madman
Super Moderator
Intravenous ketamine for postmenopausal women with treatment-resistant depression: Results from the Canadian Rapid Treatment Center of Excellence
ABSTRACT
Women are disproportionately represented amongst samples of adults with treatment-resistant depression (TRD). Ketamine has demonstrated rapid and robust efficacy in adults with TRD. Herein, we sought to determine whether the effectiveness of intravenous (IV) ketamine was influenced by menopausal status in women with TRD. We defined premenopausal women as those under the age of 45 (n = 52), while postmenopausal women (n = 54) were those over the age of 51. Participants received four IV ketamine infusions over one-to-two weeks at a community-based center for adults with TRD. The primary outcome of interest was the change in depressive symptom severity as measured by the Quick Inventory of Depressive Symptomatology Self-Report 16 (QIDSSR16) following four infusions, compared to pretreatment. The secondary outcomes were improvements in suicidal ideation (SI; i.e., QIDS-SR16 SI item), anxiety (i.e., Generalized Anxiety Disorder-7 scale), anhedonic severity (i.e., Snaith-Hamilton Pleasure Scale), and workplace and psychosocial function (i.e., Sheehan Disability Scale). Menopausal status did not influence overall treatment response, F (4, 280) = 1.83, p = .123, ηp 2 = 0.025. Both premenopausal and postmenopausal participants demonstrated similar response rates (30% and 26%, respectively) and remission rates (both 13%) to IV ketamine treatment following four infusions. Premenopausal women experienced improvements in social function more rapidly than postmenopausal women, F (2, 174) = 1.65, p = .047, ηp 2 = 0.019. Postmenopausal women experienced reduction in SI more rapidly than premenopausal women, F (4, 280) = 2.72, p = .030, ηp 2 = 0.037. These preliminary post-hoc findings provide the impetus for future studies to investigate the moderational role of menopausal status, as defined by hormone levels, on response to IV ketamine for TRD.
1. Introduction
Women are differentially affected by major depressive disorder (MDD) and are 1.7 times more likely to experience a major depressive episode in their lifetime than men (Kessler et al., 1993). Additionally, women are more likely to be prescribed antidepressants and have a higher likelihood of meeting criteria for treatment-resistant depression (TRD; McAllister-Williams et al., 2020, Thunander Sundbom and Hedborg, 2019). Menopause is a particularly vulnerable developmental period for women and approximately 20% of women experience depression during the menopausal transition (Soares, 2004). Furthermore, postmenopausal women with MDD are more likely to report suicidal ideation (SI) when compared to premenopausal and perimenopausal women (Kornstein et al., 2010). However, it remains unclear to what extent menopausal status influences patient response to conventional monoamine-antidepressants (Sloan and Kornstein, 2003; Sramek and Cutler, 2011). Extant studies have suggested that postmenopausal women experience a poorer response to monoamine-based antidepressants than premenopausal women (Pae et al., 2009).
During the perimenopause period, gonadal hormones are in flux. In particular, the steroid hormone estrogen, which has central nervous system activity, fluctuates and declines during perimenopause (Bromberger and Epperson, 2018; Dalal and Agarwal, 2015). Estrogen plays a role in increasing levels of serotonin and norepinephrine, which are commonly implicated in the pathophysiological cause of depression (Halbreich, 1997; Spinelli, 2004). As estrogen levels decrease during the menopausal transition, it is suspected that serotonin and norepinephrine levels decrease as well, which may be associated with the increased prevalence of depression during this period (Halbreich, 1997; Ryan et al., 2009; Spinelli, 2004; Steiner et al., 2003).
5. Conclusion
In summary, both premenopausal and postmenopausal women with TRD reported experiencing significant symptom relief with IV ketamine treatment. However, the reported effects are relatively small in size, and therefore there remains uncertainty in the results presented herein. Future research should endeavor to evaluate menopausal status using biochemical measures (e.g., FSH) or self-report measures of menopausal status. It is also important to determine whether more robust findings are detected with a sample that is defined by hormone level. Whether the estrogen-augmentation of IV ketamine in postmenopausal women is safe and/or synergistically effective is a testable hypothesis and would be an interesting investigatory avenue. Moreover, evaluating IV ketamine’s safety and efficacy in hormone-related mood changes, notably peripartum and postpartum depression and premenstrual dysphoric disorder (PMDD), would be especially valuable given the urgency for rapid symptom relief.
ABSTRACT
Women are disproportionately represented amongst samples of adults with treatment-resistant depression (TRD). Ketamine has demonstrated rapid and robust efficacy in adults with TRD. Herein, we sought to determine whether the effectiveness of intravenous (IV) ketamine was influenced by menopausal status in women with TRD. We defined premenopausal women as those under the age of 45 (n = 52), while postmenopausal women (n = 54) were those over the age of 51. Participants received four IV ketamine infusions over one-to-two weeks at a community-based center for adults with TRD. The primary outcome of interest was the change in depressive symptom severity as measured by the Quick Inventory of Depressive Symptomatology Self-Report 16 (QIDSSR16) following four infusions, compared to pretreatment. The secondary outcomes were improvements in suicidal ideation (SI; i.e., QIDS-SR16 SI item), anxiety (i.e., Generalized Anxiety Disorder-7 scale), anhedonic severity (i.e., Snaith-Hamilton Pleasure Scale), and workplace and psychosocial function (i.e., Sheehan Disability Scale). Menopausal status did not influence overall treatment response, F (4, 280) = 1.83, p = .123, ηp 2 = 0.025. Both premenopausal and postmenopausal participants demonstrated similar response rates (30% and 26%, respectively) and remission rates (both 13%) to IV ketamine treatment following four infusions. Premenopausal women experienced improvements in social function more rapidly than postmenopausal women, F (2, 174) = 1.65, p = .047, ηp 2 = 0.019. Postmenopausal women experienced reduction in SI more rapidly than premenopausal women, F (4, 280) = 2.72, p = .030, ηp 2 = 0.037. These preliminary post-hoc findings provide the impetus for future studies to investigate the moderational role of menopausal status, as defined by hormone levels, on response to IV ketamine for TRD.
1. Introduction
Women are differentially affected by major depressive disorder (MDD) and are 1.7 times more likely to experience a major depressive episode in their lifetime than men (Kessler et al., 1993). Additionally, women are more likely to be prescribed antidepressants and have a higher likelihood of meeting criteria for treatment-resistant depression (TRD; McAllister-Williams et al., 2020, Thunander Sundbom and Hedborg, 2019). Menopause is a particularly vulnerable developmental period for women and approximately 20% of women experience depression during the menopausal transition (Soares, 2004). Furthermore, postmenopausal women with MDD are more likely to report suicidal ideation (SI) when compared to premenopausal and perimenopausal women (Kornstein et al., 2010). However, it remains unclear to what extent menopausal status influences patient response to conventional monoamine-antidepressants (Sloan and Kornstein, 2003; Sramek and Cutler, 2011). Extant studies have suggested that postmenopausal women experience a poorer response to monoamine-based antidepressants than premenopausal women (Pae et al., 2009).
During the perimenopause period, gonadal hormones are in flux. In particular, the steroid hormone estrogen, which has central nervous system activity, fluctuates and declines during perimenopause (Bromberger and Epperson, 2018; Dalal and Agarwal, 2015). Estrogen plays a role in increasing levels of serotonin and norepinephrine, which are commonly implicated in the pathophysiological cause of depression (Halbreich, 1997; Spinelli, 2004). As estrogen levels decrease during the menopausal transition, it is suspected that serotonin and norepinephrine levels decrease as well, which may be associated with the increased prevalence of depression during this period (Halbreich, 1997; Ryan et al., 2009; Spinelli, 2004; Steiner et al., 2003).
5. Conclusion
In summary, both premenopausal and postmenopausal women with TRD reported experiencing significant symptom relief with IV ketamine treatment. However, the reported effects are relatively small in size, and therefore there remains uncertainty in the results presented herein. Future research should endeavor to evaluate menopausal status using biochemical measures (e.g., FSH) or self-report measures of menopausal status. It is also important to determine whether more robust findings are detected with a sample that is defined by hormone level. Whether the estrogen-augmentation of IV ketamine in postmenopausal women is safe and/or synergistically effective is a testable hypothesis and would be an interesting investigatory avenue. Moreover, evaluating IV ketamine’s safety and efficacy in hormone-related mood changes, notably peripartum and postpartum depression and premenstrual dysphoric disorder (PMDD), would be especially valuable given the urgency for rapid symptom relief.
