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Lamotrigine in the Treatment of Unipolar Depression with and Without Comorbidities: A Literature Review

Psychiatric Quarterly volume 83, pages 371–383 (2012)Cite this article

Abstract

To review the available data behind the use of lamotrigine in unipolar depression and common comorbid conditions. A PubMed based literature review was conducted using keywords related to lamotrigine, depression, anxiety, post traumatic stress disorder (PTSD), obsessive–compulsive disorder (OCD), and personality disorders. A large number of trials using lamotrigine for unipolar depression and various comorbid conditions were reviewed. A major limitation behind the majority of studies was a limited course of the treatment phase. The most robust data was found among studies that followed patients for over 8 weeks, and used higher dosages. Patients with comorbid anxiety states appeared to benefit. Patients with borderline personality disorder also appeared to benefit. The benefits of lamotrigine in unipolar depression have been inconsistently noted in a number of studies. This is due in part to short treatment phases, atypical domains of benefit and different patient populations across studies. Patients with more treatment-resistance, comorbid anxiety and borderline personality disorder may be more able to benefit from lamotrigine.

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Notes

  1. Unpublished studies available online.

    GlaxoSmithKline. An eight-week, multicenter, double-blind, randomized, fixed-dose evaluation of the efficacy and safety of lamotrigine (200 mg/day), desipramine (200 mg/d and, and placebo in outpatients with unipolar depression (result summary for the study SCAA2011 [105-613]). http://download.gsk-clinicalstudyregister.com/files/1666.pdf. Verfied December 12, 2011.

    GlaxoSmithKline. A randomized, multicenter, double-blind, placebo-controlled, fixed-dose, 7-week evaluation of the efficacy and safety of lamotrigine in patients with major depression (result summary for study SCA20022. http://download.gsk-clinicalstudyregister.com/files/1661.pdf. Verified December 12, 2011.

    GlaxoSmithKline. A randomized, multicenter, double-blind, placebo-controlled, fixed-dose, 7-week evaluation of the efficacy and safety of lamotrigine in treatment of a major depressive episode in unipolar depressed patients (result summary for study SCA20025). http://download.gsk-clinicalstudyregister.com/files/1663.pdf. Verified December 12, 2011.

  2. GlaxoSmithKline internal data.

References

  1. Kemp DE, Muzina DJ, Gao K, Calabrese JR, Lamotrigine. In: Schatzberg AF, Nemeroff CB (Eds). The American Psychiatric Publishing textbook of psychopharmacology. Arlington, American Psychiatric, 2009

  2. Ketter TA, Manji HK, Post RM. Potential mechanisms of action of lamotrigine in the treatment of bipolar disorders. Journal of Clinical Psychopharmacology 23(5):484–495, 2003

    PubMed  Article  CAS  Google Scholar 

  3. Smith D, Baker G, Davies G, Dewey M, Chadwick DW. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia 34(2):312–322, 1993

    PubMed  Article  CAS  Google Scholar 

  4. Calabrese JR, Bowden CL, Sachs G, et al.: A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. Journal of Clinical Psychiatry 64:1013–1024, 2003

    PubMed  Article  CAS  Google Scholar 

  5. 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. Archives of General Psychiatry 60:392–400, 2003

    PubMed  Article  CAS  Google Scholar 

  6. 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. Journal of Clinical Psychiatry 65:432–441, 2004

    PubMed  Article  CAS  Google Scholar 

  7. Frye MA, Ketter TA, Kimbrell TA, Dunn RT, Speer AM, Osuch EA, Luckenbaugh DA, Cora-Ocatelli G, Leverich GS, Post RM: A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. Journal of Clinical Psychopharmacology 20(6):607–614, 2000

    PubMed  Article  CAS  Google Scholar 

  8. Obrocea GV, Dunn RM, Frye MA, Ketter TA, Luckenbaugh DA, Leverich GS, Speer AM, Osuch EA, Jajodia K, Post RM: Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders. Biological Psychiatry 51(3):253–260, 2002

    PubMed  Article  CAS  Google Scholar 

  9. Normann C, Hummel B, Schärer LO, Hörn M, Grunze H, Walden J: Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study. Journal of Clinical Psychiatry 63(4):337–344, 2002

    PubMed  Article  CAS  Google Scholar 

  10. Barbee JG, Jamhour NJ: Lamotrigine as an augmentation agent in treatment-resistant depression. Journal of Clinical Psychiatry 63(8):737–741, 2002

    PubMed  Article  CAS  Google Scholar 

  11. Rocha FL, Hara C: Lamotrigine augmentation in unipolar depression. International Clinical Psychopharmacology 18(2):97–99, 2003

    PubMed  Article  Google Scholar 

  12. Barbosa L, Berk M, Vorster M: A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. Journal of Clinical Psychiatry 64(4):403–407, 2003

    PubMed  Article  CAS  Google Scholar 

  13. Gutierrez RL, McKercher RM, Galea J, Jamison KL. Lamotrigine augmentation strategy for patients with treatment-resistant depression. CNS Spectr. IEEE Transactions on Pattern Analysis and Machine Intelligence 10(10):800–805, 2005.

    Google Scholar 

  14. Gabriel A. Lamotrigine adjunctive treatment in resistant unipolar depression: an open, descriptive study. Depress Anxiety 23(8):485–488, 2006

    PubMed  Article  CAS  Google Scholar 

  15. Schindler F, Anghelescu IG: Lithium versus lamotrigine augmentation in treatment resistant unipolar depression: a randomized, open-label study. International Clinical Psychopharmacology 22(3):179–182, 2007

    PubMed  Article  Google Scholar 

  16. Santos MA, Rocha FL, Hara C: Efficacy and safety of antidepressant augmentation with lamotrigine in patients with treatment-resistant depression: a randomized, placebo-controlled, double-blind study. Primary Care Companion to the Journal of Clinical Psychiatry 10(3):187–190, 2008

    PubMed  Article  Google Scholar 

  17. Barbee JG, Thompson TR, Jamhour NJ, Stewart JW, Conrad EJ, Reimherr FW, Thompson PM, Shelton RC: A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression. Journal of Clinical Psychiatry 72(10):1405–1412, 2011

    PubMed  Article  CAS  Google Scholar 

  18. Mula M, Pini S, Cassano GB: The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence. Journal of Clinical Psychopharmacology 27(3):263–272, 2007 (Review)

    PubMed  Article  CAS  Google Scholar 

  19. Masdrakis VG, Papadimitriou GN, Oulis P: Lamotrigine administration in panic disorder with agoraphobia. Clinical Neuropharmacology 33(3):126–128, 2010

    PubMed  Article  Google Scholar 

  20. Kumar TC, Khanna S. Lamotrigine augmentation of serotonin re-uptake inhibitors in obsessive-compulsive disorder. Australian and New Zealand Journal of Psychiatry 34(3):527–528, 2000

    PubMed  Article  CAS  Google Scholar 

  21. Hertzberg MA, Butterfield MI, Feldman ME, Beckham JC, Sutherland SM, Connor KM, Davidson JR. A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Biological Psychiatry 45(9):1226–1229, 1999

    PubMed  Article  CAS  Google Scholar 

  22. Tritt K, Nickel C, Lahmann C, Leiberich PK, Rother WK, Loew TH, Nickel MK. Lamotrigine treatment of aggression in female borderline-patients: a randomized, double-blind, placebo-controlled study. Journal of Psychopharmacology (3):287–291, 2005

    PubMed  Article  CAS  Google Scholar 

  23. Leiberich P, Nickel MK, Tritt K, Pedrosa Gil F. Lamotrigine treatment of aggression in female borderline patients, Part II: an 18-month follow-up. Journal of Psychopharmacology 22(7):805–808, 2008

    PubMed  Article  CAS  Google Scholar 

  24. Reich DB, Zanarini MC, Bieri KA. A preliminary study of lamotrigine in the treatment of affective instability in borderline personality disorder. International Clinical Psychopharmacology 24(5):270–275, 2009

    PubMed  Google Scholar 

  25. Maltese TM: Adjunctive lamotrigine treatment for major depression. American Journal of Psychiatry 156(11):1833, 1999

    PubMed  CAS  Google Scholar 

  26. Goldsmith DR, Wagstaff AJ, Ibbotson T, Perry CM. Lamotrigine: a review of its use in bipolar disorder. Drugs 63(19):2029–2050, 2003 (Review)

    PubMed  Article  CAS  Google Scholar 

  27. Thase ME, Rush AJ: When at first you don’t succeed: sequential strategies for antidepressant nonresponders. Journal of Clinical Psychiatry 58(suppl 13): 23–29, 1997

    PubMed  Google Scholar 

  28. Fava M: Diagnosis and definition of treatment-resistant depression. Biological Psychiatry 53:649–659, 2003

    PubMed  Article  Google Scholar 

  29. Rush AJ, Trivedi MH, Wisniewski SR, et al.: Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. American Journal of Psychiatry 163(11):1905–1917, 2006

    PubMed  Article  Google Scholar 

  30. Saggese JM, Lieberman DZ, Goodwin FK: The role of recurrence and cyclicity in differentiating mood disorder diagnoses. Primary Psychiatry 13(11):43–48, 2006

    Google Scholar 

  31. Kremer I, Vass A, Gorelik I, Bar G, Blanaru M, Javitt DC, Heresco-Levy U: Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia. Biological Psychiatry 56:441–446, 2004

    PubMed  Article  CAS  Google Scholar 

  32. Wilder-Willis KE, Sax KW, Rosenberg HL, Fleck DE, Shear PK, Strakowski SM: Persistent attentional dysfunction in remitted bipolar disorder. Bipolar Disorders 3(2):58–62, 2001

    PubMed  Article  CAS  Google Scholar 

  33. Gualtieri CT, Johnson LG: Comparative neurocognitive effects of 5 psychotropic anticonvulsants and lithium. MedGenMed 23;8(3):46, 2006

    PubMed  Google Scholar 

  34. Marciani MG, Stanzione P, Mattia D, Spanedda F, Bassetti MA, Maschio M, Bernardi G: Lamotrigine add-on therapy in focal epilepsy: electroencephalographic and neuropsychological evaluation. Clinical Neuropharmacology 21(1):41–47, 1998

    PubMed  CAS  Google Scholar 

  35. Tiihonen J, Wahlbeck K, Kiviniemi V: The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophrenia Research 109(1–3):10–14, 2009 (Review)

    PubMed  Article  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Medicine, Carilion Clinic-Virginia Tech Carilion School of Medicine, Roanoke, VA, USA

    Adam Daniel Zavodnick

  2. Veterans Affairs Medical Cente, 1970 Roanoke Boulevard—116A7, Salem, VA, 24153, USA

    Adam Daniel Zavodnick

  3. Psychiatry Service, Veterans Affairs Medical Center, Salem, VA, USA

    Rizwan Ali

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  2. Rizwan Ali
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Correspondence to Adam Daniel Zavodnick.

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Zavodnick, A.D., Ali, R. Lamotrigine in the Treatment of Unipolar Depression with and Without Comorbidities: A Literature Review. Psychiatr Q 83, 371–383 (2012). https://doi.org/10.1007/s11126-012-9208-4

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  • DOI: https://doi.org/10.1007/s11126-012-9208-4

Keywords

  • Anxiety Disorder
  • Lamotrigine
  • Generalize Anxiety Disorder
  • Personality Disorder
  • Post Traumatic Stress Disorder