Premenstrual worsening of mood is common among women with depression, but little is known about how often women with bipolar disorder experience worsening of their mood premenstrually. In a study by Payne et al. (2007), premenstrual symptoms were reported by twice as many women diagnosed with mood disorders (mixture of  Bipolar Disorder and Major Depressive Disorder) than by women who did not have a psychiatric diagnosis (67.7% vs. 33.7%).  These results suggest that PMS symptoms are particularly common in women with bipolar disorder and major depressive disorder. However, this study involved women reporting prior experiences with PMS, which is not always as accurate as studies that involve prospective monitoring to obtain real-time reporting of PMS symptoms.  Such prospective studies of PMS in women with bipolar disorder are sparse and have inconsistent conclusions.

In a study involving prospective daily monitoring of mood symptoms across two menstrual cycles, Karadag et al. (2004) compared premenstrual symptoms in women with bipolar disorder who were treated with lithium and/or valproate to premenstrual symptoms in healthy women.  Relative to the non-premenstrual time, the healthy women experienced more mood symptoms premenstrually than did the women with bipolar disorder. Results of this study suggest that mood and behavior fluctuate less across the menstrual cycle in women whose bipolar disorder is well treated than in a comparison group of women without psychiatric illness. Another study by Shivakumar et al. (2008) examined the relationship between bipolar disorder and premenstrual symptoms using prospective daily monitoring for three months.  They found that depression and mania symptoms did not significantly increase premenstrually.

A study involving prospective monitoring of PMS symptoms in women with bipolar disorder treated with mood-stabilizers (Viguera et al, 2005) sought to determine how often women with bipolar disorder who seek treatment for premenstrual symptoms are confirmed to have premenstrual exacerbation of bipolar disorder when they complete a daily mood diary across one menstrual cycle.  Results of this study show that approximately 50% of 15 women had a substantial deterioration in their mood during the premenstrual week relative to their postmenstrual time.  The remaining 50% of these women were shown to have ongoing mood problems throughout their menstrual cycle, not just premenstrually.  Those bipolar women with PMS then went on to be treated with quetiapine (Seroquel) in addition to the other bipolar medications that they were already taking.   The addition of quetiapine improved premenstrual symptoms overall, with the greatest improvement seen in mood swings specifically, suggesting that optimization of treatment with additional medications may be helpful.  Findings from this study also suggests that prospective monitoring of mood across the menstrual cycle is a helpful tool to determine if premenstrual worsening is present or if mood disturbance is persistent across the menstrual cycle.

Hadine Joffe, MD, MSc
Rachel VanderKruik, BA

Payne JL, Roy PS, Murphy-Eberenz K, Weismann MM, Swartz KL, McInnis MG, Nwulia E, Mondimore FM, MacKinnon DF, Miller EB, Nurnberger JI, Levinson DF, DePaulo JR Jr, Potash JB. Reproductive cycle-associated mood symptoms in women with major depression and bipolar disorder. J Affect Disord. 2007 Apr; 99(1-3):221-9.

Karadag F, Akdeniz F, Erten E, Pirildar S, Yucel B, Polat A, Atmaca M. Menstrually related symptom changes in women with treatment-responsive bipolar disorder. Bipolar Disord. 2004 Jun;6(3):253-9.

Shivakumar G, Bernstein IH, SuppesT; Stanley Foundation Bipolar Netweork, Keck PE, McElroy SL, Altshuler LL, Frye MA, Nolen WA, Kupka RW, Grunze H, Leverich GS, Mintz J, Post RM.  Are bipolar mood syptoms affected by the phase of the menstrual cycle? J Womens Health (Larchmt). 2008 Apr; 17(3):373-8.

Viguera A, Soares C, Joffe H, Coleman J, Petrillo L, Gottschall H, Whitfield T, Cohen S. Open Label Quetiapine for Premenstrual Worsening of Bipolar Disorder: From Screening to Treatment.  In: American Psychiatry Association 2005, May 21-26; Atlanta, GA; 2005.

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