Rapid Responses to:

EDITORIALS: Timothy G Dinan Lithium in bipolar mood disorder BMJ 2002; 324: 989-990 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Uncertainty in the maintenance treatment of bipolar disorder: the need for BALANCE

John R Geddes, See below - too many to fit in here   (2 May 2002)

Evidence for lithium is inadequate

Joanna Moncrieff   (3 May 2002)

Improving outcomes

Stewart M Herring   (25 August 2003)

Uncertainty in the maintenance treatment of bipolar disorder: the need for BALANCE 2 May 2002
John R Geddes, Senior Clinical Research Fellow Department of Psychiatry, University of Oxfgord, See below - too many to fit in here Send response to journal: Re: Uncertainty in the maintenance treatment of bipolar disorder: the need for BALANCE	We agree with Professor Dinan’s statement in his recent editorial that there is considerable evidence that lithium is an effective maintenance treatment in bipolar disorder1. Our recent Cochrane review found that lithium reduced the relative risk of relapse in bipolar disorder by 42% (95% confidence interval 30 to 52%)2. We also accept that the widespread switch away from lithium – especially in the USA – is based on marketing and/or opinion rather than compelling evidence. The absence of good evidence for valproate does not mean, of course, that lithium is more efficacious or more acceptable than valproate. It is also possible that the combination of lithium plus valproate is more effective than either drug alone. We are, therefore, less confident in accepting the unequivocal recommendation that lithium should remain the first line treatment. There is genuine clinical uncertainty about this issue - and such wide international variations in clinical practice - that there is an overwhelming case for a clinical trial comparing lithium and valproate 3;4. We are currently conducting BALANCE, a large UK randomized trial comparing valproate monotherapy, lithium monotherapy and combination therapy with valproate plus lithium5. BALANCE is a large collaborative trial funded by the Stanley Foundation, a US mental health charity and the trial drugs have been generously donated by Sanofi-Synthelabo. BALANCE has been designed and conducted entirely independently of the pharmaceutical industry. Clinicians and patients are welcome to participate in this pivotal clinical trial. Further information on BALANCE is available at the addresses below. Tel 01865 223731 Email balance@psych.ox.ac.uk WWW: www.psychiatry.ox.ac.uk/balance/ References 1. Dinan TG. Lithium in bipolar mood disorder. BMJ 2002;324:989-90. 2. Burgess S, Geddes J, Hawton K, Townsend E, Jamison K, Goodwin G. lithium for maintenance treatment of mood disorders. Cochrane Database Syst.Rev. 2001 3. Geddes J,.Goodwin G. Bipolar disorder: clinical uncertainty, evidence- based medicine and large-scale randomised trials. Br.J Psychiatry Suppl 2001;41:s191-s194. 4. Lawrie, S. M., Scott, A. I., and Sharpe, M. C. Evidence-based psychiatry - do psychiatrists want it and can they do it? Health Bull.Edinb. 58(1), 25-33. 2000. 5. Geddes, J. R, Rendell, J. M., and Goodwin, G. M. BALANCE: a large simple trial of maintenance treatment for bipolar disorder. World Psychiatry 1, 48-51. 2002. John Geddes, Guy Goodwin, Jennifer Rendell, Jane Hainsworth, Emma Van der Gucht, Heather Young, Ian Anderson, Jonathan Cavanagh, John Cookson, Nicol Ferrier, Allan Young, Sophia Frangou, Jan Scott, Peter Jones, Chris Kelly, Glyn Lewis, Keith Lloyd, Richard Morriss, Christine Healey, Malcolm Peet, Ian Reid, Peter Tyrer, Ed Juszczak, Douglas G Altman
Evidence for lithium is inadequate 3 May 2002
Joanna Moncrieff, Senior Lecturer, University College London Department of Psychiatry and Behavioural Sciences, Riding House St, London W1N 8AA Send response to journal: Re: Evidence for lithium is inadequate	Dear Sir, I was disappointed that Dinan’s editorial did not reflect on the inadequacies of the evidence base for the use of lithium prophylaxis in bipolar disorder (1). Randomised controlled trials conducted so far do not provide good evidence that lithium is effective (2). The great majority of such trials, including the only large trial to show superiority of lithium over placebo (3), were withdrawal trials. Since there is now good evidence that withdrawing lithium increases the risk of relapse above that predicted by the natural history of the disorder, these trials do not provide information about the effect of starting lithium in the first place (4). The recent prospective study conducted in the US found no difference between lithium and placebo (5). This is consistent with numerous naturalistic follow-up studies that have failed to demonstrate any clear evidence that lithium improves long-term outcome (6). The phenomenum of withdrawal induced relapse also implies that, unless lithium is taken continuously and forever, lithium may make outcomes worse than they would be without any treatment. I do not want to suggest that other drug treatments are better. None have been found to be superior to lithium in comparative trials. If lithium’s efficacy is in doubt, then so is the whole enterprise of pharmacological prophylaxis for bipolar disorder. It is undoubtedly difficult for psychiatrists and others to accept that this may be the case. Manic depression is a devastating condition and they will want to offer some hope to sufferers. However, it is beholden to us as doctors to reflect the uncertainty of the evidence and to be sure that we are not doing more harm than good. Yours sincerely, Joanna Moncrieff References 1) Dinan TG. Lithium in bipolar mood disorder. BMJ 2002;324:989-990. 2) Moncrieff J. Lithium revisited. A re-examination of the placebo controlled trials of lithium prophylaxis in manic depressive disorder. British Journal of Psychiatry 1995;167:569-574. 3) Prien RF, Caffey EM, Klett CJ. Prophylactic efficacy of lithium in manic depressive illness. Archives of General Psychiatry 1973;28:337-341. 4) Suppes T, Baldessarini RJ, Faedda GL, Tohen M. Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. Archives of General Psychiatry 1991;48:1082-1088. 5) Bowden CL, Calabrese JR, McElroy SL, Gyulai I, Wassef A, Petty F et al. A randomised, placebo controlled 12 month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Archives of General Psychiatry 2000;57:481-488. 6) Moncrieff J. Lithium: evidence reconsidered. British Journal of Psychiatry 1997;171:113-119.
Improving outcomes 25 August 2003
Stewart M Herring, Secretary MDF Scotland Abbeymill, Seedhill Road Paisley PA1 1TJ Send response to journal: Re: Improving outcomes	The British Association for Psychopharmacology guidelines (1 p171) state that best dose is as high as possible without causing significant side effects and as an individual who takes lithium I finally reached this conclusion independently after 16 years and many spells in hospital. I'd prefer to be somewhere between 800 and 900 mg but unfortunately 100 is the smallest manufactured dose of the particular sustained release preparation (priadel). This suggests that manufacturing the drug in smaller quantities has the potential to improve patients quality of life, improve concordance and avoid the risk of dismissing a useful drug as ineffective. Stewart Herring (1) G.M. Goodwin et al. Evidence-based guidelines for treating bipolar disorder:recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology 17(2)(2003) 149-173 Competing interests:   None declared