The effect of flurbiprofen on steady-state plasma lithium levels.

STUDY OBJECTIVE: To evaluate the effects of flurbiprofen therapy on the pharmacokinetics of lithium. DESIGN: Placebo-controlled, single-blind, crossover study. SETTING: University-affiliated hospital. PATIENTS: Eleven healthy women with bipolar disorder. INTERVENTIONS: The subjects received therapeutic doses of lithium administered as an immediate-release capsule every 12 hours. In addition, they received one placebo tablet every 12 hours during phase I and flurbiprofen 100 mg every 12 hours during phase II of the study. MEASUREMENTS AND MAIN RESULTS: Steady-state pharmacokinetic parameters were measured for each phase. Lithium trough plasma concentration (Cmin) and area under the curve were statistically significantly increased (p < 0.05) when patients received flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour lithium urine excretion, although the changes did not reach statistical significance. Clinically significant increases in Cmin appeared to be associated with a greater than 1000-microgram/24 hour decrease in urinary excretion of prostaglandin E2. CONCLUSION: Patients with clinically normal renal function may experience an increase in lithium levels with the initiation of flurbiprofen therapy.

Self-reported premenstrual exacerbation of depressive symptoms in patients seeking treatment for major depression.

BACKGROUND: Very little research has examined the frequency with which women with major depressive disorder experience premenstrual exacerbation (PME) of depression or the characteristics of those who report such worsening. The NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provides a unique opportunity to evaluate PME in depressed women seeking treatment in primary care or psychiatric settings. METHOD: This report presents data from the first 1500 participants enrolled in the STAR*D study. Premenopausal women with major depressive disorder were asked if they experienced a worsening of their depressive symptoms 5-10 days prior to menses. Those reporting PME were compared with those reporting no PME with regard to sociodemographic characteristics, course of illness features, symptom presentation, general medical co-morbidity, functional impairment, and quality of life. RESULTS: Of 433 premenopausal women not taking oral contraceptives, 64% reported a premenstrual worsening of their depression. Women who reported PME had a longer duration of their current major depressive episode [30.7 (S.D. = 73.7) months versus 13.5 (S.D. = 13.2) months; p=0.001], as well as greater general medical co-morbidity. Women reporting PME were also more likely to endorse symptoms of leaden paralysis, somatic complaints, gastrointestinal complaints, and psychomotor slowing, and were less likely to endorse blunted mood reactivity. CONCLUSIONS: PME is endorsed by the majority of premenopausal women with major depressive disorder and appears to be associated with a longer duration of depressive episode. PME is a common and important clinical issue deserving of further attention in both research and practice.