Pharm - Schizophrenia and Schizoaffective Disorders

What is responsible for psychotic disorders?

Dopaminergic dysfunction. Excessive limbic dopaminergic activity is linked to positive symptoms.

What is linked to negative and cognitive symptoms of schizophrenia?

Reduced cortical signaling.

What other neurotransmitter plays a role in psychotic and affective disorders?

Serotonergic dysfunction (5-HT1A and 5-HT2A). Hypofunction of NMDA receptors also implicated.

Why are FGA used far less than SGA?

They are linked to significant adverse effects, especially extrapyramidal side effects (nerve pathways that control involuntary movements and muscle tone)

What is the MOA of FGA?

Block receptors for dopamine, ACh, histamine and norepi. So they have A LOT of side effects.

What is the therapeutic use of FGA?

Primary indication is to suppress sx during acute psychotic episodes. When taken chronically, can reduce recurrence.

Lifelong treatment is required!

What are the 4 types of extrapyramidal symptoms (EPS)?

1. Acute dystonia

2. Parkinsonism

3. Akathisia

4. Tardive dyskinesia (most troubling)

What is acute dystonia?

Sudden, involuntary muscle cx causing abnormal posture or repetitive movements.

Onset is minutes to hours after starting or increasing med.

Includes: torticollis, limb dystonia, eyes roll up.

Treatment: IV Benztropine or diphenhydramine

Usually not life threatening! Resolves with prompt treatment

What is antipsychotic induced parkinsonism?

A movement disorder caused by dopamine blockade in the nigrostriatal pathway from antipsychotic meds.

Onset is days to week after starting or increasing med.

No rest tremor in leg seen.

Includes: masked facies, rigidity, pill rolling tremor.

Treatment: reduce dose, switch med, same treatment as AD if needed.

What is antipsychotic induced akathisia?

Subjective feeling of inner restlessness and an uncontrollable need to be in constant movement.

Onset is days to week after starting or increasing med.

Includes: inner feeling of restlessness, pacing, impaired functioning (sometimes)

Treatment: reduce or stop med, beta-blockers or benzos if needed

Typically improve within days to weeks (if recognized and treated)

What is tardive dyskinesia?

Late-onset movement disorder caused by long-term use of dopamine blocking meds.

Onset occurs after ≥3 months of use of meds.

May persist or worsen even after drug is stopped.

Includes: lip smacking, UE movements, LE movements.

Can be irreversible!

Treatment: d/c med, use VMAT2i like Valbenazine or Deutetrabenzine.

What is neuroleptic malignant syndrome (NMS)?

Rare but serious reaction. Onset is 24-72 hours. 5-20% fatality rate. More common with high potency FGA.

Includes: high fever, muscle rigidity, AMS, profuse sweating, elevated CK, HTN.

Treatment: supportive measures, d/c med, Dantrolene (drug of choice) or Pramipexole.

What are other adverse effects of FGA?

Anticholinergic effects

Orthostatic hypotension, which improves after 2-3 months of therapy.

Sedation

Neuroendocrine effects like gynecomastia, galactorrhea, etc.

Agranulocytosis (FGA highest risk is chlorpromazine, SGA highest risk is clozapine)

Severe arrhythmias (chlorpromazine, haloperidol, thioridazine and pimozide have risk for QT prolongation)

Which drugs are low-potency FGA?

Chlorpromazine and Thioridazine.

Which drugs are medium potency FGA?

Perphenazine

Which drugs are high potency FGA?

Haloperidol (most common FGA rx) and Fluphenazine

Which drugs have a low/moderate/very high risk of EPS?

Chlorpromazine - Moderate

Thioridazine - Low

Perphenazine - Moderate

Haloperidol - VERY HIGH

Fluphenazine - VERY HIGH

What is the correlation of sedation effect and medication potency?

Low potency drugs have HIGH sedation risk

Medium potency drugs have MODERATE sedation risk

High potency drugs have LOW sedation risk

What is the correlation of orthostatic hypotension effect and medication potency?

Low potency drugs have HIGH OH effect

Medium and high potency drugs have LOW OH effect

What is the correlation of anti-Ach effect and FGA drugs?

Chlorpromazine has moderate anti-Ach effect

Thioridazine has high anti-Ach effect

ALL OTHER DRUGS have low anti-Ach effect.

What is the correlation of metabolic effect and FGA drugs?

Low potency drugs AND Haloperidol have moderate metabolic effect

Perphenazine and Fluphenazine have neutral metabolic effect.

What is the correlation of significant QT prolongation risk and FGA drugs?

Low potency drugs AND Haloperidol have significant QT prolongation risk.

Perphenazine and Fluphenazine DO NOT have significant QT prolongation risk.

What is the correlation of prolactin increase risk and FGA drugs?

Low potency and medium potency drugs have LOW risk.

Haloperidol has slight risk.

Fluphenazine has moderate risk.

Describe Aripiprazole

Very common SGA, "entry-level medication"

Partial D2 and 5-HT1A agonist. 5-HT2A antagonist.

Common ADE: Akathisia (insomnia in adults; sedation in kids)

Lower metabolic risk (weight neutral); reports of compulsive behavior

Describe Clozapine

DON'T start on this med, this is good for treatment resistance (failed ≥2 meds)

Common ADE: Weight gain (high metabolic risk), sedation, sialorrhea (excessive salivation, paradoxical AE), hypotension

BBW for neutropenia, watch for myocarditis

Describe Olanzapine

Commonly used med.

Common ADE: Weight gain, sedation

High metabolic risk!!! Warning for DRESS

Describe Paliperidone

ONLY FDA approved med for schizoaffective disorder

Common ADE: EPS, weight gain, dyspepsia

Describe Quetiapine

Commonly used drug

Common ADE: Sedation, dry mouth, hypotension

Low EPS risk but substantial sedation.

Describe Risperidone

Commonly used drug

Common ADE: EPS (Parkinsonism, akathisia), sedation, tremor

CYP2D6 substrate (significant DDI with fluoxetine and paroxetine)

Describe Ziprasidone

Commonly used drug

Common ADE: Somnolence, EPS, dizziness

Lower metabolic risk.

Describe Asenapine

Common ADE: Sedation, dysgeusia, oral hypoesthesia with SL preparation

Available as SL and transdermal, for patients with PO issues or so they can't fake taking the drug

Describe Brexiprazole

Common ADE: Akathisia, somnolence.

Lower metabolic risk; reports of compulsive behavior (like Ari!)

Describe Cariprazine

Common ADE: EPS, akathisia, somnolence

Late-occurring AE due to drug's long half-life

Describe Iloperidone

Common ADE: Dizziness, dry mouth, fatigue

Slow dose titration to minimize risk of severe OH

Which drugs have the highest phototoxic effects?

Chlorpromazine and thioridazine (FGA) and Clozapine (SGA)

Why can you not use antipsychotics in elderly for dementia related psychosis?

They double the rate of mortality, mostly from cardiac events or pneumonia.

What is the BBW of Clozapine?

Life-threatening severe neutropenia. Also linked to myocarditis. Reserved for treatment resistant schizophrenia!

Is there a significant difference in efficacy between FGA and SGA?

2 studies have shown NOT!

Which 3 meds have shown to be more efficacious than other meds (both FGAs and SGAs)?

Clozapine, olanzapine and risperidone.

Which medication is the ONLY FDA approved med for SAD?

Paliperidone

Which drugs are given in IM route?

Paliperidone 1,3 and 6 months

Risperidone 2 weeks to 2 months

How should dosing of antipsychotics be managed over time?

Since it is a lifelong treatment, annual attempts should be made to lower the dose to prevent long-term adverse effects like TD.

Which add-on therapy is good for patients with bipolar subtype schizophrenia/SAD?

Lithium and Valproate

Lithium is great for suicidal patients.

Which add on therapy is good for preventing disease recurrence in bipolar subtype patients?

Lamotrigine

Which add on therapy is good for patients with depressive subtype schizophrenia/SAD?

SSRIs. Never do antidepressant monotherapy!!!