Antipsychotics

D2+4 antag: Tx positive sx

o Delusions
o Hallucinations
o Disorganized thought
5-HT antag: Tx negative sx
o Affect
o Anhedonia
o Apathy
o Alogia: speech
o Attention

Low potency

Class
Typical
(1st Generation)
D2, D4 Antagonists

Takes 1-2 weeks for peak therapeutic effect; only days for adverse effects. NOT drugs of abuse.
- Antipychosis: mesolimbic + mesocortical pathways
- Anti-HAM effects
- EPS (Extra-pyrimidal): Nigrostriatal pathway (pseudoparkinsonism)
o H1 R antagonist
o Tx:Amantadine (SymmetrelTM), diphenhydramine (BenadrylTM), benztropine (CogentinTM)

Sedation
- Neuroleptic malignant syndrome (rare, anticholinergics ineffective): 20% mortality

Antiemetic
o Fever, autonomic labiality, leukocytosis, tremor, rigidity, CPK , rhabdomyolysis (26%)
o 1 R antagonist
o Tx: 1) d/c drug, 2) supportive: cooling blanket, IVF, bromocriptine or dantrolene

Hypotension
- Tardive dyskinesia (10-30% of chronic users) (worsened by anticholinergics)

Sexual dysfunction

Repetitive involuntary movement (lip smacking). Worse with longer-term antipsychotic Tx
o AntiMuscarinic effects

Typical atropine-like effects

Hypersensitive D2 Rs; Tx with Clozapine
- Weight gain
- Hyperprolactinemia: Tubuloinfundibular (Less GnRH): libido, galactorrhea, amenorrhea
- Liver enzyme elevation
- Acute effects due to dopamine antagonism
- Seizures
- Chronic effects due to D2 autoreceptors decreasing dopamine release
- Used in the treatment of: schizophrenia, bipolar (manic phase), delusional disorder.
Class Side effects
Drug
Other Effects
- Stronger EPS side effects (vs. atypical)
- Chlorpromazine(ThorazineTM)
- Less EPS (vs. high potency)
TM
o Acute dystonia: torticollis, oculogyric crises
- Thioridazine (Mellaril )
- Strong Anti-HAM

Tx: anticolinergics: benztropine (CogentinTM)
- Need eye exam:
o Akathisia (restlessness):
o Chlorpromazine: Retinal deposits

Tx: -blockers, benzodiazepines
o Thiordiazine: Corneal deposits
TM
o Parkinsonism
- Haloperidol (Haldol )
- Strong EPS (vs. low potency)
TM

Tx: anticholinergics (CogentinTM),
- Fluphenazine (Prolixin )
- Less anti-HAM (vs. low potency)
TM
Trihexyphenidyl (ArtaneTM),
Thiothixine
(Navane
)
- Pimozide: prolonged QT syndrome
Amantadine (SymmetrelTM) (releases DA),
- Trifluoperazine (SterazineTM)
- Haldol also tx Tourettes & Huntington
TM
o Perioral tremor
- Perphenazine (Trilaon )

Tx: anticolinergics: benztropine (CogentinTM)
- Pimozide (OrapTM)
High potency

More anti-emetic , antihiccup, anti-itch effects

from D2 block
Roughly equivalent
efficacies
Atypical
(2nd Generation)
5-HT2A Antagonists
First-line for schizophrenia

- Anti-HAM: H1, 1, Muscarinic antagonism

- Advantages versus typical antipsychotics
o EPS, TD
o Do not prolactin levels
o Increased efficacy, especially negative symptoms
- Disadvantages versus typical antipsychotics
o efficacious on positive symptoms
o weight gain, type II DM, metabolic syndrome
o More cardiotoxic (QT prolongation)

Clozapine (ClozarilTM) (strongest D4)

Risperidol (RisperdalTM)
Olanzepine (ZyprexaTM)
Quetiapine (SeroquelTM)
Ziprazidone (GeodonTM)
o No weight gain (vs. all others)
- Zotepine (NipoleptTM) not USA
- Aripiprazole (AbilifyTM)
- Amisulpride (SolianTM)

- Clozapine: only one with no EPS

o Agranulocytosis (1%)
o Seizures (2-5%)
- Risperdol: most EPS, hyperP
- Olanzepine: No hyperP
- Quetiapine: cataracts
o Can treat mania
o Helps insomnia causes sedation
- Ziprasidone: QT prolongation
- Aripiprazole
o weight gain
o hyperprolactinemia

Principles of therapy: try 1 medication for 4 weeks. If it fails, switch to a different medication in the same class.
Anxiolytics
Buspirone (BuSpar)
Benzodiazepines

- 5-HT1A agonist
- GABA agonists

- Used in GAD, augment treatment in MDD, OCD

-

- Sedation, dizziness, GI disturbance

-

Antidepressants
Mechanism
Tricyclic
NE+5HT Reuptake
Indications
- Depression
- Chronic pain

Serotonin-selective
Reuptake Inhibitors (SSRIs)
And 5-HT2A R antag
Indications
- MDD, PTSD
- OCD, Bulemia
- Panic disorder
- PMS

ATYPICALS

Serotonin and NE
reuptake inhibitors
(SNRIs)
Indications
- MDD
- Panic/Agoraphobia
- GAD
MAO Inhibitors
Indications (2nd line)
- MDD (atypical), SAD
- Social phobia
- Panic disorder
Mood Stabilizers
Acute episodes ? and
prophylaxis
Other indications
- Adjunct for MDD,
schizophrenia
- Alcoholism
- Aggression/impulsivity

Takes 2-3 weeks for peak therapeutic effect; only days for adverse effects. NOT drugs of abuse. Most effective for MDD.
Drug
Pharmacokinetics
Adverse Effects
- Imipramine (TofranilTM) (NE, 5-HT) - Need to establish homeostasis: takes a
- 3Cs: convulsions, coma, cardiac arrhythmias
o Also treats nocturnal enuresis
few weeks for effect
o Wide QRS, prolonged PR, prolonged QTc
- Amitriptylene (ElavilTM) (NE>5-HT) - Delay due to downregulation of
- Anti-HAM
postsynaptic ARs and presynaptic 2Rs
o Anti-H1: Sedation
o Less 1 block
TM
- Nortriptyline (Pamelor ) (NE)
o Anti-1: Hypotension (orthostasis)
- Desipramine (NorprminTM) (NE)
o Anti-Muscarinic: dry mouth, blurred vision,
- Doxepin (SinequanTM)
constipation, urinary retention, delirium
TM
- Clomipramine (Anafranil ): OCD
- Weight gain
- Maprotiline (LudiomilTM) (NE)
- Fluoxetine (ProzacTM) : preg. safe! - Delay of effect due to downregulation of
- Nausea/Vomiting/Diarrhea (most common)
o Treats comorbid hypersomnia
5-HT2A receptors
- Agitation, akathisia, insomnia (worsened)
o Only one indicated in children
- Discontinuation syndrome
- Sexual: libido, anorgasmia (), impotence ()
TM
- Sertraline (Zoloft )
o Flu-like sx, vomiting, lethargy
- Safe in overdose: minimal cardiotoxicity
o Especially with paroxetine (short t)
- Serotonin Syndrome (w/ MAOIs, Li+, Carbemaz.)
- Paroxetine (PaxilTM)
TM
- Escitalopram (Lexapro )
o Altered mental status, diaphoresis, seizures
TM
- Fluvoxamine (Luvox ): OCD too
o Autonomic: orthostasis, hyperthermia, diarrhea
- Citalopram(CelexaTM)
o Myoclonus, hypertension
o Most specific for 5-HT reuptake
- Avoid in pregnancy
- Duloxetine (CymbaltaTM)
Noradrenergic and specific serotonergic
- Mirtazapine (RemeronTM): 1, 2, 5-HT2+3 antag.
o Also diabetic neuropathy
antidepressant (NaSSA) (no reuptake)
o 2 block potentiates 5-HT1: appetite, weight
- Venlafaxine (EffexorTM)
o Also treats comorbid insomnia
o Also treats GAD
Serotonin antagonist and reuptake
- Trazodone (DesyrelTM): 1 & 5-HT1A,1C,2 antagonist
TM
- Desvenlafaxine (Pristiq )
inhibitors (SARIs)
o Short t. Priapism, orthostasis. Tx:insomnia
- Amoxapine (DefanylTM)
Norepinephrine-dopamine reuptake
- Bupropion (WellbutrinTM, ZybanTM)
o Also an antipsychotic  TD
inhibitors (NDRI) Tx: MDD > 8hrs old, SAD
o seizure risk, no sexual side effects/wt gain
- Phenelzine (NardilTM)
- Inhibit MAO irreversibly
- Not first-line because of interactions:
- Selegiline (ZelaparTM) (MAO-B)
o Long-acting (must regenerate MAO)
o TCAs & SSRIs
- Tranylcypromine (ParnateTM)
o Need 10 day washout period before
o Tyramine-rich foods (cheeses, wine, beer)
- Isocarboxazid (MarplanTM)
starting an SSRI, TCA
o Sympathomimetics, Levodopa  HTN crisis
MAO-A: 5-HT, NE, DA metabolism
- Inhibition of CYP450 causes interactions
o Buspirone  hypertension
MAO-B: DA metabolism
o Meperidine
TM
- Lithium (Lithobid ) (NE, 5-HT)
- Long-term Tx for manic episodes
- Lithium : Anything Na+  Li+ excretion ( Li)
TM
- Valproic acid (Depakote )
- Lithium
o Dose-related: GI distress, tremor, and headache
TM
- Carbamazepine (Tegretol )
o Narrow therapeutic range: 0.7-1.2 mEq
o Idiosyncratic: Arrhythmias: flat/inverted T-wave
- Lamotrigine (LamictalTM)
o Avoid in renal failure patients
(usually benign), goiter, hypoT, leukocytosis,
o Blocks IP3 cycle in NE/5-HT effects
diabetes insipidus (nephrogenic), alopecia
o Teratogenic: Ebstein anomaly (7.7%: 20x risk)
o NSAIDs (not aspirin) availability
- Valproic acid: fat, shaky, bald, yellow
o Wt gain, tremor, alopecia, jaundice, pancreatitis
o Teratogenic: neural tube defects