Antipsychotics

psychosis

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• withdrawn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