Major Depressive Disorder

Overview

Definition

• Marked by episodes of low mood and loss of interest in association with somatic symptoms
• Must present in episodes that last for ≥ 2 weeks
• Causes significant decline in patient function

Classification

Major depressive disorder (MDD) can be classified on the basis of the severity and the course of the disease.

• Severity:
  • Mild, moderate, severe 
  • Depends on the number of diagnostic symptoms present 
• Course:
  • Single versus recurrent 
  • Depressive episodes Depressive episodes Depressive states usually of moderate intensity in contrast with major depression present in neurotic and psychotic disorders. Bipolar Disorder may occur as a single event or may recur.
  • Recurrence requires some degree of resolution of symptoms as well as separation of the episodes by ≥ 2 months.

Epidemiology

• Highly prevalent, highly recurrent, disabling disease
• Ranked as the 3rd-highest cause of disease burden worldwide in 2008 by the WHO
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in adults:
  • Lifetime prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 12%–15%
  • Male-to-female ratio is 1:2.
  • 3 times more common from ages 18 to 29 years
  • Less common in elderly individuals (> 65 years old)
• No ethnic or socioeconomic differences in incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency
• Suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide:
  • ⅔ of all individuals with depression will contemplate suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide.
  • Up to 10%–15% actually complete suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide.
  • Highest rate in men > 65 years of age
• Only half of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with MDD will receive minimally sufficient treatment.

Pathophysiology

Risk factors

• Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics: more common among monozygotic twins Monozygotic twins Result from the division of a single zygote; share the same genetic material Multiple Pregnancy (75%) than among dizygotic twins Dizygotic twins Result from 2 separate eggs fertilized by 2 separate sperm; share approximately 50% of the genetic material Multiple Pregnancy (14%–19%).
• Neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission: Decrease in neurotransmitters that control mood (such as serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS, dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS, and norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS) might lead to MDD.
• Early childhood interpersonal losses: loss of parents before the age of 11 has been shown to be associated with MDD.
• Comorbid conditions:
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disorders
  • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder disorders
  • Substance use disorder
  • Serious/chronic illness
  • Cognitive distortions: negative perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment of self or the world

Catecholamine abnormalities

• Levels of neurotransmitters such as serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS, noradrenaline, and dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS are ↓ in individuals with MDD. 
• Elevation of these neurotransmitters results in relief of MDD symptoms.

Catecholamine deficiency theory

• Abnormalities in amine neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission (high or low) at nerve endings is thought to result in impaired neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission → mediates depressive states
• Monoamine oxidase Oxidase Neisseria (MAO) is an enzyme responsible for degradation of monoamines ( serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS, norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS, epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs, dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS).
• Monoamine oxidase Oxidase Neisseria inhibitors ( MAOIs MAOIs Monoamine oxidase inhibitors are a class of antidepressants that inhibit the activity of monoamine oxidase (MAO), thereby increasing the amount of monoamine neurotransmitters (particularly serotonin, norepinephrine, and dopamine). The increase of these neurotransmitters can help in alleviating the symptoms of depression. Monoamine Oxidase Inhibitors) are a class of medications used to treat depression.

Stress hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types

• Stress hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types ( cortisol Cortisol Glucocorticoids, calcitonin Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Other Antiresorptive Drugs) are increased in individuals with depression.
• Increase assumed to be a result of a hyperactive hypothalamic-pituitary-adrenal axis Hypothalamic-pituitary-adrenal axis Adrenal Hormones

Neuroanatomic theory

• Prefrontal cortex abnormalities are associated with depression.
• Theory is supported by clinical improvement in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who undergo deep brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stimulation.

Neurotrophic hypothesis Hypothesis A hypothesis is a preliminary answer to a research question (i.e., a “guess” about what the results will be). There are 2 types of hypotheses: the null hypothesis and the alternative hypothesis. Statistical Tests and Data Representation

• Untreated depression can damage vital brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification structures (e.g., hippocampus).
• This damage is mediated by glutamine Glutamine A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. Synthesis of Nonessential Amino Acids and glucocorticoid toxicity Toxicity Dosage Calculation.
• The hippocampus is very sensitive to high levels of cortisol Cortisol Glucocorticoids.

Diagnosis

Diagnostic criteria

Symptoms cause significant decline in function in social, occupational/school settings, and persist for ≥ 2 weeks. Depressed mood or anhedonia Anhedonia Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many psychotic disorders (e.g., depressive disorder, major; and schizophrenia). Schizophrenia must be among the symptoms.

Symptoms must include 5 of the following 9:

• Depressed mood, almost every day
• Anhedonia Anhedonia Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many psychotic disorders (e.g., depressive disorder, major; and schizophrenia). Schizophrenia (reduced pleasure from previously enjoyable habits)
• Appetite/weight changes (increase or decrease)
• Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbance (increase or decrease)
• Psychomotor agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus or retardation (patient is anxious and moves a lot, or barely moves)
• Loss of energy
• Feeling worthless or excessively guilty
• Trouble concentrating
• Suicidal ideation Suicidal ideation A risk factor for suicide attempts and completions, it is the most common of all suicidal behavior, but only a minority of ideators engage in overt self-harm. Suicide and/or suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide attempts

Exclude a history of:

• Other psychiatric disorders (especially bipolar Bipolar Nervous System: Histology disorder)
• Substance use 
• Medical conditions that cause depressive mood: hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism, nutritional deficiency, cerebrovascular disease

Other diagnostic factors

• Screening Screening Preoperative Care:
  • There are self- and clinician-rated questionnaires to classify depression.
  • Commonly used: Beck Depression Inventory, Patient Health Questionnaire Patient health questionnaire A self-administered version of the primary care evaluation of mental disorders (prime-md), a diagnostic tool containing modules on multiple mental health disorders including anxiety, alcohol, eating, and somatoform modules. The patient health questionnaire (phq-9) is designed specifically for mood/depression scoring each of the 9 dsm-iv criteria based on the mood module from the original prime-md. The generalized anxiety disorder scale (gad-7) scores 7 common anxiety symptoms. Psychiatric Assessment 9 
• Assessment of suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide risk: If a patient appears suicidal, always inquire.
• Laboratory evaluation
  • There are no specific tests to screen for depression; however, several lab tests are used to rule out other causes. 
  • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function ( thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH), T₃, T₄)
  • Levels of vitamin B₁₂, vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies, folic acid 
  • Urine drug screen 
• Imaging: CT and MRI of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification may be indicated to rule out organic causes. 

Mnemonic

To quickly recall the symptoms of depression, remember SIGECAPS:

• S leep LEEP Diagnostic Procedures in Gynecology disturbance
• Interest loss
• Guilty feelings 
• Energy loss
• Concentration problems
• Appetite or weight change
• Psychomotor retardation or agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
• Suicidal ideation

Subtypes of Major Depressive Disorder

Anxious depression

Symptoms include:

• Tension
• Restlessness
• Impaired concentration due to worry
• Fear that something awful might happen 
• Fear of losing control

Melancholic depression

Symptoms include:

• Loss of pleasure in most activities
• Unreactive to pleasurable stimuli
• Depressed mood that’s marked by profound despondency or despair
• Early-morning awakening Early-morning awakening Insomnia
• Psychomotor retardation or agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
• Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa or weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
• Excessive guilt

Catatonia

• Can occur in different diseases (mood disorders, psychotic disorders, autism, medical conditions)
• Symptoms include:
  • Very prominent psychomotor disturbances (increased or decreased movements)
  • Patient assumes a special posture and remains in it.
  • Examiner can change the patient’s posture, and the patient will maintain it.
  • Decreased response to external stimuli
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship refuse to follow instructions.
  • Repeating words ( echolalia echolalia Involuntary (‘parrot-like’), meaningless repetition of a recently heard word, phrase, or song. This condition may be associated with transcortical aphasia; schizophrenia; or other disorders. Schizophrenia) or movements ( echopraxia Echopraxia Tics and Tourette Syndrome) used or performed by the examiner

Psychotic depression

• Psychotic features ( hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia and delusions) occur only during mood symptoms. 
• If they occur without mood symptoms, then this is most likely schizoaffective disorder Schizoaffective disorder Schizoaffective disorder is a mental disorder that is marked by 2 components: a psychotic component (hallucinations or delusions) and a mood component (mania or depression). Patients must therefore meet the diagnostic criteria for both major mood disorder and schizophrenia. Schizoaffective Disorder.

Mixed depression

Describes a major depressive episode with subsyndromal manic or hypomanic symptoms.

Symptoms:

• Loss of pleasure in most activities
• Elevated or expansive mood
• Inflated self-esteem or grandiosity
• Talkative or pressured speech
• Flight of ideas/distractibility
• Increased energy or goal-directed activity
• Decreased need for sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep 
• Excessive involvement in pleasurable activities that cause negative consequences

Atypical depression

Symptoms include:

• Reactive to pleasurable stimuli (feels better in response to positive events)
• Increased appetite or weight gain
• Hypersomnia Hypersomnia Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., idiopathic hypersomnolence; narcolepsy; and kleine-levin syndrome) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, mental disorders, and sleep apnea syndrome). Whipple’s Disease
• Heavy feeling of limbs
• Long-standing pattern of sensitivity to interpersonal rejection

Management

General approach

• 1st-line treatment: a combination of psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy and pharmaceutical antidepressants
• Severe cases: somatic therapies such as  electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS)

Psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy

• Effect size Effect size Effect size is the standardized mean difference between 2 groups, which is exactly equivalent to the “Z-score” of a standard normal distribution. Statistical Power of psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy alone is stronger than that of antidepressants alone. 
• Requires time, financial, and emotional commitment
• Cognitive behavioral therapy Cognitive behavioral therapy A directive form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior. Psychotherapy (CBT):
  • Usually the most recommended psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy regimen for depression
  • Structured and shorter-length therapy 
  • Focuses on cognitive distortions
  • Therapist aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS the individual in identifying and correcting maladaptive thoughts and behaviors
  • Cognitive therapy alone is as effective as pharmacotherapy; however, the combination of the 2 is the most efficacious. 
• Psychodynamic therapy
  • More fluid and longer in duration 
  • Includes discussion of experiences as well as interpersonal relationships
  • Goal is to change a patient’s personality, character, and structure.

Pharmacotherapy

• Oral antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants efficacy:
  • Typically takes 4–6 weeks to see the full benefit.
  • Physical symptoms improve in the first 1–2 weeks (energy, sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep, appetite) 
  • Affective symptoms (mood, concentration, self-esteem) improve after improvement in somatic symptoms 
• Initiation of medication:
  • It is crucial to address suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide risk for every patient before initiating treatment. 
  • Selective serotonin reuptake inhibitors Selective Serotonin Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants ( SSRIs SSRIs Serotonin Reuptake Inhibitors and Similar Antidepressants) carry a black-box warning about increased suicidal ideation Suicidal ideation A risk factor for suicide attempts and completions, it is the most common of all suicidal behavior, but only a minority of ideators engage in overt self-harm. Suicide in the pediatric population.
  • Ask about any previous episodes of mania Mania A state of elevated excitement with over-activity sometimes accompanied with psychotic symptoms (e.g., psychomotor agitation, inflated self esteem and flight of ideas). It is often associated with mental disorders (e.g., cyclothymic disorder; and bipolar diseases). Bipolar Disorder, as antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants medications increase the risk of manic episodes in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with bipolar Bipolar Nervous System: Histology disorder. 
• Treatment duration:
  • 1st episode → treat for 6 months
  • 2 episodes of MDD, dysthymic disorder, strong family history Family History Adult Health Maintenance, or suicidal attempts: treat for 1–3 years
  • 3 episodes or more of MDD: lifelong treatment
  • Failure to respond to initial treatment (no improvement in 1 month): switch to another antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants with a different mechanism of action. 

Somatic therapies

Electroconvulsive therapy (ECT):

• Indicated for:
  • Cases not responding to multiple drug therapies
  • MDD with psychotic features
  • Catatonia
• Procedure done under general anesthesia General anesthesia Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery. Anesthesiology: History and Basic Concepts 
• Brief seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures are intentionally induced with small electric currents. 
• Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation the release of:
  • Neurotransmitters:
    • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS 
    • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS 
    • Norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS 
  • Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
    • Prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy 
    • TSH
    • Endorphins Endorphins One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. Receptors and Neurotransmitters of the CNS
• Typical course administered during 12 sessions.
• Side effects: complications from the general anesthesia General anesthesia Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery. Anesthesiology: History and Basic Concepts, confusion, short-term memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment problems 

Transcranial magnetic stimulation (TMS):

• Uses short pulses of magnetic energy to stimulate specific regions in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
• Does not require anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts 
• Indicated for adults with no improvement with ≥ 1 medication 
• Typical course: daily 40-minute procedure for 4–6 weeks
• Side effects: scalp discomfort/ pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 

Vagal nerve stimulation:

• Stimulation of the left vagal nerve using electronic device implanted under the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
• Exact mechanism of action unknown 

Differential Diagnosis

MDD versus stress responses

It is important to differentiate MDD from normal responses to stress or other related mood disorders.

Other differential diagnoses

• Seasonal affective disorder: regular Regular Insulin temporal relationship between the onset of major depression and a particular time of year (usually winter Winter Pityriasis Rosea) for the past 2 years. History taking can differentiate seasonal affective disorder from MDD, as remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches also occurs at a specific time of the year. Similar to MDD, antidepressants such as SSRIs SSRIs Serotonin Reuptake Inhibitors and Similar Antidepressants and CBT are effective treatment options. Light therapy (exposure to bright light) may also be used.
• Persistent depressive disorder: also known as dysthymia. Persistent depressive disorder is the continued presence of depressed mood. Dysthymia has an earlier onset, as patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will often mention that they have been depressed “all their life.” This diagnosis is distinguished from MDD, as the depressive symptoms are usually less severe. If a patient meets the diagnostic criteria for MDD, dysthymia cannot be diagnosed simultaneously.
• Adjustment disorder Adjustment disorder Adjustment disorder is a psychological response to an identifiable stressor. The condition by emotional or behavioral symptoms that develop within 3 months of exposure, and do not last more than 6 months. Adjustment Disorder: psychological response to an identifiable stressor. Adjustment disorder Adjustment disorder Adjustment disorder is a psychological response to an identifiable stressor. The condition by emotional or behavioral symptoms that develop within 3 months of exposure, and do not last more than 6 months. Adjustment Disorder is marked by emotional or behavioral symptoms that develop ≤ 3 months after exposure and that do not last > 6 months. Adjustment disorder Adjustment disorder Adjustment disorder is a psychological response to an identifiable stressor. The condition by emotional or behavioral symptoms that develop within 3 months of exposure, and do not last more than 6 months. Adjustment Disorder is a diagnosis of exclusion, and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with this disorder do not meet criteria for other psychiatric conditions. The 1st line of treatment is psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy.
• Prolonged grief disorder: a persistent, pervasive grief response which causes impairment or distress for > 12 months after the loss of a loved one. It is characterized by intense longing for and preoccupation Preoccupation Body Dysmorphic Disorder with the deceased, as well as emotional pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. The duration and intensity of grief must exceed usual social, religious, or cultural norms. The diagnosis is made based on clinical criteria. Psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy is the preferred management.