Skip to main content
×
×
Home

Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials

  • John R. Geddes (a1), Joseph R. Calabrese (a2) and Guy M. Goodwin (a1)
Abstract
Background

There is uncertainty about the efficacy of lamotrigine in bipolar depressive episodes.

Aims

To synthesise the evidence for the efficacy of lamotrigine in bipolar depressive episodes.

Method

Systematic review and meta-analysis of individual patient data from randomised controlled trials comparing lamotrigine with placebo.

Results

Individual data from 1072 participants from five randomised controlled trials were obtained. More individuals treated with lamotrigine than placebo responded to treatment on both the Hamilton Rating Scale for Depression (HRSD) (relative risk (RR)=1.27, 95% CI 1.09–1.47, P=0.002) and Montgomery– åsberg Depression Rating Scale (MADRS) (RR=1.22, 95% CI 1.06–1.41, P=0.005). There was an interaction (P=0.04) by baseline severity of depression: lamotrigine was superior to placebo in people with HRSD score >24 (RR=1.47, 95% CI 1.16–1.87, P=0.001) but not in people with HRSD score 24 (RR=1.07, 95% CI 0.90–1.27, P=0.445).

Conclusions

There is consistent evidence that lamotrigine has a beneficial effect on depressive symptoms in the depressed phase of bipolar disorder. The overall pool effect was modest, although the advantage over placebo was larger in more severely depressed participants.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials
      Available formats
      ×
Copyright
Corresponding author
John R. Geddes, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK. Email: john.geddes@psych.ox.ac.uk
Footnotes
Hide All

Declaration of interest

J.R.C. is a member of the psychiatry advisory board for GlaxoSmithKline. J.R.G. is Chief Investigator and G.M.G. is a co-investigator on the independent Medical Research Council-funded trial: Comparative Evaluation of QUEtiapine-Lamotrigine combination v. quetiapine monotherapy (and folic acid v. placebo) in people with bipolar depression (CEQUEL).

Footnotes
References
Hide All
1 Murray, CJ, Lopez, AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 349: 1436–42.
2 Judd, LL, Akiskal, HS, Schettler, PJ, Coryell, W, Endicott, J, Maser, JD, et al. A prospective investigation of the natural history of the long-term weekly 8 Lamotrigine for treatment of bipolar depression symptomatic status of bipolar II disorder. Arch Gen Psychiatry 2003; 60: 261–9.
3 Judd, LL, Akiskal, HS, Schettler, PJ, Endicott, J, Maser, J, Solomon, DA, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002; 59: 530–7.
4 Kupfer, DJ, Frank, E, Grochocinski, VJ, Luther, JF, Houck, PR, Swartz, NA, et al. Stabilization in the treatment of mania, depression and mixed states. Acta Neuropsychiatrica 2000; 12: 110–4.
5 Gijsman, HJ, Geddes, JR, Rendell, JM, Nolen, WA, Goodwin, GM. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004; 161: 1537–47.
6 Sachs, GS, Nierenberg, AA, Calabrese, JR, Marangell, LB, Wisniewski, SR, Gyulai, L, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007; 356: 1711–22.
7 American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159 (suppl 4): 150.
8 Marangell, LB, Martinez, JM, Ketter, TA, Bowden, CL, Goldberg, JF, Calabrese, JR, et al; for the STEP-BD Investigators. Lamotrigine treatment of bipolar disorder: data from the first 500 patients in STEP-BD. Bipolar Disord 2004; 6: 139–43.
9 Calabrese, JR, Huffman, RF, White, RL, Edwards, S, Thompson, TR, Ascher, JA, et al. Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials. Bipolar Disord 2008; 10: 323–33.
10 Stewart, LA, Clarke, MJ. Practical methodology of meta-analyses (overviews) using updated individual patient data. Cochrane Working Group. Stat Med 1995; 14: 2057–79.
11 Clarke, MJ, Stewart, LA. Obtaining data from randomised controlled trials: how much do we need for reliable and informative meta-analyses? BMJ 1994; 309: 1007–10.
12 First, MB, Gibbon, M, Spitzer, RL, Williams, JBW. Structured Clinical Interview for DSM–IV Axis I Disorders Research Version (SCID–I). Biometric Research, New York State Psychiatric Institute, 1996.
13 Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 5662.
14 Montgomery, SA, Åsberg, M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382–9.
15 National Collaborating Centre for Mental Health. Depression: Management of Depression in Primary and Secondary Care. National Institute for Health and Clinical Excellence, 2004 (http://www.nice.org.uk/page.aspx?o=235213).
16 Thompson, SG, Higgins, JPT. How should meta-regression analyses be undertaken and interpreted? Stat Med 2002; 21: 1559–73.
17 Sharp, SJ. Meta-analysis regression. Stata Technic Bull 1998; 42: 1622.
18 Frye, MA, Ketter, TA, Kimbrell, TA, Dunn, RT, Speer, AM, Osuch, EA, et al. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol 2000; 20: 607–14.
19 van der Loos, M, Nolen, WA, Vieta, E. Lamotrigine as add-on to lithium in bipolar disorder. Bipolar Disord 2007; 9 (suppl 1): 107.
20 Montaner, JS, O'Shaughnessy, MV, Schechter, MT. Industry-sponsored clinical research: a double-edged sword. Lancet 2002; 358: 1893–5.
21 Charney, DS, Nemeroff, CB, Lewis, L, Laden, SK, Gorman, JM, Laska, EM, et al. National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders. Arch Gen Psychiatry 2002; 59: 262–70.
22 Geddes, JR, Cipriani, A. Selective serotonin reuptake inhibitors. BMJ 2004; 329: 809–10.
23 Calabrese, JR, Rapport, DJ, Shelton, MD, Kimmel, SE. Evolving methodologies in bipolar disorder maintenance research. Br J Psychiatry 2001; 178 (suppl 41): s15763.
24 Calabrese, JR. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005; 162: 1351–60.
25 Thase, ME, Macfadden, W, Weisler, RH, Chang, W, Paulsson, B, Khan, A, et al; for the BOLDER II Study Group. Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol 2006; 26: 600–9.
26 Chalmers, TC, Lau, J. Meta-analytic stimulus for changes in clinical trials. Stat Methods Med Res 1993; 2: 161–72.
27 Easterbrook, PJ, Berlin, JA, Gopalan, R, Matthews, DR. Publication bias in clinical research. Lancet 1991; 337: 867–72.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials

  • John R. Geddes (a1), Joseph R. Calabrese (a2) and Guy M. Goodwin (a1)
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *