Comparative Prophylactic Efficacy of Lithium, Carbamazepine, and the Combination in Bipolar Disorder

Denicoff, Kirk D.; Smith-Jackson, E E; Disney, Elizabeth R.; Ali, Omar; Leverich, Gabriele S.; Post, Robert M.

doi:10.4088/jcp.v58n1102

Cited by 284 publications

(215 citation statements)

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“…54 Using Clinical Global Improvement (CGI) scores, the three treatments did not differ significantly, although a good treatment response was seen in 33% of patients on lithium, 31% on carbamazepine and 55% on the combination. Of note, the combination was significantly more effective in rapid cycling patients who did poorly on both solo agents.…”

Section: Treatment-resistant Bipolar Disorder M Gitlinmentioning

confidence: 98%

“…Over the last decade, only three controlled trials of combination maintenance treatment of bipolar disorder have been published. [52][53][54] In the only large-scale controlled study, olanzapine plus lithium or valproate was compared to lithium or valproate alone over 18 months in 99 patients who had responded to the combination for acute mania. 52 Dropout rates were very high; 69% of those on combination and 90% of those on lithium or valproate alone discontinued the study, with the majority of dropouts occurring for reasons other than relapse.…”

Section: Combination Treatmentsmentioning

confidence: 99%

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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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Section: Treatment-resistant Bipolar Disorder M Gitlinmentioning

confidence: 98%

Section: Combination Treatmentsmentioning

confidence: 99%

Treatment-resistant bipolar disorder

2006

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“…Loss of respon-sion and those who have greater decrements in T 4 and free T 4 during treatment with the drug (Roy-Byrne et al 1984;Post et al 1986). In the study of Denicoff et al (1997), the combination of lithium and carbamazepine proved much more effective for rapid-cycling patients than monotherapy with either agent. Ketter et al (1996) found that patients with global hypermetabolism, and particularly in the region of the left insula, seem more responsive to carbamazepine as compared with depressed patients with a more classical picture of frontal lobe or left insula hypometabolism.…”

Section: Carbamazepinementioning

confidence: 99%

“…Some bipolar patient subtypes are particularly prone to lithium nonresponsiveness; among these are patients with dysphoric mania and rapid cycling; a negative family history for bipolar illness in first-degree relatives; the episode sequence pattern of depression-mania-well interval (i.e., the D-M-I pattern as opposed to the M-D-I pattern); more than three episodes prior to the initiation of prophylaxis (Sarantidis and Waters 1981;O'Connell et al 1991;Denicoff et al 1997); a history of co-morbid substance abuse; and those patients with a history of head trauma or other such medical co-morbidities as multiple sclerosis, etc.…”

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confidence: 99%

“…However, there is preliminary evidence that, as in lithium treatment, rapid-cycling patients do not respond as well to carbamazepine monotherapy as do nonrapid-cycling patients (Okuma 1993;Denicoff et al 1997); whereas, those with a negative family history for bipolar illness in first-degree relatives may be included among those responsive to carbamazepine (Post et al 1987), as are those with more severe and discrete episodes of depresnative treatments described below; or more mild, and just require greater neuroleptic augmentation.…”

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confidence: 99%

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