Article

Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder

Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106, USA.
American Journal of Psychiatry (Impact Factor: 13.56). 08/1999; 156(7):1019-23.
Source: PubMed

ABSTRACT New mood stabilizers are needed that possess efficacy for all phases of bipolar disorder. This study was designed to provide preliminary evidence for the safety and efficacy of a new anticonvulsant, lamotrigine, in adult patients with bipolar disorder who had been inadequately responsive to or intolerant of prior pharmacotherapy.
A 48-week, open-label, prospective trial was conducted in 75 patients with bipolar I or bipolar II disorder. Lamotrigine was used as adjunctive therapy (N = 60) or monotherapy (N = 15) in patients presenting in depressed, hypomanic, manic, or mixed states.
Of the 40 depressed patients included in the efficacy analysis, 48% exhibited a marked response and 20% a moderate response as measured by reductions in 17-item Hamilton Depression Rating Scale scores. Of the 31 with a hypomanic, manic, or mixed state, 81% displayed a marked response and 3% a moderate response on the Mania Rating Scale. From baseline to endpoint, the depressed patients exhibited a 42% decrease in Hamilton depression scale scores, and the patients presenting with hypomania, mania, or a mixed state exhibited a 74% decrease in Mania Rating Scale scores. The most common drug-related adverse events were dizziness, tremor, somnolence, headache, nausea, and rash. Rash was the most common adverse event resulting in drug discontinuation (9% of patients); one patient developed a serious rash and required hospitalization.
These open-label data provide preliminary evidence that lamotrigine may be an effective treatment option for patients with refractory bipolar disorder; however, potential benefits must be weighed against potential side effects, including rash.

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    • "Epi RCTs 14–77 347 With VPA 28 48/69 16w 96 mg/d 117 20 With CBZ 31 61/68 16w 347 mg/d 129 9 With PHT 33 45/50 16w 359 mg/d 95 0 Farrell et al. (1996) [34] Canada Epi Open-label Children 56 With VPA 24 M 21 4 Without VPA 24 M 35 1 Calabrease et al. (1999) [35] USA Bipolar Open-label Adults 75 With VPA 48 W 15 1 LTG alone 48 W 60 6 Beghi et al. (2003) [36] "
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    • "the number needed to treat is relatively high ( Popovic et al . , 2011 ) . Nonetheless , the effectiveness of lamotrigine in acute treatment is vigorously debated . On one hand , some studies have shown the usefulness of this agent in acute treatment of bipolar depression , even in refractory and in rapid cycling patients ( Bowden et al . , 1999 ; Calabrese et al . , 1999a , 1999b ; Frye et al . , 2000 ; Vieta et al . , 2010a ) . On the other hand , benefits compared to placebo have been shown only in one of the five clinical - trials sponsored by the industry when reported sepa - rately ( Calabrese et al . , 2008 ) and in an adjunctive trial ( van der Loos et al . , 2009 ) . Nevertheless , an independent"
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    • "Building on anecdotal reports of lamotrigine's psychotropic properties in epileptic and bipolar patients, Calabrese et al (Calabrese, Bowden, McElroy, et al 1999) conducted the fi rst study to investigate its spectrum of therapeutic activity in bipolar disorder. This 48-week, open-label, prospective trial used lamotrigine as monotherapy or adjunctive pharmacotherapy in 75 patients with refractory bipolar I or II disorder, who variously presented in depressed, hypomanic, manic or mixed phases of the illness. "
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