title: Lamotrigine and GABAA receptor modulators interact with menstrual cycle phase and oral contraceptives to regulate mood in women with bipolar disorder.
abstract: OBJECTIVE
  To examine the occurrence of menstrually-entrained mood cycling in women with treated bipolar disorder as compared to healthy controls, and to explore whether there is a specific effect of lamotrigine in dampening menstrually-entrained cyclicity of mood.
  
  
  METHODS
  Observational comparison study of daily self-ratings of mood, sleep, and insomnia obtained over a mean of four menstrual cycles in 42 women with bipolar disorder taking lamotrigine as part of their treatment, 30 women with bipolar disorder receiving mood stabilizing regimens without lamotrigine, and 13 healthy controls, all with physiological menstrual cycles. Additional exploratory analysis of interactions between psychopharmacological regimen and hormonal contraceptive use in the group of women with bipolar disorder, with the addition of 19 women with bipolar disorder who were using hormonal contraceptives.
  
  
  RESULTS
  Women treated for bipolar disorder manifested lower average mood, longer average nightly sleep duration, and greater fluctuations in mood and sleep across menstrual cycle phases than healthy controls. Women with bipolar disorder who were taking lamotrigine had less fluctuation in mood both within and across menstrual cycle phases, and were more similar to the control group than to women with bipolar disorder who were not taking lamotrigine in this respect. In addition, medications with GABA-A receptor modulating effects were found to result in improved mood ratings when combined with hormonal contraceptives.
  
  
  CONCLUSIONS
  Menstrually-entrained mood fluctuation is present in women treated for bipolar disorder to a greater degree than in healthy controls. Lamotrigine may be of use in mitigating this fluctuation. GABA-A receptor modulators in general may act synergistically with hormonal contraceptives to enhance mood in women with bipolar disorder; this hypothesis merits further study.
authors.affiliation: Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States. Electronic address: trobakis@stanford.edu.
authors.forename: Thalia K
authors.initials: TK
authors.lastname: Robakis
authors.affiliation: Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States.
authors.forename: Jessie
authors.initials: J
authors.lastname: Holtzman
authors.affiliation: Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States.
authors.forename: Pascale G
authors.initials: PG
authors.lastname: Stemmle
authors.affiliation: Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Reynolds-May
authors.affiliation: Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Kenna
authors.affiliation: Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Rasgon
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology*; D003276:Contraceptives, Oral / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008597:Menstrual Cycle / Q000523:psychology*; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects*; D011795:Surveys and Questionnaires; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D003276:Contraceptives, Oral; D018691:Excitatory Amino Acid Antagonists; D011963:Receptors, GABA-A; D014227:Triazines; D000077213:Lamotrigine
keywords: Bipolar disorder; GABA-A receptor; Lamotrigine; Menstrual cycle; Menstrual entrainment; Mood cycling