Depression

Drug Therapy For Depression

Antidepressant Classes Comparison Table (Clinical Pharmacist Focus)

Class Examples MOA Notable Side Effects CYP Interactions Clinical Pearls Common Uses
SSRIs (Selective Serotonin Reuptake Inhibitors) Fluoxetine, Sertraline, Escitalopram, Paroxetine, Citalopram Inhibit SERT → ↑5-HT Sexual dysfunction, GI upset, insomnia, agitation Fluoxetine & Paroxetine: CYP2D6 inhibitors First-line; safer in overdose; dose-dependent QTc with citalopram MDD, GAD, OCD, PTSD, Panic
SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors) Venlafaxine, Duloxetine, Desvenlafaxine, Levomilnacipran Inhibit SERT & NET ↑BP (esp. venlafaxine), insomnia, nausea, sexual dysfunction Duloxetine: CYP2D6 inhibitor Useful in pain + depression; venlafaxine has dose-dependent NE effect MDD, GAD, Neuropathic pain, Fibromyalgia
TCAs (Tricyclic Antidepressants) Amitriptyline, Nortriptyline, Imipramine, Clomipramine Inhibit SERT & NET + block H1, M1, α1 Anticholinergic effects, sedation, weight gain, cardiotoxicity Substrate of multiple CYPs Lethal in overdose (QTc, arrhythmias); monitor ECG; avoid in elderly MDD, Neuropathic pain, Insomnia, Migraine
MAOIs (Monoamine Oxidase Inhibitors) Phenelzine, Tranylcypromine, Selegiline patch Inhibit MAO-A & B → ↑5-HT, NE, DA Hypertensive crisis (tyramine), serotonin syndrome, orthostasis Numerous DDI with SSRIs, sympathomimetics Rarely used; last-line; requires dietary restrictions Treatment-resistant depression
NaSSAs (Noradrenergic & Specific Serotonergic Antidepressants) Mirtazapine α2 antagonist → ↑NE & 5-HT + 5HT2/3 block Sedation, weight gain, ↑appetite, dry mouth Minimal CYP interaction Useful for insomnia, poor appetite, elderly; low sexual SE MDD, insomnia, elderly depression
NDRIs (Norepinephrine-Dopamine Reuptake Inhibitor) Bupropion Inhibits NET & DAT Insomnia, dry mouth, ↑anxiety, seizure risk CYP2D6 inhibitor No sexual dysfunction; CI in seizure, eating disorders MDD, Smoking cessation, SAD
Multimodal (Serotonergic agents) Vortioxetine, Vilazodone 5-HT reuptake inhibition + receptor modulation Nausea, mild GI issues, low sexual dysfunction Vortioxetine: CYP2D6 substrate; Vilazodone: CYP3A4 substrate Cognitive benefits (vortioxetine); take with food (vilazodone) MDD
Atypical Antipsychotics (Adjuncts) Aripiprazole, Quetiapine XR, Olanzapine/fluoxetine Dopamine + serotonin modulating Weight gain, metabolic syndrome, EPS, sedation Aripiprazole: CYP2D6/3A4 substrate Used as augmentation; monitor for metabolic changes MDD (adjunct), treatment-resistant cases
NMDA Antagonists / Fast-Acting Esketamine (nasal spray), Ketamine (IV) NMDA receptor antagonism → ↑glutamate signaling Dissociation, ↑BP, nausea, sedation Non-CYP route; monitor CNS depressant interaction Rapid-acting; REMS program; supervised administration only TRD (treatment-resistant depression)

Clinical Tips by Class (for Pharmacists)

Class Avoid In Monitoring Needs Special Use Cases
SSRIs Bipolar (unless mood stabilizer added) Na+ (elderly), QTc (citalopram), bleeding risk Anxiety comorbidity, pregnancy (sertraline preferred)
SNRIs Uncontrolled HTN, glaucoma BP, liver enzymes (duloxetine), withdrawal symptoms Pain syndromes, menopausal symptoms
TCAs Elderly, cardiac disease, suicidal patients ECG, anticholinergic burden Neuropathic pain, refractory depression
MAOIs Non-adherent patients Diet (tyramine), drug interactions Atypical depression, TRD
NaSSA Obesity (caution), severe hypersomnia Lipid profile, weight Cachexia, insomnia, elderly
NDRI Seizure risk, eating disorders BP, mental status changes Fatigue, sexual dysfunction, smoking cessation
Multimodal Severe GI intolerance (vilazodone) CYP2D6 drug interactions Cognitive complaints, MDD
Atypicals Diabetes, obesity, EPS history Weight, lipids, A1c, EPS/AIMS Augmentation in TRD
NMDA-R antagonists Psychosis, CVD BP, dissociation, abuse risk Rapid symptom control in TRD/suicidality

 

Drug Treatment of Depression

Vitamin Deficiencies 

 

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