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A long-term bipolar treatment can be in the form of a Mood-Stabilizer Monotherapy or a Mood-Stabilizer Combination Therapy. Below, we will review these therapies.
In Jane Pauley's new book, Skywriting: A Life Out of the Blue, she writes openly about the life-changing experience of Bipolar disorder. She was eventually hospitalized in the spring of 2001 with the diagnosis of manic depression. With proper treatment, she is now free of the uncontrollable mood swings.
Placebo-controlled maintenance studies of lithium conducted in the late 1960s and early 1970s found that lithium reduced the risk of mood episode relapse fourfold compared with placebo at 6 months and 1 year.[Note 1] Lithium was a bipolar treatment comparable to olanzapine in preventing relapse into bipolar depression in a recently reported 1-year maintenance trial, but olanzapine was superior to lithium in preventing relapse into a manic episode and need for hospitalization.[Note 2] Olanzapine was a bipolar treatment superior to placebo in prevention of relapse into both manic and depressive episodes in another recently reported randomized, controlled maintenance study.[Note 3]
Two studies examined the efficacy of divalproex in the maintenance of a bipolar treatment. [Notes 4,5] In the only placebo-controlled trial, neither divalproex nor lithium were superior to placebo in time to relapse into any mood episode by 1 year.[Note 5] However, in a post hoc analysis, patients who received divalproex during an open-label stabilization phase prior to randomization, and who were then randomized to divalproex or placebo, demonstrated significantly lower relapse rates in the divalproex group. In the second study, patients who responded to divalproex or olanzapine in a 3-week acute bipolar mania trial were followed for an additional 44 weeks to examine maintenance of efficacy.[Note 5] At the end of the 47-week study, there were no significant differences between the 2 agents in manic or depressive symptom reduction, although there was a trend for superior efficacy in depressive symptom improvement in the olanzapine group.
Two large, placebo-controlled, 18-month maintenance trials compared the efficacy of lamotrigine (200-400 mg/day) with lithium following stabilization after either a manic or depressive episode.[6,7] The results of these 2 studies on bipolar treatment were remarkably consistent: lamotrigine but not lithium was superior to placebo in time to relapse into a depressive episode, whereas lithium but not lamotrigine was superior to placebo in time to relapse into a manic episode. One implication of these findings is that the combination of lithium and lamotrigine might be a bipolar treatment especially effective in preventing relapse into both manic and depressive episodes, although this has not yet been tested in a randomized, controlled trial. The efficacy of lamotrigine was also examined in the relapse prevention of patients with bipolar I and II disorders with rapid cycling.[Note 8] In this 6-month trial, Calabrese and colleagues did not find significant differences in efficacy in relapse prevention between lamotrigine and placebo. However, in a post hoc analysis, there was a trend for superior efficacy for lamotrigine in the bipolar treatment II group of patients.
The majority of patients with a level 1 disorder are given a bipolar treatment with at least 2 medications in maintenance treatment. Despite this commonplace and clinically necessary practice, there are only 2 randomized, controlled trials that have assessed the efficacy of combination compared with mood-stabilizer monotherapy treatment.[Notes 9,10] Solomon and colleagues[Note 9] compared the efficacy of valproate vs placebo added to lithium in a 1-year pilot study. Patients receiving the combination experienced significantly lower relapse rates compared with patients receiving lithium and placebo. Not unexpectedly, the combination therapy group reported twice the side effect rate.
In the second study, Tohen and colleagues [Note 10] randomized patients who responded to the bipolar treatment combining the olanzapine with lithium or divalproex for acute mania to remain on the combination or revert to monotherapy with lithium or divalproex. They then followed patients for 18 months. As in the study by Solomon and colleagues,[Note 9] the combination therapy group displayed significantly lower relapse rates compared with the monotherapy group. However, the advantage of a combination therapy as a bipolar treatment was primarily in the prevention of manic relapse (combination therapy, 15% vs monotherapy, 35%). There was no significant difference in efficacy between the 2 groups in time to depressive relapse, although, again, a trend favored the combination therapy group.
Learn more about long-term Bipolar Treatment
Notes to this article on Bipolar Treatment
1. Keck PE Jr, Welge JA, Strakowski SM, et al. Placebo effect in randomized, controlled maintenance studies of bipolar disorder. Biol Psychiatry. 2000;47:748-755. Abstract
2. Tohen M, Marneros A, Bowden CL, et al. Olanzapine versus lithium in relapse prevention in bipolar disorder. Program and abstracts of the American Psychiatric Association 156th Annual Meeting; May 17-22, 2003; San Francisco, California. Abstract NR 509
3. Tohen M, Bowden CL, Calabrese JR, et al. Olanzapine versus placebo for relapse prevention in bipolar disorder. Program and abstracts of the American Psychiatric Association 156th Annual Meeting; May 17-22, 2003; San Francisco, California. Abstract NR 197
4. Bowden CL, Calabrese JR, McElroy SL, et al. Efficacy of divalproex versus lithium and placebo in maintenance treatment of bipolar disorder. Arch Gen Psychiatry. 2000;57:481-489. Abstract
5. Tohen M, Ketter TA, Zarate CA, et al. Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study. Am J Psychiatry. 2003;160:1263-1271. Abstract
6. Bowden CL, Calabrese JR, Sachs GS, et al. A placebo-controlled 18-month study of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry. 2003; In press.
7. Bowden CL, Calabrese JR, Sachs GS, et al. A placebo-controlled 18-month study of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. Arch Gen Psychiatry. 2003; In press.
8. Calabrese JR, Bowden CL, Sachs GS, et al. A double-blind placebo-controlled prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. J Clin Psychiatry. 2000;61:841-850. Abstract
9. Solomon DA, Ryan CE, Keitner GI, et al. A pilot study of lithium carbonate plus divalproex sodium for the continuation and maintenance treatment of patients with bipolar I disorder. J Clin Psychiatry. 1997;58:95-99. Abstract
10. Tohen M, Chengappa KNR, Suppes T, et al. Efficacy of olanzapine in combination with lithium or valproate in prevention of recurrence in bipolar disorder: an 18-month study. Program and abstracts of the US Psychiatric and Mental Health Congress; November 15-18, 2001; Boston, Massachusetts.
Source : Medscape
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