arterial hepatic infusion chemotherapy in metastatic liver cancer. Semin Oncol nitrogen mustard. Amj Med 1950;8:535. 1983;10:206-14. 10 Bern MM, McDermott W, Cady B. Intra-arterial hepatic infusion and intravenous adriamycin for 17 Lokich J, Ahlgren J, Gullo J. A randomised trial of standard bolus 5-fluorouracil versus protracted the treatment of hepatocellular carcinoma. Cancer 1978;42:399-405. infusional 5-FU in advanced colon cancer. Proceedings of the American Society for Clinical 11 Mavligit G, Carrasco N, Papadopoulos N, Charnsangvei C, Wallace S. Regression of ocular Oncology 1987;6:81.

Depression resistant to tricyclic antidepressants Adding lithium will often work

Up to a third of patients with major depression either fail to have, however, been less encouraging,617 and adding lithium respond or respond only partially to treatment with tricyclic is probably a more effective strategy.'7 antidepressants.' In some cases specific psychotherapeutic Ifa patient has been able to tolerate a full dose of a tricyclic or social intervention will be required, but further drug antidepressant with no improvement changing to another treatment will be considered for many. What are the pos- tricyclic antidepressant or a newer antidepressant will sibilities? probably not be worth while. If combined treatment with An initial step is to see whether the dose of the tricyclic lithium and tricyclic antidepressants has been ineffective a antidepressant may be increased. The proportion of patients monoamine oxidase inhibitor should be considered. Given in responding increases as the dose is raised, and many patients high enough doses monoamine oxidase inhibitors are effective may be able to tolerate more than the usual 150 mg daily.2 antidepressants,'8 and they often help in patients who Whether monitoring plasma concentrations of tricyclic have failed to respond to other antidepressants and electro- antidepressants can help determine correct dosage is dis- convulsive therapy.'8 '9 It was originally suggested that puted,34 and the usual course is to increase the dose until depressed patients who responded to monoamine oxidase definite but tolerable side effects are apparent.5 inhibitors were more likely to have an atypical presentation of For patients with severe depression, when endogenous depression,20 and the results of some, but not all, recent symptoms are prominent, the usual practice when treatment investigations have supported this proposal.'82' The balance

with tricyclic antidepressants is ineffective is to consider of evidence shows that patients whose depressive disorder http://www.bmj.com/ electroconvulsive therapy. At least half of this group of is characterised by mood reactivity, increased sleep and patients will improve after electroconvulsive therapy.67 appetite, and feelings of anxiety and anger will show a Subjects who are not responding to unilateral electro- good rate of response (about 70%) to monoamine oxidase convulsive therapy should have a trial of bilateral treatment inhibitors.22 Clinical impression is that such patients are before electroconvulsive therapy is abandoned.8 Electro- unlikely to be helped by electroconvulsive therapy.' convulsive therapy is particularly useful in patients with Lithium may also potentiate treatment with monoamine

psychotic depression, but in such patients combining tricyclic oxidase inhibitors, and there are reports that lithium and on 3 October 2021 by guest. Protected copyright. antidepressants with neuroleptic drugs may yield rates of tranylcypromine may relieve severe depressive states that response similar to those with electroconvulsive therapy have not responded to lithium and a tricyclic antidepressant (about 80%).9 combined or to a monoamine oxidase inhibitor given alone.23 Electroconvulsive therapy usually necessitates admission to Some believe that adding tryptophan to lithium and a hospital, and many patients are reluctant to receive it. There monoamine oxidase inhibitor may help in patients with is thus much interest in alternative drug treatments, and particularly resistant depression, and about half ofthis group recent attention has focused on the use of lithium. Two of patients may show substantial improvement with this controlled investigations have suggested that adding lithium combination.24 Good clinical effects have also been reported to tricyclic antidepressants in patients who have not responded with combining lithium, tryptophan, and clomipramine.25 produces a clear improvement in about 50-60%. 1011 Although The drugs considered most effective in resistant depression some may respond within two to three days, the more usual are characterised by their ability to produce a striking en- pattern is for a gradual remission over about three weeks hancement in some aspects of brain serotonin function.'42324 while lithium concentrations are maintained between There has been much progress recently in identifying specific 0 5-0 8 mmol/l.'2 Whether this response is attributable to an subtypes of brain serotonin receptors,26 and selective drugs antidepressant action of lithium alone'3 or to a synergism for these receptors are becoming available. Whether such between lithium and the tricyclic antidepressant is not drugs have useful antidepressant properties will therefore be clear." 14 of both clinical and scientific interest. Ineffective treatment with tricyclic antidepressants may P J COWEN also be supplemented by a small daily dose of liothyronine (triiodothyronine) (20-40 kg). Both anecdotal reports and one Medical Research Council Clinical Scientist, Medical Research Council Unit ofClinical Pharmacology, controlled trial suggest that 60-70% of patients may show Littlemore Hospital, some improvement within a few days.'5 Recent assessments Oxford OX4 4XN

BMJ VOLUME 297 13 AUGUST 1988 435 I Klein DF, Davis JM. Diagnosis and drug treatment in psvchtatrnc di'sorders. Baltimore: Williams and 14 Glue P'W, Cowen Pl, Nutt DJ, Kolakowska T, Grahame-Smith DG. The ef'f'ct of- lithium on Wilkins, 1979. 5-HI-mediated neuroendocrine responses and platelet 5-HI receptors. I'sychopharmacology 2 Quitkin FM. The importance of dosage in prescribing antidepressants. Br] Psvchiatrv 1985;147: 1986;90:398-402. 593-7. 15 Goodwin FK, Prange AJ, Post RM, Muscettola G, Lipton MA. Potentiation of antidepressant 3 American Psychiatric Association. Tricyclic antidepressantsblood level measurements and effects by L-trio-iothyronine in tricyclic non-responders. Am7 Pss'chianrv 1982;139:34-8. clinical outcome: an APA task force report. Am] Psychiatrv 1985;142:155-62. 16 Gitlin MJ, Weiner H, Fairbanks L, Hershman JM, Friedfeld N. Failure of '13 to potentiate 4 Burgess CD. Therapeutic drug monitoring in psychiatry. Is it worthwhile? Human Psycho- tricyclic antidepressant response..7 Affiective Disord 1987;13:267-72. pharmacology 1986;1:83-7. 17 Garbut IC, Mayo JP, Gillette GM, Little KY, Mason GA. Lithium potentiation of tricvclic 5 Paykel ES. Predictors of treatment response. In: Paykel ES, Coppen A, eds. Psvchopharmacology of antidepressants following lack of T3 potentiation. AmJ Ptvchtutre 1986;143:1038-9.

affective disorders. Oxford: Oxford University Press, 1979:193-220. 18 Pare CMB. The present status of monoamine oxidase inhibitors. BrJ Psychiatry 1985;146:576-84. BMJ: first published as 10.1136/bmj.297.6646.435 on 13 August 1988. Downloaded from 6 Kendell RE. The present status of electroconvulsive therapy. Br] Psychiatry 1981;139:265-83. 19 Nolen WA, van de Putte JJ, Dijken WA, Kamp JS. L-5HTP in depression resistant to re-uptake 7 Markowitz J, Brown R, Sweeny J, Mann JJ. Reduced length and cost of hospital stav for major inhibitors. An open comparative studv with tranylcypromine. Br7 Psvchiatrs 1985;147:18-22. depression in patients treated with ECT. Am] Psychiatry 1987144: 1025-9. 20 West ED, Dally PJ. Effects of iproniazid on depressive symptoms. BrMedy 1959;i: 1491-4. 8 Sackheim HA, Decina P, Kanzten M, Kerr B, Malitz S. Effects of electrode placement on the 21 Rowan P'R, Paykel ES, Parker RR. Phenelzine and amitriptvline: effect on symptoms of neurotic efficacy of titrated low-dose ECT. Am] Psychiatrv 1987;144:1449-55. depression. BrJPsychiatrv 1982;140:475-83. 9 Spiker DG, Weiss JC, Dealy RS, et al. The pharmacological treatment of delusional depression. 22 Liebowitz MR, Quitkin FM, Stewart JW, et al. Phenelzine v imipramine in atypical depression. A Am7 Psychiatry 1985;142:430-6. preliminary report. Arch Gen Psvchiatrv 1984;4:669-77. 10 DeMontigny C, Cournoyer G, Morrissette R, Langlois R, Caille G. Lithium carbonate addition in 23 Price LH, Charney DS, Heninger GR. Efficacy of lithium-tranylcypromine treatment in refractory tricyclic antidepressant-resistant unipolar depression. Arch Gen Psychiatry 1983;40:1327-34. depression. Amy P 'chtatr, 1985;142:619-23. 11 Heninger GR, Charney DS, Sternberg DS. Lithium carbonate augmentation of antidepressant 24 Barker WA, Scott J, Eccleston D. The Newcastle chronic depression study-results of a treatment treatment. Arch Gen Psychiatry 1983;40:1335-42. regime. Int Clin Psychopharmacol 1987;2:261-72. 12 Price LH, Charney DS, Heninger GR. Variability ofresponse to lithium augmentation in refractorv 25 Hale AS, Procter AW, Bridges PK. Clomipramine, trvptophan and lithium in combination for depression. Am] Psychiatry 1986;143:1387-92. resistant endogenous depression: seven case studies. Bry Psychiatrv 1987;151:213-7. 13 Worrall EP. Lithium augmentation of tricyclics. Br] Psychiatr 1986;149:520-1. 26 Fozard JR. 5-HT: the enigma variations. Trends in PharmacologicalSciences 1987;8:501-6.

Recognising over 100 000 hidden children Children who attend hospital wards without being admitted

Ready and rapid access to specialist services for children Most ward attenders came by arrangement during normal who need them is part of paediatric philosophy. Many weekday daytime hours. The visits were often short and paediatricians therefore use the ward to see patients outside entailed little waiting. About a fifth of the visits lasted for less their outpatient clinic hours. For patients who need frequent than 20 minutes and 8% for more than three hours. Visits reassessment this is often more convenient than conventional varied from brief "thank you" visits by parents, which often outpatient appointments and has the advantage of maintain- led to further discussion and counselling, and visits to collect ing the ward staffs links with the patient. The ward may also equipment for home use to those for procedures such as be used for short outpatient procedures. Until recently this sedation or catheterisation before radiographic examination workload has largely gone unrecognised and unquantified. or tests such as jejunal or bone marrow biopsy. Many Caring for Children in the Health Services is the name children, especially those attending medical wards for taken by a committee representing the British Paediatric complex procedures, would have been better categorised as Association, the National Association for the Welfare of day case admissions. Other children attended as emergencies Children in Hospital, the National Association of Health by arrangement with ward staff-many because they suffered Authorities, and the Royal College of Nursing. Last year the from chronic conditions, were well known on the ward, and http://www.bmj.com/ group produced a report showing that a quarter of children had been encouraged to attend with their problems. Another were nursed in adult or mixed adult's and children's wards.' important use of ward attendance is the early review of In its most recent report, Hidden Children, it examines the use children after discharge. of children's wards for children who attend but are not Ninety per cent ofward attenders needed nursing attention, admitted either as day cases or as inpatients and have often from more than one nurse. Doctors were involved in therefore not, until recently, been included in hospital 70% of cases, and other professionals-such as dietitians, statistics.2 The Korner committee defined ward attenders as physiotherapists, and laboratory technicians-in 17% of on 3 October 2021 by guest. Protected copyright. patients attending a ward who do not require the use of a cases. The survey has shown that the staff ofchildren's wards hospital bed.3 Since April 1987 wards have been required to undertake a lot of work that has until now been unrecorded. count them and enter them in the daily ward listing. A survey Probably well over 100 000 children in England are ward by the Caring for Children in the Health Services Committee attenders each year. of the general managers of all units in England with a There are two main lessons to be learnt. Firstly, the ward children's ward showed that ward attendance occurred in all attender system is large, well established, efficient, and types of children's wards and in all areas. Sixty five wards approved by both parents and staff and so its demands must were chosen for a more detailed study: a little over half were be recognised and met by health authorities. Secondly, mixed medical and surgical, about a quarter were children's the further development of community paediatric nursing medical wards, and about one in five was a children's surgical services might make some visits, especially to surgical wards, ward. All attendances at the ward for whatever reason by unnecessary. children or parents were recorded during a two week period in DPADDY February 1987. Fifty one wards participated, providing Consultant Paediatrician, Postgraduate Centre, information about 1051 ward attenders. Dudley Road Hospital, Most (94%) attenders were children. The remaining 6% Birmingham B18 7QH were adults attending on behalf of a child. Three fifths of the children were under 5 years old. In about halfof the hospitals I Thornes R. Where are the children? London: Caring for Children in the Health Serv,ices, 1987. 2 Thornes R. Hidden children. London: Caring for Children in the Health Services, 1988. providing adequate data ward attenders formed more than a 3 National Health Service and Department of Health and Social Security Steering Group on Health fifth of the patients passing through the ward. Services Information. First report. London: NHS and DHSS, 1982. (Korner report.)

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