Activity 3: Hypothesis Test for a Proportion Using the same data from Activity 2, we will now conduct hypothesis testing and see if our conclusions are the same as in Activity 2 using confidence intervals. We can use a z-test for a sample if it is a random sample from a population and if n (sample size) times p0 (calculated proportion) as well as n times (1 - p0 ) are both at least 10.
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Microsoft powerpoint - gsk002-307_poster 9_lginsberg_v.2.pptSafety and Efficacy of Lamotrigine for Adult Bipolar Disorder Patients
Lawrence D. Ginsberg, MD
Red Oak Psychiatry Associates, Houston, Texas
Figure 2. Patient Response and Relapse on Lamotrigine
Figure 4. After Lamotrigine Treatment CGI-I Scores
Were Mainly 1 and 2
Of the 587 subjects reviewed in this study, 72.2% were female, and the To assess the effectiveness and safety of lamotrigine in the treatment of mean age was 37.6 years (range 18-79 years). The final mean lamotrigine ± SD was 120.4±94.4 mg/day (Table 1).
Responders; no relapse
54.9% of subjects were diagnosed with bipolar I disorder, 28.3% with Responders; relapse
Chart reviews of 587 adult outpatients with DSM-IV bipolar disorder and bipolar II disorder, and 16.9% with bipolar disorder not otherwise specified treated with lamotrigine were conducted (mean age 37.6 ± 11.7 years; Nonresponders
72% female; 54.9% bipolar I, 28.3% bipolar II, 16.9% bipolar not otherwise specified). Charts of subjects who received lamotrigine in a private practice 352 subjects (59.9%) taking lamotrigine had marked-to-moderate Response status unknown**
improvement, with a CGI-I score of 1 observed in 20.6% of subjects and a setting (LDG, Red Oak Psychiatry Associates, Houston, TX) between October 1998 and May 2004 were reviewed. Treatment response was assessed with the Clinical Global Impression–Improvement (CGI-I) scale (1 = very marked 479 subjects (81.6%) responded to lamotrigine.
improvement, 2 = moderate improvement). Relapse was defined as a mood change that occurs 4 weeks after initiation of medication or the return of Of the responders, 52% did not relapse, and 29.3% relapsed. The mean time to relapse was 207.0±308.9 days (range 3-1582 days) (Figure 2).
Within each bipolar disorder type, almost al of patients’ CGI-S scores were Adult population N = 587
≥ 3 at treatment initiation (Figure 3). The majority of subjects with each Three hundred fifty-seven subjects (60.8%) taking lamotrigine had marked to Mean Days to Relapse: 207.0
bipolar subtype had CGI-I scores of 1 or 2 at titration completion (Figure 4). moderate improvement (CGI-I scores: 1, 21.1%; 2, 39.7%). Two hundred Lamotrigine response is defined as achieving a CGI-I ≤3. Relapse is defined by a change in CGI-I to ≥4 after an nineteen subjects (37.3%) relapsed during lamotrigine treatment (mean time BD = bipolar disorder; CGI-I = Clinical Global Impression of Improvement; NOS = not otherwise specified.
The most frequently reported treatment-emergent adverse events were observed lamotrigine response, or return of episode.
**Patient discontinued medication prior to fol ow-up.
to relapse = 207 days). The final mean lamotrigine dose was 120.4±94.3 mg/d. non-serious rash (12.8%) and headache (2.9%) (Table 2).
**Response unknown includes: lost to fol ow-up, patient discontinued medication prior to assessment.
Rash (12.8%) and headache (2.9%) were the most frequently reported side effects.
Lamotrigine appears effective in the treatment of bipolar disorder and was
Table 1. Study Population
Table 2. Treatment-Emergent Adverse Events on Lamotrigine
Gender (% female)
This large, retrospective study demonstrates that lamotrigine appears INTRODUCTION
Mean age (y ± SD)
effective in the treatment of bipolar disorder in adults.
Age range (y)
Lamotrigine was effective across bipolar disorder subtypes.
Lamotrigine is indicated for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients who received Final* 120.4±94.4
Mean dosages of lamotrigine were similar to those seen in previous trials.
standard therapy to treat an acute mood episode.1 *Mean lamotrigine dose ± SD (mg/d).
Lamotrigine was wel tolerated, with a low incidence of side effects and no In large, controlled, double-blind trials, lamotrigine has demonstrated antidepressant efficacy2 and has been shown to prolong the time to relapse Based on these data, placebo-controlled studies are warranted.
to a depressive episode3-5 in patients with bipolar I disorder. In patients with bipolar II disorder, lamotrigine has been shown to reduce the risk of relapse over 6 months of monotherapy6 and improve depressive symptoms.7 The objective of this study was to assess the effectiveness and safety of Figure 1. Distribution of Bipolar Subtypes
Figure 3. Across BD Subtypes, CGI-S Scores Were
lamotrigine in the treatment of bipolar disorder.
Bipolar NOS (n=99)
1. Lamictal [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2004.
2. Calabrese JR, Bowden CL, Sachs GS, Ascher JA, Monaghan E, Rudd GD. A double-blind placebo- controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry. 1999;60:79-88.
3. Bowden CL, Calabrese JR, Sachs G, et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch This is a retrospective chart review of 587 adult outpatients with DSM-IV Gen Psychiatry. 2003;60:392-400.
bipolar disorder who received treatment with lamotrigine.
4. Calabrese JR, Bowden CL, Sachs G, et al. A placebo-controlled 18-month trial of lamotrigine and Charts of subjects who received lamotrigine in a private practice setting lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry. (LDG, Red Oak Psychiatry Associates, Houston, TX) between October 1998 5. Goodwin GM, Bowden CL, Calabrese JR, et al. A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry. 2004;65:432-441.
Charts were reviewed for relapse, adverse events, scores on the Clinical 6. Calabrese JR, Suppes T, Bowden CL, et al. A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group. J Clin Psychiatry. Global Impression-Severity (CGI-S) and Clinical Global Impression- Improvement (CGI-I) scales, and lamotrigine dosages.
Bipolar I (n=322)
7. Calabrese JR, Bowden CL, McElroy SL, et al. Spectrum of activity of lamotrigine in treatment- refractory bipolar disorder. Am J Psychiatry. 1999;156:1019-1023.
Treatment response was assessed with the CGI-I scale (1 = marked improvement, 2 = moderate improvement). Subjects were considered to have responded to therapy if they achieved a CGI-I score of ≤3. Subjects Bipolar II (n=166)
were considered to have relapsed if they experienced a mood change BD = bipolar disorder; CGI-S = Clinical Global Impression of Severity; NOS = not otherwise specified.
4 weeks after initiation of medication or a return of symptoms from the original episode.
Funding provided by GlaxoSmithKline
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