Schizophrenia

Goals of therapy for psychotic disorders

long-term: remission, prevent recurrence

acute: decrease severity and duration of symptoms, increase function

at all times: decrease ADRs, increase adherence to treatment

Non-pharmacologic treatments for psychotic disorders

CBT, psychoeducation, avoidance of stimulants (caffeine, etc.) and alcohol, and avoid any other substance (illicit or other potentially drug inducing)

which drugs can induce/mimic psychotic disorders?

corticosteroids, stimulants, marijuana, DA-augmenting agents, hallucinogens

which diseases induce/mimic psychotic disorders?

HIV/AIDs, epilepsy, CVA/TBI, infections, Huntington’s Disease

what are the positive schizophrenia symptoms?

hallucinations, delusions, thought disorder, hostility, excitability

what the negative schizophrenia symptoms?

affective flattening, alogia, anhedonia, amotivation, asociality

what is catatonia

agitation, cataplexy, echopraxia, echolalia, grimacing, odd mannerisms, mutism, negativism, posturing, stupor, stereotypy, waxy flexibility

T/F: catatonia can be associated with another mental disorder, be a disorder due to another medical condition, or be unspecified catatonia

true

what is schizoaffective disorder’s similarity to schizophrenia?

must have delusions or hallucinations at least 2 weeks in absence of mood symptoms

what is schizophreniform disorder’s similarity to schizophrenia?

must meet the same criteria for the same symptoms

how does schizoaffective disorder differ from schizophrenia?

Impaired social or job dysfunction not required. Symptoms meeting criteria for mood episode are not present for substantial portion of illness duration Must have uninterrupted period of illness either a major depressive or manic episode along with symptoms meeting the criteria for schizophrenia (at
some point).

how does schizophreniform disorder differ from schizophrenia?

Impaired social or job dysfunction not required. Shorter duration (1-6 months)

what is aripiprazole (Abilify) FDA approved for?

schizophrenia, bipolar disorder, MDD, symptoms of autism, and symptoms of Tourette’s

what is asenapine SL (Saphris) FDA approved for?

schizophrenia and bipolar disorder

what is asenapine patch (Secuado) FDA approved for?

schizophrenia

what is brexipiprazole (Rexulti) FDA approved for?

schizophrenia, MDD, and agitation associated with Alzheimer’s

what is cariprazine (Vryalar) FDA approved for?

schizophrenia, bipolar disorder, MDD

what is clozapine (Clozaril, Fazaclo) FDA approved for?

schizophrenia and schizoaffective

what is Iloperidone (Fanapt) FDA indicated for?

schizophrenia and bipolar disorder

what is lumateperone (Caplyta) FDA approved for?

schizophrenia, bipolar disorder depression

what is lurasidone (Latuda) FDA approved for?

schizophrenia, bipolar disorder

what is olanzapine (Zyprexa) FDA approved for?

schizophrenia, bipolar disorder, MDD (with fluoxetine)

what is olanzapine + samidorphan (Lybalvi) FDA approved for?

schizophrenia and bipolar disorder

what is paliperidone (Invega) FDA approved for?

schizophrenia and schizoaffective

what is pimavanserin (Nuplazid) FDA approved for?

Parkinson’s Disease Psychosis

what is quetiapine (Seroquel) FDA approved for?

schizophrenia, bipolar disorder, and MDD

what is risperidone (Risperdal) FDA approved for?

schizophrenia, bipolar disorder, symptoms associated with autism

what is xanomeline and trospium (Cobenfy) FDA approved for?

schizophrenia

what is ziprasidone (Geodon) FDA approved for?

schizophrenia and bipolar disorder

T/F: all second-generation antipsychotics have a BBW for suicidal thoughts

true

what are the general pharmacotherapy recommendations for antipsychotics?

must monitor for effectiveness and side effects, continuation of medication for those whose symptoms have improved, give clozapine for patients with treatment-resistant schizophrenia or those with substantial risk of suicide or suicide attempts, long-acting injectable antipsychotics for those who prefer them

what is the general approach for long-acting injectable antipsychotics?

all require an oral challenge, some require an oral overlap, all have different duration of action and dose schedules, all have different indications for use, all have unique administration instructions (IM, SQ), many have unique needle requirement (patient weight, admin location), none are administered for STAT use or via IV (short acting can be STAT or PRN), none require a concurrent oral dose beyond overlap, be vigilant for unintended concomitant PO and IM, they have different reconstitution directions, storage may differ, and should confirm renal dose eligibility

which antipsychotic needs dose adjustments for CrCl < 80 mL/min

paliperidone

which antipsychotics are available as long-acting injectables?

aripiprazole, olanzapine, paliperidone, and risperidone

which aripiprazole LAI are FDA approved for schizophrenia and bipolar?

Abilify Maintena and Abilify Asimtufii

which aririprazole LAI is indicated for just schizophrenia?

Aristada

what is olanzapine’s LAI (Relprevv) FDA approved for?

schizophrenia

which paliperidone LAI’s are FDA approved for schizophrenia and schizoaffective disorder?

Erzofri, Invefa Sustenna

which paliperidone LAI’s are FDA approved for only schizophrenia?

Invega Trinza and Invega Hafyera

which risperidone LAI’s are FDA approved for schizophrenia and as mono or adjunctive therapy to lithium or VPA for maintenance BP-I?

Risperdal Consta and Rykindo

which risperidone LAI’s are FDA approved for only schizophrenia?

Risvan and Uzedy

what is treatment resistance?

considered as lack of improvement in symptoms despite receiving 2 optimized monotherapy trials of APS of different classes at a duration for at least 2-8 weeks

how do you treat treatment resistance to antipsychotics?

consider clozapine earlier for patients with suicidal, violent, or persistent aggression, clozapine has demonstrated superiority over other agents given these conditions

when can polypharmacy be used for psychotic disorders?

when 3 or more failed trials of monotherapy have been documented, during cross titration of APS, or augmentation of clozapine

first line therapies for first-episode of schizophrenia

quetiapine, risperidone or haloperidol (olanzapine probably not ideal to use)

first line therapies for multi-episodes of schizophrenia

any SGA (except for lurasidone) or haloperidol

what are the second line options for schizophrenia?

SGA, FGA, or clozapine

what is the third line option for schizophrenia?

clozapine

what is the fourth line treatment for schizophrenia?

clozapine augmentation

what are the general monitoring recommendations for psych meds?

baseline labs, medical hx, psychiatric assessment, medication response, adverse drug effects, past adherence, past successes, past failures, monitor for/manage comorbid conditions, patients on benzos do periodic pill counts/UDS/CRX agreements

facts regarding first episode schizophrenia treatment:

lower doses may be needed (metabolic not dose related), generally more sensitive to EPS/metabolic side effects and therefore more critically the use of first line olanzapine.

what are the effects on the mesocortical pathway when an antagonist is administered?

worsening of negative symptoms

what are the effects on the mesolimbic pathway when an antagonist is administered?

relief of positive symptoms

what are the effects on the nigrostriatal pathway when an antagonist is administered?

extrapyramidal symptoms and abnormal movements

what are the effects on the tuberoinfundibular pathway when an antagonist is administered?

increase in prolactin release

what are the universal ADRs for second gen antipsychotics (SGA)?

orthostatic hypotension/syncope/falls

metabolic changes, blood dyscrasia

EPS, TD

hyperprolactinemia

seizures, cognitive/motor impairment

body temperature dysregulation, dysphagia

QTc prolongation

first dose monitoring considerations (cognitive/motor impairment, caution with first dose), monitor for any potential allergic reactions with first dose

how can you manage orthostatic hypotension/syncope/fall ADRs of SGA?

warn patients and use lowest effective dose — avoid concomitant medication use that can worsen this effect

how can you manage metabolic change ADRs of SGA?

Warn patient to report symptoms of hyperglycemia (thirst, hunger, GI upset, increased urination, tired/weakness, fruity smelling breath or confusion)

T/F: SGAs are more likely to have metabolic changes than FGAs

true

examples of metabolic changes seen with SGA use:

hyperglycemia, hyperlipidemia, weight gain

which SGAs are among the APS with the highest metabolic risk?

clozapine, olanzapine, and quetiapine

how can you manage blood dyscrasia ADRs from SGA?

Can be managed - generally, not a need for discontinuation but change of agent can resolve issue (ANC/WBC decreases). Clozapine has thresholds that prompt action see package insert to avoid agranulocytosis

how can you manage EPS/TD ADRs from SGAs?

Prevention is key!! Use APS with less likely EPS profile, can use anticholinergics to mitigate EPS exacerbations, and can give benazines for TD

what are acute dystonias?

Painful prolonged muscle contractions that are involuntary. Can be buccal, facial, oculogyric, and may involve back, arms, and legs

What is the onset for acute dystonias?

24-96 hours after dose change or drug started

risk factors for acute dystonias include:

high potency or high dose FGA, men, younger age

how do you treat acute dystonias?

decrease or d/c offending agent, IM STAT anticholinergics (benztropine or diphenhydramine), IM STAT benzos (lorazepam or diazepam)

what is pseudoparkinsonism

presence of bradykinesia, tremor, pill rolling, cogwheel rigidity, postural and oral abnormalities

when do pseudoparkinsonism symptoms begin?

1-2 weeks after dose change or drug started

risk factors for pseudoparkinsonism

high potency or high dose, FGA, females, older age

how do you treat pseudoparkinsonism?

decrease or d/c offending agent, scheduled PO anticholinergics (benztropine or trihexyphenidyl), or propranolol if tremor continues

what is akathisia

restlessness, pacing, shuffling, compulsion to stay in motion, subjective feelings of distress

when does akathisia start?

hours-days after start or dose change

risk factors for akathisia

high potency or high dose, FGA, SGAs (aripiprazole risperidone, paliperidone)

how to treat akathisia

decrease or d/c offending agent, beta blockers (propranolol), benzos, anticholinergics

what is tardive dyskinesia

tongue thrusting, chewing, lip smacking, grimacing, limb twisting, rocking, can be permanent and disfiguring

when does tardive dyskinesia start?

late (months to years after initiation)

risk factors for tardive dyskinesia

high potency or high dose, FGA, female, older age, AA, anticholinergics can mask TD development, use caution

how do you treat tardive dyskinesia?

Prevention is priority! D/c offending agent, switch to clozapine or quetiapine, VMAT (benazine), off label options are offered for last resort 

how do you manage hyperprolactinemia?

avoid APS with strong dopamine antagonism, may require switch to less strong antagonist/mixed serotonin (Iloperidone for example)

which medications are benazines?

deutetrabenazine (Austedo) and valbenazine (Ingrezza)

what a benazines?

vesicular monoamine transport 2 or “VMAT” inhibitors

MOA of benazines

reversible inhibitors result in depletion of monoamines including dopamine

how do you manage seizures (ADRs of SGAs)?

Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold (including concomitant medications contributing to lower seizure threshold). Consider use of mood stabilizing antiepileptic agent when clinically appropriate/necessary.

how do you manage cognitive/motor impairment (ADRs of SGA)?

Warn patient to use caution driving/operating machinery. Consider first dose in controlled setting to determine pharmacologic impact. Use agent with lesser risk in higher risk person. Using lowest effective dose, and slower titrations, may help.

how do you manage body temperature dysregulation (ADR from SGAs)?

APS may disrupt the body’s ability to reduce core body temperature. Strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use APS with caution in patient who may experience these conditions and educate patients to report body temperature changes

how to manage dysphagia

Educate patient to use caution if experiencing trouble swallowing

how to manage QTc prolongation

APS specific (and patient predisposing risks). Optimal to have a baseline QTc measurement and after starting a drug with QTC risk. Consider crediblemed calculator and risk scores for comprehensive recommendations.

how do you manage impulsivity ADRs?

consider change from dopamine agonist to agent with stronger dopamine antagonism

how do you manage GI hypomotility

Especially constipating APS or when prescribed significant anticholinergic burden: Screen for constipation prior to starting APS and monitor throughout course and consider preventative laxatives/bowel preps in high-risk patient

how to manage post injection delirium-sedation syndrome (PDSS)

REMS requires: registration of prescriber, patient and pharmacy and only administered in a registered facility that has access to emergency response services.

Prevention strategies: aspirate after insertion into gluteal muscle to ensure no blood (if blood discard needle and restart with a new kit). Do not massage injection site. Ensure 3-hour continuous observation post injection at site where administration occurred. Patient should not drive rest of the day.

which medications have highest risk for anticholinergic effects?

Clozapine, olanzapine and low potency FGA (chlorpromazine and thioridazine)

how to manage bp elevations for children

If BP becomes elevated, clinical consideration for switch of APS

which medication lists: increases in systolic and diastolic blood pressure occurred in children and adolescents and did not occur in adults?

quetiapine

how to manage hypothyroidism ADRs

discontinuation of medication

T/F: quetiapine lists dose-related decreases in thyroid hormone levels

true

which SGAs have high risk for dystonias?

paliperidone

which SGAs gave high risk of pseudoparkinsonism

ziprasidone

which SGAs have a high risk for akathisia

aripiprazole

which SGAs are high risk for QTc prolongation

ziprasidone