Treatment of Schizophrenia

What are positive symptoms of schizophrenia?

-hallucinations

-delusions

-disorganized speech

-disorganized behavior

What are negative symptoms of schizophrenia?

-alogia

-avolition

-affective blunting

-anhedonia

-asociality

What are cognitive deficits seen with schizophrenia?

-attention

-memory

-executive functions

What are mood symptoms associated with schizophrenia?

-depression

-suicidality

-anxiety

What are hallucinations?

-false sensory perceptions occurring in the absence of relevant external stimuli

-Types:

• auditory: hearing voices

• visual: seeing things

• olfactory

• gustatory

• tactile

• somatic: physical sense within the body

What are delusions?

-false beliefs that are firmly held, despite the facts and despite inconsistency with the culture

-Types:

• bizarre

• reference

• control

• religious

• grandiose

• somatic

• persecutory

What are disorganized speech?

-loose associations: unrelated ideas shift from one subject to another

-tangentiality: inability to have goal directed associations of though; never gets from original point to desired goal

-circumstantiality: indirect speech that is delayed in reaching the point but eventually gets from original point to desired goal

What is disorganized behavior?

-silliness

-catatonic behaviors

-unusual dress or grooming

-untriggered swearing or shouting

-inappropriate sexual behavior

Negative symptoms:

alogia: poverty of speech

-avolition: lack of self initiated , goal directed activity ; includes poor hygiene

-affect blunting: lack of interest in pleasurable activites

-asociality: withdrawal, isolation

How do you diagnose schizophrenia?

-two or more of the following, each present for a significant portion of time during a 1 month period:

• delusions*

• hallucinations*

• disorganized speech*

• grossly catatonic behaviors

• negative symptoms

*at least one of these symptoms must be present

-continuous signs of the disturbance persist for at least 6 months; must include active phase and may include prodromal or residual periods

-exclusion of other causes of psychosis

What can be some medications or conditions that present as psychotic symptoms?

-medical conditions: neurological, endocrine, metabolic, autoimmune

-substance induced: amphetamines, cocaine, PSP, LSD

-other psychotic disorders: schizoaffective disorders, schizophreniform

-mood disorders: mania or depression

-personality disorders: schizotypal , schizoid, paranoid

True/False: most patients experience at least 1 relapse within 5 years

-true

What is the class of medications used to treat schizophrenia?

-antiphyscotics

Which antipsychotics act at D2 receptor antagonism?

-All FGAs: block D2 receptors

-Almost all SGAs

Which antipsychotics have D2 receptor partial agonism?

-aripiprazole

-brexpiprazole

-cariprazine

Which antipsychotics have -HT2A receptor antagonism?

-All SGAs

Which antipsychotics have 5-HT1A receptor agonism?

-ziprasidone

What antipsychotics have 5-HT1A receptor partial agonism?

-aripiprazole and brexipiprazole : can’t be used for treatment resistant depression and bipolar depression

-lurasidone

Rexulti ( brexipiprazole):

-MOA: partial D2 and 5-HT1 agonist ; antagonist at 5-ht2A

Vraylar ( Cariprazine):

-MOA: partial agonist at D2 and D3 receptors

-Partial agonist at 5-HT1A receptor

-Antagonist at 5HT2A receptor

Captlyta ( lumateperone):

-MOA: antagonist 5-HT2A and D2 receptors

What happens in the mesolimbic pathway in patients with schizophrenia?

-too much dopamine which causes overactivity and positive symptoms

What happens in the mesocortical system of schizophrenia patients?

-underactivity of this system leads to less dopamine and this causes negative and cognitive symptoms

True/False: D2 antagonism in the mesolimbic pathway leads to the antipsychotic effects

-true

What is the effect of blocking D2 receptors in the tuberoinfundibular pathway?

-can increase prolactin levels

In this pathway when you block D2 you can cause EPS:

-nigrostriatal pathway

Blocking D2 receptors in this pathway can lead to negative symptoms becoming worse in the schizophrenic patient:

-Mesocortical

What is the effects of blocking 5-HT2A receptors in the meocortical tract?

-you can see an improvement in cognitive and negative symptoms

Blocking this receptor can lead to orthostatic hypotension:

-alpha-1 antagonism

Blocking this receptor causes somnolence and weight gain:

-histamine 1 antagonism

Blocking this receptor causes increased appetite:

-5-HT2C

What are the effects of blocking muscarinic receptors?

-cause anticholinergic side effects

Which antipsychotics must be given with food?

-ziprasidone and lurasidone ( take with > 350 calories)

Which medication should not be taken with food?

-asenapine bioavailability is much lower when swallowed or given with food

What antipsychotics must be dosed twice a day due to shorter half life?

-quetiapine and ziprasidone

What is the black boxed warning for all antipsychotics?

-increased mortality in elderly patients with dementia related psychosis

-elderly patients with dementia related related psychosis treated with antipsychotics drugs are at an increased risk of death.

EPs symptom: Acute dystonia:

-prolonged tonic contractions

-onset: happens within hours to days of therapy initiation or dosage increases

-drug related risk factors: FGAs have high potency ; high dosage

-Patient related risk factors: younger age, male gender, previous history of dystonia

-complications: can be painful

-prevention; anticholinergics

-management: treat with parenteral agent , anticholinergic or diphenhydramine, BZD

EPS symptoms: Akathisia

-inner restlessness + motor restlessness ( ants in my pants)

-onset: within days to weeks of therapy initiation or dosage increases

-drug-related risk factors: FGAs, high potency, high dosage

-Patient related risk factors: advanced age , female

-complications: misdiagnosis of psychotic agitation ; can lead to impulsivity or aggression

-Management: switch to SGA, decrease dosage, 1st line: beta blockers, 2nd line: BZDs

Pseudoparkinsonism EPS effect:

-tremor, rigidity, bradykinesia, postural abnormalities

-Onset: within weeks to months of initiation or dosage increase

-drug-related risk factors: FGAs, especially high potency , high dosage

-Patient related factors: older age, AIDS, female gender

-Complications: misdiagnosis of depression, misdiagnosis of negative symptoms, can lead to falls/injuries

-Management: switch to SGA ; decrease dosage, treat with anticholinergic , treat with amantadine

Tardive dyskinesia EPS effects:

-abnormal , involuntary movements

-Onset: after months to years of therapy

-Drug-related risk factors: FGAs, Higher mean daily dosage, Longer duration ,Total cumulative dosage ,Concomitant anticholinergic med

-Patient related risk factors: older age, female gender, mood disorder, diabetes mellitus, organic brain disease, occurrence of acute EPS

-Complications: possible interference with ADLs, can become irreversible

-Prevention: lowest and shortest duration possible, preferential use of SGAs, routine screening

-Management: decrease dosage or discontinue drug; Switch to SGA

What can be some metabolic side effects of antipsychotics?

-weight gain, glucose dysregulation, lipid changes

Which antipsychotics cause low weight gain?

-aripiprazole , ziprasidone, lurasidone

What antipsychotics cause a lot of weight gain/

-clozapine and olanzapine

What is the average weight gain seen in patients on antipsychotics?

-weight gain at 10 weeks is 0.5-5.0 kg on average

What is the leading cause of death in schizophrenia paients?

-CVD

Which antipsychotic has the highest QTC prolongation?

-Thioridazine (35.8 msec)

What is the side effects of Clozapine?

-sedation, anticholinergic effects, sialorrhea, orthostasis, tachycardia, metabolic abnormalities

What is the black boxed warning for Clozapine?

-agranulocytosis, seizures, myocarditis, orthostasis

Clozapine monitoring:

-REMS program: must monitor ANC levels ( ANC >1500 mcg/mL)

-if ANC is normal: check ANC weekly for 6 months ; check every other week for 6 months, then check monthly then after

What is neuroleptic malignant syndrome?

-potential fatal adverse effect of antipsychotics

-signs: rigidity, elevated temp. , autonomic dysfunction, and altered consciousness

-lower risk with SGAs ; rechallenge: use SGA -wait at least 2 weeks after recovery

BZDs, antihistamines, and ethanol can have what effects when taking with antipsychotics:

-additive sedative effects

When antipsychotics are taking with to cause increase anticholinergic effects?

-benztropine, antidepressants

What medications if taken with antipsychotics can lead to additive hypotensive effects?

-diuretics, beta-blockers, ACE inhibitors

Which medications if taking together can cause hematologic effects/

-clozapine taking with carbamazepine

Which medications if taking together can cause respiratory ffects?

-clozapine and BZDs

Which medication is still given to treat schizophrenia, but it can cause QTC prolongation?

-Ziprasidone

Which antipsychotics should not be taken if the patient smokes?

-olanzapine, asenapine, clozapine

How do you dose antipsychotics in the acute phase?

-initiate therapy and titrate dose over several days to average effective dose

-subsequent titrations may be made every 1-2 weeks based on response and tolerability

How do you dose antipsychotics in maintenance phase?

-lower doses may be needed to maintain remission of symptoms than to treat acute episodes.

-After 1 year of therapy , may attempt a very gradual ( every 3-6 months) dosage reduction while closely monitoring the patient

How do you dose long acting injectables?

-start or convert patient to an oral dosage form of the desired antipsychotic medications

-convert oral dosage form to LAI

What is the black boxed warning for Zyprexa LAI?

-black boxed warning for post-injection delirium/sedation syndrome

Which LAI does not require oral bridge?

-Invega Sustenna

What is the treatment for agitation?

-IM BZDs: Ativan 1-2 mg q2-4 hrs.

-IM FGAs: haloperidol 5 mg ( usually given with benztropine and diphenhydramine)

-IM SGAs: geodon, zyprexa, abilify

-Combo IM BZD + IM FGA or SGA