Lithium for Maintenance Treatment
of Mood Disorders
(Cochrane Review)
Burgess S, Geddes J, Hawton K, Townsend E, Jamison K, Goodwin G.
ABSTRACT
A substantive amendment to this systematic review was last made on 19
March 2001. Cochrane reviews are regularly checked and updated if necessary.
Background: Mood disorders are common, disabling and tend to be
recurrent. They carry
a high risk of suicide.
Maintenance treatment, aimed
at the prevention of relapse, is therefore of vital importance. Lithium has
been used for some years as the mainstay of maintenance treatment in bipolar
affective disorder, and to a lesser extent in
unipolar disorder. However,
the efficacy and effectiveness of prophylactic lithium therapy has been
disputed.
Low suicide rates in lithium-treated patients have led to claims
that lithium has a specific anti-suicidal effect. If so, this is of
considerable importance as treatments for mental disorders in general have
not been shown convincingly to be effective in suicide prevention.
Objectives: 1. To investigate the efficacy of lithium treatment in
the prevention of relapse in recurrent mood disorders. 2. To examine the
effect of lithium treatment on consumers' general health and social
functioning, its acceptability to consumers, and the side-effects of
treatment.3. To investigate the hypothesis that lithium has a specific
effect in reducing the incidence of suicide and deliberate self-harm in
persons with mood disorders.
Search strategy: The Cochrane Collaboration Depression, Anxiety
and Neurosis Controlled Trials Register (CCDANCTR) and The Cochrane
Controlled Clinical Trials Register (CCTR) were searched. Reference lists of
relevant papers and major text books of mood disorder were examined.
Authors, other experts in the field and pharmaceutical companies were
contacted for knowledge of suitable trials, published or unpublished.
Specialist journals concerning lithium were hand searched.
Selection criteria: Randomised controlled trials comparing lithium
with placebo, where the stated intent of treatment was maintenance or
prophylaxis. Participants were males and females of all ages with diagnoses
of mood disorder. Discontinuation studies (in which all participants had
been stable on lithium for some time before being randomised to either
continued lithium treatment or placebo substitution) were excluded.
Data collection and analysis: Data were extracted from the
original reports independently by two reviewers. The main outcomes studied
were related to the objectives stated above. Data were analysed for all
diagnoses of mood disorder and for bipolar and unipolar disorder separately.
Data were analysed using Review Manager version 4.0.
Main results: Nine studies were included in the review, reporting
on 825 participants randomly allocated to lithium or placebo. Lithium was
found to be more effective than placebo in preventing relapse in mood
disorder overall, and in bipolar disorder. The most consistent effect was
found in bipolar disorder (random effects OR 0.29; 95% CI 0.09 to 0.93 ). In
unipolar disorder, the direction of effect was in favour of lithium, but the
result (when heterogeneity between studies was allowed for) did not reach
statistical significance. Considerable heterogeneity was found between
studies in all groups of patients. The direction of effect was the same in
all studies; no study found a negative effect for lithium. Heterogeneity may
have been due to differences in selection of participants, and to differing
exposures to lithium in the pre-study phase resulting in variable influence
of a discontinuation effect. There was little reported data on overall
health and social functioning of participants under the different treatment
conditions, or on the participants' own views of their treatment.
Descriptive analysis showed that assessments of general health and social
functioning generally favoured lithium. Small absolute numbers of deaths and
suicides, and the absence of data on non-fatal suicidal behaviours, made it
impossible to draw meaningful conclusions about the place of lithium therapy
in suicide prevention.
Reviewers' conclusions: This systematic review indicates that
lithium is an efficacious maintenance treatment for bipolar disorder. In
unipolar disorder the evidence of efficacy is less robust. This review does
not cover the relative efficacy of lithium compared with other maintenance
treatments, which is at present unclear. There is no definitive evidence
from this review as to whether or not lithium has an anti-suicidal effect.
Systematic reviews and large scale randomised studies comparing lithium with
other maintenance treatments (e.g. anti-convulsants, antidepressants) are
necessary. Outcomes relating to death and suicidal behaviour should be
included in all future maintenance studies of mood disorder.
Citation: Burgess S, Geddes J, Hawton K, Townsend E, Jamison K,
Goodwin G.. Lithium for maintenance treatment of mood disorders (Cochrane
Review). In: The Cochrane Library, Issue 4, 2004. Chichester, UK: John Wiley
& Sons, Ltd.
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