169 In the original studies by the manufacturer, 22% of leuprolidetreated patients and 54% of goserelin-treated patients suffered from significant depressive symptoms.170,171 These findings (for both medications) have been replicated in subsequent case series.172,173 Furthermore, a retrospective study found that approximately 80% of patients treated with leuprolide suffered from significant Inhibitors,research,lifescience,medical depressive Pifithrin-�� purchase symptoms (eg, Hamilton Rating Scale for Depression-21 score ≥ 20).174 However, a lack of prospective studies makes it difficult to identify the risk associated with these medications. Interestingly, prophylactic treatment with SSRIs appears to prevent the development of depressive symptoms in these patients.169,174

Clomiphene citrate, a selective estrogen receptor modulator used to induce ovulation, has been associated with mood lability and depressed mood in two cross-sectional studies.175,176 In the larger of these studies, 67 of 162 (41%) of clomiphene-treated women experienced depressed mood Inhibitors,research,lifescience,medical and 75 of 162 (45%) experienced mood swings Inhibitors,research,lifescience,medical during treatment.176 Unfortunately, there are no prospective studies that evaluate the association between clomiphene and psychiatric symptoms; nevertheless, given the evidence from cross-sectional studies, care should be taken when prescribing this medication to infertile women. In sum, there is mixed evidence regarding the depressogenic effects of medications for the treatment of infertility.

Although progesterone-containing contraceptives caused the most concern through case reports and retrospective studies, systematic prospective studies have revealed that these medications Inhibitors,research,lifescience,medical are rarely linked to depressive symptoms. Preliminary cross-sectional and retrospective studies also suggest a possible link between depression and the use Inhibitors,research,lifescience,medical of GnRHagonists and clomiphene citrate; however, prospective studies will be required to confirm these associations. Varenicline Varenicline, a nicotinic receptor partial agonist, is used clinically to facilitate smoking cessation. Since its introduction, it has been scrutinized as several case reports and retrospective studies have noted worsening mood and suicidal ideation during its use177,178; these

findings have led to a Food and Drug Administration warning about varenicline.179 However, large observational cohort studies have failed to confirm an increase in depression or suicidal risk180,181; further, an open-label study found a significant and decrease in depressive symptoms during treatment with varenicline.182 The finding that smoking cessation itself can precipitate depressive symptoms in patients with nicotine dependence may partly explain the early case reports linking varenicline and depression.183 Therefore, while idiosyncratic depressive reactions are possible during treatment with varenicline, there is no clear evidence that this medication is depressogenic. Further studies should be performed to further clarify these findings.