© 2003 The Royal College of Psychiatrists
Correspondence |
Lithium augmentation in treatment-refractory unipolar depression
Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK
Department of Psychological Medicine, Institute of Psychiatry, London, and Maudsley Hospital, London, UK
Stimpson et al (2002) have taken an ‘all or nothing’ approach to evaluating randomised controlled trials (RCTs) for their systematic review. Their rigorous procedures eliminated over 98% of the 919 RCTs considered (although we note that the flow chart in Fig. 1 appears to ‘lose’ 166 of them without explanation). As a consequence, they have provided a matchless summary of the very best evidence about intervention for treatment-refractory unipolar depression but have left undescribed the very large quantity of remaining levels of evidence.
In 1999 Bauer and Dopfmer identified 11 placebo-controlled studies of lithium augmentation. As always, the trials were of varying quality; nevertheless, they concluded (using the three studies of highest quality, two of which were used by Stimpson et al) that there is ‘firm evidence’ in favour of lithium as an augmentation strategy for treatment-refractory unipolar depression, with a number needed to treat of 3.7. They supported their conclusion by performing a separate analysis adding a further six studies (that used either lower doses or shorter duration of lithium augmentation) and found a similar, indeed slightly stronger, effect size (Bauer & Dopfmer, 1999).
We note that there have been no studies of lithium augmentation against placebo for treatment-resistant unipolar depression that are of a suitable quality for a systematic review in the approximately 3-year period between the acceptance dates of the two papers cited above. We suggest that many clinicians now consider the weight of evidence (at many levels) supporting the use of lithium as an augmentation strategy for treatment-refractory unipolar depression sufficiently compelling. Thus, it is unusual for our service dedicated to treatment-resistant depression to receive referrals of patients not yet tried on lithium. Although further and better RCTs of lithium augmentation would be welcome (even Bauer & Dopfmer identified only 234 subjects studied), many would feel that other questions now have more clinical salience. Pressing examples might include whether psychological treatments are effective in these patients, how they compare with lithium augmentation, and how olanzapine augmentation (for which a large body of evidence is emerging; see Dube et al, 2002) compares with both.
REFERENCES
- Bauer, M. & Dopfmer, S. (1999) Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. Journal of Clinical Psychopharmacology, 19, 427-434.[CrossRef][Medline]
- Dube, S., Anderson, S.W., Paul, S., et al (2002) Metaanalysis of olanzapine—fluoxetine use in treatment resistant depression. International Journal of Neuropsychopharmacology, 5 (suppl. 1), 105-106.
- Stimpson, N., Agrawal, N. & Lewis, G.
(2002) Randomised controlled trials investigating
pharmacological and psychological interventions for treatment-refractory
depression. Systematic review. British Journal of
Psychiatry, 181,
284-294.
[Abstract/Free Full Text]
Authors' reply
Division of Psychiatry, University of Bristol, Cotham House, Cotham Hill, Bristol BS6 6JL, UK
University of Wales College of Medicine, Cardiff, UK
Chelsea and Westminster Hospital, London, UK
G.L. has received payments for lectures from the pharmaceutical industry.
According to Drs Lee and Cleare ‘many clinicians’ regard the current evidence for lithium augmentation in treatment-refractory depression as ‘compelling’. They are correct in repeating one of the principles of evidence-based medicine, that all levels of evidence need to be taken into account when making clinical decisions.
Previous systematic reviews of this area have included patients who have
had 
3 weeks' treatment with an antidepressant or who have bipolar
disorder. We do not think that many UK psychiatrists would consider lithium
augmentation in unipolar depression that had not responded to an
antidepressant for only 3 weeks. For patients with bipolar disorder, most UK
psychiatrists, we think, would in any case be treating with lithium or another
mood-stabiliser. Our inclusion criteria, which were set before the review
started, were based therefore upon sensible and pragmatic clinical
considerations.
We too were surprised and shocked by the lack of randomised evidence to support lithium augmentation; but it is also important to remember that lithium may well be effective, even though the evidence to support its use is extremely weak.
Lithium has a number of potentially serious side-effects, even at normal therapeutic doses (Bell et al, 1993). When we discuss the advantages and disadvantages of lithium with our patients we are unable to provide them with much more than clinical anecdote in its favour. We certainly have no idea from empirical research about the severity of depression for which lithium augmentation might be effective.
We have a collective responsibility to our patients to provide them with good-quality research evidence to justify the treatments we recommend. As a profession we need to address areas of uncertainty such as this using well-designed RCTs that will inform clinical practice.
REFERENCES
- Bell, A. J., Cole, A., Eccleston, D., et al
(1993) Lithium neurotoxicity at normal therapeutic levels.
British Journal of Psychiatry,
162,
689-692.
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