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Cochrane Database Syst Rev. 2003;(3):CD003834.

Lithium for schizophrenia.

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Klinik für Psychiatrie und Psychotherapie, Klinikum rechts der Isar der TU-München, Ismaningerstr. 22, München, Germany.

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Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them lithium.


To review the effects of lithium for the treatment of schizophrenia and schizophrenia-like psychoses.


The reviewers searched the Cochrane Schizophrenia Group's register (March 2002). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted pharmaceutical companies and authors of relevant studies to identify further trials and to obtain original patient data.


All randomised controlled trials comparing lithium to antipsychotics or to placebo (or no intervention), whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses.


Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence interval (CI) estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. Continuous data were analysed using weighted mean differences (WMD).


The review currently includes 20 studies with a total of 611 participants. Most studies were small, of short duration and incompletely reported, but a number of authors were willing to share their data with us. Three studies comparing lithium with placebo as the sole treatment showed no difference in any of the outcomes we analysed. In eight studies comparing lithium with antipsychotic drugs as the sole treatment more participants in the lithium group left the studies early (n=270, RR 1.8, CI 1.2 to 2.9, NNT 9, CI 5 to 33). Several of the outcomes relating to these studies suggested that lithium is less effective than antipsychotic drugs, but it was difficult to summarise the data, because a variety of rating scales were used in the studies. Eleven studies examined whether the augmentation of antipsychotic drugs with lithium salts is more effective than antipsychotic drugs alone. More participants who received lithium augmentation had a clinically significant response (n=244, RR 0.8, CI 0.7 to 0.96, NNT 8, CI 4 to 33). However, statistical significance became borderline when participants with schizoaffective disorders were excluded in a sensitivity analysis (n=120, RR 0.8, CI 0.6 to 1.0, p=0.07). Furthermore, more participants in the lithium augmentation groups left the studies early (n=320, RR 2.0 CI 1.3 to 3.1, NNT 7, CI 4 to 14), suggesting a lower acceptability of lithium augmentation compared to those on antipsychotics alone. No superior efficacy of lithium augmentation in any specific aspect of the mental state was found. While based on very little data, there were no differences between groups for adverse events.


There is no randomised trial based evidence that lithium on its own is an effective treatment for people with schizophrenia. The evidence available on augmentation of antipsychotics with lithium is inconclusive, but it justifies further, large, simple and well-designed trials. These should concentrate on two target groups: 1) people with no affective symptoms, so that trialists can determine whether lithium has an effect on the core symptoms of schizophrenia, 2) people with schizoaffective disorders for whom lithium is widely used in clinical practice, although there is no evidence to support this use.

[Indexed for MEDLINE]

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