Women With Depressive Symptoms

1. Women With Depressive Symptoms Roles of the Nurse and Nurse Practitioner Panelist Moderator Denise Vanacore, PhD, CRNP, ANP-BC, FNP-BC, PMHNP-BC Graduate Program Director and Professor Gwynedd Mercy University Gwynedd Valley, Pennsylvania Deborah V. Thomas, EdD, APRN, PMHCNS-BC, PMHNP-BC, CMP Emeritus Professor & Director PMHNP Program University of Louisville School of Nursing; Psychiatric Nurse Practitioner Private Practice Louisville, Kentucky

2. Program Introduction/Background Major depressive disorder (MDD) is a significant population health issue MDD requires assessment for • Special types of depression • Comorbid medical and psychiatric conditions • Barriers to care (eg, rural areas) Develop therapeutic alliance with patients Select appropriate level of treatment Provide patient/family care and collaboration with patient and family

3. Assessing Patients With MDDBy Nurses and Nurse Practitioners • Patient Assessment • Accurate case diagnosis and case conceptualization • Patient and family history • Includes medical and psychiatric history • Past or current substance use or abuse • Includes nicotine and caffeine • Assess for past or ongoing trauma: social, physical, emotional abuse • Obtain collateral information from the family, if possible American Psychiatric Association. Treatment of MDD/2010.

4. Screening Tools for Assessing MDDConsiderations, Usefulness, and Limitations* • Considerations[a] • Usefulness[b] • Limitations[c] • Assists in diagnosis of depression • Helps quantify depression severity • Assists in depression treatment • Shows symptom improvement/no improvement • Providers and patients • May miss diagnostic features • May not reflect actual degree of impairment • Does not capture comorbid mental health issues • Based on criteria prior to Diagnostic Statistical Manual (DSM)-IV-TR or DSM-V • Use correct screening tool • Edinburgh Scale for patient who is pregnant • Psychometric properties of screening tool • Reliability/validity for depressive episode • Time to complete and score • Cost (free tools) *Applicable to nurses/nurse practitioners. a. Anderson EJ, et al. BCMJ. 2002;44:415-419; b. U.S. Preventive ServicesTask Force. Ann Intern Med. 2009;151:784-792; c. DeJesus RS, et al. Mayo Clin Proc. 2007;82:1395-1402.

5. Available Screening ToolsFor the Nurse and Nurse Practitioner* *Scoring can be completed by nurses and documented in chart by nurse practitioners, depending on state/facility requirements or policies/procedures. a. Kroenke K, et al. J Gen Intern Med. 2001;16:606-613; b. Hirschfeld RM. Prim Care Companion J Clin Psychiatry. 2002;4:9-11; c. Ghaemi SN, et al. J Affect Disord. 2005;84:273-277; d. Navaratne P, et al. Sci Rep. 2016;6:33544. Patient Health Questionnaire (PHQ)-9[a] • Scored 5, 10, 15, 20: mild, moderate, moderately severe, or severe depression (range, 0-27) • PHQ-9 score ≥ 10: 88% sensitivity/88% specificity for major depression Mood Disorder Questionnaire (MDQ)[b] • Correctly identified 7 out 10 patients with bipolar disorder, 9 out 10 without • Patients with MDD should be screened to rule out bipolar disorder Bipolar Spectrum Diagnostic Scale (BSDS)[c] • Identified 76% of patients with a bipolar diagnosis (bipolar I, II, NOS) • Identified 85% of unipolar-depressed patients as not having bipolar disease Edinburgh Postpartum Depression Scale (EPDS) (if appropriate)[d] • Validated antenatal and postpartum screening tool for minor/major depression

6. Available Screening ToolsFor the Nurse and Nurse Practitioner* (cont) *Scoring can be completed by nurses and documented in chart by nurse practitioners, depending on state/facility requirements or policies/procedures. a. Topp CW, et al. Psychother Psychosom. 2015;84:167-176; b. Psychiatric Research Unit, WHO-5, 1998; c. Posner K, et al. Am J Psychiatry. 2011;168:1266-1277; d. Harris KM, et al. PLoS One. 2015;10:e0127442; e. U.S. Department of Veteran Affairs. PTSD. 2019. World Health Organization Well-Being Index (WHO-5)[a] • Measures general well-being[a] • Raw score, 0-25; score <13 indicates poor well-being and testing for depression[b] Columbia Suicide Severity Rating Scale (C-SSRS)[c] • Designed to distinguish domains of suicidal ideation and suicidal behavior • Can be used for suicide prevention or as a treatment guide Suicidal Affect-Behavior-Cognition Scale (SABCS)[d] • Assessing affect, behavior, cognition allows some insight into the experience of the patient contemplating suicide • Re-testing can show clinically meaningful changes in suicidality Clinician-Administered PTSD Scale (CAPS-5)[e] • Gold standard for assessing post-traumatic stress disorder (PTSD) • Corresponds to DSM criteria for PTSD

7. Symptoms of Depression in MDD* • Mood changes[b] • Feeling sad, hopeless, helpless • Loss of interest in activities • Anxiety and/or depression (often twins) • Behavioral changes[b] • Restlessness or irritability • Changes in appetite (increased or decreased) • Changes in sleeping (increased or decreased) • Cognitive changes[b] • Difficulty concentrating • Distractibility • Difficulty making decisions *Applicable to nurse practitioners. a. Remick RA. CMAJ. 2002;167:253-260; b. American Psychiatric Association. Treatment of MDD/2010. SIG E CAPS[a] Sleep Interest Guilt Energy Concentration Appetite Psychomotor movement Suicidal ideation

8. Diagnosing Depression in WomenCriteria for the Nurse Practitioner Tolentino JC, Schmidt SL. Front Psychiatry. 2018;9:450. PSYCOM. Depression definition. 2019. DSM-V brief criteria • Depressed mood most of day, nearly every day (subjective/objective); sadness/emptiness • Markedly decreased interest/pleasure (subjective/objective) • Significant weight loss without dieting or weight gain; decreased or increased appetite most days • Insomnia/hypersomnia nearly every day • Psychomotor agitation or retardation nearly every day (observable by others, not ONLY subjective feelings of restlessness/slowed down)

9. Diagnosing Depression in WomenCriteria for the Nurse Practitioner (cont) Tolentino JC, Schmidt SL. Front Psychiatry. 2018;9:450. PSYCOM. Depression definition. 2019. DSM-V brief criteria • Fatigue/loss of energy nearly every day • Feelings of worthlessness/excessive or inappropriate guilt (which may be delusional) nearly every day • Decreased ability to think/concentrate, indecisiveness, nearly every day (subjective/objective) • Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without specific plan, or suicide attempt or a specific plan for suicide

10. Chronic StressImpact on Depression • Decline in rate of new neuron formation in hippocampus[a] • Compromises immune functioning[a] • Increased risk of physical illnesses • Increased risk of depression Effects of chronic stress • Influences serotonin, norepinephrine, dopamine, or neurotransmitter systems[b] • Individuals who are socially isolated or have poor coping skills • Patients receiving antidepressants showed increased neuron formation[a] a. Leonard BE, Myint A. Hum Psychopharmacol. 2009;24:165-175. b. Kumar A, et al. J Pharm Bioallied Sci. 2013;5:91-97.

11. Importance of a Strong Immune System • Bidirectional communication: immune system, central nervous system, endocrine system • Compromised immune system = increased vulnerability to illness (physical or mental) • Psychological or social stressors can impair immune functioning • Death of loved one • Marital or couple separation • Social failures • Job loss • Correlation between degree of stress and weakening of immune system • Developmental trajectory • Genetic factors (preload), personality traits, social/environmental interaction, and conditions can lead to mild inflammation, anxiety, and perceptions of social threat • Adolescence: elevated inflammatory response • Adulthood: anxiety and depression Slavich G, Irwin M. Psychol Bull. 2014;140:774-815.

12. Inflammation in MDDCause and Effect • Patients with MDD have higher levels of circulating cytokines[a] • Tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-1 and IL-6 higher in patients with MDD than healthy controls • Peripheral immune activation may be involved in pathophysiology of MDD • Further study needed to determine precise peripheral immune profile associated with MDD • Results from a systematic review and meta-analysis[b] • Antidepressant therapy significantly reduced peripheral levels of TNF-α, IL-6, IL-10, and C-C motif ligand 2 chemokine • Antidepressant therapy decreased peripheral inflammation • Effect not observed to consistently differ between responders and non-responders; further study needed a. Köhler CA, et al. Acta Psychiatr Scand. 2017;135:373-387. b. Köhler CA, et al. Mol Neurobiol. 2018;55:4195-4206.

13. Inflammatory Biomarkers in MDDTrials of Specific Antidepressants • Multicenter open-label randomized clinical trial: adults with MDD and low baseline CRP levels[a] • Results: assessment of CRP may aid in individualizing antidepressant therapy • Patients with low levels of CRP (> 1 mg/L) showed greater improvement on MADRIS* score with escitalopram than nortriptyline (3 points) • Patients with higher CRP levels showed greater improvement on MADRS* score with nortriptyline than escitalopram (3 points) • Double-blind, placebo-controlled, randomized trial: adults with treatment-resistant depression (TRD)[b] • Results: infliximab† treatment significantly reduced high-sensitivity CRP after 12 weeks of therapy compared with placebo • Conclusion: TNF-α antagonism: no generalized efficacy in TRD; improvement of depressive symptoms may occur in patients with high baseline inflammatory biomarkers *MADRS=Montgomery Åsberg Depression Rating Scale. †More study data are needed before TNF inhibitor therapy is routinely used for MDD in the office setting. a. Uher R, et al. Am J Psychiatry. 2014;171:1278-1286; b. Raison CL, et al. JAMA Psychiatry. 2013;70:31-41.

14. Inflammatory Biomarkers in MDDTrials of Specific Antidepressants (cont) • Double-blind, randomized, placebo-controlled trial: adults with serotonin reuptake inhibitor (SSRI)-resistant MDD[a] • Meta-analysis of 4 studies of celecoxib* in patients with depressive episodes[b] • Received L-methylfolate* 15 mg/d (60 days), placebo (30 days), followed by L-methylfolate 15 mg/d for 30 days or placebo for 60 days • Results: higher efficacy observed when L-methylfolate used as adjunct to SSRIs in patients nonresponsive to treatment • Finding enhanced in patients with metabolic and genetic markers related to inflammation and folate metabolism disturbance • Results: adjunctive use of celecoxib with antidepressant therapies provided significantly better efficacy compared with placebo • Further studies (longer duration and larger sample sizes) needed to evaluate efficacy/tolerability of adding nonsteroidal anti-inflammatory agents to antidepressant therapies for MDD *More study data are needed before L-methylfolate and nonsteroidal anti-inflammatory therapies are routinely used for MDD in the office setting. a. Papakostas GI, et al. J Clin Psychiatry. 2014;75:855-863; b. Na KS, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2014;48:79-85.

15. Barriers to Accessing Depression CareRural Areas RHiHub. Rural mental health. 2018. RHIHub. Barriers to treatment. 2019. Poor access to care or no available care • Shortage of mental health care providers • Overlap with other public health crises: drug abuse and suicide Reluctance to seek care: lack anonymity; shame/stigma associated with mental health issues Crisis-driven mode vs preventive mode • Lack of money/insurance for physician visits/medications • Billing issues (low reimbursement rates for mental health services) • Lack of transportation or need to drive long distances to receive mental health care

16. Addressing Depression in Rural Areas a. Mace S, et al. Telehealth. March 2018. b. FierceHealthcare. Broadband access. May 21, 2019. c. RHIHub. Barriers to treatment. 2019. Telehealth or telebehavioral health[a,b] • Issues with internet access, computer literacy, ability to use computer; need for state licensed professionals to provide care Improvement in provider reimbursement is needed[c] Collaboration between primary care providers (PCPs) and mental health providers • Assessment, diagnosis, and treatment of MDD, especially in women • Nurses/nurse practitioners can provide education to women with depression using evidence-based interventions

17. Goals of Depression CareRole of the Nurse Practitioner • Reduce symptoms Collaboration with patient, nurse, nurse practitioner, and any other healthcare provider • Reduce severity of symptoms • Symptom remission • Restore function • Prevent relapse and recurrence Kennedy S. J Psychiatry Neurosci. 2002;27:233-234.

18. Pharmacologic Treatments for MDDInformation for Nurse Practitioners • Types of Pharmacologic Treatments • Methylenetetrahydrofolate reductase (MTHFR) • MTHFR polymorphism results in an inability to process folic acid or folate[a] • MTHFR polymorphism also leads to treatment-resistant depression[b] • SSRIs[c-e] • Serotonin norepinephrine reuptake inhibitors (SNRIs)[c,e] • Tricyclic antidepressants: older; effective; higher risk of side effects and overdose[a,c] • Monoamine oxidase inhibitors: restrictions with diet, use with other medications[a,c] • Atypical antipsychotics[d,e] • Augmenting agents: low-dose lithium and atypical antipsychotics (off-label)[c,d] • Enhances effect of the antidepressant • Lithium: properties of neurogenesis,[f] suicide-protective qualities[c] • Novel agents: intravenous ketamine (off-label)[d,e] and esketamine nasal spray (FDA approved March 2019)[g] a. Wan L, et al. Translational Psychiatry. 2018;8:242; b. Duprey RP. Neuropsychiatry (London).2016;6:43-46; c. American Psychiatric Association. Treatment of MDD/2010; d. Trangle M, et al, ICSI, March 2016; e. Fasipe OJ. Arch Med Health Sci. 2018;6:81-94; f. Zanni G, et al. Sci Rep. 2017;18;7:40726; g. FDA. Esketamine approval, March 6, 2019.

19. Nonpharmacologic Treatments for MDDInformation for Nurse Practitioners • Types of Nonpharmacologic Treatments • Counseling:[a,b] important part of therapeutic process • Psychotherapy[a,b] • Cognitive behavioral therapy[a] • Interpersonal therapy[a] • Electroconvulsive therapy[a,b] • Transcranial magnetic stimulation:[a,b] newer modality • Mindfulness meditation:[a] self-care activity • Light therapy:[b] self-care activity • Community resources (eg, support groups) • Self-help books[a,b] (library or bookstore) a. American Psychiatric Association. Treatment of MDD/2010. b. Trangle M, et al, ICSI, March 2016.

20. Patient Case: Olivia • 21-year-old female • Diagnosed with MDD • Lives in Minnesota and travels to Wisconsin for treatment because health care in rural Minnesota is very limited • Treatment plan • Multiple medication failures, often due to side effects • Treatment with a multimodal therapy (eg, vortioxetine) may be successful for this patient • Nonpharmacologic treatments (eg, meditation, exercise, psychotherapy) may enhance therapy

21. Patient and Family Education for MDDInformation for Nurses and Nurse Practitioners Provide education throughout MDD management to patients and family members • Look for and recognize signs/symptoms of depression • Understand that depression is a medical illness • Awareness of safety concerns, triggers, and risk factors • Functional consequences and impairment • Lifestyle modification

22. Patient and Family Education for MDDInformation for Nurses and Nurse Practitioners (cont)

23. Patients With Residual MDD SymptomsImportance of Additional Education* • Reinforce • Importance of keeping scheduled appointments • Importance of taking medication as directed and discussing side effects • Assist • Use of a journal for questions or concerns (eg, symptoms, medication issues) • Practice self-care activities (eg, diet, exercise routine, meditation) • Support • Local support groups or online resources • Use of Smartphone apps (eg, track moods, time management, reminders to exercise or take medications) *Applicable to nurses/nurse practitioners.

24. Concluding Remarks Treatment outcomes in MDD may be improved by • Identifying depressive clinical subtypes • Using measurement-based symptom tracking • Recognizing patients' own treatment objectives • Identifying physical and mental comorbidities • Awareness of inflammatory processes • Histories of drug intolerances (vs true nonresponses)

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