BALANCE: a large simple trial of maintenance treatment for bipolar disorder.
Year: 2002
Type: article
Abstract: Despite recent developments in the treatment of the acute manic and depressive phases of bipolar disorder, the frequently recurrent nature of the disorder means that ongoing treatment for long-term relapse prevention is often needed. Drugs that are effective in the acute phase are commonly continued in remission to prevent or delay another relapse, but it is unclear which of these drugs is most effective or whether a combination of individually less than ideal drugs may be better than any monotherapy. Lithium effectively halves the relapse rate but it is not effective for all patients and it has a narrow therapeutic index (1). This often leads to low levels of treatment adherence and acute discontinuation may result in new episodes of illness (2). Lower plasma levels improve tolerability and adherence but probably at the cost of optimum efficacy (3). Alternative drug treatments, such as carbamazepine and valproate, have emerged, prompted by the analogy between recurrence in bipolar disorder and the recurrence of seizures in epilepsy (4). Valproate seems to be effective and well tolerated in acute mania (5), although the evidence in maintenance is equivocal, and it is unclear if lithium or valproate is superior (6).
Combinations of drugs, particularly lithium plus valproate, are both recommended and frequently used in clinical practice for mood stabilization, especially for patients who have not responded to monotherapy (7,8). Synergy between lithium and valproate may occur because their putative mechanisms of action converge on signal transduction pathways critical for neurotransmitter function and neuroprotection (9). Clinically, the combination of moderate doses of lithium plus valproate may be more effective than either drug alone.
In the US, use of valproate (both alone and in combination with lithium) for the acute and maintenance treatment of bipolar disorder has increased dramatically since the early 1990s - prescriptions for valproate in bipolar disorder have now overtaken those for lithium (8,10,11). By contrast, in the UK and Europe lithium is still the most frequently used mood stabilizer (12). These variations in clinical practice reflect the absence of evidence, rather than failure to implement it, and highlight the current uncertainty about the appropriate places of lithium and valproate.
Source: Europe PMC (PubMed Central)
Institutions: Warneford Hospital, University of Oxford
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1583228078