Major Depressive Disorder Treatment Overview

Major Depressive Disorder (MDD) Treatment

• Symptoms: Lasting weeks/months. Involve sadness, helplessness, worthlessness, impaired sleep & concentration, anhedonia (loss of pleasure), physical pain, multiple symptoms impacting daily life.

Stress Response (HPA Axis)

• Mechanism: The amygdala detects stress, alerting the hypothalamus. The hypothalamus prompts the pituitary to release ACTH, signaling the adrenal glands to release cortisol & adrenaline for "fight or flight" response. This is controlled by the sympathetic nervous system (SNS).
• MDD Connection: High cortisol levels negatively impact brain cells and plasticity, potentially contributing to the condition.

Depressed Brain Changes

• Chemical Imbalances: High cortisol levels, low levels of Brain-Derived Neurotrophic Factor (BDNF), and increased inflammation are linked to MDD.
• Neurological Changes: Structural differences, including decreased dendritic branching (especially in the prefrontal cortex, hippocampus, & amygdala), decreased hippocampus volume and neurogenesis (birth of new cells), are observed. This leads to decreased plasticity and the brain's ability to regulate the HPA axis.
• Dexamethasone Suppression Test: Used to assess cortisol levels.

Antidepressant Treatments

Electroconvulsive Therapy (ECT)

• Mechanism: Induces seizures through electrical stimulation, potentially rebooting the brain.
• Pros: Fast-acting and effective.
• Cons: Short-lived effect, time-consuming, memory loss.

Tricyclic Antidepressants (TCAs)

• Mechanism: Block the reuptake of serotonin and norepinephrine.
• Pros: Effective for treating MDD.
• Cons: Block other receptors (Ach, histamine, epinephrine), leading to undesirable side effects like confusion, memory impairment, sedation, and cardiotoxicity (especially in overdose).
• Metabolism: Long duration of active metabolites in the body, specifically longer in older individuals.

Monoamine Oxidase Inhibitors (MAOIs)

• Mechanism: Inhibit the activity of Monoamine Oxidase (MAO), either permanently or temporarily.
• Pros: Effective, particularly in treatment-resistant patients.
• Cons: Tyramine in food interacts with MAOIs, requiring dietary restrictions. Also, potential for cardiotoxicity if combined with adrenaline-like drugs.

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Mechanism: Primarily block serotonin reuptake.
• Pros: Relatively safe mechanism.
• Cons: Potential for "serotonin syndrome" with cognitive disturbances, autonomic nervous system issues, neuromuscular impairments, and sexual dysfunction. Also discontinuation syndrome upon cessation.

Dual-Action Antidepressants

• Mechanism: Target serotonin and norepinephrine reuptake to address multiple symptoms.
• Examples: Venlafaxine (Effexor), desvenlafaxine (Pristiq), duloxetine (Cymbalta).
• Pros: Potentially fewer side effects than TCAs.
• Cons: Potential sexual side effects and elevated blood pressure.

Monoamine Hypothesis and Beyond

• Mechanism: Antidepressants primarily alter monoamine neurotransmitter levels (serotonin and norepinephrine), but beyond this, they may increase BDNF, decrease oxidative stress, increase allopregnanolone, and increase hippocampal neurogenesis to enhance neuroplasticity.

Future Treatments

• Needs: Faster therapeutic onset, improved efficacy, and reduced side effects.
• Potential Approaches: NMDA receptor antagonists to stimulate synaptic plasticity. Also anti-inflammatory drug treatment.

Explore the symptoms, treatment options, and neurological changes associated with Major Depressive Disorder (MDD). This quiz covers the connection between stress response mechanisms and MDD, including the impact of cortisol on brain function. Test your understanding of this complex mental health condition and its treatment strategies.