Latest maintenance data on lithium in bipolar disorder
Introduction
Lithium is widely regarded as the gold standard for long-term treatment of bipolar disorder. However, the early trials that established lithium as a maintenance treatment have been criticised because a number of them employed discontinuation designs, whereby patients who were stable on lithium were randomised either to continued lithium treatment or placebo substitution. It is now recognised that abrupt withdrawal of lithium can provoke a new episode of mania (Goodwin, 1994, Suppes et al., 1991) and this may have driven increases in the number of early placebo relapses, producing inflated estimates of the apparent therapeutic efficacy of lithium. This weakness has probably been over-stated in the most sceptical current analysis (Moncrieff, 1997) because when the more extreme discontinuation designs were excluded there is still a treatment benefit (Burgess et al., 2001). Nevertheless, other factors such as the emphasis on acute treatment as a model for long-term treatment, the introduction of new medicines with apparent potential for bipolar disorder, the side-effect burden, neurotoxicity in overdose, and the difficulties associated with long-term lithium use may also have contributed to lithium’s diminishing reputation for effectiveness in recent years (Goodwin, 2002).
This paper describes how recent positive results from long-term studies of lamotrigine in bipolar I disorder, which included lithium as an active comparator, should increase confidence in the use of lithium for maintenance therapy. Additional issues surrounding the long-term use of lithium are also considered.
Section snippets
Previous maintenance data
A meta-analysis of randomised, placebo-controlled trials of lithium as maintenance treatment for mood disorders has been performed (Burgess et al., 2001). After elimination of studies with a discontinuation design, nine studies were included in the review (n=825). Overall, lithium was more effective than placebo in preventing all relapses (irrespective of the definition used) in patients with mixed diagnoses of mood disorder (unipolar, bipolar, and unspecified) over periods of up to 4 years
Latest evidence from lamotrigine studies
New data on the efficacy of lithium come from two large randomised, double-blind, placebo-controlled, 18-month trials of lamotrigine and lithium in the prevention of relapse and recurrence of mood episodes in patients with bipolar I disorder (Calabrese et al., in press; Bowden et al., 2003). The two studies were prospectively designed for combined analysis, and pooled results have recently been reported (Goodwin et al., submitted). Individual and combined results from the two studies are
Methods
Patients aged 18 years or over were included in these studies if they had a current or recent (within 60 days) episode of DSM-IV depression (study GW605/2003) or mania, hypomania, or mixed mood states (study GW606/2006). Both studies consisted of a 2-week screening phase, followed by an 8- to 16-week open-label period during which lamotrigine (100–200 mg/day) was initiated and other psychotropic drugs were discontinued (Fig. 1). Patients were enrolled in the double-blind phase of the study if
Use in different subtypes of bipolar disorder
As demonstrated above, lithium is clearly effective in preventing relapse or recurrence of unselected bipolar I disorder. Current evidence supports the use of lithium in patients with a classic presentation of the illness. The Multicenter Study of Long-Term Treatment of Affective and Schizoaffective Psychoses (MAP study) compared the differential efficacy of lithium versus carbamazepine in 171 patients with bipolar disorder over a period of 2.5 years (Kleindienst and Greil, 2000). A
Conclusions
Results from the lamotrigine bipolar trials have demonstrated that lithium is effective as maintenance therapy in bipolar I disorder independent of an enriched or discontinuation study design. These new findings, therefore, substantially increase the confidence in long-term lithium treatment. In particular, the relative efficacy of lithium against different poles of the illness is now more clearly defined; lithium has significant efficacy against manic relapse, while its effect against
References (22)
- et al.
Lithium neurotoxicity: the development of irreversible neurological impairment despite standard monitoring of serum lithium levels
J Clin Neurosci
(2002) - et al.
Pattern of response to divalproex, lithium, or placebo in four naturalistic subtypes of mania
Neuropsychopharmacology
(2002) - et al.
A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder
Arch Gen Psychiatry
(2003) - Burgess, S., Geddes, J., Hawton, K., Townsend, E., Jamison, K., Goodwin, G., 2001. Lithium for maintenance treatment of...
- Calabrese, J.R., 2003. Latest maintenance data on lamotrigine in bipolar disorder. European Neuropsychopharmacology,...
- Calabrese, J.R., Bowden, C.L., Sachs, G., Yatham, L.N., Behnke, K., Mehtonen, O.-P., Montgomery, P., Ascher, J., Paska,...
- et al.
A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder
Arch Gen Psychiatry
(2000) - et al.
Bipolar disorder: clinical uncertainty, evidence-based medicine and large-scale randomised trials
Br J Psychiatry Suppl
(2001) - et al.
Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder
N Engl J Med
(1989) Rationale for long-term treatment of bipolar disorder and evidence for long-term lithium treatment
J Clin Psychiatry
(2002)
Recurrence of mania after lithium withdrawal. Implications for the use of lithium in the treatment of bipolar affective disorder
Br J Psychiatry
Cited by (29)
Smartphone as a monitoring tool for bipolar disorder: a systematic review including data analysis, machine learning algorithms and predictive modelling
2020, International Journal of Medical InformaticsCitation Excerpt :The recurrent and chronic nature of bipolar disorder results in a vast impact on psychosocial functioning and quality of life [1], as well as a high burden of this disease [4] and high socio-economical costs [5]. The risk of a new episode can be reduced significantly by the treatment with mood stabilizing drugs [6]. Early pharmacological intervention is crucial as it reduces the conversion rates to full-blown illness and decreases the severity of symptoms [7].
Changes in mood stabilizer prescription patterns in bipolar disorder
2016, Journal of Affective DisordersCitation Excerpt :In addition to treatment for acute depressive and manic episodes, there is effective prophylactic treatment available for bipolar disorder. It has been known for more than half a century that lithium effectively prevents new episodes (Geddes and Briess, 2007; Goodwin, 2002; Goodwin and Geddes, 2003), and lithium is still recommended as a first line maintenance treatment option according to national and international treatment guidelines (APA, 2002; Goodwin, 2009; NCCMH, 2006; SBU, 2004; Suppes et al., 2005; Yatham et al., 2013, 2009). Lithium is known as a mood stabilizer.
The effects of n-acetylcysteine and/or deferoxamine on manic-like behavior and brain oxidative damage in mice submitted to the paradoxal sleep deprivation model of mania
2015, Journal of Psychiatric ResearchCitation Excerpt :Since its discovery 50 years ago, lithium still remains the most prescribed and effective treatment for BD. However, a great number of patients taking lithium present with some side effects, and some residual symptoms persist even with the appropriate use of the medication, which can impair the patients adherence to treatment (Goodwin and Geddes, 2003; Coryell, 2009; Curran and Ravindran, 2014). There is some difficulty in developing new drugs to treat this illness, because little is known about the pathophysiology of this disorder (Zarate et al., 2006).
Aripiprazole monotherapy in the treatment of bipolar disorder: A meta-analysis
2011, Journal of Affective DisordersCitation Excerpt :There is a concern on aripiprazole and olanzapine maintenance data because the relevant studies included patients which were responders specifically to the study under investigation during the acute phase. It seems that all compounds are either exclusively or more likely to prevent manic episodes with the exception of lamotrigine which has the opposite properties (Goodwin and Geddes, 2003). The current paper presents a complete meta-analysis of all available data concerning the use of aripiprazole in bipolar disorder, including unpublished trials.
Asenapine modulates mood-related behaviors and 5-HT<inf>1A/7</inf> receptors-mediated neurotransmission
2017, CNS Neuroscience and Therapeutics