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Goodwin GM, Bowden CL, Calabrese JR, Grunze H, Kasper S, White
R, Greene P, Leadbetter R.
Department of Psychiatry, University of Oxford,
Warneford Hospital, Oxford OX3 7JX, England, UK.
A pooled analysis
of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance
in bipolar I disorder.
J Clin Psychiatry. 2004 Mar;65(3):432-41.
BACKGROUND:
Two clinical trials, prospectively designed for combined analysis, compared placebo,
lithium, and lamotrigine for treatment of bipolar I disorder in recently depressed
or manic patients. METHOD: 1315 bipolar I patients (DSM-IV) enrolled in the initial
open-label phase, and 638 were stabilized and randomly assigned to 18 months of
double-blind monotherapy with lamotrigine (N = 280; 50-400 mg/day fixed dose or
100-400 mg/day flexible dose), lithium (N = 167; serum level of 0.8-1.1 mEq/L),
or placebo (N = 191). The primary endpoint was time from randomization to intervention
for a mood episode. Data were gathered from August 1997 to August 2001. RESULTS:
Lamotrigine and lithium were superior to placebo for time to intervention for
any mood episode (median survival: placebo, 86 days [95% CI = 58 to 121]; lithium,
184 days [95% CI = 119 to not calculable]; lamotrigine, 197 days [95% CI = 144
to 388]). Lamotrigine was superior to placebo for time to intervention for depression
(median survival: placebo, 270 days [95% CI = 138 to not calculable]; lithium,
median not calculable; lamotrigine, median not calculable). Lithium and lamotrigine
were superior to placebo for time to intervention for mania (median survival not
calculable for any group). Results of additional analyses adjusted for index mood
were similar; however, only lithium was superior to placebo for intervention for
mania. There was no evidence that either active treatment caused affective switch.
Adverse event analysis indicated more diarrhea (19% vs. 7%, p <.05) and tremor
(15% vs. 4%, p <.05) in lithium-treated patients compared with lamotrigine-treated
patients. CONCLUSIONS: Lamotrigine and lithium stabilized mood by delaying the
time to treatment for a mood episode. Lamotrigine was effective against depression
and mania, with more robust activity against depression. Lithium was effective
against mania.
[Abstract] Ichim
L, Berk M, Brook S.
Department of Psychiatry, University of the Witwatersrand
Medical School, Parktown, South Africa.
Lamotrigine compared with
lithium in mania: a double-blind randomized controlled trial.
Ann
Clin Psychiatry. 2000 Mar;12(1):5-10.
"BACKGROUND: Preliminary data from
case reports and small open trials suggest a role for lamotrigine in the treatment
of bipolar disorder, although controlled data for the manic phase are lacking.
METHOD: Thirty inpatients with a DSM-IV diagnosis of bipolar I disorder, currently
manic, were randomly allocated to receive either lamotrigine (25 mg once daily
for 1 week, 50 mg once daily for the second week, and 100 mg once daily for the
last 2 weeks) or lithium (400 mg twice daily) in a 4-week randomized, double-blind,
clinical trial. RESULTS: Both treatments improved symptoms of mania, as assessed
by the Mania Rating Scale, Brief Psychiatric Rating Scale, Clinical Global Impression
severity and improvement scales, and the Global Assessment of Functioning scale.
There were no significant differences between groups at any time point, suggesting
that the dose escalation required for lamotrigine did not adversely affect its
onset of action. Secondary outcome measures, including the use of lorazepam as
rescue medication, did not differ between the groups. No significant adverse events
were noted in either group. CONCLUSION: In this pilot study, lamotrigine was as
effective as lithium in the treatment of patients with bipolar disorder hospitalised
for acute mania." [Abstract] |
Bowden CL, Calabrese JR, Sachs G, Yatham LN, Asghar
SA, Hompland M, Montgomery P, Earl N, Smoot TM, DeVeaugh-Geiss J; Lamictal 606
Study Group.
Department of Psychiatry, University of Texas Health Science Center
at San Antonio, 78229, USA. bowdenc@uthscsa.edu
A placebo-controlled
18-month trial of lamotrigine and lithium maintenance treatment in recently manic
or hypomanic patients with bipolar I disorder.
Arch Gen
Psychiatry. 2003 Apr;60(4):392-400.
"BACKGROUND: Lamotrigine has been
shown to be an effective treatment for bipolar depression and rapid cycling in
placebo-controlled clinical trials. This double-blind, placebo-controlled study
was conducted to assess the efficacy and tolerability of lamotrigine and lithium
compared with placebo for the prevention of relapse or recurrence of mood episodes
in recently manic or hypomanic patients with bipolar I disorder. METHODS: After
an 8- to 16-week open-label phase during which treatment with lamotrigine was
initiated and other psychotropic drug regimens were discontinued, patients were
randomized to lamotrigine (100-400 mg daily), lithium (0.8-1.1 mEq/L), or placebo
as double-blind maintenance treatment for as long as 18 months. RESULTS: Of 349
patients who met screening criteria and entered the open-label phase, 175 met
stabilization criteria and were randomized to double-blind maintenance treatment
(lamotrigine, 59 patients; lithium, 46 patients; and placebo, 70 patients). Both
lamotrigine and lithium were superior to placebo at prolonging the time to intervention
for any mood episode (lamotrigine vs placebo, P =.02; lithium vs placebo, P =.006).
Lamotrigine was superior to placebo at prolonging the time to a depressive episode
(P =.02). Lithium was superior to placebo at prolonging the time to a manic, hypomanic,
or mixed episode (P =.006). The most common adverse event reported for lamotrigine
was headache. CONCLUSIONS: Both lamotrigine and lithium were superior to placebo
for the prevention of relapse or recurrence of mood episodes in patients with
bipolar I disorder who had recently experienced a manic or hypomanic episode.
The results indicate that lamotrigine is an effective, well-tolerated maintenance
treatment for bipolar disorder, particularly for prophylaxis of depression."
[Abstract] Calabrese
JR, Suppes T, Bowden CL, Sachs GS, Swann AC, McElroy SL, Kusumakar V, Ascher JA,
Earl NL, Greene PL, Monaghan ET.
University Hospitals of Cleveland, Case Western
Reserve University School of Medicine, Ohio, USA.
A double-blind,
placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar
disorder. Lamictal 614 Study Group.
J Clin Psychiatry. 2000
Nov;61(11):841-50.
"BACKGROUND: Patients with rapid-cycling bipolar disorder
are often treatment refractory. This study examined lamotrigine as maintenance
monotherapy for rapid-cycling bipolar disorder. METHOD: Lamotrigine was added
to patients' current psychotropic regimens and titrated to clinical effect during
an open-label treatment phase. Stabilized patients were tapered off other psychotropics
and randomly assigned to lamotrigine or placebo monotherapy for 6 months. Time
to additional pharmacotherapy for emerging symptoms was the primary outcome measure.
Secondary efficacy measures included survival in study (time to any premature
discontinuation), percentage of patients stable without relapse for 6 months,
and changes in the Global Assessment Scale and Clinical Global Impressions-Severity
scale. Safety was assessed from adverse event, physical examination, and laboratory
data. RESULTS: 324 patients with rapid-cycling bipolar disorder (DSM-IV criteria)
received open-label lamotrigine, and 182 patients were randomly assigned to the
double-blind maintenance phase. The difference between the treatment groups in
time to additional pharmacotherapy did not achieve statistical significance in
the overall efficacy population. However, survival in study was statistically
different between the treatment groups (p = .036). Analyses also indicated a 6-week
difference in median survival time favoring lamotrigine. Forty-one percent of
lamotrigine patients versus 26% of placebo patients (p = .03) were stable without
relapse for 6 months of monotherapy. Lamotrigine was well tolerated; there were
no treatment-related changes in laboratory parameters, vital signs, or body weight.
No serious rashes occurred. CONCLUSION: This was the largest and only prospective
placebo-controlled study of rapid-cycling bipolar disorder patients to date; results
indicate lamotrigine monotherapy is a useful treatment for some patients with
rapid-cycling bipolar disorder." [Abstract] Calabrese
JR, Bowden CL, Sachs GS, Ascher JA, Monaghan E, Rudd GD.
Case Western Reserve
University, Cleveland, Ohio, USA.
A double-blind placebo-controlled
study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal
602 Study Group.
J Clin Psychiatry. 1999 Feb;60(2):79-88.
"BACKGROUND:
More treatment options for bipolar depression are needed. Currently available
antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers
appear to be less effective in treating depression than mania. Preliminary data
suggest that lamotrigine, an established antiepileptic drug, may be effective
for both the depression and mania associated with bipolar disorder. This is the
first controlled multicenter study evaluating lamotrigine monotherapy in the treatment
of bipolar I depression. METHODS: Outpatients with bipolar I disorder experiencing
a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day)
or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the
Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression
Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions
scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly
visit. RESULTS: Lamotrigine 200 mg/day demonstrated significant antidepressant
efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared
with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day
also demonstrated efficacy compared with placebo on several measures. The proportions
of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine
200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events
and other safety results were similar across treatment groups, except for a higher
rate of headache in the lamotrigine groups. CONCLUSION: Lamotrigine monotherapy
is an effective and well-tolerated treatment for bipolar depression." [Abstract] Bowden
CL, Mitchell P, Suppes T.
Department of Psychiatry, University of Texas, Health
Science Center at San Antonio, 78284-7792, USA.
Lamotrigine in the
treatment of bipolar depression.
Eur Neuropsychopharmacol.
1999 Aug;9 Suppl 4:S113-7.
"Several case reports and open studies have
reported the efficacy of lamotrigine in bipolar depression. A randomised placebo-controlled
7-week study comparing two doses of lamotrigine with placebo in 195 patients with
moderate to severe bipolar depression has now been completed. Lamotrigine was
superior to placebo after 3 weeks as assessed by changes in the Montgomery-Asberg
Depression Rating Scale (MADRS). A response, defined as more than 50% improvement
on the MADRS occurred in 56 and 48% of the lamotrigine 200 and 50 mg/day groups,
respectively, compared with 29% for placebo (P<0.05). There was no evidence
that lamotrigine destabilised mood or precipitated mania. Tolerability was good
and there were no cases of serious rashes. Preliminary results from an ongoing
study also indicate that lamotrigine is more effective than gabapentin in bipolar
depression. In conclusion, lamotrigine is effective in alleviating bipolar depression,
without causing mood destabilisation. Slow dosage escalation yields good tolerability."
[Abstract] |
