Detection and Management of Perimenopausal Mood Instability

Educational Objectives

The goal of this program is to improve the diagnosis and management of perimenopausal mood instability. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate symptoms of perimenopausal mood instability from major depressive disorder and generalized anxiety disorder (GAD).
2. Implement appropriate management strategies for perimenopausal mood instability, with or without depression or GAD.

Summary

Perimenopausal mood instability (PMI): ≤68% of women in perimenopause experience PMI; estrogen is an effective treatment; patients typically feel anxious, irritable, and moody, have insomnia and hot flashes, and have difficulty concentrating at work; differentiation between depression and hormonally driven mental health issue is crucial; perimenopausal women in mid 40s have multiple symptoms; prevalence is ≤80% of women in their late 40s or early 50s

PMI vs depression: in PMI, 100% of individuals report irregular periods, 80% have hot flashes, and a vast majority have urinary or vaginal symptoms; common symptoms of both PMI and major depression include sexual and weight disturbances, memory changes, and brain fog

Etiologyof PMI: explained based on the biopsychosocial model; neurotransmitters in the brain, primarily norepinephrine, dopamine, and serotonin, are involved in the regulation of mood and anxiety; estrogen and progesterone interact with brain neurotransmitters; estrogen modulates norepinephrine and serotonin; depression symptoms in perimenopause are likely related to fluctuations in the levels of estrogen and progesterone; women are protected from some forms of psychosis because of the protective effects of estrogen; progesterone targets areas of the brain that are similar to those targeted by antianxiety, sleep, and pain medications, and has calming and sleep-promoting effects in postmenopausal women; hormone levels fluctuate rapidly during perimenopause, causing symptoms of PMI; the hallmark of PMI is fluctuating mood symptoms (eg, irritability, low mood, tearfulness, decreased energy)

Major depressive disorder: 25% of women may experience major depression at some point in their perimenopause-to-menopausal transition and have twice the risk for new-onset depression, even if they have no history of depression; Patient Health Questionnaire-9 is used to differentiate depression from PMI; diagnosis is positive if a patient has ≥5 symptoms in the past 2 wk; the patient may be categorized as having mild, moderate, severe, and very severe depression

Generalized anxiety disorder (GAD): often mimics PMI in the perimenopausal period; hot flashes may feel like a panic attack, with increased sweating and heart rate; the GAD-7 score is used to diagnose GAD as well as severity

Guidelines for treatment of perimenopausal depression (PMD): Maki et al (2018) — there was no difference in the presentation of depression, but it was complicated by the presence of perimenopausal symptoms; antidepressants were equally effective in managing women with PMD of all ages; estrogen was effective for treatment of PMI in perimenopause but not in the postmenopausal period; 45% to 68% of perimenopausal women may report symptoms of PMD, with increased prevalence among Hispanic women; multiple psychological and sociocultural factors affect the risk; hysterectomy and premature ovarian insufficiency were associated with increased risk for PMD

Psychological therapy: cognitive behavior therapy (CBT) is the most effective therapy for anxiety, depression, and insomnia; evidence demonstrates benefit for management of hot flashes; specific CBT approaches exist for insomnia; CBT can be performed with mindfulness; mindfulness involves observance of one’s thoughts, feelings, and emotions without becoming emotionally attached to them; CBT identifies cognitive distortions and helps evaluate thought content and recognize when one starts to exhibit catastrophizing behavior; CBT is effective for insomnia because it helps replace ruminative thoughts that keep the individual awake; mindfulness techniques (eg, paced breathing) are effective for depression and PMI; however, paced breathing is not effective for hot flashes

Pharmacotherapy for PMI: estrogen is effective for management of PMI in the perimenopausal period but is not approved by the US Food and Drug Administration to treat PMI; estrogen use causes mood stability and improvement in low mood; it can be administered as hormone therapy alone or as part of continuous oral contraception (symptoms tend to recur in pill-free intervals)

Comorbid depression and/or anxiety and PMI: patients with coexisting PMI and major depression require treatment for symptoms of PMI; progestins help to improve sleep; exercise is recommended for improvement of sleep, hot flashes, and mood; first-line therapy for moderate or severe depression is antidepressants, ie, selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs); medications are most effective in combination with psychotherapy; start with a small dose and inform patients of adverse effects (eg, sweating, insomnia); symptoms generally improve in a few weeks; patients with PMI and mild depression or anxiety benefit from estrogen therapy; estrogen therapy is recommended for early menopause, premature ovarian insufficiency, or surgical menopause, and should be given until the average age of menopause; estrogen is not indicated for postmenopausal depression in the absence of other symptoms

General antidepressants: only desvenlafaxine (Khedezla, Pristiq) has a randomized controlled trial for use in menopause-related mood disorders; some agents promote drowsiness and have a calming effect (eg, paroxetine [Brisdell, Paxil, Pexeva], venlafaxine [Effexor]), whereas others may be activating (eg, sertraline [Zoloft], fluoxetine [Prozac, Rapiflex, Sarafem]); it is recommended to use antidepressants according to patient symptoms; bupropion (eg, Aplezin, Budeprion, Wellbutrin) does not possess any sexual adverse effects; advise avoidance of caffeine with bupropion and recommend intake during the day as it may interfere with sleep if taken at night

Methods of hormone delivery: include transdermal estrogen with oral progestin or an intrauterine device (eg, Liletta, Mirena, Skyla), and oral contraception; vasomotor symptoms may improve in 3 wk; transdermal estradiol has ≈25% the strength of an oral medication, ie, it might be insufficient to provide cycle control or contraception; oral contraception is recommended in individuals requiring contraception or cycle control

Contraindications to postmenopausal estrogen: include active liver disease, breast cancer or other hormone-dependent cancer, and personal history of heart attack, stroke, or venous thromboembolic event; family history of breast cancer, heart attack, stroke, and migraine with aura are not contraindications for estrogen use; SSRIs, SNRIs, or gabapentin are recommended for individuals who do not prefer estrogen

Duration of hormone therapy: based on risk vs benefit analysis and shared decision-making with patient

Readings

Bromberger JT, Kravitz HM. Mood and menopause: findings from the Study of Women's Health Across the Nation (SWAN) over 10 years. Obstet Gynecol Clin North Am. 2011 Sep;38(3):609-25. doi: 10.1016/j.ogc.2011.05.011. PMID: 21961723; PMCID: PMC3197240; Clayton AH, Ninan PT. Depression or menopause? Presentation and management of major depressive disorder in perimenopausal and postmenopausal women. Prim Care Companion J Clin Psychiatry. 2010;12(1):PCC.08r00747. doi: 10.4088/PCC.08r00747blu. PMID: 20582297; PMCID: PMC2882813; Cohen LS, Soares CN, Joffe H. Diagnosis and management of mood disorders during the menopausal transition. Am J Med. 2005 Dec 19;118 Suppl 12B:93-7. doi: 10.1016/j.amjmed.2005.09.042. PMID: 16414333; Delamater L, Santoro N. Management of the perimenopause. Clin Obstet Gynecol. 2018 Sep;61(3):419-432. doi: 10.1097/GRF.0000000000000389. PMID: 29952797; PMCID: PMC6082400; Gava G, Orsili I, Alvisi S, et al. Cognition, mood and sleep in menopausal transition: The role of menopause hormone therapy. Medicina (Kaunas). 2019 Oct 1;55(10):668. doi: 10.3390/medicina55100668. PMID: 31581598; PMCID: PMC6843314; Gordon JL, Sander B, Eisenlohr-Moul TA, et al. Mood sensitivity to estradiol predicts depressive symptoms in the menopause transition. Psychol Med. 2021 Jul;51(10):1733-1741. doi: 10.1017/S0033291720000483. Epub 2020 Mar 11. PMID: 32156321; Maki PM, Kornstein SG, Joffe H, et al. Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations. Menopause. 2018;25(10):1069-1085. doi:10.1097/GME.0000000000001174; Moeini A, Machida H, Cahoon SS, et al. Preinvasive epithelial disease of the vulvar. Handbook of Gynecology. 2016;1-14 https://doi.org/10.1007/978-3-319-17002-2_10-1; Musial N, Ali Z, Grbevski J, et al. Perimenopause and first-onset mood disorders: A closer look. Focus (Am Psychiatr Publ). 2021 Jul;19(3):330-337. doi: 10.1176/appi.focus.20200041. Epub 2021 Jul 9. PMID: 34690602; PMCID: PMC8475932; Preti M, Igidbashian S, Costa S, et al. VIN usual type-from the past to the future. Ecancermedicalscience. 2015;9:531. Published 2015 Apr 29. doi:10.3332/ecancer.2015.531; Toffol E, Heikinheimo O, Partonen T. Hormone therapy and mood in perimenopausal and postmenopausal women: a narrative review. Menopause. 2015 May;22(5):564-78. doi: 10.1097/GME.0000000000000323. PMID: 25203891.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Adam’s lecture includes information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Adams was recorded at 2022 Pacific NW Update in OBGYN and Women’s Health, held in Portland, OR, on October 20-21, 2022, and presented by Oregon Health & Science University. For information about upcoming CME activities from this presenter, please visit ohsu.edu/education/continuing-education. Audio Digest thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

OB700801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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