Antidepressants (General) Flashcards
Unipolar Depression
One direction of depressive symptoms
Bipolar Disorder
Depression alternating with mania
Depression Symptoms
Emotional:
- Sadness, Anxiety, Overwhelmed
Biological:
- Aches, Headaches, Sleep disturbance, Significant weight changes
Depression Pathophysiology (Monoamine Theory)
Depression is caused by deficient of monoamine transmitters, noradrenaline, and 5-HT
Mania is caused by excess
Evidence of Monoamine Theory
Tricyclic Antidepressants blocks NE and 5-HT reuptake
–> Increase NE and 5-HT in synapse
–> Increase mood
Reserpine inhibits NA and 5-HT storage
–> Decrease NA and 5-HT in body
–> Decrease body
Issues with Monoamine Theory
Inconsistent Result:
- Neurochemical effects of antidepressants is very rapid, however, antidepressant effects take weeks to form
–> What is happening in between giving monoamine and its antidepressive effects
- Ketamine’s antidepressant effect works rapidly, however, it does not increase NA
Depression Neuroendocrine Mechanism
(Cortisol)
HPA Axis (Hypothalamus-Pituitary-Adrenocortical)
Stimulation of HPA (Caused by stress, illness, time of day, etc.)
- Hypothalamus releases CRH
- Anterior Pituitary releases ACTH
- Adrenal Glands release Cortisol (Stress Hormone)
Depression Neuroendocrine Mechanism
(Glutamate)
Stress enhances the excitotoxic effects of glutamate mediated by NMDA receptors
–> Expression of genes that promotes neural apoptosis
Depression Neuroendocrine Mechanism
(Neuron Loss)
Cortisol and Excitotoxic Glutamate promote Detrimental Gene Transcription Responses
–> Promotes Neural Apoptosis
–> Inhibits Neurogenesis
Promoting Depressive Symptoms
Depression Neuroendocrine Mechanism
(Neuron Gain)
NA, 5-HT, BDNF (Brain Derived Neurotrophic Factor) promote Beneficial Gene Transcription Responses
–> Promotes Neurogenesis
–> Inhibits Neural Apoptosis
Promoting Depressive Symptoms
Conventional Anti Depressants
(Inhibitors of Monoamine Uptake)
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- Tricyclic Antidepressants (TCAs)
–> NE and 5-HT Reuptake Inhibitors - Mixed 5-HT and NE Reuptake Inhibitors
(SNRIs) - NE Dopamine Reuptake Inhibitors (NDRI)
- St John’s Wort
–> 5-HT and NE Reuptake Inhibitor
Conventional Anti Depressants
(Receptor Blocking Antidepressant)
Serotonin-2 Antagonists / Serotonin Reuptake Inhibitors (SARI)
–> Blocks 5HT-2
Noradrenergic/Specific Serotonergic Agent (NaSSA)
Monoamine Oxidase Inhibitors (MAOI)
- Irreversible, non competitive, non selective inhibitors
–> Inhibit MAO-A and MAO-B
(Phenelzine, Tranylcypromine) - Reversible, MAO-A Selective Inhibitors
(Moclobemide)
Rapid Acting Antidepressants (RAADs)
Non-Competitive NMDA Receptor Channel Blocker
- Ketamine
Effects of Antidepressants
(NE Reuptake Blockade)
Antidepressant Effect, Vasoconstrictor
Side Effect: Too much NE
- Causes tremors, tachycardia, and erectile problems
–> Avoid using with anything that increases heart rate
Effects of Antidepressants
(5-HT Reuptake Blockade)
Antidepressant, Anti-Anxiety, Anti-Panic, Anti-Obsessional
Side Effects: Affects other 5-HT Receptors
- Nausea, Dyspepsia, Headache, Sexual Side Effects
Potentiation of drugs with serotonin properties, caution regarding serotonin syndrome
Effects of Antidepressants
(DA Reuptake Blockade)
Elevate Prolactin
Side Effects: Too much DA
- Aggravation of Psychosis
Effects of Antidepressants
(5-HT1A Agonism)
Antidepressant, Anxiolytic, Anti Aggressive
Effects of Antidepressants
(5-HT2A Blockade)
Anxiolytic, Antidepressant, Antipsychotic, Antimigraine, Improved Sleep
Side Effects:
- Hypotension, Ejaculatory Problems, Sedation, Weight Gain
Effects of Antidepressants
(M1 Ach Blockade)
Dry mouth, blurred vision, urinary retention, constipation
Makes anticholinergic drugs stronger
Effects of Antidepressants
(H1 Blockade)
Side Effects: Sedation, Postural Hypotension
Effects of Antidepressants
(a1 Blockade)
Side Effects: Postural Hypotension, Dizziness, Reflex Tachycardia
Effects of Antidepressants
(a2 Blockade)
CNS Effect: Possible decrease in depressive symptoms
Adverse Effects of SSRIs
Enhanced effect on 5-HT Receptors
- Nausea, anorexia, insomnia, headache, nervousness, sexual dysfunction
Risk of Serotonin Syndrome
QT Interval Prolongation –> Citalopram
Serotonin Modulator and Stimulator Benefits
Vortioxetine is more specific
Agonist: 5-HT1A and 5-HT1b
Antagonist: For other 5-HT
Due to being a specific agonist and its antagonist action –> Lower Side Effects
- Less sedation
- Less insomnia
- Less weight gain
Serotonin-1A Agonist / Serotonin Reuptake Inhibitor (Mechanism)
Vilazodone
SSRI
Agonist for 5-HT1A
Secondary Amines (Effects)
Greater NE Reuptake Inhibition than 5-HT effect
–> More NE Side Effects
Tertiary Amines (Effects)
More 5-HT Reuptake Inhibition
–> More 5-HT Side Effects
TCAs (Side Effects)
Affect Muscarinic, Histamine, and 5-HT Receptors
Overdose: Arrhythmia
- Anticholinergic
–> Dry mouth, blurred vision, constipation,
urinary retention - Antihistamine
–> Sedation - Antimuscarinic
Venlafaxine
Non-Selective for 5-HT and NE uptake
- 5-HT Reuptake Inhibitor at low dose
- NE Reuptake Inhibitor at high dose
Similar to TCAs, lack major receptor blocking actions
–> Fewer Side Effects
Bupropion
NDRI: NA and DA reuptake inhibitor
Helps in quitting smoking
Lowers seizure threshold
- Makes it easier to get seizure
–> Do not use with patients that are in risk of seizure
Trazodone
SARI: Serotonin 2 Antagonist + Serotonin Reuptake Inhibitor
Blocks 5-HT2A and 5-HT2C
Blocks 5-HT Reuptake
Strong sedation effect:
- Should be taken at night
Mirtazapine
NaSSA: Noradrenergic/Specific Serotonergic Agent
Blocks alpha 2 adrenoceptor and 5-HT2C receptors
–> Enhance NA and 5-HT release
Potent Antihistamine effect at H1
Also blocks 5-HT2A and 5-HT3 receptors
- Less sexual dysfunction and nausea side effects
No anticholinergic side effects
Monoamine Oxidase (Different Types)
MAO-A (Main Antidepressant Target)
- Degrades 5-HT and NE
MAO-B
- Degrades phenylethylamine and dopamine
Hypertensive Crisis
MAO in gut inactivates amines like tyramine
- Tyramine produces unwanted effects
If using a MAO inhibitor then there is no MAO to inactivate Tyramine
–> Can cause hypertensive crisis
Also avoid using OTC cough/cold agents that contain sympathomimetics
