Mestranol/Norethindrone

Sitagliptin is a dipeptidyl peptidase-IV (DPP-4) inhibitor used for the treatment of patients with type 2 diabetes mellitus. This randomized, placebo-controlled, 2-period, crossover study evaluated the effect of sitagliptin on the pharmacokinetics of 17 α-ethinyl estradiol (EE(2)) and norethindrone (NET) in healthy female subjects who were receiving oral contraceptives for >3 months prior to enrollment. A total of 18 subjects with normal menstrual cycles received the oral contraceptive pill ORTHO-NOVUM(®) 7/7/7 on days 1 to 28 for 2 successive cycles, and on days 1 to 21 were randomly assigned to receive sitagliptin 200 mg/day (2 × 100 mg tablets) or placebo using a computer-generated allocation schedule. Blood samples for determination of plasma EE(2) and NET concentrations were collected predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours postdose on day 20 or 21 of each treatment period. The GMRs (90% confidence interval [CI]) for the AUC(0-24 hr) of EE(2) and NET were 0.99 (0.93, 1.06) and 1.03 (0.97, 1.09), respectively, and for C(max) were 0.97 (0.86, 1.10) and 0.98 (0.89, 1.07), respectively. The coadministration of sitagliptin 200 mg/day with an oral contraceptive for 21 days did not lead to clinically meaningful alterations in the pharmacokinetics of EE(2) and NET.

Depression and headaches are frequently associated comorbid disorders. In previous reports psychiatrists have tended to regard headaches as an accompanying symptom of depression while neurologists have tended to have the opposite opinion. The following case report characterizes migraine as a prime cause of major depression. A 27-year-old woman presented because of a self-poisoning attempt with 12 mg of alprazolam. She had been suffering from major depression and sporadic headaches from the age of 24. After onset of the symptoms she had often injured herself by cutting her arm and attempted to suicide by self-poisoning. A variety of antidepressants had failed to improve her symptoms and she had been diagnosed as having borderline personality disorder comorbid with major depression. A medical interview at her first visit revealed that her major depressive episode had been predominantly characterized by atypical features in DSM-IV such as overeating hypersomnia leaden paralysis interpersonal rejection sensitivity and mood reactivity. She had also suffered persistent aura and premonitory symptoms of migraine such as scintillating scotomas photopsia and phonophobia.1 Lomerizine a calcium channel antagonist was first administered at 10 mg/day for treatment of the migraine in combination with valproic acid at 600 mg/day. This medication led to prompt resolution of her self-injury and suicidal behaviors but depressive mood with a series of migraine attacks paralleling each menstrual period persisted. Therefore additionally the patient was prescribed Ortho-Novum®7/7/7 an oral contraceptive containing ethinyl estradiol and norethindrone to prevent ovulation. With this medication all the symptoms immediately disappeared. Lomerizine and valproic acid were gradually withdrawn and no recurrence has been noted for over 1 year. Depression is one of the common premonitory symptoms of migraine and a first-line treatment strategy for migraine showed some degree of clinical effectiveness on the depressive episode in the present case.12 Accordingly it was considered that the patients major depression was also a premonitory symptom of migraine. Ovarian hormones can alter neurotransmitter system theorized to play an important role in the pathogenesis of migraine.3 Although hormonal treatment of migraine is not a first-line strategy due to an increased risk of ischemic stroke oral contraceptives can have a broad effect on the character and frequency of migraine.45 We suggest that clinicians should check for the complication of migraine in depressive patients. Depressive patients with migraine might show a preferential response to management of migraine rather than medication with common antidepressants. In female patients it is also prudent to be aware of any symptomatic relevance to the menstrual cycle and that oral contraceptives have the potential to treat such problems. (full-text)