Rx Antidepressants


    1.     Physical sx (appetite, sleep, psychomotor, energy) improves 1-3 weeks.

    a. Cognitive+ emotional takes 4-6 weeks

    2.     If experience new or stronger thoughts of suicide, contact MD

    a. People may be suicidal but too tired to carry out, AD improve energy before mood, may incr risk

    Does NOT increase risk of suicide, but increases thinking.

    b. Adolescents may have increased restlessness, which may incr suicide. (AD-induced restlessness inv. Proportional to age) (esp Paxil and Effexor)  Feel as though suicide only way to end restlessness?  (Studies: no incr complete suicide, but increased thinking and maybe attempts).

    c. Theoretical, no evidence!

    3.     If feel better in 6 weeks, continue to take for 6-12mo.

    a. If older age, psychotic, refractory, frequent, may need >2yrs.

    4.     If mood suddenly switches, too much energy, contact MD

    a. Mania/Hypomania either S/E or bipolar unmasked (may need to switch drug)

    (If that's the case, need antidepressant + mood stabilizer)

    5.     Do not stop AD Tx abruptly

    a. W/D: (not Life threatening), dizziness, n/v, chills, insomnia “Electric-shock-like sensations, visual, anxiety, agitation, mania.

    b. Fluoxetine (Prozac) half-life is long, self-tapering, no W/D

    c. Buproprion no W/D

    6.     Not all AD work for all people (r/a in 3-4weeks)

    a. 60-75% response rate, if switch to another offers another 60-75%

    b. If no response in 3-4 weeks, likelihood of response is 20%

    7.     Tell all MDs you are on it

    a. Drug interactions

    b. P450 inhibition (minimal effect: sertraline, citalopram (Celexa), escitalopram (Cipralex)

    c. Never SSRI’s + MAOi (Serotonin syndrome: confusion, hypomania, agitation, myoclonus, hyperreflex, seating, diarrhea, fever, death)



    -       Block serotonin reuptake, increase serotonin in the synaptic cleft

    -       Why takes 3-4 weeks to work (considering cocaine is also a serotonin, DA, and NE reuptake inhibitor works instantly)

    o   In depressed brain, low serotonin causes upregulation of post-synaptic serotonergic receptors.  Research shows that depression does not improve until receptors are downregulated, and # goes back to normal.



    • Weight Neutral (in theory should drop weight)
    • Non-toxic

     1.  Sexual Dysfunction (90% incidence)

    • Libido/interest (usualy normal, Venlafaxine decr)
    • Potency OK
    • Ejaculation/organism (frequent)***  - can fix with Busperone

      2.  Activation/Sedation, Anxiety/Insomina

    Fluoxetine > paroxetine > sertraline = citalopram = escitalopram > fluvoxamine

    Activating                                                                                                       Sedating

    • sedation from H1 and M1 blockade (the three are good for sleep/wake cycle)
      • M1 - anticholinergic: dry mouth, constipation, urinary retention.
      • H1 - antihistamine: 

      3.  Restlessness (akathisia), fine tremor

    • Tx restlessness w/ B-blockers, benzos, dose reduction
    • Fine tremor (peripheral B-adrenergic stim) responds to B-blockers, dose reduction

      4.  Sweating

    • (not understood, esp in summer, may need to switch drugs)

      5.  Others: Bruxism, dizziness, dry mouth, dystonia, headache, SIADH


    Drug Name (Brand) Dosing (mg/day) +Act/-Sed Notes
    Fluoxetine (Prozac) Start: 20mg (20-80mg) ++++

    - No withdrawal (VERY LONG half-life - weeks)

        Can use to bridge when stopping other SSRI's

    - Safe in kids

    Paroxetine (Paxil) Start: 20mg (20-60mg) +++

    - ++ restlessness, esp in kids. (inversely related to age)

    - Do not use in kids

    Sertraline (Zoloft) Start: 50mg (50-200mg) +

    - Popular choice

    - Very effective, also dopaminergic effects 

    - No P450 interactions, neutral w/ sleep/wake cycle

    - Level 1: Superior to: Fluoxetine, pooled

    Citalopram (Celexa) Start: 20mg (20-40mg) ~

    - QTc prolon

    gation, careful!

    - No P450 interactions, neutral w/ sleep/wake cycle

    Escitalopram (Cipralex) Start: 10mg (10-20mg) ~

    - QTc prolongation, careful!

    - No P450 interactions, neutral w/ sleep/wake cycle

    - Level 1: superior to Citalo, Dulox, Parox, pooled

    Fluvoxamine (Luvox) Start: 50mg (100-300mg) - - - -

    - Sedating


    Risk of sexual dysfunction Antidepressant

    Low (<10%)

    (Close to placebo)




    Medium (10-30%)





    High (>30%)















    • Also help with pain
    • First line therapy for anxiety+depression
    • Mechanism: also NE reuptake inhibitor
    • S/E:same as SSRI + insomnia (NE), HTN (NE), maybe more sexual dysfunction.


    • Venlafaxine(Effexor)   Start: 75mg (75-375mg)
      • ++Restlessness
      • **HYPERTENSION**
      • Also affects libido/interest
      • ***W/D*** intradose, short half-life (W/D in 36hrs)
      • Level 1: Superior to Duloxetine, Fluoxetine, pooled SSRIs
    • Duloxetine(Cymbalta)  [Depression + pain]   Start: 60mg (60-120mg)
    • Desvenlafaxine(Pristiq)   [does not use P450 2D6??]  Start: 50mg (50-100mg)


    • Indication: Pain + depression
    • FATAL IN OVERDOSE (ARRHYTHMIA, coma, convulsions)
    • 3° amines: amitriptyline (Elavil), clomipramine (OCD) (Anafranil), doxepin
    • 2° amines: desipramine, nortriptyline, etc…
    • Mechanism:
      • Reuptake inhibition of 5HT, NE, DA (Weaker than SSRI, except clomipramine)
    • S/E:
      • Weaker 5HT S/E
      • Block: M1 (Anticholinergic): dry mouth, blurry vision, constipation, delayed urination
      • Block a1: Dizziness, postural hypotension, sedation
      • Block H1: sedation, wt Gain
      • (Clomipramine is serotenergic, Same S/E as SSRI)


    • Indication: refractory depression
    • Overdose very toxic, but safer than TCAs
    • Mechanism:
      • Blocks MAO-A (brain) – Increases 5HT in cleft
      • MAO-B (GI) – Detox Tyromine in bowel.  Otherwise Tyromine absorbed as potent pressor agent àHTN crisis (if block, restrict diet)
    • Phenelzine(Nardil)
    • Tranylcypromine(Parnate)
    • Indications: Anxiety and depression, reserved for refractory.
    • MAOIs and SSRIs are most dangerous -àserotonin syndrome.  Need to wash out one with 5x half-lives before starting another.
      • Old guidelines 1965: only cottage cheese, toast, water, new guidelines more liberal.
      • S/E: anticholinergic
        • Insomnia
        • Postural hypotension
        • Weight gain (Phenelzine)
        • Diet restriction

    Reversible Inhibitor of MAO-A (RIMA)

    • Moclobemide(Manerix)
      • Rarely used, efficacy not established in severe depression
      • Well tolerated, no sex dysfunction, no dietary restriction, can combine w ssri.

    Serotonin Antagonist and Reuptake Inhibitor (SARI)

    • Trazodone(Desyrel)   Start: 150-200mg (150-300mg)
      • AT low doses (<200mg/day): does not block 5HT reuptake, but blocks 5HT2 causing:
        • non-addictive sedation
        • Not antidepressant
      • Safe to combine with MAOi, do not use in bipolar people.
      • S/E: increased libido, and priapism (painful erection)
    • AT high doses (>= 200mg/day): 5HT reuptake inhibitor and 5HT2 receptor blocker
      • Antidepressant
      • Often too sedating  (but sedating effect may plateau with higher doses)
      • Do not use with MAOi

    Norepinephrine Dopamine Reuptake Inhibitor (NDRI)

    • Mechanism: Reuptake of NE and D2 inhibited (the only non-serotinergic antidepressant)
    • Bupropion (Wellbutrin, Zyban) Start: 150mg (Dose: 150-300mg/day)
      • ​Wellbutrin TID
      • Wellbutrin SR (Sustained Release) is BID
      • Wellbutrin XL (Extended Release) is OD

    ​    Effects:

    • Dopaminergic: like cocaine S/E
      • Wt loss
      • D2: Helps addiction to cocaine/smoking (Cocaine addiction is a dopaminergic roller-coaster, if not using, dopamine low, so seek substance to incr dopamine), this gives free dopamine
      • NE: Activating+++ (Worsens anxiety), Incr sustained HTN, Insomnia, risk of SEIZURE
      • Prosexual
    • First line: depression w/ anergia, amotivation, and hypersomnia.
    • Potentially tx social phobia and PTSD, but can worsen anxiety (????)

    Noradrenergic and Specific Serotonergic Agent (NaSSA)

    • Mechanism:
      • releases 5HT and NE from presynaptic terminal
      • Blocks 5HT2A – reverses 5HT sexual dysfunction, anxiolytic, sedating
      • Blocks 5HT2C – anxiolygic, sedating, inr appetite + wt gain
      • Blocks 5HT3A – antiemetic
      • (Blocks M1 – anticholinergic)
    • Mirtazapine(Remeron)  Start: 30mg (Maint: 30-60mg)


    • First line anxiety +depression
    • Depression+insomnia
    • Depression + GI issues (works as odansetron)
    • Reverse sexual dysfunction by SSRI+SNRI
    • SE: too much weight gain + sedation.
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