Major Depressive Disorder Treatment Quiz

Major Depressive Disorder (MDD) Treatment

Symptoms of MDD: Sadness, helplessness, worthlessness, impaired sleep, concentration, anhedonia, physical pain; symptoms must significantly impair daily life.
Stress Response (HPA Axis): The amygdala identifies a stressor, triggering the hypothalamus, which signals the pituitary gland to release ACTH. ACTH stimulates adrenal glands to release cortisol and adrenaline (activating hormones). This entire chain involves the sympathetic nervous system.
Neurobiology of Depression:
- Chemical Imbalances: High cortisol levels negatively impact brain cells; Cortisol influences brain plasticity. A dexamethasone suppression test can help assess cortisol levels. Low levels of Brain-Derived Neurotrophic Factor (BDNF) are associated with depression. Inflammation (an immune response dysregulation) correlates with MDD.
- Structural Differences: Elevated cortisol, diminished BDNF are characteristic and dendritic branching decreases (in the prefrontal cortex, hippocampus, and amygdala). This impacts structural volume and plasticity. The hippocampus, where neurogenesis (cell birth) occurs, shrinks in depression. The neurogenic hypotheses suggest a connection between decreased neurogenesis and depression.
Treatment Normalizes Structural Changes: Antidepressant treatment corrects the abnormalities mentioned regarding cortisol, BDNF and dendritic branching, improving plasticity.

Antidepressant Treatments

Electroconvulsive Therapy (ECT): Induces seizures via electrical stimulation; a rapid method of treatment.
- Positives: Fast acting and effective
- Negatives: Short-lived effects, time-consuming treatment, memory loss
Tricyclic Antidepressants (TCAs):
- Example: Imipramine (Tofranil) – named for their chemical structure.
- Development: Originally antipsychotics
- Positives: Block serotonin and norepinephrine reuptake .
- Negatives: Block acetylcholine, histamine, and epinephrine receptors; causes unwanted side effects (confusion, impairment, sedation, cardiotoxicity).
- Metabolism: Long-lasting, but cognitive side effects are prominent in elderly patients
Monoamine Oxidase Inhibitors (MAOIs):
- Example: Selegiline transdermal patch (Emsam).
- Development: Originally developed to treat tuberculosis
- Positives: Inhibit MAO activity—either irreversibly or reversibly.
- Negatives: MAO metabolizes tyramine; cardiotoxicity if not careful with diet and other medications.
- Side effects and effectiveness: Effective, but requires dietary restrictions may be effective when other methods fail:
Selective Serotonin Reuptake Inhibitors (SSRIs):
- Positives: Inhibit serotonin reuptake. Little effect on other monoamines and post-synaptic serotonin receptors.
- Negatives: Can cause "serotonin syndrome," cognitive disturbances, autonomic nervous system dysfunction, neuromuscular issues, agitation, and sexual dysfunction; discontinuation syndrome. Not as effective as older treatment options:
Dual-Action Antidepressants:
- Positives: Target serotonin and norepinephrine reuptake; aimed to reduce unwanted side effects with minimal effects on other neurotransmitters.
- Examples: Venlafaxine (Effexor), desvenlafaxine (Pristiq), duloxetine (Cymbalta)
- Positives: Treats neuropathic pain (fibromyalgia, diabetic neuropathy).
- Negatives: May lead to sexual dysfunction and hypertension.

Monoamine Hypothesis and Beyond

Monoamine Hypothesis: One theory suggesting an influence of monoamines on depression.
Beyond Monoamines: Other mechanisms explain antidepressants' action. Antidepressants increase BDNF, dendritic branching, neurogenesis as well as reduce oxidative stress and increase allopregnanolone.
Neurogenesis: These improvements enhance neuroplasticity.

Future of Treatment

Need for Improvement: Faster treatment onset, greater efficacy, fewer side effects are needed.
Experimental Options: Non-monoamine approaches, such as NMDA receptor antagonists, are being investigated. These drugs could induce burst of glutamate. The implication is potential stimulation of synaptic plasticity for treatment. Anti-inflammatory drugs are also being examined.