Complexities of Major Depressive Disorder Podcast

Major depressive disorder (MDD) is one of the most common mental disorders in the United States. Primary care clinicians and mental health nurse practitioners are integral to addressing this common and chronic condition, as they are often at the front lines of diagnosing and managing patients with MDD. This peer exchange podcast featuring Linda Cabage, APRN, PMHNP-BC, and Katherine Sullivan, PMHNP-BC, allows busy practitioners to listen to a review of diagnostic challenges around this common and complex condition.


KS: Hello and welcome. I’m Kate Sullivan, a psychiatric mental health nurse practitioner. I am so glad to be here today to discuss major depressive disorder, or MDD, with my colleague, Linda Cabage. Welcome, Linda.

LC: Thank you, Kate. It’s nice to see you. I am also a psychiatric mental health nurse practitioner, and like Kate said, we are happy to be here today to discuss this important topic. Major depressive disorder, MDD, is one of the most common mental disorders in the United States.1 The prevalence of MDD among US adults in 2020 was estimated to be 21 million individuals, which represents 8.4% of all US adults.1 MDD has one of the highest burdens of disease worldwide and can have a major impact on the quality of life of patients.2,3 Primary care clinicians and psychiatric nurse practitioners are essential to addressing this common and chronic condition, as we are often at the front lines of diagnosing and managing patients with MDD.

KS: That’s right, Linda. Screening for depression is recommended as part of routine primary care in all adults.4 However, approximately half of patients are not screened for depression by their healthcare providers.5 Multiple studies have suggested that the diagnosis of MDD is missed in up to 50% of primary care patients.6,7

LC: Let’s review the diagnosis of MDD for just a moment. MDD may be diagnosed when an individual has a persistently low or depressed mood and/or anhedonia, also known as decreased interest in pleasurable activities. Additional symptoms that can uncover this diagnosis may include feelings of guilt or worthlessness, lack of energy, poor concentration, appetite changes, psychomotor retardation or agitation, sleep disturbances, or suicidal thoughts.8 Five or more of these symptoms should be present during the same 2-week period and represent a change from previous functioning to diagnose a patient with MDD. Importantly, at least 1 of the 5 symptoms that are present must be depressed mood or anhedonia.8 A diagnosis based on a single episode is possible, although the disorder is recurrent in most cases.8

KS: Linda, I find it useful to think of the mnemonic “SIG–E–CAPS” to remember the symptoms of MDD. SIG-E-CAPS stands for:

  • Sleep: insomnia or hypersomnia
  • Interest: reduced, with loss of pleasure
  • Guilt: often unrealistic
  • Energy: mental and physical fatigue
  • Concentration: distractibility, memory disturbance, indecisiveness
  • Appetite: decreased or increased
  • Psychomotor: retardation or agitation
  • Suicide: thoughts, plans, behaviors.

Despite the clear diagnostic criteria we reviewed, MDD can be commonly misdiagnosed and underdiagnosed in the primary care setting, which may contribute to poor treatment outcomes.9,10 This is a reason why using validated screening and diagnostic tools, such as the 9-item Patient Health Questionnaire, also called PHQ-9, is an important practice in identifying and managing patients with MDD.11 We know that the PHQ-2 and PHQ-9 are widely used in primary care settings, as patients may complete the PHQ-9 while awaiting their visit with the clinician, and it can be quick to score.12

LC: I like that mnemonic, too, Kate. It's a good reminder of the importance of screening all of our patients. Let’s move on to discuss some of the diagnostic challenges and the possibilities of misdiagnosing MDD. Things we as clinicians can keep in mind are common characteristics of patients with MDD, and some groups of patients that may be more likely to be underdiagnosed. In the United States, the median age of onset of MDD is around 30 years old.13 MDD is more common among neurodivergent people, younger adults, individuals with lower incomes, and in adults who are divorced, separated, or widowed.14,15 Patients who are more likely to have MDD diagnosis missed include men, people over age 75, individuals who are Black, Indigenous, people of color, or BIPOC, and uninsured patients.5

I also keep in mind that MDD is a diagnosis of exclusion. That means potential medical causes of depression should be ruled out before diagnosing an individual with MDD. It is also important to consider other psychiatric conditions, including but not limited to bipolar disorder.8

KS: There are also symptoms we may not associate with MDD that we should carefully consider. These include psychotic features, which can occur in approximately 16% to 54% of patients diagnosed with MDD.16,17 MDD with psychotic features tends to be more common among patients with more severe depressive symptoms. It can also be associated with a more difficult course of illness and worse functional impairment than MDD without psychotic features.16 One study of inpatients with MDD with psychotic features noted that the 3 most common misdiagnoses were MDD without psychotic features, depression not otherwise specified, and mood disorder not otherwise specified.17

LC: I also try to remember that older adults are often misdiagnosed and undertreated.18 Healthcare providers may mistake MDD in older adults as a natural reaction to the life changes associated with aging. Older adults may likewise ascribe depressive symptoms to normal aging and may not seek help. They may not understand that with appropriate treatment, they could feel better.

KS: That’s an important point, Linda. There are several reasons for these missed diagnoses and missed opportunities to relieve suffering. For example, older patients may also present with different symptoms than younger patients.

LC: The symptoms we may be most familiar with, such as depressed mood, are more likely to present in younger patients.19 Younger patients also may be more likely to present with hyperphagia, hypersomnia, fatigue, poor concentration, and agitation. On the other hand, older patients are more likely to present with loss of appetite, insomnia, physical tiredness, cognitive deficits, gastrointestinal complaints, and psychomotor retardation.19

KS: Absolutely. And studies have shown that depressive disorders are associated with elevated mortality and decreased quality of life in older patients.20 Early detection and management of depressive symptoms in older adults can contribute to the improvement of mental disorders and quality of life, showing us how important it is to consider this diagnosis in our patients.20

In addition to considering age-related differences in presentation and the variations in diagnosis, I also like to consider minoritized populations. The prevalence of diagnosed MDD is 31% lower in majority Black communities and 39% lower in majority Hispanic communities as compared to majority White communities.20 If we assume that MDD prevalence is likely similar across different US communities, regardless of ethnoracial make-up, this suggests that MDD could be underdiagnosed in these populations.20

LC: That’s right, Kate. Other factors may be at play here as well. In this case, I believe stigma may be more of a factor in deciding to seek care in Black and Hispanic communities. In fact, one survey found that 54% of Black respondents and 47% of Hispanic respondents, compared to only 38% of White respondents, felt that individuals with mental health conditions are looked down upon in their communities.21 Also, we can’t forget about the potential for healthcare providers to hold implicit bias, which can be a barrier to accessing care. Black patients can be more likely to have their emotional symptoms minimized by clinicians and less likely to have access to comprehensive medical care, including psychiatric care.22

KS: There may also be differences in how patients present based on varying ethnoracial backgrounds. Black patients with mental health needs, for example, may be more likely to present to care with somatic complaints.22

LC: That leads us into a discussion of some symptoms that may be more common within a major depressive disorder diagnosis – anxiety and anhedonia. I try to remind myself that depression and anxiety often present together, with rates ranging from 40% to 50%.23 Healthcare providers should be aware of all the presenting symptoms when considering a diagnosis…

KS: …especially concerning anxiety symptoms as part of a major depressive episode, Linda. The DSM-5 lists anxious distress as one specifier for depressive disorders.8 Anxious depression is diagnosed when a patient has at least 2 of the following symptoms for the majority of the days of a major depressive episode: feeling keyed up or tense, feeling unusually restless, having difficulty concentrating because of worry, being afraid that something awful may happen, or feeling that they may lose control of themselves.8 Among patients diagnosed with MDD, the prevalence of anxious depression is estimated to be 54% to 78%.24

LC: That’s right. In fact, about 75% of patients diagnosed with MDD have symptoms characterized by this anxiety specifier.14 Higher levels of anxiety in MDD can be associated with inferior treatment outcomes.25 In particular, such patients have a lower likelihood of remission and may experience a longer period before achieving remission.25 This underscores the importance of recognizing the heterogeneity of depressive disorders among patients diagnosed with MDD.

KS: Another symptom of interest is anhedonia. Higher levels of anhedonia in MDD can also be associated with poorer treatment outcomes.24 As we reviewed earlier, anhedonia is one of the core symptoms of MDD according to the DSM-5 criteria and has important functional consequences for patients. Anhedonia can be a barrier to engagement, motivation, and enjoyment of life.26

LC: These are all important points, Kate. Our listeners might be wondering, how are these symptoms assessed?

KS: Well, assessing specific symptoms in patients with diagnosed MDD, such as anxiety and anhedonia, can be done using clinical scales. The Hamilton Anxiety Rating Scale, or HAM-A, is a clinician-rated instrument used for quantifying anxiety symptoms.27 This 14-item rating scale can be used to assess anxiety symptoms in patients with MDD and has been used in clinical trials to measure effects on anxiety symptoms.27

LC: Another scale to consider is the Hamilton Depression Rating Scale, or HAM-D. The HAM-D includes an anxiety/somatization subscale focusing on 6 items out of the total of 17. There’s psychic anxiety, somatic anxiety, somatic symptoms, hypochondriasis, and insight. Somatic symptoms can be both general and specific to gastrointestinal symptoms.28

KS: Finally, you may want to consider using the Montgomery–Åsberg Depression Rating Scale, or MADRS. Some investigators have found it helpful to assess overall depressive symptoms and anhedonia separately. Overall, severity of depressive symptoms can be assessed using the MADRS total score, while anhedonia can be separately assessed using the MADRS 5-item anhedonia subscale. This subscale includes 5 of the 10 items from the MADRS, including apparent sadness, reported sadness, concentration difficulties, lassitude, and inability to feel.29

KS: With all of what we have discussed today, it is important that we recognize the urgency surrounding the unmet needs of MDD patients, as MDD is commonly misdiagnosed and underdiagnosed, particularly in the primary care setting.9,10 A comprehensive understanding of the differential diagnosis for MDD, and an awareness of the challenges in diagnosing MDD in different patient populations, can help healthcare providers in ensuring they consider MDD as a diagnosis when appropriate. Accurate initial and ongoing assessment, as well as early and adequate management of the disease, are important in optimizing patient outcomes. Delayed diagnosis and delayed initiation of antidepressant treatment make it less likely that a patient will be able to achieve remission.30

LC: The heterogeneity of depressive disorders is so important to consider. Patients with anxiety symptoms as part of their MDD, for example, exhibit worse functioning, poorer quality of life, and less than optimal treatment outcomes.24 We should remember the usefulness of clinical scales in assessing specific symptoms and changes in symptom severity over time, and we should encourage using these tools in our day-to-day clinical practice.

KS: Once a diagnosis of major depressive disorder is confirmed, partnering with patients and using shared decision-making while considering different treatment options and individualized management strategies is important.31 We hope that the material reviewed today helps each of you in your continued work through the complexities and challenges in working with patients diagnosed with MDD. I want to thank my colleague, Linda, for joining me today.

LC: It’s been a pleasure, Kate. And thank you all for joining us for this discussion. Remember, the NP Psych Navigator website can serve as a useful and accessible resource with more information for you and your patients on identifying and managing MDD and other mental health conditions. Goodbye!

Kate Sullivan, PMHNP-BC

Kate Sullivan is an American Nurses Credentialing Center board-certified adult psychiatric nurse practitioner who provides psychiatric evaluation and medication management services for adults 16 years old and over. Kate has been a psychiatric nurse practitioner for 12 years, and has worked in private practice, specializing in complex trauma, forensics, end of life issues, and LGBTQIA and neurodivergent populations. She currently works at a respected neuropsychology practice, Knoxville Behavioral & Mental Health Services, where she is the sole prescriber. Kate serves on the Crisis Stabilization Team for the Knoxville Police Department and is a regular teacher in their Police Academy on the subject of posttraumatic stress disorder. She had a major research paper on bipolar disorder published in 2020 and is a revered speaker, across the state and nationally, on a diverse array of subjects. She continues to be highly sought after as a thought leader in her field by a multitude of private firms, first responder departments, medical and other research groups.

Linda Cabage, APRN, PMHNP-BC

Linda Cabage is a board-certified psychiatric-mental health nurse practitioner in Maryville, Tennessee, a suburb of Knoxville. After graduating from the University of Tennessee, Linda worked in community mental health before starting her own private practice, where she has continued to see patients of all ages for the past 10 years and provides medication management and psychotherapy. She worked as a registered nurse in oncology, geriatrics, and mental health before becoming a nurse practitioner. Her additional interests include complementary and alternative medicine, cultural awareness, care equity for marginalized groups, particularly LGBTQ+ populations, and academic research. She is currently a PhD candidate investigating the effects of the COVID-19 pandemic on nurse practitioners providing care to patients via telehealth. Linda enjoys gardening, cooking, reading, spending time with 2 young adult sons, traveling with her husband, and being manipulated by their 2 yellow tabby cats. 


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