A Placebo-Controlled 18-Month Trial of Lamotrigine and Lithium Maintenance Treatment in Recently Manic or Hypomanic Patients With Bipolar I Disorder

Bowden, Charles L.; Calabrese, Joseph R.; Sachs, Gary S.; Yatham, Lakshmi N.; Asghar, Shaheen; Hompland, Magne; Montgomery, Paul; Earl, N.; Smoot, Tonya M.; DeVeaugh-Geiss, Joseph

doi:10.1001/archpsyc.60.4.392

Cited by 616 publications

(527 citation statements)

References 52 publications

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“…Two recent maintenance studies have reported that lithium was not superior to placebo in delaying a new depressive episode, whereas lamotrigine was superior to placebo, with similar results in a combined analysis (Bowden et al, 2003a;Calabrese et al, 2003;Goodwin et al, 2004). An earlier maintenance study of lithium indicated an increased rate of depressive episodes in both rapid cycling and nonrapid cycling patients compared with placebo (Dunner et al, 1976), and a crossover study indicated little long-term benefit on depressive symptoms in bipolar disorder (Denicoff et al, 1994).…”

Section: Discussionmentioning

confidence: 83%

“…Recent randomized, placebo-controlled trials in patients with bipolar I disorder have demonstrated the significant but limited prophylactic efficacy of lithium, divalproex, lamotrigine and olanzapine (Bowden et al, 2000(Bowden et al, , 2003aCalabrese et al, 2003;Tohen et al, 2003). However, little data exist to aid psychiatrists in selecting the treatment most likely to be well tolerated and efficacious during maintenance therapy for a given patient.…”

Section: Introductionmentioning

confidence: 99%

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Relationship of Mania Symptomatology to Maintenance Treatment Response with Divalproex, Lithium, or Placebo

Bowden

Collins

McElroy

et al. 2005

Neuropsychopharmacol

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Euphoric and mixed (dysphoric) manic symptoms have different response patterns to divalproex and lithium in acute mania treatment, but have not been studied in relationship to maintenance treatment outcomes. We examined the impact of initial euphoric or dysphoric manic symptomatology on maintenance outcome. Randomized maintenance treatment with divalproex, lithium, or placebo was provided for 372 bipolar I patients, who met improvement criteria during open phase treatment for an index manic episode. The current analysis grouped patients according to the index manic episode subtype (euphoric or dysphoric), and evaluated the impact on maintenance treatment outcome. The rate of early discontinuation due to intolerance during maintenance treatment was higher for initially dysphoric patients (N ¼ 249) than euphoric patients (N ¼ 123; 15.7 vs 7.3%, respectively; p ¼ 0.032). Both lithium (23.2%) and divalproex (17.1%) were associated with more premature discontinuations due to intolerance than placebo (4.8%; p ¼ 0.003 and 0.02, respectively) in the initially dysphoric patients. Among initially euphoric patients, treatment with lithium was associated with significantly more premature discontinuations due to intolerance compared to placebo (18.2 vs 0%; p ¼ 0.03), and divalproex was significantly (p ¼ 0.05) more effective than lithium, but not placebo in delaying time to a depressive episode. Initial euphoric mania appeared to predispose to better outcomes on indices of depression and overall function with divalproex maintenance than with either placebo or lithium. Dysphoric mania appeared to predispose patients to more side effects when treated with either divalproex or lithium during maintenance therapy.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Relationship of Mania Symptomatology to Maintenance Treatment Response with Divalproex, Lithium, or Placebo

Bowden

Collins

McElroy

et al. 2005

Neuropsychopharmacol

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“…Some studies, for example, those conducted by Bowden et al (2003), Calabrese et al (2000Calabrese et al ( , 2003Calabrese et al ( , 2005, Keck et al (2007), Suppes et al (2009, 2005, 2006 and Vieta et al (2008 b) incorporated a stabilization period into the study design after which non-responsive patients or those not considered clinically stable did not participate further. This could be viewed as artificial selection of the most responsive patients, which would limit the comparability between studies.…”

Section: Discussionmentioning

confidence: 99%

“…For example, some studies defined relapse as initiation of treatment at the discretion of the treating physician (e.g. Bowden et al 2003 ;Calabrese et al 2000Calabrese et al , 2003, some studies included hospitalization in their criteria for relapse (e.g. Bowden et al 2000b ;Greil et al 1997 ;Keck et al 2007), and others defined relapse according to changes in scales such as the Hamilton Rating Scale for Depression (HAMD), Young Mania Rating Scale (YMRS), Mania Rating Scale (MRS), and Montgomery-Å sberg Depression Rating Scale (MADRS) (e.g.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials

Vieta

Günther²,

Locklear

et al. 2011

Int. J. Neuropsychopharm.

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The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of o6 months' duration with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combination treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of relapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical antipsychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents.

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“…19,20 Since the design for these two studies is identical, with the exception of the pole of the most recent episode (recently manic/hypomanic 19 vs depressed 20 ), the results of these two studies were combined and the data reanalyzed. 13 In this analysis, lamotrigine effectively prolonged the time to intervention for both manias and depressions independently compared to placebo (P = 0.034 and 0.009, respectively).…”

Section: Recently Validated Treatment Options In Bipolar Disordermentioning

confidence: 99%

Treatment-resistant bipolar disorder

2006

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Despite the remarkable increase in medications validated as effective in bipolar disorder, treatment is still plagued by inadequate response in acute manic or depressive episodes or in long-term preventive maintenance treatment. Established first-line treatments include lithium, valproate and second-generation antipsychotics (SGAs) in acute mania, and lithium and valproate as maintenance treatments. Recently validated treatments include extended release carbamazapine for acute mania and lamotrigine, olanzapine and aripiprazole as maintenance treatments. For treatment-resistant mania and as maintenance treatments, a number of newer anticonvulsants, and one older one, phenytoin, have shown some promise as effective. However, not all anticonvulsants are effective and each agent needs to be evaluated individually. Combining multiple agents is the most commonly used clinical strategy for treatment resistant bipolar patients despite a relative lack of data supporting its use, except for acute mania (for which lithium or valproate plus an SGA is optimal treatment). Other approaches that may be effective for treatment-resistant patients include high-dose thyroid augmentation, clozapine, calcium channel blockers and electroconvulsive therapy (ECT). Adjunctive psychotherapies show convincing efficacy using a variety of different techniques, most of which include substantial attention to education and enhancing coping strategies. Only recently, bipolar depression has become a topic of serious inquiry with the dominant controversy focusing on the place of antidepressants in the treatment of bipolar depression. Other than mood stabilizers alone or the combination of mood stabilizers and antidepressants, most of the approaches for treatment-resistant bipolar depression are relatively similar to those used in unipolar depression, with the possible exception of a more prominent place for SGAs, prescribed either alone or in combination with antidepressants. Future work in the area needs to explore the treatments commonly used by clinicians with inadequate research support, such as combination therapy and the use of antidepressants as both acute and adjunctive maintenance treatments for bipolar disorder. With the first report of lithium's efficacy in 1949 by Cade, bipolar disorder has the longest record of treatment efficacy among the major Axis I disorders. Furthermore, after more than half a century of clinical research, multiple agents from many different pharmacological classes have shown at least some efficacy, while many other agents (albeit without a consistent database demonstrating their utility) are prescribed regularly by clinicians. Yet, despite this plethora of choices, treatment of bipolar disorder remains suboptimal from the points of view of clinicians and patients alike. Whether measured by recovery time from manic or depressive episodes or preventive efficacy of maintenance treatments, bipolar disorder is characterized by sluggish responses, inadequate responses, poor compliance and recurrences in controlled cli...

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A Placebo-Controlled 18-Month Trial of Lamotrigine and Lithium Maintenance Treatment in Recently Manic or Hypomanic Patients With Bipolar I Disorder

Cited by 616 publications

References 52 publications

Relationship of Mania Symptomatology to Maintenance Treatment Response with Divalproex, Lithium, or Placebo

Relationship of Mania Symptomatology to Maintenance Treatment Response with Divalproex, Lithium, or Placebo

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials

Treatment-resistant bipolar disorder

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