Antidepressants

Categories:

  • Selective Serotonin Reuptake Inhibitors (SSRIs)
    • Notes:
      • Increased risk of suicide in 0-24 y/o upon initiation (black box)
      • More gestures and Ideations, no more completions
      • Decreased risk of suicide in ≥65 y/o upon initiation (white men)
    • Drug Interactions:
      • Paroxetine ≥ Sertraline ≥ Citalopram
      • Also helpful for anxiety associated depression
    • SE (General):
      • Sexual dysfunction is the MCC of noncompliance and MC SE (50-80%)
      • Akathisia
      • Early: HA/Nausea, dizziness, insomnia, anxiety
      • Nonspecific: Flu-like, GI upset, Psych symptoms
      • Late: sexual dysfunction and weight gain
    • Citalopram (Celexa)
      • Dose: 20mg up to 20-40mg daily (40mg max effective)
      • Weak CYP2D6 inhibitor
      • Use:
        • Treats anxiety symptoms better than other SSRIs
        • Least likely to have drug interaction
        • Low P450
      • SE: More cardiotoxic, May Prolong Qt interval (blockade of KCNH2 gene potassium channel)
        • 20mg: 8.5ms, 40mg: 12.6ms, 60mg: 18.5ms
        • Use 20mg if ≥60 or hepatic dysfunction
    • Escitalopram (Lexapro)
      • Dose: 10mg up to 10-20mg daily (10mg max effective)
      • Most serotonin specific of SSRIs
        • Most potent SSRI
      • Use: Paraphilias, GAD, Chronic pain
        • Post-MI depression due to low drug reaction potential
        • Low p450, fewer SE than citalopram, rapid
      • SE: QTc Prolongation: 10mg: 4.5ms, 20mg: 6.6ms, 30mg: 10.7ms
    • Fluoxetine (Prozac)
      • Dose: 20mg up to 20-80mg daily
      • Potent CYP2D6 inhibitor
      • Use: OCD, Bulimia, Panic Disorder
        • Can be used with olanzapine for acute bipolar depression
        • Doesn’t need to be tapered when stopping, long half-life
      • SE: May cause agitation/anxiety and insomnia initially, sexual dysfunction, may cause weight loss
        • Nausea, vomiting, diarrhea
        • QTc prolongation (4.5ms)
    • Fluvoxamine (Luvox)
      • 50mg daily, max 300mg divided daily
      • CYP3A4, 2C10, 1A2 inhibitor
        • Most drug interations
      • Use: OCD only
        • No QTc Prolongation (-5.0ms)
    • Paroxetine (Paxil)
      • Dose: 20mg up to 20-60mg daily (50mg max effective)
      • Potent CYP2D6 inhibitor
      • Use: Premature ejaculation, Body dysmorphic disorder, SAD, OCD, PTSD
      • Potent CYP2D6 inhibitor
        • No QTc prolongation
      • SE: Most likely to have side effects, Dizziness, most sedating and anticholinergic SSRI, highest rate of sexual dysfunction, higher rate of weight gain (30%), highest rate of discontinuation syndrome, sedating, constipation
        • Cardiac septal defects in kids (pulm htn)
    • Sertraline (Zoloft)
      • Dose: 50mg up to 50-200mg daily
        • Increased absorption with food
      • Weak CYP2D6
      • Use: PMDD, PTSD, SAD, OCD, Post-MI
        • Best for breastfeeding
      • SE: delayed ejaculation, QTc Prolongation, Bruxism (better with buspirone), generic may be activating, bruising, hair loss
        • 3.0ms
        • Most likely to cause GI upset (Nausea ≥ Diarrhea)
        • May displace warfarin increasing PTT
  • Selective Norepinephrine Reuptake Inhibitors (SNRIs)
    • Notes:
      • Nausea (MC), Sexual dysfunction, Hypertension (not duloxetine), Pseudo-anticholinergic effects (constipation, dizziness, dry mouth, sweating, agitation, anxiety, tachycardia) due to increased synaptic NE
    • Duloxetine (Cymbalta)
      • Dose: 20 mg up to 60mg daily (BID dosing may decrease SE)
        • Aka Yantreve
      • MOA: 5HT = NE at all doses
        • Moderate CYP2D6
      • Use: MDD, stress incontinence, panic disorder
        • FDA approved for diabetic neuropathy, fibromyalgia
        • Pain with depression
        • Useful in diabetics with peripheral neuropathic pain
        • Rapid symptom relief, few side effects
        • Only SNRI w/o BP effects
      • SE: Avoid in renal failure, Hepatic failure in liver disease, may increase HbA1c, Insomnia
        • Nausea, dry mouth, constipation
        • Prompt discontinuation due to side effects
        • Less likely to cause HTN
    • Desvenlafaxine (Pristiq)
      • Dose: 50mg daily
      • MOA: Inhibits 5HT and NE
        • Active metabolite of venlafaxine and levo-milnacipran
        • Avoids hepatic CYP2D6 metabolism
        • Less likely to increase BP than Effexor
      • Use: MDD, GAD, Panic Disorder, Menopause, Cocaine dependence
        • Rapid, few side effects, low cytochrome P-450 effects
        • No Weight gain
    • Milnacipran
      • Racemic mixture of levo- and dextro-milnacipran
      • Use: Fibromyalgia (FDA)
        • No CYP450 interaction, NET ≥SERT selectivity
      • SE: HTN, Tachycardia, GI symptoms, hyperhidrosis, ED
    • Levo-Milnacipran (Fetzima)
      • 20mg; max 40-120mg daily
      • Use: MDD
        • More potent enantiomer of milnacipran
        • Inhibits BACE-1 (B-amyloid plaques)
      • SE: HTN, Tachycardia, GI symptoms, hyperhidrosis, ED
    • Venlafaxine (Effexor)
      • Dose: 37.5mg up to 75-375mg daily XR
      • MOA: Inhibits 5HT ≥ NE low dose, NE ≥ 5HT at high dose
        • Inhibits CYP2D6
      • Use: MDD, GAD, Panic Disorder, Menopause, Cocaine dependence
        • Rapid, few side effects, low cytochrome P-450 effects
        • No Weight gain
      • SE: May cause diastolic hypertension, activating, “stimulant effect”, Increases diastolic BP, most cardiotoxic SNRI, headache, constipation, sweating, Anxiety and HTN in high doses, discontinuation syndrome
        • Nausea and sexual side effects in 30% due to NE not 5HT
        • May have withdrawal
  • Atypical Antidepressants
    • Bupropion (Wellbutrin)
      • Dose: 150mg up to 300-450mg daily
      • MOA: NE and Dopamine reuptake inhibitor, increasing activity
        • Metabolized by CYP2B6 to hydroxy- which is a moderate CYP2D6 inhibitor
        • CYP2B6 substrate
      • Use: Smoking cessation, MDD w/seasonal pattern, Adult ADHD, Obesity
        • Good for weight loss, hypersomnia, smoking cessation, no sexual side effects
        • Not good for anxious patients
      • SE: Agitation, insomnia, anorexia, sweating, false positive for amphetamines on UDS, headache, tremor, dry mouth, psychosis
        • Avoid in pregnancy
      • CI: Seizures, Bulimia and Anorexia Nervosa, epilepsy
        • Check for hypokalemic, hypochloremic metabolic alkalosis (self-induced vomiting seen in Bulimia Nervosa) prior to initiating
        • Seizure risk is 2% at 600mg, 0.1% with 300-450mg, almost same as other antidepressants (0.05%)
    • Mirtazapine (Remeron)
      • Dose: 7.5mg up to 15-45mg daily
        • <30mg = sedation
        • ≥30mg = activating (more NE)
      • MOA: Presynaptic Alpha-2 antagonist
        • Increased NE and 5-HT release
        • Selective postsynaptic 5-HT receptor antagonist
          • Increased 5-HT1 receptor neurotransmission, antagonist at 5-HT2 and 5-HT3 receptor
        • Antagonizes H1 receptors
        • Clearance impaired in liver disease by 30%, 50% in renal disease, elderly (males 40%, females 10%)
      • Use: Insomnia
        • Sleep, Depression, Hunger (Weight Gain)
        • Don’t break it in half, sedative already
        • Additive effects with alcohol and benzos (substrate)
        • Increases appetite, weight gain, increases mood, sleep
          • Lacks sexual side effects
      • SE: Drowsiness (54%), Xerostomia (25%), Weight Gain (12%), Sedation, Thrombocytopenia, Bone marrow suppression and neutropenia, hypertriglyceridemia, increase in appetite, constipation (13%), Disorientation and tachycardia, increased cholesterol, decreased ANC
    • Maprotiline (Ludiomil)
      • D2 blocker (NET ≥SERT inhibition)
      • TCA like adverse effects, seizures, high NET affinity
      • Use: Anxiety with depressive features
    • Nefazodone (Serzone)
      • 50mg BID up to 300mg BID
      • 5-HT2A antagonists (relatively selective), Alpha1 receptor blockade, CYP3A4 inhibitor, weak Serotonin reuptake inhibitor (antagonist and agonist of serotonin receptor)
      • Sedation, dose related GI effects < SSRIs
      • Rare sexual effects, hypotension
        • Short half life
      • Use: Insomnia
      • Black Box Warning: Fulminant liver failure
    • Trazodone (Desyrel)
      • MOA: 5-HT2A antagonist (relatively selective), Alpha-1 receptor blockade, CYP3A4 substrate, 5HT2C receptor agonist
        • Vasodilation, Short half life
      • Use: Insomnia in depression
        • Depression: 150mg up to 150-600mg daily
        • Sleep: 25-50mg qPM
      • Pronounced sedation, dose related GI effects < SSRIs
      • SE: Rare sexual effects, priapism (<1%), hypotension, sedation
    • Vilazodone (Viibryd)
      • Dose: 10mg daily, goal 40mg daily, 10mg per week increase
      • SSRI + 5HT1 partial agonist (MDD + GAD)
        • CYP3A4
      • Use:
        • Less Sexual and Weight gain SE
      • SE: Nausea and Diarrhea ≥ SSRIs, discontinuation syndrome
    • Vortioxetine (Trintellix)
      • Serotonergic, nausea, Sexual side effects
      • Processing speed increase
      • SSRI + 5HT1A full agonist/5HT1B partial agonist, 5-HT3/7/1D antagonist
  • Monoamine Oxidase Inhibitors (MAOIs)
    • Avoid: beer, wine, aged cheese, soy sauce, bananas, smoked meat
    • SE: MCly Orthostatic hypotension and weight gain, paresthesia (from B6 deficiency), mania
      • highest rates of sexual dysfunction of all antidepressants, Anorgasmia
      • Activation, insomnia, and restlessness
      • Confusion at higher doses
      • Hypertensive Crisis (0.02%)
      • Delirium-like discontinuation with psychosis, excitement, and confusion
        • Meperidine is specifically contraindicated
      • Need 2-week washout
    • Nonselective
      • MOA: Irreversibly inhibit MAOA/B
      • Isocarboxazid (Marplan)
        • 10mg BID, max 60mg daily
        • Use: Geriatric Depression
      • Tranylcypromine (Parnate)
        • 30mg daily to 60mg in divided doses
        • Use: Atypical Depression
      • Phenelzine (Nardil)
        • 15mg TID to 90mg TID
        • Non-selective blockade of MAO
        • More sedating than selegiline and tranylcypromine
        • Pain, Eating, Panic disorders
    • Selective
      • Selegiline (Emsam)
        • Dose: 6mg-12mg transdermal patch (24hr)
        • MOA: MAO-B irreversible inhibition at low doses
          • Increased dopamine
          • MAO-A inhibition if given transdermally
        • Use: Parkinson’s drug
          • No dietary restriction if used in low dosages
        • SE: Orthostatic hypotension
      • Rasagiline
  • Tricyclic Antidepressants (TCAs)
    • General
      • MOA: Block NE and serotonin reuptake at synapse, some block Dopamine reuptake
        • Inhibition of NE and 5-HT can trigger convulsions/seizures
        • Also block muscarinic acetylcholine receptors
          • Orthostatic hypotension due to alpha blockade
          • H1 receptors also blocked
        • Class 1A Antiarrhythmic agents at low doses, arrhythmic agents at high doses
      • 2nd MCC of lethal OD in US (amitriptyline ≥ rest combined), death in 8.5/1000 OD
      • SE: Convulsions, Coma, Cardiotoxicity, Respiratory Depression, Hyperpyrexia, Prolonged QRS, weight gain, sedation
        • Cholinergic rebound on discontinuation (flu like)
        • Delirium (amitriptyline)
        • Seizures (2% clomipramine)
        • Acute Hepatitis (0.1%)
      • CI: Narrow-angle Glaucoma
    • Secondary Amines
      • General
        • High affinity for blocking NE reuptake (NE ≥ 5HT)
        • Fever, anticholinergic effects, weight gain
      • Desipramine (Norpramin)
        • Dose: 25-50mg daily up to 100-300mg daily
        • Least sedating TCA (most noradrenergic)
        • SE: LFT elevation (AST≥≥≥ALT)
      • Maprotiline (Ludiomil)
        • Dose: 25mg TID, max 225mg daily
        • Lacks 5HT reuptake inhibition (mainly NE reuptake)
        • SE: Sedating
      • Nortriptyline (Pamelor)
        • Dose: 25-50mg daily up to 150-200mg daily
        • Use: Elderly depression, cardiac diseases, pruritus, smoking cessation, QTc Prolongation
          • Least likely to cause orthostatic hypotension (low acnticholinergic)
    • Tertiary Amines
      • Notes:
        • 5HT ≥ NE
        • Have more anticholinergic side effects and sedation
        • Agitation, blurry vision, fever, constipation, urinary retention, confusion
        • Myotonic jerking, delirium, sedation, coma
      • Amitriptyline (Elavil)
        • Dose: 25-50mg daily up to 100-200mg daily
        • Use: Depression w/insomnia, chronic pain
        • SE: Orthostatic hypotension (causing falls), Sedating
          • Semiannual EKG due to risk of QT prolongation
          • Most anticholinergic
      • Amoxapine (Asendin)
        • Dose: 50mg BID, max 400mg daily
        • MOA: D2 blocker (5HT = NE, weak DA)
          • Blockade of NE and 5-HT reuptake
        • Use: MDD w/Psychotic Features
          • Dopamine receptor blockade (antidepressant)
            • Anti-dopaminergic effects (Parkinson’s, ED)
            • Unique to drug in class (may cause EPS)
        • SE: higher seizure risk, TD
          • Most dangerous in overdose
      • Clomipramine (Anafranil)
        • Dose: 25mg daily, max 250mg daily
        • Most serotoninergic, most sexual effects
        • Use: OCD
      • Doxepin (Sinequan)
        • Dose: 25-75mg daily up to 100-300mg daily
        • MOA: 5HT = NE, highly sedation
          • Most antihistamine
        • Use: GAD, PUD, pruritis
        • SE: Sedating, antihistaminergic, anticholinergic
      • Imipramine (Tofranil)
        • Dose: 25-50mg daily up to 100-200mg daily
        • MOA: 5HT = NE
        • Use: Panic disorder with agoraphobia, enuresis, eating disorders, but has a high relapse rate
        • SE: Orthostatic hypotension, prolonged QT, LFT elevation (AST≥≥≥ALT)
      • Protriptyline (Vivactil)
        • Less sedating than doxepin, nor/amitriptyline, imipramine
        • Good for job alertness

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