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Lithium and mortality

Medway Hospital, Windmill Road, Gillingham, Kent ME7 5NY

F. Falodun

West Suffolk Hospital, Hardwick Lane, Bury St Edmunds IP33 2QZ

In their study of mortality in patients with affective disorder commenced on lithium, Brodersen et al (2000) paint an unfairly negative picture of the efficacy of lithium. They compared mortality in patients with affective disorders who were started on lithium, irrespective of their compliance with treatment, with that of the general population. This gives a false impression that lithium could increase mortality. To assess the efficacy of lithium, they should ideally have compared those who were compliant with the treatment with those who were not and also with the general population, as Kallner et al (2000) did. The latter study clearly demonstrates that even though affective disorder patients have an increased mortality compared with the general population, lithium has a definite antisuicidal effect. Moreover, in unipolar depression, suicide rates increased only after patients discontinued lithium. These two studies also show how the methodology can affect the findings.

EDITED BY MATTHEW HOTOPF

REFERENCES

Brodersen, A., Licht, R. W., Vestergaard, P., et al (2000) Sixteen-year mortality in patients with affective disorder commenced on lithium. British Journal of Psychiatry, 176, 429-433.[Abstract/Free Full Text]

Kallner, G., Lindelius, R., Petterson, U., et al (2000) Mortality in 497 patients with affective disorders attending a lithium clinic or after having left it. Pharmacopsychiatry, 33, 8-13.[Medline]

Authors' reply

Mood Disorders Research Unit, Aarhus University Hospital, Skovagervej 2, DK-8240 Risskov, Denmark

EDITED BY MATTHEW HOTOPF

Gracious & Falodun find that our study of mortality in affective disorder patients commenced on lithium (Brodersen et al, 2000) paints an unfairly negative picture of lithium's efficacy. They object to our intention-to-treat analysis of all patients commenced on lithium irrespective of compliance, which showed a significantly elevated standardised mortality ratio (SMR) of 2.5. They suggest that we should have compared compliant with non-compliant patients and with the general population, as did Kallner et al (2000).

Kallner et al actually reported — even in patients compliant with lithium — that mortality in general (SMR=1.6) and suicide in particular (SMR=14.0) were significantly elevated. They also found that mortality was even higher in non-compliant patients, a result which may very well be valid. However, comparison of compliant with non-compliant patients introduces a considerable selection bias, since patients are not randomly allocated to the two groups. Rather, patients with comorbidity, such as drug and alcohol misuse and other predictors of negative outcome (Vestergaard et al, 1998) select themselves to the non-compliant patient group. Therefore, a finding that non-compliant patients fare worse than compliant patients may testify only to the existence of negative predictor variables among patients who were non-compliant, instead of supporting the efficacy of lithium treatment. Neither our study nor Kallner et al's allow conclusions as to whether or not lithium has specific antisuicidal effects exceeding what can be inferred from its ability to prevent recurrent illness episodes in affective disorder patients.

The efficacy of long-term prophylactic treatment with lithium has been questioned frequently (Moncrieff, 1995). We believe, as apparently do Gracious & Falodun, that despite its shortcomings lithium is a very helpful tool in the psychiatric armamentarium. Arguments that support the efficacy (or inefficacy) of long-term lithium treatment should, however, rest on sound scientific evidence.

REFERENCES

Brodersen, A., Licht, R. W., Vestergaard, P., et al (2000) Sixteen-year mortality in patients with affective disorder commenced on lithium. British Journal of Psychiatry, 176, 429-433.

Kallner, G., Lindellius, R., Petterson, U., et al (2000) Mortality in 497 patients with affective disorders attending a lithium clinic or after having left it. Pharmacopsychiatry, 33, 8-13.

Moncrieff, J. (1995) Lithium revisted. A re-examination of the placebo-controlled trials of lithium prophylaxis in manic—depressive disorder. British Journal of Psychiatry, 167, 569-574.[Free Full Text]

Vestergaard, P., Licht, R. W., Brodersen, A., et al (1998) Outcome of lithium prophylaxis: a prospective follow-up of affective disorder patients assigned to high and low serum lithium levels. Acta Psychiatrica Scandinavica, 98, 310-315.[Medline]

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gracious, K. S. Articles by Licht, R. W. Search for Related Content PubMed Articles by Gracious, K. S. Articles by Licht, R. W.