Intended for healthcare professionals



BMJ 1998; 316 doi: (Published 02 May 1998) Cite this as: BMJ 1998;316:1330

Lithium -

EDITOR-Jefferson's justification of lithium as a "tried remedy" requires scrutiny.1 Impeaching clinical trials because of methodological problems is easy game, but Moncrieff's determined scepticism is refreshing,2 and a counterbalance to the bias of proving that psychotropic medication is effective.

Jefferson does not mention that doubts have also been raised about the value of lithium from evidence in routine clinical practice.3 A meta-analysis of more recent placebo controlled lithium discontinuation studies did not find as great a difference between relapse rates on lithium and placebo (37.5%-53.5%) as previous reviews.4 Rapid withdrawal is associated with higher relapse than gradual withdrawal (62%-29%).4 The finding of such a difference suggests that nonspecific factors are important. Unblinding can occur in clinical trials of lithium, compromising their results.5

Despite Jefferson, the issue of the effectiveness of lithium prophylaxis has not been foreclosed. No withdrawal study has included a no drug control group as an addition to the standard double-blind placebo design, so that withdrawal to placebo and no drug can be compared, giving an estimation of the placebo effect of withdrawal of medication when the primary treatment is merely tablet taking. Nor has any study of the discontinuation of lithium attempted to measure whether the blind has been broken. Correlation can be made with relapse and symptom ratings to determine whether degree of unblinding is associated with measured efficacy.

This improved design should provide more data to evaluate the evidence for the effectiveness of lithium, even if it does not give the certainty that Jefferson would like. Denial of the extent to which lithium is a placebo effect in clinical practice does not serve the interests of the many patients who are reliant on this medication. Jefferson quotes Ambroise Paré who readily discarded ineffective remedies and was also critical of remedies that were highly esteemed by others.

D B Double, Consultant Psychiatrist, Norfolk Mental Health Care, Hellesdon Hospital, Drayton High Road, Norwich NR2 2AE. (

1. Jefferson JW. Lithium. Still effective despite its detractors. BMJ 1998;316:1330-1

2. Moncrieff J. Lithium: evidence reconsidered. Br J Psychiatry 1997;171:113-9

3. Greenberg RP, Fisher S. Mood-mending medicines: Probing drug, psychotherapy, and placebo solutions. In: Fisher S, Greenberg RP, ed. From placebo to panacea - Putting psychiatric drugs to the test. New York: Wiley, 1997:115-172

4. Baker JP. Outcomes of lithium discontinuation: a meta-analysis. Lithium 1994;5:187-192

5. Double DB. Lithium revisited. [letter] Br J Psychiatry 1996; 168: 381-2

Competing interests: No competing interests

03 May 1998
D B Double
Consultant Psychiatrist, Norfolk mental Health Care NHS Trust
Hellesdon Hospital, Norwich NR6 5BE