This systematic review indicates that lithium is more effective than placebo as a treatment for acute mania but increases the risk for somnolence and tremor .
Limited evidence suggests little or no difference between lithium and other mood stabilisers ( valproate , carbamazepine ) or antipsychotics ( risperidone , quetiapine , haloperidol ) .
Olanzapine may be an exception , as it is probably slightly more effective than lithium .
There is uncertain evidence that risperidone may also be more effective than lithium .
Lithium is probably more effective at treating acute mania than topiramate .
When compared to placebo , lithium was more likely to cause adverse events .
More , rigorously design ed , large-scale studies are needed to definitively conclude if lithium is superior to other interventions in treating acute mania
BACKGROUND Bipolar disorder is a common condition associated with high morbidity ; developing efficacious , safe treatments is therefore essential .
Lithium is an effective maintenance treatment for bipolar disorder .
It acts as mood stabiliser and reduces the risk of suicide .
However , evidence assessing the efficacy of lithium in the treatment of acute mania is less robust .
Current evidence -based guidelines cite multiple anti-dopaminergic and mood-stabilising agents as initial treatments : more definite evidence is needed to decide if lithium should be the first-line therapy .
OBJECTIVES 1 .
To assess the effects of lithium in comparison with placebo or other active treatment in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.2 .
To review the acceptability and tolerability of treatment with lithium in comparison with placebo or other active treatments in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder .
Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial.
BACKGROUND Lithium carbonate and valproate semisodium are both recommended as monotherapy for prevention of relapse in bipolar disorder , but are not individually fully effective in many patients . If combination therapy with both agents is better than monotherapy , many relapses and consequent disability could be avoided . We aim ed to establish whether lithium plus valproate was better than monotherapy with either drug alone for relapse prevention in bipolar I disorder . METHODS 330 patients aged 16 years and older with bipolar I disorder from 41 sites in the UK , France , USA , and Italy were r and omly allocated to open-label lithium monotherapy ( plasma concentration 0.4 - 1.0 mmol/L , n=110 ) , valproate monotherapy ( 750 - 1250 mg , n=110 ) , or both agents in combination ( n=110 ) , after an active run-in of 4 - 8 weeks on the combination . R and omisation was by computer program , and investigators and participants were informed of treatment allocation . All outcome events were considered by the trial management team , who were masked to treatment assignment . Participants were followed up for up to 24 months . The primary outcome was initiation of new intervention for an emergent mood episode , which was compared between groups by Cox regression . Analysis was by intention to treat . This study is registered , number IS RCT N 55261332 . FINDINGS 59 ( 54 % ) of 110 people in the combination therapy group , 65 ( 59 % ) of 110 in the lithium group , and 76 ( 69 % ) of 110 in the valproate group had a primary outcome event during follow-up . Hazard ratios for the primary outcome were 0.59 ( 95 % CI 0.42 - 0.83 , p=0.0023 ) for combination therapy versus valproate , 0.82 ( 0.58 - 1.17 , p=0.27 ) for combination therapy versus lithium , and 0.71 ( 0.51 - 1.00 , p=0.0472 ) for lithium versus valproate . 16 participants had serious adverse events after r and omisation : seven receiving valproate monotherapy ( three deaths ) ; five lithium monotherapy ( two deaths ) ; and four combination therapy ( one death ) . INTERPRETATION For people with bipolar I disorder , for whom long-term therapy is clinical ly indicated , both combination therapy with lithium plus valproate and lithium monotherapy are more likely to prevent relapse than is valproate monotherapy . This benefit seems to be irrespective of baseline severity of illness and is maintained for up to 2 years . BALANCE could neither reliably confirm nor refute a benefit of combination therapy compared with lithium monotherapy . FUNDING Stanley Medical Research Institute ; Sanofi-Aventis
This systematic review indicates that lithium is more effective than placebo as a treatment for acute mania but increases the risk for somnolence and tremor .
Limited evidence suggests little or no difference between lithium and other mood stabilisers ( valproate , carbamazepine ) or antipsychotics ( risperidone , quetiapine , haloperidol ) .
Olanzapine may be an exception , as it is probably slightly more effective than lithium .
There is uncertain evidence that risperidone may also be more effective than lithium .
Lithium is probably more effective at treating acute mania than topiramate .
When compared to placebo , lithium was more likely to cause adverse events .
More , rigorously design ed , large-scale studies are needed to definitively conclude if lithium is superior to other interventions in treating acute mania
BACKGROUND Bipolar disorder is a common condition associated with high morbidity ; developing efficacious , safe treatments is therefore essential .
Lithium is an effective maintenance treatment for bipolar disorder .
It acts as mood stabiliser and reduces the risk of suicide .
However , evidence assessing the efficacy of lithium in the treatment of acute mania is less robust .
Current evidence -based guidelines cite multiple anti-dopaminergic and mood-stabilising agents as initial treatments : more definite evidence is needed to decide if lithium should be the first-line therapy .
OBJECTIVES 1 .
To assess the effects of lithium in comparison with placebo or other active treatment in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.2 .
To review the acceptability and tolerability of treatment with lithium in comparison with placebo or other active treatments in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder .