Antidepressants Overview and Mechanism

Groups of Antidepressants

• SSRI: Selective Serotonin Reuptake Inhibitors
• SNRI: Serotonin-Norepinephrine Reuptake Inhibitors
• NDRI: Norepinephrine-Dopamine Reuptake Inhibitors
• NARI: Norepinephrine Reuptake Inhibitors
• SARI: Serotonin Antagonist and Reuptake Inhibitors
• NASSA: Noradrenergic and Specific Serotonergic Antidepressants
• SMS: Serotonin Modulator and Stimulator
• TCA: Tricyclic Antidepressants
• iMAO: Irreversible Monoamine Oxidase Inhibitors

Mode of Action of Antidepressants

• Varies by class, generally involves modulation of neurotransmitters such as serotonin, norepinephrine, and dopamine

SSRIs Key Points

• Primarily inhibit SERT (serotonin transporter), with some action on NAT (norepinephrine transporter)
• Generally safe, overdose can be fatal but lower risk
• No significant interaction with alcohol
• Weight gain can occur, but not widespread
• High risk of suicidal thoughts in teenagers
• Possible drug-drug interactions with CYP2D6 and 3A4
• Adverse effects include gastrointestinal irritation, sexual dysfunction, and anhedonia

Common SSRIs

• Sertraline
• Fluoxetine
• Fluvoxamine
• Paroxetine
• Citalopram
• Escitalopram

Fluoxetine Details

• Antagonist of 5-HT2A and inhibits CYP2D6
• Weakest SERT inhibitor compared to other SSRIs
• Muscarinic effects lead to sedation
• Noted for its potential drug-drug interactions

Drug of Choice for Teens with Anorexia/Bulimia

• Fluoxetine is preferred due to its efficacy and safety profile

SNRIs Overview

• Mechanism includes 5-HT and norepinephrine blockage
• Side effects include insomnia, sexual impairment, appetite changes, and hypertension
• Common drugs in this group: Venlafaxine, desvenlafaxine, Duloxetine (also indicated for neuropathic pain)

NDRI Characteristics

• Minimal effect on serotonin systems
• Suitable for smoking cessation
• Associated risk of seizures, especially in anorexic patients
• Main mechanism increases serotonin leading to potential initial insomnia/anxiety
• Bupropion is the only drug in this category

NARI Insights

• Drugs include Reboxetine and Atomoxetine (used for ADHD)
• Mechanism blocks NAT with a ratio of SERT to NAT at 20:1
• Side effects encompass sexual dysfunction, constipation, insomnia, anxiety, and restlessness

Trazodone Profile

• Classified as SARI
• Inhibits SERT, agonizes 5-HT1A, and antagonizes H1, alpha-1 receptors
• Major side effects include hypotension and sedation
• Affected by CYP2D6 and CYP3A4 enzymes
• Indicated for various conditions including sexual disorders and insomnia

Mirazapine Overview

• Classified as NASSA
• Agonizes alpha-2, 5-HT2A/C, and 5-HT3 receptors
• Promotes weight gain and increased appetite

Vortioxetine Information

• Mechanism involves SERT inhibition, 5-HT1A agonism, and 5-HT3 antagonism
• Side effects include pruritus, nausea, and vivid dreams
• Substrate for CYP2D6, recommended for patients with depression and insomnia
• Enhances cognitive function without affecting sexual dysfunction

Agomelatine Details

• Mechanism involves MT1 and MT2 agonism and 5-HT2C antagonism
• Resynchronizes circadian rhythms by increasing melatonin release
• Substrate for CYP1A2, monitor for hepatotoxicity
• Single bedtime dose, unsuitable for alcoholics due to liver risk

TCA Mechanism and Effects

• Inhibits reuptake of serotonin, norepinephrine, and dopamine
• Clomipramine particularly affects serotonergic receptors
• Imipramine and desipramine impact adrenergic receptors
• Amitriptyline and Nortriptyline affect both serotonin and norepinephrine pathways

iMAO Characteristics

• Irreversible inhibition of monoamine oxidase enzymes
• Moclobemide specifically inhibits MAO-A
• Effects on neurotransmitters rank as 5-HT > NA > D
• Positive effects on cognition; caution with side effects including weight gain, hypotension, and CNS stimulation
• Antidote for hypertensive crisis is Phentolamine

Esketamine Overview

• NMDA antagonist that inhibits GABA interneurons
• Increases glutamate release, indicated for resistant depression in combination with other antidepressants
• Administered intranasally under supervision; careful monitoring of blood pressure is required
• Treatment phases include induction, optimization, and maintenance

Tianeptine Profile

• Functions as a reuptake enhancer
• Exhibits anti-craving effects in alcoholics