Untitled Quiz

Major Depressive Disorder (MDD)

• MDD is a mood state characterized by feelings of sadness, despair, anxiety, emptiness, discouragement, hopelessness, or appearing tearful.
• It's a combination of signs and symptoms.
• It's also a mental disorder with a distinct clinical condition, such as unipolar major depression.

Learning Objectives

• Understand the prevalence of depression in various populations (developed vs. developing countries, sex, race, and age).
• Explain the pathophysiological mechanisms of depression.
• Recognize signs and symptoms of MDD.
• Recommend appropriate antidepressant therapy based on treatment phase and patient history.
• Apply pharmacokinetic principles and patient-specific data in choosing the best medication.
• Monitor treatment efficacy and adjust medications based on patient response and tolerability.

Assessment

• Assess history of present illness (depressive symptoms and their context, suicide risk).
• Evaluate general medical illness.
• Obtain family history and social history.
• Perform mental status examination and physical examination.
• Conduct laboratory evaluation.
• Screen for depression.
• Utilize diagnostic instruments.

Epidemiology

• Estimated lifetime prevalence is 12% in developed countries; 9% in developing countries like China, Mexico, and Brazil.
• Depression is two times more common in females.
• Within different racial groups, the prevalence of MDD varies according to the data presented
• It's the 11th greatest cause of disability and mortality globally.
• In the United States, major depression ranks second among all diseases and injuries, followed by persistent depressive disorder (dysthymia), which ranks 20th.

Pathogenesis

• Genetic factors influence response to antidepressants.
• Early life adversity and childhood trauma contribute.
• Social factors, such as isolation, poor social relationships, and criticisms, impact depression.
• Psychological factors including negative thought patterns, early life losses, self-esteem issues, and difficulties managing losses and relationships contribute to MDD.
• General medical disorders such as epilepsy, Parkinson's disease, Heart failure, HIV/AIDS, and cancer, can cause or increase the risk of MDD.
• Medications like glucocorticoids and interferons also increase the risk of MDD.

Neurobiology

• Neurotransmitters, such as monoamines (serotonin, norepinephrine, and dopamine), are essential for brain function and emotional regulation.
• The neurotransmitter GABA acts as an inhibitory neurotransmitter, while glutamate acts as the primary excitatory neurotransmitter in the brain.
• These neurotransmitters and their roles in emotions, sleep, pain, homeostasis, signaling, memory, and cognition play a role in MDD

Diagnostic Criteria & Classification (DSM-5)

• Five (or more) symptoms present over a two-week period, representing a change from previous functioning. At least one symptom must be depressed mood or loss of interest or pleasure.
• Depressed mood (sadness, emptiness, hopelessness, irritability).
• Markedly diminished interest or pleasure in activities.
• Significant weight loss, weight gain, or changes in appetite.
• Insomnia or hypersomnia.
• Psychomotor agitation or retardation (observable by others).
• Fatigue or loss of energy.
• Feelings of worthlessness or guilt.
• Diminished ability to think or concentrate.
• Recurrent thoughts of death or suicide attempt.
• The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
• The episode is not attributable to the direct physiological effects of a substance or to another medical condition.
• The occurrence of major depressive episode is not better explained by other mental disorders.
• There has never been a manic or hypomanic episode.

Mild to Moderate Major Depression

• Manifestations include absence of suicidal or homicidal ideation or behavior, and no psychotic features or aggression.
• Intact judgment and no imminent risk of harm to self or others.
• Usually treated as outpatient or in a partial/day hospital program.

Treatment Goals

• The primary goals of initial treatment include symptom remission and restoring baseline functioning.

Treatment

• Antidepressants plus psychotherapy.
• Classes of antidepressants, selecting an AD based on factors such as side effects, and the appropriate dose.
• Psychotherapy (Cognitive-Behavioral Therapy [CBT] or Interpersonal Psychotherapy [IPT] ).
• Randomized trials show greater efficacy with combined pharmacotherapy and psychotherapy.

Antidepressants

• Second-generation antidepressants (SSRIs, SNRIs, atypical antidepressants, serotonin modulators)
• First-generation antidepressants (TCAs, MAOIs)
• Detailed table of medications and their uses.

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Frequently used first-line antidepressants due to efficacy, tolerability, and safety in overdose.
• Inhibit serotonin reuptake in the synapse.
• Efficacy is similar across various SSRIs.
• Tables detail different SSRIs, their doses, methods of administration, potential drug-drug interactions (DDI), and metabolism/elimination routes.
• Side effects (e.g., sexual dysfunction, weight gain).
• Instructions for switching between SSRIs and tapering doses to avoid discontinuation syndrome and serotonin syndrome.
• Detailed information about serotonin syndrome- its causes, symptoms, clinical features including agitation, delirium, diaphoresis, tachycardia, hypertension, and hyperthermia., helpful tests (e.g., CBC, electrolytes, BUN, CPK), differential diagnoses (e.g., neuroleptic malignant syndrome, anticholinergic toxicity), and treatment in cases of serotonin syndrome.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• Used for treating major depression, amongst other conditions.
• Block the reuptake of serotonin and norepinephrine within neuronal synapses.
• Detailed tables outline SNRIs, their use, doses, administration routes, DDI, and metabolism/elimination routes.
• Side effects, including insomnia, agitation, sexual dysfunction, and urinary hesitancy.

Atypical Antidepressants

• Used for patients resistant to or intolerant of other antidepressants.
• Detailed tables detail atypical antidepressants, administration, DDIs, and metabolism/elimination routes.
• Side effects for specific drugs are given.

Serotonin Modulators

• Used as first-line treatment if the drug demonstrates strong characteristics.
• Detailed tables of information on serotonin modulators detailing their action, administration, DDIs, and metabolism/elimination routes

Tricyclic Antidepressants (TCAs)

• Older class of antidepressants.
• Detailed table outlining different TCAs, their mechanism of action, and potential side effects including anticholinergic effects, cardiac effects, including hypotension and potential for severe arrhythmias, and sexual dysfunction.

Monoamine Oxidase Inhibitors (MAOIs)

• Not typically a first-line treatment.
• Inhibits MAO- enzyme that breaks down monoamines)
• Dietary restrictions is a crucial aspect of treatment.
• Detailed table providing information on different MAOIs, their administration, and potential DDI, including hypertensive crisis.

Psychotherapy

• Cognitive-behavioral therapy (CBT), interpersonal psychotherapy (IPT), family therapy, problem-solving therapy, and others are efficacious for mild to moderate depression.
• Psychotherapy shows comparable efficacy with antidepressants, especially in an initial treatment.

Severe Major Depression

• Clinical features include suicidal ideation or behavior, psychotic features (delusions or hallucinations), catatonia, and grossly impaired judgment.
• A combination approach of pharmacotherapy (SNRI or SSRI or other antidepressant) and psychotherapy is preferred.
• Electroconvulsive therapy (ECT) is an alternative treatment option for patients requiring a rapid response, especially those with severe suicidal or life-threatening behaviors.

St. John's Wort

• An over-the-counter (OTC) product known as Hypericum perforatum.
• Has affinity to various neurotransmitter receptors.
• Efficacy has conflicting results in studies.
• Significant drug interactions.
• Should not be used in conjunction with other antidepressants.

Treatment Approach

• Explains phases of treatment for depression: acute, continuation, and maintenance phases, duration, and goals.

Treatment Failure

• If no response to antidepressants after 12 weeks or due to intolerance, consider switching to an alternate agent, augmentation therapy, or electroconvulsive therapy.
• Detailed order of preference for choosing an additional or alternative treatment (e.g., from SSRI or SNRI to atypical, then serotonin modulator, and then TCA or MAOI).

Special Populations (Elderly, Pregnancy, Pediatrics)

• Treatment approaches for elderly patients, pregnant patients, and pediatric patients (including specific drug restrictions)
• The risks associated with using antidepressants in these groups.

Augmentation Therapy

• Supplemental medications (second-generation antipsychotics, lithium, thyroid hormone, anticonvulsants, or a serotonin agonists) when response to initial agents is insufficient.

General Considerations

• Providing a general approach and considerations for selecting an antidepressant based on the individual's symptoms, comorbidities or preferences and known responses to previous treatments (e.g. family history of response to antidepressants).

Side Effects

• Discusses common side effects for each class of antidepressants, such as diarrhea, nausea, sexual dysfunction, somnolence, and weight gain.
• Emphasizes the importance of careful dose titration in order to reduce side effects and enhance adherence in patients.