Schizophrenia Flashcards
APA Treatment Guidelines for Clozapine in Schizophrenia
Clozapine for patients with treatment-resistant schizophrenia or those with substantial risk of suicide or suicide attempts
Treatment Resistant Definition (probably not on exam)
Treatment resistance generally considered lack of improvement with at least 2 APS from different classes at optimal dose for at least 8 weeks (some guidelines state fewer weeks)
Chlorpromazine (Thorazine)
First Generation Antipsychotic
FDA Approved for Schizophrenia and acute psychosis
Low prolactin + potency (low EPS risk, high anticholinergic risk)
Thioridazine (Mellaril)
First Generation Antipsychotic
FDA approved for schizophrenia
Low prolactin + potency (low EPS risk, high anticholinergic risk)
Fluphenazine (Prolixin)
First Generation Antipsychotic
FDA approved for schizophrenia
High prolactin + potency antipsychotic (high EPS risk, low anticholinergic risk)
Haloperidol (Haldol)
First Generation Antipsychotic
FDA approved for Schizophrenia, Tourette’s, Acute Psychosis, Problematic/Hyperactive behavior
High prolactin + potency antipsychotic (high EPS risk, low anticholinergic risk)
Perphenazine (Trilafon)
First Generation Antipsychotic
FDA approved for schizophrenia
Thiothixene (Navane)
First Generation Antipsychotic
FDA approved for schizophrenia
Loxapine (Loxitane)
First Generation Antipsychotic
FDA approved for schizophrenia and bipolar disorder (BPD)
Trifluoperazine (Stelazine®)
First Generation Antipsychotic
FDA approved for schizophrenia and anxiety
Molindone (Moban)
First Generation Antipsychotic
FDA approved for schizophrenia
First Generation Antipsychotics - Class AE / BBW
• Extrapyramidal side effects (EPS)
• QTc prolongation
• Prolactin elevation
• Dermatologic
• Photosensitivity
• Blue-gray skin
• Orthostatic Hypotension
• Altered thermoregulation
• Black box: dementia related psychosis
(i.e.: elderly patients with dementia receiving these drugs for behavioral problems, not primary SMI (serious mental illness))
Second Generation Antipsychotics (SGA) - Class AE/BBW
• Metabolic syndrome: Hypertriglyceridemia, Hyperglycemia, Weight Gain (waist circumference)
• QTc prolongation
• Blood dyscrasia/neutropenias
• Seizure threshold
• Anticholinergic effects
• Sedation
• Prolactin elevation
• Ophthalmic effects
• Black box: Dementia related psychosis
Aripiprazole (Abilify)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia, Bipolar Disorder, MDD augmentation, symptoms associated with Autism, Tourette’s
Activating; less sedating. May cause insomnia, akathisia & restlessness. Associated with impulsivity.
Available: oral tablet, solution, Mycite, Initio injection and LAI
1 of 4 for MDD Augmentation!
1 of 4 for LAI!
Brexpiprazole (Rexulti)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia, MDD, agitation due to Alzheimer’s Disease (dementia)
Long half life (91 hours), akathisia reported (dose related), less metabolic side effects. Associated with impulsivity.
Available: oral tablet (only)
2 of 4 for MDD augmentation!
Olanzapine (Zyprexa)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia, Bipolar Disorder, MDD (with fluoxetine)
Metabolic risk (weight gain!), FDA box warning (REMS) post injection
delirium/sedation syndrome (PDSS) with LAI, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), QTc risks, anticholinergic effects
Do not administer with Lorazepam - profound sedation
Available: oral tablet, ODT, short acting IM, LAI
3 of 4 approved for MDD augmentation!
2 of 4 agents available as LAI
Quetiapine (Seroquel)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia, Bipolar Disorder, MDD
Metabolic risks, sedating, misuse reported, inappropriately used as sleep aid (off label), cataract development reported (baseline screening recommended), hypothyroidism, QTc risk, anticholinergic effects
Available: oral tablet (IR and XL)
4 of 4 approved for MDD augmentation!
Which antipsychotics are FDA approved for MDD augmentation?
Aripiprazole (Abilify)
Brexpiprazole (Rexulti)
Olanzapine (Zyprexa) with fluoxetine
Quetiapine (Seroquel)
All 4 SGAs
Asenapine (Saphris)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia and Bipolar Disorder
Less weight gain, less anticholinergic & sedation. Do not drink/eat after SL dose (10 minutes min), contraindicated (CI) severe hepatic disease, High risk QTc (but rate), monitor for anaphylaxis after 1st dose. Skin site reactions also seen; Do not apply heat to patch area
Available: SL tab, topical patch
Only SGA available as topical patch!
Cariprazine (Vraylar)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia and Bipolar Disorder
Long half life (91 hours) and metabolites also attributed to the late occurring adverse effects when these accumulate, akathisia reported (dose related), less metabolic side effects.
Available: oral capsule (only)
Clozapine (Clozaril, Fazaclo)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia and Schizoaffective Disorder (not BPD)
Gold standard for refractory illness or sooner if suicidal risk. Metabolic risks (greatest), FDA boxed warnings for blood dyscrasias (REMS program includes specific schedule based on frequency of monitoring), QTc prolongation, bradycardia, myocarditis. Seizure risk with higher serum concentrations (greater than 600mg daily dose), constipation, GI hypomotility with severe complications (impaction) hypersalivation. Hepatotoxicity, fever, PE, anticholinergic toxicity. Dose interruption greater than 48 hours requires re-titration from starting dose, regardless of reason for gap.
CYP1A2 Metabolism = Smoking Cigarettes REDUCES serum concentrations. Vaping/NRT don’t affect CYP1A2
ANC required weekly for first 6 months, pt must maintain a minimum of 1,500/mm3
Available: oral tablet, ODT, oral suspension
Iloperidone (Fanapt)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia and Bipolar Disorder
Orthostatic hypotension, priapism, no prolactin elevation reported, QTc warning (but rare), less sedation, 50% dose reduction with conflicting CYP inhibitors, avoid in hepatic impairment. Slow titration required
Available: oral tablet
Lumateperone (Caplyta)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia and Bipolar Disorder
Lurasidone (Latuda)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia and Bipolar Disorder
Neurologic ADRs in patients with dementia/Lewy bodies/PD. No notable metabolic SE or EPS reported. Sedation greater than placebo
Available: oral capsule
Olanzapine + samidorphan (Lybalvi)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia and Bipolar Disorder (not MDD like Olanzapine alone)
Same as Olanazapine with additional risk of opioid withdrawal if opioid use/dependent. High risk of death with OD due to blunted opioid blockade. Review PI for this combination and when used with fluoxetine or when combined with lithium/valproate for DDI screens.
Samidorphan is an opioid-system modulator (similar to naltrexone) – acts on mu-opioid receptor with the goal of reducing metabolic effects of olanzapine
Available: oral tablet
Paliperidone (Invega)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia and Schizoaffective Disorder (No BPD)
Metabolite of risperidone, QTc risk, GI obstruction in those with severe narrowing, priapism, thrombotic thrombocytopenic purpura (TTP), antiemetic effects
Available: oral tablet (OROS delivery), LAI
3 of 4 agents available via LAI!
Pimavanserin (Nuplazid)
Second Generation Antipsychotic (SGA)
FDA approval for Parkinson’s Disease Psychosis (only agent not for schizophrenia, BPD, or MDD)
No dopamine action (exclusively serotonin), hence the unique FDA approval. Use for hallucinations/delusions in PDP, avoid in renal compromised (less than 30ml/min) and in combo with conflicting CYP, QTc risks.
Available: oral tablet
Risperidone (Risperdal)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia, Bipolar Disorder, and symptoms associated with autism
Prolactin elevation reported, EPS more likely than other SGA, priapism, TTP, antiemetic effects
Available: oral tablet, ODT, oral solution, LAI
4 of 4 agents available via LAI!
Ziprasidone (Geodon)
Second Generation Antipsychotic (SGA)
FDA approval for Schizophrenia and Bipolar Disorder
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and other severe cutaneous reactions (ie SJS), QTc risks, take with food for improved absorption, priapism, rash and urticaria
Available: oral tablet, short acting injection (requires reconstitution)- NIOSH drug
Universal Antipsychotic Precautions
Neuroleptic Malignant Syndrome (NMS)
Body temperature dysregulation
Dysphagia and varying QTc impacts
Increase FDA box warning (increased mortality) for dementia related psychosis
FDA box warning only for those agents with FDA indication for MDD augmentation
Which antipsychotic medications are available as Long Acting Injectables (LAI)?
FGA:
Fluphenazine (Prolixin)
Haloperidol (Haldol)
SGA:
Aripiprazole (Abilify)
Olanzapine (Zyprexa)
Paliperidone (Invega)
Risperidone (Risperdal)
Oral challenge of the same drug before initiating LAI is best practice (to detect allergy)
Which agents have the highest DRESS risk?
Olanzapine (Zyprexa)
Ziprasidone (Geodon)
Black Box Warning for Antipsychotics
“Increased mortality in elderly patients with dementia-related psychosis: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death….”
Dexmedetomidine (Igalmi)
• FDA approved for treatment of acute agitation in adults with schizophrenia and bipolar disorders
• Selective alpha-2 adrenergic receptor agonist
• Sublingual film (can also be used as a buccal film)
• Administration must be done under healthcare supervision
• May give up two additional doses at least 2 hours apart - Extra doses not recommended for systolic blood pressure (SBP) < 90 mmHg or diastolic blood pressure (DBP) < 60 mmHg; postural BP decrease in SBP ≥ 20 mmHg or DBP ≥ 10 mmHg
SL administration: No food/drink for 15 minutes
Buccal administration: No food/drink for 1 hour
Pediatric FDA Approvals
Aripiprazole*
Asenapine
Brexiprazole*
Lurasidone*
Olanzapine
Paliperidone
Quetiapine*
Risperidone
*Black box: Suicidal thoughts and behaviors in children, adolescents and young adults
Short Acting/Acute Injectable Antipsychotics
FGA:
Chlorpromazine (doesn’t have LAI)
Haloperidol (“B52”)
Fluphenazine
SGA:
Olanzapine
Ziprasidone (doesn’t have LAI)
Most LAIs are injected every..?
2-4 weeks
Invega Hafyera is q6months
Most are IM deltoid or gluteal ROA except Perseris and Uzedy which are SC abdominal (or upper arm too for Uzedy)
Acute Distonias
Painful prolonged muscle contractions. Involuntary buccal, facial, oculogyric. May involve back, arms and legs
Onset 24-96 hrs after dose change or drug started
High Risk APs: High potency or high dose FGA. Younger men
Treatment:
IM Anticholinergics
IM BZDs
Decrease dose or D/C offending agent
Pseudo-parkinsonism
Bradykinesia, tremor, pill rolling, cogwheel rigidity, postural and oral abnormalities
Onset 1-2 weeks after dose change or drug started
High Risk APs: High potency or high dose FGA, Older age, Females
Treatment: Anticholinergics
Decrease dose or D/C offending agent
Akathisia
Restlessness, pacing, shuffling, compulsion to stay in motion. Subjective feelings of distress
Onset Hours to days after start or dose change
High Risk APs: High potency FGA, aripiprazole, risperidone
Treatment: Beta Blockers
Decease dose or D/C offending agent
Tardive Dyskinesia
Tongue thrusting, chewing, lip smacking, grimacing, limb twisting, rocking
Onset Late (months to years after initiation)
High Risk APs: High potency or high dose FGA, Female, older age, AA
Treatment: Prevention, DC offending agent
Anticholinergics can mask symptoms!
Use of “benazines” to treat what condition? How?
Treat Tardive Dyskinesia
Inhibition of VMAT2
• Provides reversible reductions of dopamine release into the synaptic cleft
• Reduces the amount of dopamine available to hypersensitive postsynaptic dopamine D2 receptors
Valbenazine (Ingrezza)
Deutetrabenazine (Austedo)
Deutetrabenazine (Austedo)
6mg BID x7 days then may increase at 6mg intervals per day until MDD 48mg. TDD 12mg or more should be divided into 2 doses. • Lower doses recommended if switching from valbenazine
• Treatment gaps greater than 1 week require retitration
Hepatic: contraindicated in patients with hepatic impairment.
Renal: no dose adjustments recommended
Take with food
CI: another benazine or MAOi
CYP3A4 inhibitor/inducer coadministration? Not applicable
Use with Strong CYP2D6 Inhibitor or Poor CYP2D6 metabolizers: Dose reduction: Do not exceed 18 mg per dose or 36 mg per day
May prolong QTc interval
Valbenazine (Ingrezza)
40mg QD x7 days then 80mg QD
Hepatic: moderate to severe impairment (Child-Pugh
score 7 to 15): The recommended dose is 40 mg daily.
Renal: severe impairment (CrCl less than 30 mL/min): Use is not recommended.
CI: another benazine or MAOi
Reduce dose with CYP3A4 inhibitor, not recommended to use with strong CYP3A4 inducer due to reduced efficacy
Consider dose reduction based on tolerability if given with Strong CYP2D6 Inhibitor. Poor CYP2D6 metabolizers may warrant dose reduction, but no recommendation
May prolong QTc interval
Which agents have the highest risk for developing NMS?
High Potency Antipsychotics:
Haloperidol
Fluphenazine
All agents have some risk though
