Schizophrenia Flashcards
Schizophrenia dx
2 or more of sx in significant percent of 1 month time period (less if treated) or only 1 sx if bizarre delusions or hallucinations
- social /occ dysfunction at least 6 months, incl 1 month of sx (unless txd)
Duration of sx for schizophreniform vs brief psychotic episode
Brief psychotic episode 1 day to 1 month (with return to preempt of function)
Schizophreniform disorder 1 month to 6 months
Schizoaffective disorder dx
Sx similar to schizophrenia
Plus underlying affective component to disorder - either mania depression or mixed episode
- residual sx may be less severe and less chronic than in schizophrenia
- must be mood episode concurrent with sx meeting criterion A for schizophrenia
Schizophreniform disorder dx
Sx similar to schizophrenia but duration of illness is at least 1 month to max of 6 months
- therefore social or Occupational functioning impairment is not a dx requirement (6 month req)
Onset sx of schizophrenia
Can be abrupt or insidious but
Prodromal phase usually characterize by NEGATIVE sx
Pathophysiology of schizophrenia - dopamine
Dopamine - hyperactivity in limbic system leading to positive sx
Dopamine - hypo functioning in prefrontal cortex leading to negative sx
Pathophysiology of schizophrenia - serotonin 5-HT
Serotonin -increase in serotonin transporter density in subcortical regions no change in cortical regions
Use of 5-HT antagonists leads to increased dopamine release in prefrontal cortex
Pathophysiology of schizophrenia - glutamate and NDMA
Glutamate corticostriatal pathway inhibits dopamine function in ventral striatum - deficiencies in glutamate produce sx similar to dopamine hyperactivity
NMDA - receptor dysfunction may play a role - use of NMDA antagonists leads to positive sx by increasing dopamine release in limbic areas and reducing dopamine release from ventral tegumental area leading to negative sx
ACT
Non pharm tx of schizophrenia
Assertive Community Treatment
**shiwn to reduce hospitalizations and homelessness among schizo pt
System of care with multidisciplinary team for persons at risk (repeated hospitalizations, homelessness)
Other non Pharm tx of schizo
Supported employment, skills training,
Cognitive behavioral therapy - may benefit but sustained relapse benefit has been difficult to sho
Token economy - involve particular behavioral interventions for patients based on social learning principles to address personal hygiene , social interactions, other issues
Family services- for both pt and family, shown to reduce relapse and re hospitalization in some pts,
Non pharm medical interventions for schizophrenia
Repetitive transcranial magnetic stimulation (rTMS)
- effective for acute tx of refractory auditory hallucinations - effects last 8-12 weeks - se include seizure and syncope
Electroconvulsive therapy (ECT)
- insufficient evidence for tx of core symptoms of schizophrenia - most efficacy may be seen if pt is catatonic or has depressive sx - se include anterograde and retrograde amnesia, status epilepticus, laryngospasm and peripheral nerve palsy
First gen high potency antipsychotics
Fluphenazine Haloperidol Pimozide (only FDA for Tourette's ) Trifluoperazine Thiothixene
Low potency antipsychotics
Chlorpromazine
Thioridazine
Chlo and Thio = Low
Mid potency antipsychotics FGA
Loxapine
Perphenazine
Dopamine tract effect when blocked: mesocortical (aka prefrontal cortex)
Worsening negative sx
Dopamine tract effect when blocked: Mesolimbic (basal ganglia)
Relief of positive sx
Dopamine tract effect when blocked: nigrostriatal (substantia nigra)
Extra pyramidal sx
Dopamine tract effect when blocked: tuberoinfundibular (hypothalamus)
Increase prolactin release
Antipsychotic effect mediated by what dopamine mechanism
Decrease in central dopaminergic transmission, likely related to blockade of post synaptic D2 receptors in Mesolimbic area and possibly mesocortical area
Maximal D2 blockade with how much haloperidol ?
2 to 5 mg
Dose of fluphenazine decanoate IM, conversion from oral
Multiply oral dose by 1.25 to get decanoate dose
Eg 10mg qday -> 12.5 mg q 2 weeks IM dec
- oral can dc 2-4 days after injection given
Haldol convert from oral to dec
Q4weeks
-initial injection shouldn’t exceed 100mg, second inj in 3-4 days to eval tolerability
2 methods
1) loading dose method:
Give 20x PO dose in 1 inj or a series over 1 week if dose >200mg IM and stop oral once inj have finished
** then maint dose 10x PO
2) no loading dose
Give IM dose of 10x oral dose and taper PO slowly over next 3-4 wks
What FGA causes most, least sedation
Chlorpromazine most
Molindone least
Eps moa
Post synaptic dopamine block on basal ganglia allows cholinergic activity to predominate - eps result
Agents with more anticholinergic activity cause less eps but all FGA cause eps
Moa of orthostatic hypotension
Due to alpha adrenergic blockade
Phenothiazines that cause EKG changes and which change they cause
Chlorpromazine and thioridazine
Most common: flattened T waves
Also Qt prolongation and PR prolongation
ST depression
Dose related eps of SGA
Most to least
Risperidone = paliperidone
Olanzapine=zip=aripip=ilo=asenap
Quet=cloz
Increased prolactin SGA
Most to least Paliperidone Risperidone Olan=Zip=quet=cloz=ilo=asen=Lura Aripip
Increase levels don’t correlated with adverse effect
Tardive dyskinesia SGA
Rare for clozapine
Very low for:
risp olan, zip ari Pali asen lura
Anticholinergic SGA
Clozapine>
olanzapine
quetiapine
Pali risp zip ari ilo asen
Most orthostatic SGA
Clozapine
Then quet
Then risp
Most seizure threshold lowering SGA
Clozapine
Olanzapine
Then others
Most lft SGA
Olanzapine and quetiapine
Weight gain SGA
Clozapine = Olanzapine Quetiapine Risp = Pali Ilo Lura Asen Zip Arip
SGA not to use with class 1A or class III antiarrhythmics or other drugs prolonging QT
Ziprasidone
Paliperidone
Dose adjustment for aripip
2d6 inhibitor - cut arip dose in half
3a4 inhibitor - cut arip dose in half
3a4 inducer - double arip dose
Asenapine dose adjustment
1a2 Inhibitors may increase asen levels - ex fluvoxamine
Coadministered with paroxeinr increased levels 2 fold
Clozapine dose adjust
1a2 inhibits may increase levels, inducers (cigs) may decrease
Benzos may increase risk of respiratory depression
3a4 inducers may lower response
VPA may reduce clozapine concns
Citalopram may increase levels
Iloperidone dose adjust
2d6 inhibitor
3a4 inhibitor
Lurasidone dose adjust
3a4 inducer or inhibitor
Olanzapine dose adjust
1a2 inhibit or inducer incl charcoal
CNS depressants
Orthostatic hypotn
May antag effects of levodopa and DA agonists
Paliperidone dose adjust
None really , avoid pro arrhythmic
Quetiapine dose adjust
Cation with 3a4 inhibitors
Increased clearance with phenytoin and thioridazine caution with other inducers
Loraz cimet minor interactions
Risperidone dose adjust
Major 2d6
Minor 3a4
Antag effects of levodopa
Clozapine, VPA can decrease clearance
Ziprasidone dose adjust
Cbz decreases levels
Ketocon increases levels
Safest antipsychotics during pg
Clozapine - class B But can cause gestational DM
Definition of treatment refractory schizophrenia
At least 3 periods of tx in preceding 5 years Neuroleptic agent of 2 diff classes Adequate dose at least 1000mg chlorpromazine equivalents) For 6 weeks Without sx relief No period of good fxn in 5 years
Slowing of voluntary movement
Akinesia (type of
Also pill rolling movements
Higher potency have higher risk
Treatment of tardive dyskinesia
No gold Standard DC drug if possible Vitamin E may help Switch to clozapine Reserpine may suppress movement Branch chain AA Donepezil? Prevention ** use antipsychotic only appropriately at lowest dose for lowest duration **anticholinergic may increase risk for TD and doesn't help resolve cause
Schizophrenia dx sx
Delusions Hallucinations Disorganized speech Grossly disorganized / catatonic behavior Negative sx
What makes a second generation antipsychotic ?
Less risk eps at antipsychotic dose
5ht2a antagonism at mesocortical pathway
Fast dissociation from DA receptor specifically for clozapine quetiapine
Aripiprazole partial antag at d2 Mesolimbic
