Antipsychotic Agents & Lithium

Question 1

What are the essentials of dx for schizophrenia? (6)

Answer 1

Social withdrawal

Loose thought associations

Autistic absorption in inner thoughts

Auditory hallucinations

Delusions

Sx ≥ 6 months duration

Question 2

What plays a role in schizophrenia?

Answer 2

Serotonin: 5-HT2A receptor blockade

Dopamine: blockade of postsynaptic D2 receptors

Glutamate: hypofunction of NMDA receptors

Question 3

Out of all of the first generation antipsychotics (FGAs), which causes the most wt gain?

Answer 3

Chlorpromazine

Question 4

Which FGA causes significant QT prolongation?

Answer 4

Thioridazine

Question 5

Which 2nd-gen antipsychotics should be taken w/ food? How many calories are required?

Answer 5

Lurasidone: ≥ 350 calories

Ziprasidone: ≥ 500 calories

Question 6

Which 2nd generation antipsychotics cause wt gain?

Answer 6

Olanzapine (avoid in 1st antipsychotic episode)

Quetiapine (dose related)

Question 7

All antipsychotics should be tapered slowly before discontinuation to avoid cholinergic rebound.
Which drug is this especially important for?

Answer 7

Clozapine

Question 8

What is the MOA of lithium?

Answer 8

Increase the volume of brain structures involved in emotional regulation

S/a the prefrontal cortex, hippocampus, & amygdala (reflecting its neuroprotective effects)

Question 9

What does lithium do at a neuronal level?

Answer 9

Reduces excitatory (dopamine & glutamate) but increases inhibitory (GABA) neurotransmission

Question 10

Which 2 drug classes cause decreased clearance of lithium?

Answer 10

Thiazides & NSAIDs

Question 11

What are ADEs of lithium?

Answer 11

Tremor

Edema

Hypothyroidism*

Renal dysfunction

Pregnancy category D*

Question 12

What are 3 newer drugs used for bipolar disorder?

Answer 12

Carbamazepine

Lamotrigine

Valproic acid

Question 13

What is an ADE of lamotrigine (1 of the newer drugs for bipolar d/o)?

Answer 13

Rash*

Question 14

How do you initially treat hypomania?

Answer 14

Initiate mood stabilizer: lithium, valproate, carbamazepine, or SGAs

Question 15

If initial tx for hypomania fails, what is your next step?

Answer 15

Consider 2 drug combo:

Lithium + an anticonvulsant or SGA

Anticonvulsant + another anticonvulsant or SGA

Question 16

How do you initially treat mania?

Answer 16

2 or 3 drug combos + a benzo &/or antipsychotic for short term adjunctive tx of agitation or insomnia

Question 17

If initial tx for mania fails, what is your next step?

Answer 17

Consider 3 drug combo:

Lithium + anticonvulsant + antipsychotic

Anticonvulsant + another anticonvulsant + antipsychotic

Question 18

If 3-drug therapy fails in the tx of mania, what is your next step?

Answer 18

Consider ECT or add clozapine

Question 19

How do you initially treat a mild to moderate depressive episode?

Answer 19

Initiate mood-stabilizer: lithium, quetiapine, lurasidone

Question 20

How do you initially treat a severe depressive episode?

Answer 20

Optimize current mood stabilizer or initiate: lithium, quetiapine, or lurasidone

Question 21

If initial treatment for severe depressive episode fails, what is your next step?

Answer 21

Consider carbamazepine or adding antidepressant

Question 22

If second form of tx fails for severe depressive episode, what is the 3rd step?

Answer 22

Consider 3-drug combo:

Lithium + lamotrigine + antidepressant

Lithium + quetiapine + antidepressant

Question 23

If 3rd form of tx fails for severe depressive episode, what is the 4th step?

Answer 23

Consider ECT

Question 24

What are the 4 dopaminergic pathways?

Answer 24

Mesolimbic: + sx

Mesocortical: - sx

Nigrostriatal: EPS & tardive dyskinesia

Tuberophypophyseal: hyperprolactinemia

Question 25

What are overall characteristics of antipsychotics?

Answer 25

Well absorbed Lipid soluble Bound to plasma proteins Metabolized by liver enzymes, renally eliminated Long 1/2 lives

Question 26

What are relative side effects of antipsychotics?

Answer 26

``` Sedation EPS Anticholinergic Orthostasis Wt gain Prolactin ```

Question 27

What agents are used to treat EPS?

Answer 27

``` Antimuscarinics Antihistaminic Dopamine agonist Benzos B-blockers ```

Question 28

How long should you continue antipsychotic therapy after remission of the 1st episode?

Answer 28

At least 12 months Many recommend tx for at least 5 yrs

Question 29

How do you switch from 1 antipsychotic to another?

Answer 29

Taper & discontinue the 1st over at least 1-2 wks while the 2nd antipsychotic is initiated & tapered upward

Question 30

What is lithium used for?

Answer 30

Manic phase of bipolar d/o Prevents mood swings

Question 31

What 2 classes of meds may need to be included during the initiation of lithium or valproic acid for bipolar d/o?

Answer 31

Antipsychotics & benzos due to slow onset of lithium & valproic acid

Question 32

What can precipitate mania in bipolar pts?

Answer 32

Monotherapy w/ antidepressants

Question 33

What are ADEs of carbamazepine (1 of the newer drugs for bipolar d/o)?

Answer 33

Hematotoxicity & induction of drug metabolism

Question 34

What are ADEs of valproic acid (1 of the new drugs for bipolar d/o)?

Answer 34

Hepatic dysfunction Wt gain Inhibition of drug metabolism