Clinical Depression/Major Depressive Disorder (MDD): Symptoms, Causes, Risk, and Treatment

Clinical depression involves persistent feelings of sadness, hopelessness, and loss of interest in activities once enjoyed. It affects a person’s thoughts, emotions, and behaviors, significantly impacting their daily functioning and quality of life. To be diagnosed with MDD, an individual must experience at least five symptoms for a minimum of two weeks, including depressed mood or loss of interest, along with changes in sleep, appetite, energy levels, concentration, and self-worth.

Clinical depression often arises from a complex interplay of various influences. Genetic predisposition, alterations in brain chemistry, chronic stress, trauma, and certain medical conditions like cancer or heart disease can all contribute to the development of depression.  contribute to the development of MDD, according to the  National Research Council and Institute of Medicine. (2009).  Diagnosis of MDD involves a thorough evaluation by a psychiatrist, including a detailed assessment of symptoms, medical history, and potential underlying causes. Blood tests may be ordered to rule out other medical conditions that can mimic depression.

According to Kamenov et al. (2017), psychotherapy and pharmacotherapy, the treatment of clinical depression involves a combination of psychotherapy and medication. Cognitive-behavioral therapy (CBT) and interpersonal therapy are effective forms of psychotherapy that help individuals identify and change negative thought patterns and behaviors. Antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs), can help regulate brain chemistry and alleviate symptoms. In some cases, electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) may be recommended for treatment-resistant depression.

While both clinical depression and anxiety can co-occur and share some symptoms, they are distinct conditions. Depression primarily involves persistent low mood and loss of interest, while anxiety is characterized by excessive worry and fear. Depression tends to focus on past experiences and feelings of worthlessness, whereas anxiety is often future-oriented and involves anticipation of potential threats. 

What is clinical depression (MDD)?

Clinical depression, also known as major depressive disorder (MDD), is a common mental disorder characterized by a persistently depressed mood and a loss of interest or pleasure in activities, according to a Cleveland Clinic article titled “Clinical Depression (Major Depressive Disorder)” (Nov 2022). It is a severe medical condition that affects how a person feels, thinks, and behaves, causing significant impairment in daily functioning. 

To receive a diagnosis of MDD, an individual must experience at least five symptoms, including depressed mood or loss of interest, for at least two weeks. These symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Major depressive disorder is characterized by feelings of sadness, tearfulness, emptiness, or hopelessness that persist nearly every day. Individuals may experience angry outbursts, irritability, or frustration over minor matters. A hallmark symptom is the loss of interest or pleasure in most or all normal activities, such as hobbies, sports, or sexual activities. 

Other common symptoms include significant changes in appetite and weight, sleep disturbances (insomnia or sleeping too much), fatigue or loss of energy, difficulty thinking or concentrating, and recurrent thoughts of death or suicide.

The cause of MDD results from a complex interplay of genetic, biological, environmental, and psychological factors. Risk factors include a family history of depression, significant life changes or stressors, certain medical conditions, and the use of certain medications. 

MDD affects people of all ages but is more common in women and typically begins in the 20s, although it can develop at any age. In 2021, the prevalence of major depressive episodes was higher among adult females (10.3%) compared to males (6.2%), according to a 2023 report from the National Institute of Mental Health.

MDD is a significant public health concern, with the World Health Organization projecting it to be the leading cause of disease burden worldwide by 2030. 

The lifetime prevalence of MDD is estimated to be between 5% and 17%. It is associated with a high risk of suicide, with about two-thirds of individuals with MDD contemplating suicide and 10-15% committing suicide, according to a study titled “Prevalence of Suicidality in Major Depressive Disorder” by Hong Cai ( Sep 2021). 

Treatment of MDD involves a combination of psychotherapy (such as cognitive-behavioral therapy or interpersonal therapy) and antidepressant medications. With proper treatment, many individuals with MDD can achieve remission and improved quality of life.

What are the types of clinical depression (MDD)?

The main types of clinical depression (major depressive disorder), according to a WebMD study titled “Types of Depression and How to Recognize Them” by Jabeen Begum (July 11, 2024), include melancholia, psychotic depression, and antenatal or postnatal depression.

Melancholia

Melancholia is a severe form of depression characterized by significant physical symptoms. Individuals with melancholia experience a slowing of movement, profound sadness, and an inability to find pleasure in any activities. It is often considered a distinct subtype of major depressive disorder due to its unique symptom profile, according to Kendra Kubala’s 2022 review “What to know about melancholic depression” in Medical News Today.

Psychotic Depression

Psychotic depression is a type of major depressive disorder that includes symptoms of psychosis, such as delusions or hallucinations. People with psychotic depression experience delusions (false beliefs) or hallucinations (seeing or hearing things that aren’t there) alongside typical depression symptoms. This subtype is particularly severe and often requires a combination of antidepressant and antipsychotic medications. Psychotic depression is associated with a higher risk of suicide and requires prompt and aggressive treatment, according to Wagner, G. S., McClintock et al. 2011. Major Depressive Disorder with Psychotic Features May Lead to Misdiagnosis of Dementia: Journal of Psychiatric Practice.

Antenatal or Postnatal Depression

Antenatal depression refers to depression that occurs during pregnancy, while postnatal depression occurs after childbirth. Symptoms include severe mood swings, exhaustion, and a sense of hopelessness, which can interfere with the ability to care for oneself and the baby. Postnatal depression affects approximately 10-15% of new mothers, according to a study titled “Prevalence of postpartum depression and interventions utilized for its management” by Reindolf Anokye (2018).

It is crucial to address this form of depression promptly to ensure the well-being of both the mother and the child. Antenatal depression can have significant impacts on pregnancy outcomes and fetal development.

These subtypes of major depressive disorder highlight the diverse manifestations of clinical depression, each requiring specific diagnostic and therapeutic approaches to manage effectively.

What are the symptoms of clinical depression (MDD)?

The main symptoms of clinical depression (major depressive disorder, MDD) include persistent sadness, loss of interest in activities, and several other emotional, physical, and cognitive changes, according to a post on the National Institute of Mental Health titled “Depression.”

• Sadness or loss of interest in activities: A persistent sadness or a lack of interest in activities once enjoyed, which lasts for most of the day, nearly every day.
• Irritability: Frequent angry outbursts or irritability over minor matters.
• Restlessness: A sense of agitation or restlessness, often unable to sit still.
• Feelings of emptiness: A pervasive sense of emptiness or hopelessness.
• Hopelessness or pessimism: Persistent hopelessness or a pessimistic outlook on life.
• Fatigue: Chronic tiredness and lack of energy, making even small tasks seem exhausting.
• Difficulty sleeping or sleeping too much: Insomnia or oversleeping, disrupting standard sleep patterns.
• Difficulty eating or overeating: Changes in appetite, leading to weight loss or weight gain.
• Weight changes: Noticeable weight loss or gain unrelated to dieting.
• Headache: Frequent headaches or other unexplained physical problems.
• Digestion problems: Gastrointestinal issues without a clear physical cause.
• Thoughts of suicide: Frequent thoughts of death, suicidal ideation, or suicide attempts.
• Engaging in high-risk behaviors: Increased engagement in risky behaviors without regard for consequences.
• Becoming withdrawn: Social withdrawal and isolation from friends and family.
• Substance use: Increased use of alcohol or drugs as a coping mechanism.
• Isolation: A tendency to isolate oneself from social interactions.
• Difficulties with responsibilities: Struggles with fulfilling school, work, or family duties.
• Sexual dysfunction: Reduced interest in or difficulty with sexual activities.

Clinical depression affects millions of people worldwide and can significantly impair daily functioning. According to the Mayo Clinic, approximately one in six people will experience a major depressive episode in their lifetime, and up to 16 million adults in the United States suffer from clinical depression annually. 

The National Institute of Mental Health emphasizes that MDD is a leading cause of disability and a significant contributor to the global burden of disease. Treatment involves a combination of medication and psychotherapy, which is more effective than either treatment alone.

What are the symptoms of clinical depression (MDD) in children?

The main symptoms of clinical depression (Major Depressive Disorder) in children include sad or irritable mood, loss of interest or pleasure, changes in sleep patterns, changes in appetite or weight, fatigue or energy loss, difficulty concentrating, feelings of worthlessness or guilt, physical complaints and thoughts of death or suicide, according to Dr. Black S’s 2024 post “Pediatric Depression” in the Medscape journal.

• Sad or irritable mood: Children may appear persistently sad, tearful, or irritable for extended periods, lasting at least two weeks.

• Loss of interest or pleasure: Children may lose interest in activities they previously enjoyed, including hobbies, sports, or spending time with friends.

• Changes in sleep patterns: Children may experience insomnia, difficulty falling asleep, or sleeping excessively.

• Changes in appetite or weight: Significant weight loss or gain or changes in eating habits may occur.

• Fatigue or energy loss: Children may feel tired, lethargic, or lack motivation to engage in daily activities.

• Difficulty concentrating: Problems with focus, memory, or decision-making may be present, often affecting school performance.

• Feelings of worthlessness or guilt: Children may express excessive self-criticism or unwarranted feelings of guilt.

• Physical complaints: Unexplained headaches, stomachaches, or other physical symptoms that don’t respond to treatment may occur.

• Thoughts of death or suicide: In severe cases, children may express thoughts of death or engage in suicidal behavior.

Research from the National Institute of Mental Health indicates that approximately 3.2% of children aged 3-17 years in the United States have been diagnosed with depression. 

It’s important to note that symptoms may vary in severity and presentation depending on the child’s age and developmental stage. Early identification and intervention are crucial for effective treatment and prevention of long-term consequences.

Why are signs of clinical depression seen more in women compared to men?

Signs of clinical depression are seen more in women compared to men due to a combination of biological, hormonal, and social factors, according to Di Benedetto et al. (2024). Depression in Women: Potential Biological and Sociocultural Factors Driving the Sex Effect. Neuropsychobiology.

This study highlights that regardless of ethnicity or financial status, women experience depression at least twice as often as males. The unique clinical and course characteristics of depression in women lend credence to particular etiopathogenetic variables. Female patients are significantly more likely to experience unusual symptoms such hypersomnia, hyperphagia, and hyperreactivity of the mood, as well as increased susceptibility to stress, seasonality, longer episode durations, higher recurrence rates, and more chronicity.

Women are nearly twice as likely to be diagnosed with depression, and this disparity begins around puberty and persists throughout life. Biological factors such as fluctuating hormone levels during puberty, menstruation, pregnancy, postpartum, and menopause significantly contribute to this increased risk. 

In 2010, for instance, the global yearly prevalence of depression in men and women was 3.2% and 5.5, respectively. In 2002, the prevalence was 2.9% in men and 5.0% in women in Canada. The prevalence was 3.6% in males and 5.8% in women, according to Shi, P., Yang, et al. (2021). A Hypothesis of Gender Differences in Self-Reporting Symptom of Depression.

Furthermore, societal stressors such as gender inequality and cultural expectations can exacerbate depressive symptoms in women. Neuroimaging studies have shown sex differences in brain regions associated with depression, suggesting that both hormonal and neurobiological factors contribute to the higher prevalence of depression in women.

What are the causes of clinical depression (MDD)?

The causes of clinical depression (Major Depressive Disorder or MDD) include genetic factors, brain chemistry imbalances, environmental stressors, and certain medical conditions.

• Genetic factors: Genetics is the study of genes, heredity, and genetic variation in living organisms. Depression occurs in people with a similar family history, with heritability estimated at 40-50%, according to the National Institute of Health Journal titled “Major Depressive Disorder” by Navneet Bains (April 2023).

• Brain chemistry: Brain chemistry refers to the complex chemical processes within the brain. According to Sekhon S. and Gupta V. Mood 2024 “Mood Disorder” in StatPearls Publishing Journal, imbalances in neurotransmitters like serotonin, norepinephrine, and dopamine significantly affect mood regulation.

• Environmental stressors: Environmental stressors are factors present within the environment that can adversely affect biological systems. Traumatic, stressful events, chronic stress, loneliness, and adverse childhood experiences can trigger depression.

• Medical conditions: Medical conditions are a broad category of health issues that affect the human body, e.g., heart disease, diabetes, cancer, and mental health disorders. The National Mental Institute of Mental Health article, “What is Depression,”  2024, suggests that certain illnesses, such as thyroid disorders, cancer, and chronic pain, can contribute to the development of depression.

• Personality traits: Personality traits define an individual’s behavior, thoughts, and emotions.  According to Yavari, S. et.al (2023). Self-esteem and optimism in patients with major depression disorder Annals of Medicine and Surgery, individuals with low self-esteem or a pessimistic outlook are more susceptible to depression.

• Hormonal changes: Hormonal changes are changes in the body’s chemistry and can significantly impact personality traits. The Johns Hopkins Medicine Journal, “Can Menopause Cause Depression?” suggests that pregnancy, postpartum period, and menopause increase the risk of depression in women.

• Substance use: Substance use is the consumption of any psychoactive substance, including legal and illegal drugs such as alcohol, tobacco, cannabis, cocaine, heroin, methamphetamine, and prescription medication. Alcohol and drugs cause and escalate depressive symptoms.

• Social isolation: Social isolation is the lack of social interaction or connection with others. Loneliness and lack of social support are associated with an increased risk of depression, according to Wu, P.  (2008). “The Relationship Between Depressive Symptom Levels and Subsequent Increases in Substance Use Among Youth With Severe Emotional Disturbance. Journal of Studies on Alcohol and Drugs.

It’s important to note that depression often results from a complex interplay of these factors rather than a single cause.

What are the biological and chemical causes of clinical depression (MDD)?

The biological and chemical causes of clinical depression (MDD)  are primarily genetic factors, neurotransmitter imbalances, hormonal changes, and brain structure abnormalities, according to a study titled “Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention” by England MJ (2009).

• Genetic Factors: Genes are the basic units of heredity that determine our traits and characteristics. Family history and genetic predisposition play a significant role in the risk of developing MDD. Individuals with relatives who have depression are more likely to experience it themselves, suggesting that inherited traits influence susceptibility to the disorder, according to Bains N, Abdijadid S. Major Depressive Disorder.  StatPearls Publishing; 2024.
• Neurotransmitter Imbalances: Neurotransmitter Imbalances occur when the levels of certain chemicals in the brain, such as serotonin and dopamine, are not functioning properly. According to the National Institutes of Health (US) review 2007, changes in neurotransmitter systems are central to understanding the biological underpinnings of depression. Information about Mental Illness and the Brain.
• Hormonal Changes: Hormones are chemical messengers that regulate various bodily functions, including mood. If there is a change in hormones such as cortisol and estrogen, it causes the development of depression, according to Kundakovic M, Rocks D. Sex hormone fluctuation and increased female risk for depression and anxiety disorders, Front Neuroendocrinol Journal. This study showed that the natural hormonal shifts associated with menstruation, postpartum, and menopause increase the risk of anxiety and depression due to periodic neurochemical adaptations, specifically in the serotonergic function that is crucial for mood regulation and anxiety levels. This “withdrawal” or drop in estrogen during these shifts increases the risk of anxiety and depression.
• Brain Structure Abnormalities: Brain chemistry is the physical makeup of the brain, including its size, shape, and connections. According to Trifu SC et al., Brain changes in depression. PMCID Journal, individuals with depression may have structural abnormalities in certain areas of the brain associated with emotion regulation and decision-making.
• Environmental Factors: Environmental factors are external influences that can contribute to the development of depression. These include traumatic events, chronic stress, or exposure to certain toxins or substances. The WHO 2023 report, “Depressive disorder (depression),” suggests that stressful life events, such as trauma or loss, can trigger or worsen depression symptoms.

Understanding these biological and chemical factors is essential for developing effective treatment strategies for MDD, as they highlight the disorder’s complex interplay between genetics, brain chemistry, and hormonal regulation.

What are the different causes of clinical depression (MDD) in men and women?

The leading causes of clinical depression (MDD) in men and women are hormonal changes, genetics and family history, chronic illness, physical health, and life circumstances and culture, as reviewed by Bains N, Abdijadid  & S. Major Depressive Disorder. StatPearls Publishing.

• Hormonal Changes: Hormonal changes are defined as fluctuations in levels of hormones such as estrogen, testosterone, and progesterone, which can affect an individual’s mood. Fluctuations during puberty, pregnancy, postpartum depression, perimenopause, and menopause can significantly impact mood, according to Kundakovic M, Rocks D. Sex hormone fluctuation and increased female risk for depression and anxiety disorders, Front Neuroendocrinol Journal. Other issues include premenstrual problems,
• Genetics and Family History: Genetics is defined as the study of genes and their role in inheritance. Studies have shown that individuals with a family history of depression are at a higher risk of developing MDD. According to a Stanford Medicine article on “Major Depression and Genetics,” genetic factors contribute to about 40% of the risk for developing depression.
• Chronic Illness and Physical Health: Chronic illness refers to any medical condition that is long-lasting and can significantly impact an individual’s physical health. There’s a link between chronic illness and increased rates of depression in both men and women, as reviewed by Zhou P, Wang et al. “Association between chronic diseases and depression in the middle-aged and older adult Chinese population,” Front Public Health. 2023.
• Life circumstances and culture: Life circumstances include major life events, trauma, and stress that can trigger depression in both men and women. Additionally, cultural factors such as societal expectations and gender roles can contribute to the development of MDD in men and women. According to the Office of the Surgeon General (US) and the Center for Mental Health Services (US); 2001, different cultures have varying rates of depression due to differences in attitudes toward mental health and seeking treatment.

The prevalence of MDD is significant, affecting 5% to 17% of people at some point in their lives, with a higher prevalence in women and specific age groups, according to the National Institute of Mental Health post, “Major Depression.” Early and accurate diagnosis is crucial for effective treatment and management of this standard and severe mental health condition.

Understanding these causes is crucial for effective treatment and prevention strategies, as tailored approaches can significantly improve outcomes for those affected by MDD.

How do we diagnose clinical depression (MDD)?

Clinical depression is diagnosed through a comprehensive evaluation process that includes a clinical interview, symptom assessment, duration and severity evaluation, exclusion of other conditions, use of diagnostic criteria, screening tools, physical examination, and laboratory tests, according to the Cleveland article “Clinical Depression (Major Depressive Disorder)” (Nov 2022).

• Clinical Interview: A clinical Interview is a dialogue between the clinician and the client to gather information about the client’s current mental health status, background, and present concerns. A mental health professional conducts a thorough interview to gather information about the patient’s symptoms, medical history, family history, and psychosocial factors.
• Symptom Assessment: Symptom Assessment is the process of evaluating and diagnosing a patient’s symptoms to determine the underlying cause of their discomfort or illness. The clinician evaluates for critical symptoms of MDD, including persistently low or depressed mood, anhedonia (decreased interest in pleasurable activities), feelings of guilt or worthlessness, lack of energy, poor concentration, appetite changes, psychomotor retardation or agitation, sleep disturbances, and suicidal thoughts.
• Duration and Severity Evaluation: Symptoms must be present for at least two weeks and cause significant distress or impairment in social, occupational, or other important areas of functioning.
• Exclusion of Other Conditions: Duration and severity evaluation assesses how long a particular activity or event has been going on and how much impact it has had. In project management, duration and severity evaluation are crucial for understanding a project’s progress and identifying potential risks that may arise. The clinician rules out other potential causes of depressive symptoms, such as medical conditions, substance use, or bipolar disorder.
• Use of Diagnostic Criteria: The diagnosis is based on the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). To meet the criteria for MDD, an individual must have five or more symptoms, including either depressed mood or anhedonia.
• Screening Tools: Screening Tools identify potential candidates for a job position. Standardized depression rating scales such as the Patient Health Questionnaire-9 (PHQ-9), Hamilton Rating Scale for Depression (HAM-D), or Beck Depression Inventory (BDI) are used to assess symptom severity and aid in diagnosis.
• Physical Examination and Laboratory Tests: Physical examination and laboratory tests evaluate a patient’s health by assessing their body systems and obtaining information through various methods such as observation, palpation, percussion, and auscultation. A complete physical examination and routine laboratory tests are often performed to rule out underlying medical conditions that could contribute to depressive symptoms.

Diagnosing clinical depression (MDD) is a complex process that involves multiple components. It requires a comprehensive evaluation by a qualified mental health professional to accurately diagnose and provide appropriate treatment for those struggling with MDD.

What are the DSM-5 criteria for the diagnosis of clinical depression (MDD)?

The DSM-5 criteria for the diagnosis of clinical depression (Major Depressive Disorder or MDD) include the presence of five or more symptoms during the same two-week period, representing a change from previous functioning, according to a study titled “DSM-5 Changes: Implications for Child Serious Emotional Disturbance”.

The symptoms include depressed mood, loss of interest or pleasure, significant weight changes, sleep disturbances, psychomotor changes, fatigue, feelings of worthlessness or guilt, difficulty concentrating, and thoughts of death or suicide. 

To meet the diagnostic criteria, an individual must experience at least five of these symptoms, with at least one being a depressed mood or loss of interest/pleasure, for a minimum of two weeks.

The diagnostic procedure for Major Depressive Disorder (MDD) involves the following steps:

• Symptom Assessment: Symptom Assessment identifies, evaluates, and monitors symptoms. Evaluate the presence and severity of depressive symptoms, ensuring they have been present for at least two weeks.

• Functional Impairment: Functional Impairment is the limitation or restriction of an individual’s ability to perform everyday activities due to a physical, mental, or emotional condition. Determine if the symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

• Exclusion of Other Causes: Excluding other causes means ruling out potential causes of a particular phenomenon or event. For example, symptoms attributable to substance use, medication side effects, or other medical conditions should be excluded.

• Differential Diagnosis: Differential Diagnosis identifies and distinguishes between diseases or conditions with similar signs and symptoms. Distinguish MDD from other mood disorders, such as bipolar disorder or persistent depressive disorder (dysthymia).

• Severity Evaluation: Severity evaluation assesses and determines the seriousness or harm caused by a particular event, incident, or situation. Assess the severity of the depressive episode (mild, moderate, or severe) based on the number and intensity of symptoms and functional impairment.

The diagnostic procedure for MDD is a comprehensive process that involves gathering information about an individual’s symptoms, and functional impairment, ruling out other potential causes, and distinguishing it from other mood disorders. Seeking professional help and support is essential for individuals experiencing symptoms of MDD.

What are the recommended treatments for clinical depression (MDD)?

The options for the treatment of clinical depression (MDD) include FDA-approved medications, psychotherapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and ketamine, according to a study titled “Major Depressive Disorder”  by Navneet Bains (April 2003).

• FDA-approved medications: FDA-approved medications are approved by the Food and Drug Administration (FDA) for treating specific medical conditions.  These include several classes of antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRIs) like citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil, Pexeva), sertraline (Zoloft), and vilazodone (Viibryd). SSRIs are typically the first line of treatment due to their favorable side effect profiles. 
• Other classes include Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), tricyclic antidepressants (TCAs), and Monoamine Oxidase Inhibitors (MAOIs). Recent FDA approvals also include gepirone, which targets the serotonin 1A receptor and is noted for fewer side effects like sexual dysfunction and weight gain.
• Psychotherapy: Psychotherapy is a treatment that involves various therapeutic approaches such as Cognitive Behavioral Therapy (CBT), Interpersonal Psychotherapy (IPT), Mindfulness-Based Cognitive Therapy (MBCT), psychodynamic therapy, and supportive therapy. CBT changes negative thought patterns and behaviors associated with depression.
• Electroconvulsive Therapy (ECT): ECT involves brief brain electrical stimulation while the patient is under anesthesia. It is particularly effective for severe depression, acute suicidality, and treatment-resistant cases. Despite its efficacy, ECT is often reserved for cases where other treatments have failed due to its invasive nature.
• Transcranial Magnetic Stimulation (TMS): Transcranial Magnetic Stimulation is a non-invasive brain stimulation technique that uses magnetic fields to stimulate nerve cells in the brain. It is FDA-approved for treatment-resistant depression and is less invasive than ECT, making it an attractive option for patients who have not responded to medications.
• Vagus Nerve Stimulation (VNS): Vagus Nerve Stimulation involves a surgical implant device stimulating the vagus nerve. It is approved for long-term adjunctive treatment of treatment-resistant depression, particularly in patients who have failed multiple medication trials.
• Esketamine: Esketamine is an antidepressant that is used to treat major depressive disorder in adults who have not been responding well to other anti-depressant medications. Administered as a nasal spray, esketamine is used in conjunction with an oral antidepressant for treatment-resistant depression. It is particularly noted for its rapid onset of action, making it beneficial for patients with suicidal ideation or behavior.

These treatment options are supported by extensive research and are tailored to address the diverse needs of patients with MDD, providing a comprehensive approach to managing this complex condition.

How is clinical depression (MDD) different from anxiety?

The main difference between clinical depression (Major Depressive Disorder, MDD) and anxiety is that MDD is characterized primarily by persistent feelings of sadness and hopelessness. In contrast, anxiety is defined by excessive worry and fear about potential threats or dangers, according to Dr Karin Gepp’s 2022 review on the Medical News Today. 

Clinical depression (Major Depressive Disorder or MDD) and anxiety are distinct mental health conditions with some key differences, although they often co-occur. Depression is primarily characterized by persistent feelings of sadness, hopelessness, and reduced energy, along with a loss of interest in activities once enjoyed. 

In contrast, anxiety is marked by excessive worry, nervousness, and a sense of dread about future events, often accompanied by physical symptoms like agitation and restlessness. While both conditions affect sleep, concentration, and overall functioning, depression tends to involve more profound mood changes and a lack of motivation. In contrast, anxiety typically involves heightened alertness and fear responses. 

Nearly 50% of individuals diagnosed with MDD also experience anxiety disorders, indicating a complex relationship where one can exacerbate the other, according to Hopwood M’s 2023 study on Anxiety Symptoms in Patients with Major Depressive Disorder.

Proper diagnosis by a mental health professional is crucial, as treatment approaches may differ depending on whether a person is experiencing depression, anxiety, or both.

What is the DSM-5 code for clinical depression (MDD) with anxious distress?

The DSM-5 code for major depressive disorder (MDD) with anxious distress is not separate but rather a specifier added to the existing MDD codes. Here’s a table presenting the relevant codes and specifications described in Substance Abuse and Mental Health Services Administration 2016 Jun.

Severity	Single Episode	Recurrent Episode	With Anxious Distress
Mild	F32.0	F33.0	Add specifier
Moderate	F32.1	F33.1	Add specifier
Severe	F32.2	F33.2	Add specifier

Clinicians should add the specifier “with anxious distress” to the appropriate MDD code to indicate anxious distress. For example, a single episode of moderate MDD with anxious distress would be coded as F32.1 with the anxious distress specifier.

The anxious distress specifier was introduced in DSM-5 to identify patients with MDD who also experience significant anxiety symptoms. This is important because anxiety symptoms are common in MDD, with studies showing that between 40% and 60% of patients with MDD also have anxiety symptoms.

The criteria for the anxious distress specifier include the presence of at least two of the following symptoms during the majority of days of a major depressive episode or persistent depressive disorder:

1. Feeling keyed up or tense
2. Feeling unusually restless
3. Difficulty concentrating because of worry
4. Fear that something awful may happen
5. Feeling that the individual might lose control of himself or herself

The severity of anxious distress is further specified as mild (2 symptoms), moderate (3 symptoms), moderate-severe (4-5 symptoms), or severe (4-5 symptoms with motor agitation).

Research has shown that the presence of anxious distress in MDD is associated with poorer outcomes. 

In the Netherlands Study of Depression and Anxiety (NESDA), 54.2% of patients with MDD met the criteria for anxious distress. This study found that the DSM-5 anxious distress specifier was a better predictor of clinical outcomes in patients with MDD compared to the DSM-IV diagnosis of anxiety disorders.

Does clinical depression (MDD) cause anxiety, or does anxiety cause clinical depression (MDD)?

Both clinical depression and anxiety conditions cause and escalate each other, rather than one definitively causing the other. Anxiety disorders, such as generalized anxiety disorder, panic disorder, and separation anxiety disorder, frequently co-occur with MDD.

According to Hopwood, M’s (2023) study in Neurology and Therapy Journal,  approximately 50-75% of patients with MDD meet the DSM-5 criteria for anxious depression. In many cases, anxiety precedes the onset of depression, with approximately 60-70% of patients with comorbid anxiety and depression experiencing anxiety first.

However, it’s important to note that depression also triggers or worsens anxiety symptoms. The persistent low mood, negative thinking patterns, and reduced ability to cope associated with MDD can lead to increased worry and fear about various aspects of life, potentially developing into an anxiety disorder.

Regardless of which condition appears first, the presence of both anxiety and depression often results in more severe symptoms, worse psychosocial functioning, poorer quality of life, and a longer time to achieve remission compared to MDD without anxiety. Therefore, healthcare providers must assess and treat both conditions concurrently for optimal patient outcomes.

What test is used for clinical depression (MDD) and anxiety?

The Kessler Psychological Distress Scale (K10) is widely used as a clinical test for depression and anxiety. Developed by Professor Ronald Kessler at Harvard Medical School, the K10 is a 10-item questionnaire that measures psychological distress based on questions about anxiety and depressive symptoms experienced in the most recent 4-week period. Healthcare professionals, including Australian GPs and mental health practitioners, commonly employ this self-report measure to assess the level of support a patient may need.

The K10 test yields scores ranging from 10 to 50, with higher scores indicating greater psychological distress. Scores under 20 suggest the individual is likely to be well, 20-24 indicate a mild mental disorder, 25-29 suggest a moderate mental disorder, and scores of 30 and over point to a likely severe mental disorder. Research has shown that approximately 13% of the adult population scores 20 or higher, and about 25% of patients seen in primary care settings score 20 or above. 

How can clinical depression disorder and anxiety disorder be prevented?

To prevent clinical depression disorder and anxiety disorder, use evidence-based strategies like regular exercise, a healthy diet, stress management, adequate sleep, social connections, and professional help when needed, according to a Healthline article titled “Coping with Depression” by Anna Gotter ( January 2024).

• Regular exercise: Exercise is any activity that maintains or increases physical fitness and overall health, such as walking, running, cycling, swimming, and strength training. Physical activity releases endorphins, natural mood boosters that can reduce stress hormones like cortisol. The U.S. Department of Health and Human Services recommends at least 150 minutes of moderate or 75 minutes of vigorous per week.
• Take a clean diet: A clean diet is free from processed foods, artificial additives, and refined ingredients. Eating a balanced diet rich in fruits, vegetables, lean proteins, and omega-3 fatty acids can help regulate mood and reduce inflammation associated with depression and anxiety. Limiting alcohol, caffeine, and sugar consumption is also essential, as these substances can exacerbate symptoms.
• Manage stress: Managing stress is the act of taking action to reduce and cope with everyday pressures that lead to a feeling of being overwhelmed. Techniques such as mindfulness meditation, deep breathing exercises, and progressive muscle relaxation can help reduce anxiety and prevent depressive episodes. Additionally, keeping an anxiety journal can help identify triggers and patterns, allowing for better management of symptoms.
• Have enough sleep: Enough sleep is getting the recommended number of hours of rest each night. According to Hirshkowitz M, Whiton K’s 2015 National Sleep Foundation report, you must get 7-9 hours of quality sleep per night. Establish a consistent sleep schedule and create a relaxing bedtime routine to improve sleep quality.
• Keep strong social connections: Social connections are regular interactions with supportive friends and family members. They provide emotional support and reduce feelings of isolation. Building and nurturing these relationships can serve as a protective factor against mental health issues.
• Get Professional Help: Professional help involves getting assistance from trained or certified individuals with expertise in a specific area. If you experience persistent symptoms or have a family history of depression or anxiety, consult a mental health professional. They provide early intervention strategies, therapy, or medication if necessary.

By implementing these preventive measures, you reduce your risk of developing clinical depression and anxiety disorders.