Major Depressive Disorder

Major depressive disorder (MDD), commonly called depression, is a unipolar mood disorder characterized by persistent low mood and loss of interest in association with somatic symptoms for a duration of ≥ 2 weeks. Major depressive disorder has the highest lifetime prevalence among all psychiatric disorders. Biologic, psychosocial, and genetic factors contribute to depression. Treatment methods include pharmacotherapy, 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 neuromodulation therapies such as electroconvulsive therapy (ECT). The leading cause of death associated with MDD is 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, which is more common in the elderly population.

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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 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
  • Prevalence in adults: 
    • Lifetime prevalence: 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
  • 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 commit 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 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 (75%) than among dizygotic twins (14%–19%).
  • Neurotransmission Neurotransmission The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. The plasma membranes of the 2 neurons are placed very close together, and the space between the 2 neurons is called the synaptic cleft. The molecules that mediate the interaction are called neurotransmitters. Synapses and Neurotransmission: Decrease in neurotransmitters that control mood (such as serotonin) might lead to MDD.
  • Cognitive distortions: negative perception of self or the world shown to render susceptibility to MDD
  • Early childhood interpersonal losses: loss of parents before the age of 11 has been shown to be associated with MDD.

Catecholamine abnormalities

  • Levels of neurotransmitters such as serotonin, noradrenaline, and dopamine are ↓ in individuals with MDD. 
  • Elevation of these neurotransmitters results in relief of MDD symptoms.

Monoamine oxidase deficiency theory

  • Monoamine oxidase (MAO) is an enzyme responsible for degradation of monoamines (serotonin, norepinephrine, epinephrine, dopamine).
  • Abnormalities in amine neurotransmission (high or low) at nerve endings is thought to result in impaired neurotransmission → mediates depressive states
  • Monoamine oxidase inhibitors Monoamine oxidase inhibitors 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 (MAOIs) 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

  • 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 (cortisol, calcitonin) are increased in individuals with depression.
  • Increase assumed to be a result of a hyperactive hypothalamic-pituitary-adrenal axis

Neuroanatomic theory

  • Prefrontal cortex abnormalities are associated with depression.
  • Theory is supported by clinical improvement in patients who undergo deep brain stimulation.

Neurotrophic hypothesis

  • Untreated depression can damage vital brain structures (e.g., hippocampus).
  • This damage is mediated by glutamine and glucocorticoid toxicity.
  • The hippocampus is very sensitive to high levels of cortisol.

Diagnosis

DSM-V diagnostic criteria

Symptoms cause significant decline in function in social, occupational/school setting, and persist for ≥ 2 weeks. Depressed mood or anhedonia must be among the symptoms.

Symptoms include:

  • Depressed mood, almost every day
  • Anhedonia (reduced pleasure from previously enjoyable habits)
  • Appetite/weight changes (increase or decrease)
  • Sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep disturbance (increase or decrease)
  • Psychomotor agitation or retardation (patient is anxious and moves a lot, or barely moves)
  • Loss of energy
  • Feeling worthless or excessively guilty
  • Trouble concentrating
  • Suicidal ideation 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 disorder Bipolar disorder Bipolar disorder is a highly recurrent psychiatric illness characterized by periods of manic/hypomanic features (distractibility, impulsivity, increased activity, decreased sleep, talkativeness, grandiosity, flight of ideas) with or without depressive symptoms. Bipolar 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:
    • There are self- and clinician-rated questionnaires to classify depression.
    • Commonly used: Beck Depression Inventory, Patient Health Questionnaire 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 function (thyroid-stimulating hormone (TSH), T3, T4)
    • Levels of vitamin B12, vitamin D, folic acid 
    • Urine drug screen 
  • Imaging: CT and MRI of brain may be indicated to rule out organic causes. 

Mnemonic

To quickly recall the symptoms of depression, remember SIGECAPS:

  • Sleep disturbance
  • Interest loss
  • Guilty feelings 
  • Energy loss
  • Concentration problems
  • Appetite or weight change
  • Psychomotor retardation or agitation
  • Suicidal ideation

Classes 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
  • Psychomotor retardation or agitation
  • Anorexia or weight loss
  • 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 refuse to follow instructions.
    • Repeating words (echolalia) or movements (echopraxia) used or performed by the examiner

Psychotic depression

  • Psychotic features (hallucinations 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 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 
  • 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
  • Heavy feeling of limbs
  • Long-standing pattern of sensitivity to interpersonal rejection

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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 antidepressants
  • Severe cases: somatic therapies such as  electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS)

Psychotherapy

  • Effect size 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
  • 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 
    • 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 Antidepressant Medications efficacy:
    • Typically takes 4–6 weeks to see the full benefit.
    • Physical symptoms improve in the first 1–2 weeks (energy, sleep, appetite) 
    • Affective symptoms (mood, concentration, self-esteem) improve after improvement in physical 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 Serotonin Reuptake Inhibitors 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 Antidepressant Medications (SSRIs) carry a black-box warning about increased suicidal ideation in the pediatric population.
    • Ask about any previous episodes of mania, 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 Antidepressant Medications medications increase the risk of manic episodes in patients with bipolar disorder Bipolar disorder Bipolar disorder is a highly recurrent psychiatric illness characterized by periods of manic/hypomanic features (distractibility, impulsivity, increased activity, decreased sleep, talkativeness, grandiosity, flight of ideas) with or without depressive symptoms. Bipolar Disorder
  • Treatment duration:
    • 1st episode → treat for 6 months
    • 2 episodes of MDD, dysthymic disorder, strong family history, 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 Antidepressant Medications with a different mechanism of action. 
Table: Comparison of 2nd-generation antidepressants
Class Mechanism of action Benefits Common side effects Examples
SSRIs Inhibit serotonin transporter → ↑ 5-HT levels in synaptic cleft
  • 1st-line AD
  • Wide therapeutic index
  • Effective for treatment of other conditions:
    • Anxiety disorders
    • OCD OCD Obsessive-compulsive disorder (OCD) is a condition characterized by obsessions (recurring and intrusive thoughts, urges, or images) and/or compulsions (repetitive actions the person is compelled to perform) that are time-consuming and associated with functional impairment. Obsessive-compulsive Disorder (OCD)
    • Eating disorders
    • PTSD PTSD Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress Disorder (PTSD)
  • Sexual dysfunction
  • Weight gain
  • Increased risk for 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
  • Sertraline
  • Fluoxetine
  • Paroxetine
  • Citalopram
  • Escitalopram
SNRIs Inhibit NET and SERT in the presynaptic terminal → ↑ NE and 5-HT levels in synaptic cleft Effective for treatment of other conditions:
  • Anxiety and panic disorder Panic disorder Panic disorder is a condition marked by recurrent and episodic panic attacks that occur abruptly and without a trigger. These episodes are time-limited and present with cardiorespiratory (palpitations, shortness of breath, choking), GI (nausea, abdominal distress), and neurologic (paresthesias, lightheadedness) symptoms. Panic Disorder
  • Chronic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain (especially neuropathic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain)
  • Higher rates of discontinuation symptoms
  • Sexual dysfunction
  • Venlafaxine
  • Duloxetine
Atypical ADs Inhibit norepinephrine, serotonin, or dopamine reuptake in the presynaptic terminal
  • Bupropion:
    • Little to no effect on weight
    • No sexual dysfunction
    • Activating effect may help with fatigue.
    • Helps with smoking cessation
  • Mirtazapine and trazodone:
    • Sedating properties may help with anxiety and insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia.
    • Faster onset of action than SSRIs
  • Bupropion:
    • Insomnia
    • Tremor
    • Increases risk of 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
  • Mirtazapine
    • Sleepiness
    • Drowsiness
    • Increased appetite
  • Trazodone:
    • Sedation
    • Priapism
  • Bupropion
  • Mirtazapine
  • Trazodone
AD: 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 Antidepressant Medications
5-HT: 5-hydroxytryptamine (serotonin)
NET: norepinephrine transporter
OCD OCD Obsessive-compulsive disorder (OCD) is a condition characterized by obsessions (recurring and intrusive thoughts, urges, or images) and/or compulsions (repetitive actions the person is compelled to perform) that are time-consuming and associated with functional impairment. Obsessive-compulsive Disorder (OCD): obsessive-compulsive disorder Obsessive-compulsive disorder Obsessive-compulsive disorder (OCD) is a condition characterized by obsessions (recurring and intrusive thoughts, urges, or images) and/or compulsions (repetitive actions the person is compelled to perform) that are time-consuming and associated with functional impairment. Obsessive-compulsive Disorder (OCD)
PTSD PTSD Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress Disorder (PTSD): posttraumatic stress disorder Posttraumatic Stress Disorder Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress Disorder (PTSD)
SERT: serotonin transporter
SNRI: serotonin–norepinephrine reuptake inhibitor
SSRI: selective serotonin reuptake inhibitor
Table: Comparison of 1st-generation antidepressants
Class Mechanism of action Benefits Common side effects Examples
MAOIs Irreversibly inhibit the enzyme MAO in the nerve terminal to prevent degradation of monoamines (5-HT, NE, and DA)
  • Can be effective in treating depression refractory to other medications
  • Suited for bipolar depression, panic disorder Panic disorder Panic disorder is a condition marked by recurrent and episodic panic attacks that occur abruptly and without a trigger. These episodes are time-limited and present with cardiorespiratory (palpitations, shortness of breath, choking), GI (nausea, abdominal distress), and neurologic (paresthesias, lightheadedness) symptoms. Panic Disorder and social phobia
  • Rarely used clinically
  • Numerours food and drug interactions → can cause hypertensive crisis or serotonin syndrome Serotonin syndrome Serotonin syndrome is a life-threatening condition caused by large increases in serotonergic activity. This condition can be triggered by taking excessive doses of certain serotonergic medications or taking these medications in combination with other drugs that increase their activity. Serotonin Syndrome
  • Strong discontinuation symptoms
  • Phenelzine
  • Selegiline
TCAs Decrease the reuptake of 5-HT and norepinephrine via inhibition of the SERT and NET in the presynaptic membrane Effective for treatment of other conditions:
  • Chronic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain (esp. neuropathic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, fibromyalgia Fibromyalgia Fibromyalgia is a chronic pain syndrome characterized by widespread body pain, chronic fatigue, mood disturbance, and cognitive disturbance. It also presents with other comorbid symptoms such as migraine headaches, depression, sleep disturbance, and irritable bowel syndrome. Fibromyalgia)
  • Obsessive compulsive disorder ( OCD OCD Obsessive-compulsive disorder (OCD) is a condition characterized by obsessions (recurring and intrusive thoughts, urges, or images) and/or compulsions (repetitive actions the person is compelled to perform) that are time-consuming and associated with functional impairment. Obsessive-compulsive Disorder (OCD))
  • PTSD PTSD Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress Disorder (PTSD)
  • ADHD
  • Anorexia nervosa Anorexia Nervosa Anorexia nervosa is an eating disorder marked by self-imposed starvation and inappropriate dietary habits due to a morbid fear of weight gain and disturbed perception of body shape and weight. Patients have strikingly low BMI and diverse physiological and psychological complications. Anorexia Nervosa, bulimia nervosa Bulimia nervosa Bulimia nervosa is an eating disorder marked by recurrent episodes of binge eating accompanied by inappropriate compensatory behaviors (laxatives or diuretics use, self-induced vomiting, fasting, or excessive exercise) to counteract the effects of binge eating and prevent weight gain. Bulimia Nervosa
  • Anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs side effects
  • Overdose leads to 3 Cs:
    • Convulsion
    • Cardiotoxicity (arrhythmia)
    • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
  • Nortriptyline
  • Amitriptyline
  • Doxepin
  • Clomipramine
DA: dopamine
5-HT: 5-hydroxytryptamin (serotonin)
MAO: monoamine oxidase
MAOI: monoamine oxidase inhibitor
NET: norepinephrine transporter
SERT: serotonin transporter
TCA:tricyclic 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 Antidepressant Medications

Somatic therapies

Electroconvulsive therapy (ECT):

  • Indicated for: 
    • Cases not responding to multiple drug therapies
    • MDD with psychotic features
    • Catatonia
  • Procedure done under general anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. 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 trigger the release of:
    • Neurotransmitters:
      • Dopamine 
      • Serotonin 
      • Norepinephrine 
    • Hormones: 
      • Prolactin 
      • TSH
      • Endorphins
  • Typical course administered during 12 sessions.
  • Side effects: complications from the general anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts, confusion, short-term memory problems 

Transcranial magnetic stimulation (TMS):

  • Uses short pulses of magnetic energy to stimulate specific regions in the brain
  • Does not require anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. 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 Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain 

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. Structure and Function of the Skin
  • 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.

Table: Comparison of MDD to stress responses
Disorder Distinguishing features Duration 1st-line treatment
MDD
  • Patient must fulfill diagnostic criteria.
  • Marked distress
  • No lifetime history of bipolar episodes
≥ 2 weeks Antidepressants + 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 (CBT)
Normal stress response
  • No marked distress
  • Patient is able to function and is simply sad.
Usually doesn’t last > 9 months Reassurance
Acute grief reaction
  • Normal response to loss
  • Most of the patient’s sadness is focused on the loss.
  • Symptoms come in waves.
  • Less decline in function than MDD
  • No feeling of hopelessness or worthlessness
  • Varies widely
  • Usually begins after the triggering event
  • Resolves or vastly improves within 6–12 months
Reassurance
Complicated grief
  • Similar symptoms to acute grief, but more intense and severe
  • Greater decline in function than MDD
  • No feeling of hopelessness or worthlessness
Symptoms last > 6–12 months Psychotherapy (CBT)

Other differential diagnoses

  • Seasonal affective disorder: regular temporal relationship between the onset of major depression and a particular time of year (usually winter) for the past 2 years. History taking can differentiate seasonal affective disorder from MDD, as remission also occurs at a specific time of the year. Similar to MDD, antidepressants such as SSRIs 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 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: psychologic 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 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.

References

  1. Le, T., Bhushan, V. (2019). First Aid for the USMLE Step 1, 29th ed. New York: McGraw-Hill Medical, p. 549.
  2. Sadock, B. J., Sadock, V. A., & Ruiz, P. (2014). Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 11th ed. Philadelphia: Lippincott Williams and Wilkins.
  3. Bauer, I. (2021). Depressive disorders: update on diagnosis, etiology, and treatment. DeckerMed Medicine. Retrieved March 11, 2021, from https://www.sciencegate.app/document/10.2310/psych.1640
  4. Rush RUSH Abdominal and cardiac evaluation with sonography in shock (ACES) and rapid ultrasound for shock and hypotension (RUSH) are point-of-care ultrasound (POCUS) examinations indicated in cases of nontraumatic, undifferentiated hypotension, or shock. ACES and RUSH: Resuscitation Ultrasound Protocols, A. (2020). Unipolar major depression in adults: choosing initial treatment. UpToDate. Retrieved March 10, 2021, from https://www.uptodate.com/contents/unipolar-major-depression-in-adults-choosing-initial-treatment
  5. Anttila, S. A., Leinonen, E. V. (2001). A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Reviews 7:249–264. https://doi.org/10.1111/j.1527-3458.2001.tb00198.x
  6. Watanabe, N., Omori, I. M., Nakagawa, A., Cipriani, A., Barbui, C., Churchill, R., Furukawa, T. A. (2011). Mirtazapine versus other antidepressive agents for depression. Cochrane Database of Systematic Reviews 12:CD006528. https://doi.org/10.1002/14651858.CD006528.pub2
  7. Puyat, J. H., Kazanjian, A., Goldner, E. M., Wong, H. (2016). How often do individuals with major depression receive minimally adequate treatment? A Population-based, data linkage study. Canadian Journal of Psychiatry 61(7):394–404. https://doi.org/10.1177/0706743716640288
  8. Pae, C. U., Vöhringer, P. A., Holtzman, N. S., Thommi, S. B., Patkar, A., Gilmer, W., Ghaemi, S. N. (2012). Mixed depression: a study of its phenomenology and relation to treatment response. Journal of Affective Disorders 136:1059–1061. https://doi.org/10.1016/j.jad.2011.11.024 https://www.uptodate.com/contents/catatonia-treatment-and-prognosis?search=Major%20depressive%20disorder&topicRef=1725&source=see_link

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