Lithium versus antidepressants in the long-term treatment of unipolar affective disorder
University of Verona, Department of Medicine and Public Health, Section of Psychiatry, Policlinico G.B.Rossi, 37134 Verona, Italy. andrea.cipriani@ univr.it Cochrane database of systematic reviews (Online)
(Impact Factor: 6.03).
02/2006; 18(4):CD003492. DOI: 10.1002/14651858.CD003492.pub2
The main rationale for the use of lithium in the long-term treatment of unipolar affective disorder is its efficacy in treating bipolar affective disorder and resistant depression. However, there is considerable uncertainty about which pharmacological intervention is most effective in the long-term treatment of recurrent unipolar affective disorder.
To assess the effects of lithium versus antidepressants for the long-term treatment of recurrent affective disorder.
We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) on 2/9/2005. Reference lists of relevant papers and major textbooks of affective disorder were checked. Experts in the field and pharmaceutical companies were contacted regarding unpublished material.
Randomised controlled trials comparing lithium against antidepressant medication for the long-term treatment of patients with a diagnosis of affective disorder.
Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials.
Eight trials involving 475 people were included. Two of the studies included a mixed group of participants with either bipolar or unipolar disorder. Relapse was defined as admission to hospital and when all kinds of relapses were considered (both depressive and manic), there was a statistically significant difference in favour of lithium (relative risk (RR) fixed effect 0.34, 95% CI 0.14 to 0.82). The results did not exclude the point of no effect, when the random-effects model was used (RR random effects 0.40, 95% CI 0.14 to 1.18). There were no other statistically significant differences between lithium and antidepressants according to all other outcomes considered. Manic or depressive relapse was defined as prescription of non-study medication for mood disorder, manic or depressive relapse (as defined by the study authors), quality of life, social functioning, occupational functioning, overall drop-out rate, drop-out rate due to side-effects, troublesome side-effects, mortality due to all causes and specifically suicides.
There was adequate efficacy evidence for lithium or antidepressants preventing relapse in unipolar affective disorder, however their relative efficacy was unknown. When considering lithium or antidepressant long-term therapy, patients and clinicians should take into account the patient's clinical history, the side-effects and the individual's likely adherence to the recommended treatment regime. Large-scale, long-term randomised trials in unselected groups of subjects with unipolar affective disorder are needed.
Available from: John R Geddes
- "That lithium can prevent mood episodes has been recognized since the 1960s (Abou-Saleh and Coppen 1986). Since then, lithium has become a mainstay of preventative treatment in bipolar disorders, as well as in unipolar depression (Cipriani et al. 2006). Furthermore, lithium has been recommended for the treatment of acute mania and for the augmentation of antidepressants in unipolar depression (Katona 1995; Bauer et al. 2014). "
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In a previous meta-analysis of randomized controlled trials comparing lithium with placebo as a long-term treatment in bipolar disorders, we observed a clear preventative effect for manic episodes; however, the effect was equivocal for depressive episodes. Since then, the evidence base has grown further. In this update, we furthermore present the data on efficacy of lithium in comparison to alternative drug treatments. In addition, we analyze the data comparing lithium with placebo and other treatments regarding drop-outs due to reasons other than a mood episode and completion of study (no mood episode and no drop-out to reasons other than a mood episode).
Randomized controlled trials (RCTs) were sought comparing lithium with placebo and lithium with an alternative treatment in bipolar disorders where the stated intent of treatment was prevention of mood episodes. To this purpose, the Cochrane Central Register of Controlled Trials (CENTRAL) was searched. Reference lists of relevant papers and major textbooks of mood disorders were examined. Authors, other experts in the field, and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished.
For the comparison of lithium with placebo, seven trials (1,580 participants) were included. Lithium was more effective than placebo in preventing overall mood episodes (random effects RR 0.66, 95% CI 0.53 to 0.82), manic episodes (random effects RR 0.52, 95% CI 0.38 to 0.71), and, dependent on the type of analyses applied, depressive episodes (random effects RR 0.78, 95% CI 0.59 to 1.03; fixed effect RR 0.73, 95% CI 0.60 to 0.88). Lithium was inferior to placebo in leading to drop-outs for reasons other than a mood episode (random effects RR 1.33, 95% CI 1.07 to 1.65) but superior to placebo on study completion (random effects RR 1.69, 95% CI 1.12 to 2.55). For the comparison of lithium with anticonvulsants, seven trials were included (n = 1,305). In prevention of manic episodes, lithium showed superiority compared to anticonvulsants (random effects RR 0.66, 95% CI 0.44 to 1.00). However, there was no significant difference regarding prevention of overall mood episodes, depressive episodes, dropping-out to reasons other than a mood episode, or study completion.
The evidence base for lithium in the long-term treatment of bipolar disorders has strengthened. With no other drug available having such ample and consistent evidence for its efficacy lithium remains the most valuable treatment option in this indication.
Available from: Antonello Pani
- "Lithium is the most effective long-term therapy for bipolar disorder [1,2] and is also effective in unipolar depression . However, there has been concern about its safety . "
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The adverse renal effects of lithium have long been known, but glomerular insufficiency had been considered an unlikely event until recently, when new studies have raised concern regarding very long-term treatment. In this cross-sectional study, we examined glomerular function in a cohort of patients treated with lithium for up to 33 years and a control group of lithium-naïve patients treated with other mood-stabilizers.
Patients with a diagnosis of recurrent or persistent affective disorders, examined between 1 October 2007 and 31 December 2009, were screened. Demographic and clinical data were extracted from clinical charts regarding two study groups: one for patients treated with lithium for at least 12 months and the other for patients never exposed to lithium. Multivariate regression analysis was applied: the dependent variable was the estimated glomerular filtration rate (eGFR) calculated from the last available serum creatinine value using the Modification of Diet in Renal Disease Study Group equation; the following independent variables, potentially associated with renal dysfunction, were included: gender, current age, duration of lithium treatment, cigarette smoking, hypertension, diabetes and dyslipidemia.
eGFRs lower than 60 ml/min were significantly more frequent in the group treated with lithium (38/139 = 27.3%) compared to lithium-naïve patients (4/70 = 5.7%) (P = 0.0002; Fisher's test). Regression analysis showed a significant effect on eGFR of age, gender and duration of lithium treatment but no effect of cigarette smoking, hypertension, diabetes or dyslipidemia. eGFR was estimated to decrease by 0.64 ml/min (95% confidence interval = 0.38 to 0.90; P = 0.00) for each year of lithium treatment.
The duration of lithium treatment is a risk factor for glomerular failure, in addition to advancing age. For example, all patients aged 60 years or older may be estimated to undergo Stage 3 or more severe chronic kidney disease (namely an eGFR less than 60 ml/min) if treated with lithium for 30 years. These data may be added to the current debate on the balance between the protective effects of lithium on recurrent affective disorders and suicide and the risk of renal disease.See related commentary article here http://www.biomedcentral.com/1741-7015/11/34.
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ABSTRACT: Lithium is one of the most widely used drugs in neuropsychopharmacology. Preclinical scientists have made several advances in ascertaining the molecular mechanisms of action of this cation; such as its ability to stabilize monoamine levels, to interact with second messengers, and its neuroprotective effects, possibly over suicidal behaviors. Nevertheless, there remains a gap of knowledge between the pharmacological advances and the number of reliable clinical trials, creating a lack of evidence-based medicine to support medical prescriptions. In this review we examine lithium’s molecular mechanisms of action and evaluate their relevance in clinical applications.
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