Comprehensive Guide to Antidepressants and
Depression: Mechanisms, Monoamine and
Neurotrophic Hypotheses, SSRIs, SNRIs,
TCAs, MAOIs, Atypical Agents, NMDA
Modulators, GABA Modulators, Clinical
Indications, Adverse Effects,
Contraindications, Pregnancy Considerations,
and Evidence-Based Management of Major
Depressive Disorder and Treatment-Resistant
Depression Complete Questions Provided
with A+ Graded Rationales Latest Updated
2026
5-HT
__________ may be most important NT involved in feelings of wellbeing
Biogenic Amine Theory (Monoamine Hypothesis)
• Monoamine (NE, 5-HT, DA) deficiency in key brain locations leads to depression
• Overproduction/excess = mania
Does not explain why:
• Antidepressants have ~immediate effect on neurotransmission (NE, 5-HT, DA) YET
• Response takes several (≥ 2) weeks
• Most antidepressants ultimately down regulate amine receptors
Neurotrophic hypothesis
States that:
• Brain-derived neurotrophic factor (BDNF) and other nerve growth factors regulate neural
plasticity, resilience, and neurogenesis.
• Depression associated w/ ↓ BDNF → ↓ neurotrophic support
Pscyhotherapy
1|Page
, • 1st line for mild-moderate depression
• Effects additive with pharmacotherapy
• Usually provided over 2-4 months
TCAs
-Amitriptline
-Amoxapine
-Clomipramine
-Desipramine
-Doxepin
-Imipramine
-Maprotiline
-Nortriptyline
-Protriptyline
-Trimipramine
SSRIs
-Citalpram
-Excitalopram
-Fluoxetine
-Fluvoxamine
-Paroxetine
-Sertraline
SNRIs
-Desvenlafaxine
-Duloxetine
-Levomilnacipran
-Venlafaxine
Atypical Antidepressants
-Bupropion
-Mirtazapine
-Nefazodone
-Trazodone
-Vilazodone
-Vortioxetine
MAOIs
2|Page
Depression: Mechanisms, Monoamine and
Neurotrophic Hypotheses, SSRIs, SNRIs,
TCAs, MAOIs, Atypical Agents, NMDA
Modulators, GABA Modulators, Clinical
Indications, Adverse Effects,
Contraindications, Pregnancy Considerations,
and Evidence-Based Management of Major
Depressive Disorder and Treatment-Resistant
Depression Complete Questions Provided
with A+ Graded Rationales Latest Updated
2026
5-HT
__________ may be most important NT involved in feelings of wellbeing
Biogenic Amine Theory (Monoamine Hypothesis)
• Monoamine (NE, 5-HT, DA) deficiency in key brain locations leads to depression
• Overproduction/excess = mania
Does not explain why:
• Antidepressants have ~immediate effect on neurotransmission (NE, 5-HT, DA) YET
• Response takes several (≥ 2) weeks
• Most antidepressants ultimately down regulate amine receptors
Neurotrophic hypothesis
States that:
• Brain-derived neurotrophic factor (BDNF) and other nerve growth factors regulate neural
plasticity, resilience, and neurogenesis.
• Depression associated w/ ↓ BDNF → ↓ neurotrophic support
Pscyhotherapy
1|Page
, • 1st line for mild-moderate depression
• Effects additive with pharmacotherapy
• Usually provided over 2-4 months
TCAs
-Amitriptline
-Amoxapine
-Clomipramine
-Desipramine
-Doxepin
-Imipramine
-Maprotiline
-Nortriptyline
-Protriptyline
-Trimipramine
SSRIs
-Citalpram
-Excitalopram
-Fluoxetine
-Fluvoxamine
-Paroxetine
-Sertraline
SNRIs
-Desvenlafaxine
-Duloxetine
-Levomilnacipran
-Venlafaxine
Atypical Antidepressants
-Bupropion
-Mirtazapine
-Nefazodone
-Trazodone
-Vilazodone
-Vortioxetine
MAOIs
2|Page
