Psychiatry Pharmacology

• MECHANISM:
• - block dopamine receptors (potency correlates to D2R affinity)
• *typical antipsychotics block D2R more strongly than atypical (except risperdone)
• - side effects due to blockage of 5HT2R
• * takes several days to weeks to have effect

• INDICATIONS:
• - schizophrenia
• - tourette's
• - bipolar
• - Huntington's
• - acute mania
• - psychotic depression
• - acute delerium
• - drug induced psychosis

• ADVERSE EFFECTS:
• - EPS (dose-dependent)
• - Hyperprolactinemia
• - QTc prolongation
• - NMS
• - akathisia
• - lower seizure threshold
• - sedation
• - anticholinergic side effects
• - orthostatic hypotension

• DRUGS:
• - Thioridazine (Mellaril)
• - Chlorpromazine (Thorazine)
• - Perphenazine (Trilafon)
• - Thiothixene (Navane)
• - Haloperidol (Haldol)
• - Fluphenazine (Prolixin)

Thioridazine

• - EPS: low
• - Sedation: high
• - Hypotension: high
• - Anticholinergic: high

- higher incidence of cardiotoxicity

Chlorpromazine

• - low potency
• - t_1/2 = 10-40hrs

• - EPS: low
• - Sedation: high
• - Hypotension: high
• - Anticholinergic: med

• - high incidence of metabolic effects (wt gain, lipids, gluc)
• - agranulocytosis
• - skin discoloration/photosensitivity
• * also indicated for n/v

Perphenazine

• - Mid potency
• - t_1/2 10-20hrs

• - EPS: medium
• - Sedative: low
• - Hypotensive: low
• - Anticholinergic: low

Thiothixene

• - high potency
• - t_1/2 10-20hrs

• - EPS: high
• - Sedative: low
• - Hypotensive: low
• - Anticholinergic: low

• - akithisia is common
• - ocular pigment changes

Haloperidol

• - high potency
• - t_1/2 12-36hrs

• - EPS: high
• - Sedative: low
• - Hypotensive: low
• - Anticholinergic: low

• - "gold standard" of D2 blockade
• - decanoate: depot shot (qmonth)
• - available in all routes

Fluphenazine

• - potency high
• - t_1/2 10-20hrs

• - EPS: high
• - Sedative: med
• - Hypotensive: low
• - Anticholinergic: low

- decanoate available

• MECHANISM:
• - potent 5HT2 antagonists
• - weaker D2 affinity that FGAs
• - serotonin blockade protects against movement side effects

• INDICATIONS:
• - same as typical but with different approvals
• - acute mania (but not yet studied in maintenance)
• - augmentation of SSRI in MDD
• - PTSD
• - bulimia

• ADVERSE EFFECTS:
• - weight gain/metabolic syndrome (DM, DKA)

• DRUGS:
• - Risperidone (Risperdal)
• - Quetiapine (Seroquel)
• - Olanzapine (Zyprexa)
• - Ziprasidone (Geodon)
• - Clozapine (Clozaril)
• - Aripiprazole (Abilify)
• - Iloperidone (Fanapt)
• - Paliperidone (invega)

Risperidone

- strong D2 and 5HT2 antagonist

• Side Effects:
• - low EPS if < 6mg
• - orthostatic hypoTN, c reflex tachycardia
• - insomnia
• - hyperprolactinemia
• - weight gain

• Misc:
• - decanoate form available

Quetiapine

• - low D2 and 5HT2 affinity
• - high histamine affinity

• Side Effects:
• - orthostatic hypoTN
• - somnolence
• - weight gain (fewer metabolic sxs than olanzapine)
• - dyspesia

Olanzapine

- high D2, 5HT2, muscarinic and histaminergic affinity

• Side Effects:
• - drowsiness
• - dry mouth
• - akithisia
• - insomnia
• - +++ wt gain (avg > 20lbs/yr)
• - HLD
• - DM, DKA

• Misc:
• - twice as costly as other atypicals

Ziprasidone

• Side Effects:
• - dizziness, postural hypoTN
• - prolactin elevation
• - nausea
• - QTc prolongation

• Misc:
• - must give with food, 300 cal (slow down gastric emptying to allow for absorption)
• - mandatory pre-tx EKG

Clozapine

- strong histamine affinity, low D2

• * ONLY AGENT EFFECTIVE IN REFRACTORY SCHIZOPHRENIA
• * some evidence for reversing TD

• Side Effects:
• - orthostatic hypoTN
• - sedation
• - tachycardia
• - constipation
• - hypersalivation
• - +++ wt gain
• - +++ HLD, hyperglycemia (w DKA)
• * Agranulocytosis

• Misc:
• - mandatory EKG prior to use
• - weekly CBC x6months, then biweekly after
• - register in national database

Aripiprazole

- strong dopaminergic antagonist, also partial agonist (may get stimulation at high doses)

* no QTc prolongation or increased prolactin

• Side Effects:
• - headache
• - n/v
• - sedation with high doses
• - anxiety

Iloperidone

- dopaminergic, strong serotonergic, low histamine

• Side Effects:
• - orthostasis
• - weight gain

Paliperidone

• - Amantadine
• - Benztropine
• - Diphenhydramine

Amantadine

MOA: augments dopaminergic transmission

Indications: EPS

• Side Effects:
• - insomnia
• - dizziness
• - impaired concentration

Benztropine

• MOA:
• - muscarinic/acetylcholine antagonist
• - antihistamine

• Indications:
• - Parkinsonism
• - EPS
• - acute dystonia
• - akithisia

• Side Effects:
• - anticholinergic (dry mouth, constipation, urinary retention)

• MECHANISM:
• - inhibit 5HT reuptake (increased 5HT in cleft)
• - no difference in efficacy but may have difference in tolerability

• CHOICE OF SSRI:
• - based on half-life and drug-drug interactions

• ADVERSE EFFECTS:
• - withdrawal if d/c'd too quickly
• - Serotonin Syndrome with MAOIs
• - Suicidality
• - GI effects
• - Insomnia
• - Sedation
• - Sexual dysfunction
• - can cause mania
• - antiplatelet effects
• - rare hyponatremia in elderly

• DRUGS:
• - Citalopram
• - Escitalopram
• - Fluoxetine
• - Fluvoxamine
• - Paroxetine
• - Sertraline

Citalopram

t1/2: 33hrs

• Notes:
• - SSRI of choice to minimize interactions with other meds

Escitalopram

t1/2: 30hrs

• Notes:
• - enantiomer of citalopram
• - somewhat fewer side effects that citalopram

Fluoxetine

t1/2: 15days

• Notes:
• - can be activating
• - metabolites are activating (self tapers) --> OD is relatively safe
• - best choice for pregnancy
• - also approved for eating disorders

Paroxetine

t1/2: 21hrs

• Notes:
• - can be sedating
• - shortest half life
• - taper off to avoid withdrawal

Sertraline

t1/2: 26hrs

• Notes:
• - moderately activating and sedating

• MECHANISM:
• - inhibit reuptake of 5HT and NE

• ADVERSE EFFECTS:
• - less sexual side effects than SSRIs (10%)

• NOTES:
• - better at treating physical sxs (anergia, focus)
• - "activating"

• DRUGS:
• - venlafaxine
• - duloxetine

Venlafaxine

• MOA:
• - blocks 5HT and NE reuptake (much more 5HT)
• - very little anticholinergic or H1

• ADVERSE EFFECTS:
• - dose dependent HTN
• - insomnia
• - n/v
• - anxiety
• - dizziness

• NOTES:
• - avoid with MAOIs

Duloxetine

• MOA:
• - blocks serotonin and NE reuptake

• ADVERSE EFFECTS:
• - n/v
• - anorexia
• - dry mouth, dizziness, constipation
• - fatigue/insomnia
• - sexual SEs

• MECHANISM:
• - irreversibly inhibits MAO (tyramine accumulates when MAO-A is inhibited)

• ADVERSE EFFECTS:
• - 2 wks after d/c to replenish
• - food interactions: aged cheese, wine, chinese food, tofu, aspartame)

• INDICATIONS:
• - MDD (esp with atypical features)
• - anxiety
• - panic disorder
• - social phobia
• - OCD

• DRUGS:
• - Phenelzine
• - Tranylcypromine
• - Iscocarboxazid
• - Selegiline

• - Bupropion
• - Mirtazapine
• - Trazodone

Bupropion

• MOA:
• - inhibit NE reuptake and dopaminergic neurotransmission

• INDICATIONS:
• - MDD
• - ADHD
• - bipolar depression (with SSRI)
• - smoking cessation

• ADVERSE EFFECTS:
• - insomnia
• - HA
• - constipation, dry mouth
• - n/v
• - tremor
• - lowers seizure threshold

• NOTES:
• - no sexual, weight gain or sedation side effects
• - do NOT use in pts with eating disorder
• - do NOT use with MAOIs

Mirtazapine

• MOA:
• - agonist at: 5HT2, 5HT3, alpha

• INDICATIONS:
• - MDD
• - dysthymia
• - anxiety
• - bulimia
• - chronic pain

• ADVERSE EFFECTS:
• - low sexual side effects
• - increased appetite, dry mouth
• - constipation
• - fatigue
• - orthostatic hypotension

• NOTES:
• - good choice for elderly with depression
• - some risk for agranulocytosis

• MOA:
• - inhibits presynaptic 5HT reuptake
• - antagonizes at alpha and H

• ADVERSE EFFECTS:
• - sedation
• - orthostatic hypotension
• - priapism

• - Lithium
• - Valproic Acid
• - Lamotrigine
• - Carbamazepine
• - Oxcarbazepine

• MOA:
• - unknown

• INDICATIONS:
• - bipolar
• - unipolar mood disorder
• - impulse control

• ADVERSE EFFECTS:
• - GI distress
• - weight gain
• - tremor
• - cognitive impairement
• - diabetes insipidus
• - thyroidtoxic
• - leukocytosis

• TOXICITY:
• - n/v/d
• - tremor
• - increased DTR
• - ataxia
• - confusion
• - arrhythmia

• NOTES:
• - Ebstein's anomaly in first trimester pregnancy
• - affected by renal clearance

Valproic Acid

• MOA:
• - acts on PKC and GABA
• - blocks Na channel

• INDICATIONS:
• - Bipolar disorder (good for acute mania, rapid cycling)
• - mood lability
• - impulse behavior

• ADVERSE EFFECTS:
• - n/v
• - sedation
• - tremor
• - low platelets
• - pancreatic and hepatotoxic
• - hair loss

• NOTES:
• - first line for acute mania
• - follow CBC and LFTs
• - birth defects!

Lamotrigine

• MOA:
• - effects Na channels that modulate glutamate and aspartate release

• INDICATIONS:
• - bipolar depression (not good for acute mania)

• ADVERSE REACTIONS:
• - dizziness
• - sedation
• - HA
• - ataxia
• - rash (SJS)

• NOTES:
• - multiple drug interactions

Carbamazepine

• MOA:
• - inactivation of voltage-dependent Na channels

• INDICATIONS:
• - Bipolar (good for rapid cycling)
• - cyclothymia
• - impulse control disorder

• ADVERSE EFFECTS:
• - GI sxs
• - sedation
• - dizziness
• - ataxia
• - confusion
• - rash (SJS)
• - fatal thrombocytopenia
• - agranulocytosis
• - aplastic anemia

• NOTES:
• - less efficacious for Li or VPA for acute mania or maintenance
• - CI in BBB

Hydroxyzine

• MOA:
• - antihistamine

• INDICATION:
• - anxiety

• ADVERSE EFFECTS:
• - sedation
• - hypotension
• - paradoxical excitement and agitation

Buspirone

• MOA:
• - partial agonist at 5HT, D2

• INDICATION:
• - anxiety

• ADVERSE EFFECT:
• - restlessness
• - nervousness

Ambien

• MOA:
• - binds GABA R

• INDICATION:
• - insomnia

• ADVERSE EFFECTS:
• - dizziness
• - GI upset
• - anterograde amnesia

• NOTES:
• - rapid onset
• - avoid with benzos/EtOH
• - can be habit forming

Eszopiolone

• MOA:
• - binds GABA R

• INDICATIONS:
• - insomnia

• ADVERSE EFFECTS:
• - HA
• - somnolence
• - dizziness
• - n/v