Antipsychotics

psychosis

* a severe mental disturbance that involves a profound misinterpretation of perceptions or loss of contact w/ reality
* leads to inappropriate ability to interact w/ other or w/ environment
* featured in various disorders

psychotic symptoms

* hallucinations
* delusions
* disorganized speech
* disorganized or catatonic behavior

positive symptoms

something added to a pt’s normal presentation

* hallucinations
* delusions
* disorganized speech
* grossly disorganized or catatonic behavior

negative symptoms

something taken away from a pt’s normal presentation

* affective flattening (impaired outward display of emotions)
* alogia (decreased speech fluency)
* avolition (lack of motivation)
* anhedonia
* asociality

cognitive symptoms

decreased cognitive function

* poor concentration
* memory disturbances
* inability to plan
* difficulty executing tasks
* poor abstraction
* impaired decision making

prodromal phase

* withdrawn
* odd beliefs
* peculiar behavior

acute episode

* lose touch w/ reality
* hallucinations
* delusions
* flat or inappropriate affect
* difficulty w/ self-care

psychosis diagnosis

* 2 or more of the following persisting for significant portion of at least a 1 month period:
* delusions
* hallucinations
* disorganized speech
* grossly disorganized or catatonic behavior
* negative symptoms
* symptoms associated w/ significant social/occupational dysfunction
* continuous signs for at least 6 months (prodromal/residual symptoms)

schizophrenia

* imbalance in dopamine (increased in certain areas of brain)
* other neurotransmitters likely play a role as well

antipsychotic MOA

MOA: dopamine blockage or dopamine AND serotonin blockage

typical

* dopamine blockage
* 1st generation
* decrease positive symptoms, but can cause movement disorders

atypical

* dopamine and serotonin blockage
* 2nd generation
* reduced risk for EPS and TD
* potentially better at improving negative symptoms and cognition
* greater risk of metabolic ADRs

dopamine receptor blockade

* therapeutic
* improved **positive** symptoms of psychosis
* ADRs
* worsening **negative** symptoms and **cognition**
* extrapyramidal movement disorders (EPS) and tardive dyskinesia (TD)

dopamine and serotonin receptor blockade

* therapeutic
* reduced EPS and risk of TD
* possible improvement in negative symptoms and cognition
* ADRs
* sedation
* weight gain

typical antipsychotics

* chlorpromazine
* thioridazine
* perphenazine
* loxapine

high potency typical

* haloperidol
* fluphenazine

extrapyramidal symptoms

* dystonia
* pseudoparkinsonism
* akathisia

dystonia

* sustained muscle contractions
* twisting, repetitive movements/abnormal postures
* can look like tremor/seizure
* painful and scary
* typically involve tongue, jaws, eyes, neck, limbs, toes
* usually occur 24-96 hours after dose

dystonia treatment

* diphenhydramine (benadryl)
* benztropine (cogentin)
* benzodiazepines

pseudoparkinsonism

* akinesia, bradykinesia, slowed speech
* S/S
* resting tremor
* pilling rolling tremor
* cogwheel rigidity
* gait/posture changes
* usually reversible within weeks of d/c

pseudoparkinsonism treatment

* benztropine (Cogentin)
* trihexyphenidyl (Artane)

akathisia

* motor restlessness or inability to sit still
* S/S
* pacing
* shifting/shuffling
* foot tapping
* “inner restlessness”
* occurs in 20-30% of pts on typical antipsychotics

akathisia treatment

* beta blockers
* benzodiazepines

EPS treatment strategies

* decrease antipsychotic dose
* switch from high- to low-potency typical antipsychotic
* switch from typical to atypical
* use adjunctive medication

tardive dyskinesia

* involuntary abnormal movements which generally occur after long-term antipsychotic therapy
* face, tongue, lips, neck, trunk
* early signs may be reversible
* if not detected early, may be irreversible
* may interfere w/ ability to speak, chew, swallow

tardive dyskinesia treatment

* **PREVENTION KEY: most important intervention**
* early detection
* AIMS scale every 3-6 months
* switch to atypical antipsychotics
* Valbenazine and Deutetrabenazine
* decreases presynaptic dopamine
* modest symptom improvement
* sedation & dry mouth >5%

atypical antipsychotics

* clozapine (Clozaril)
* olanzapine (Zyprexa)
* risperidone (Risperidal)
* quetiapine (Seroquel)
* ziprasidone (Geodon)
* aripiprazole (Abilify)
* paliperidone (Invega)

atypical effects

* therapeutic effect
* decreases negative symptoms
* improve cognition
* ADRs
* movement disorders (EPS)
* weight gain
* hyperlipidemia
* weight gain

clozapine

* unique effectiveness for treatment of:
* persistent psychotic symptoms
* negative symptoms
* suicidality
* 1-2% develop agranulocytosis
* blood monitoring required weekly for first 6 months, every 2 weeks for 6 months, then monthly
* reserved for **TREATMENT RESISTANT PATIENTS**

antipsychotic BBW

* increased rate of death in elderly patients w/ dementia receiving antipsychotics for treatment of behavioral disorders

dosage forms

* Oral
* tablets or capsules
* liquid
* quick dissolving
* Injection
* short acting (quick control of aggression/harm)
* long acting (depot, lasts months)

1-7 days

Therapy time course

* decreased agitation/hostility
* decreased aggression/anxiety
* normalization of sleep and appetite

1-2 weeks

Therapy time course

* improvement in socialization and mood

3-6 weeks (or >)

Therapy time course

* improvement in thought disorder (hallucinations, delusions)

residual sx

Therapy time course

* fixed delusions and hallucinations