Antipsychotics Flashcards
DSM-5 Criteria for
Schizophrenia
* > 2 of following symptoms
present for 1 month period:
(5)
- delusions
- hallucinations
- disorganized speech
- grossly disorganized or
catatonic behavior - negative symptoms
(affective blunting, alogia
or avolition) - significant effect
major areas of
functioning - continuous signs of
disturbance persist for
at least 6 months - symptoms are not due to a
another psychiatric illness,
medical disorder or
substance induced
Schizophrenia
(3)
Primary Negative
Symptoms
Psychotic or
Positive
Symptoms
Primary
Cognitive
Symptoms
Proposed Pathophysiology of
Schizophrenia
- dopamine theory
Uses for Antipsychotics
* FDA Approved Indications
(4)
* Off-Label Uses
(5)
– Schizophrenia
– Bipolar Disorder
– Adjunctive Therapy in Major
Depressive Disorder
– Autism Spectrum Disorder
– Anxiety Disorders
– PTSD
– OCD
– Psychosis (other than
schizophrenia)
– Acute treatment of
aggression and agitation
Adverse Effects by Receptor
Blockade
* Dopamine antagonism
– Extrapyramidal Side Effects (EPS) – “movement
disorders”
» Dystonic reaction
» Pseudoparkinsonism
» Akathisia
» Tardive dyskinesia
– Hyperprolactinemia –
» galactorrhea, menstrual irregularities /
amenorrhea, gynecomastia, sexual dysfunction
Extrapyramidal Side Effects (EPS)
Acute Dystonia
- acute dystonic reaction - “severe muscle spasm”
eye-oculogyric crisis neck-torticollis
back-retrocollis tongue-glossospams
pharyngeal-laryngeal dystonia - incidence: 2-64%
- pathophysiology: imbalance between DA and ACh
- onset: usually occurs during first 5 days of treatment or
after a dosage increase - risk factors: high potency AP, large doses, IM
administration, young males - treatment
– acute treatment - AC agent [ex. benztropine (Cogentin)], diphenhydramine
(Benadryl) or a benzodiazepine
– chronic treatment - decrease dose, change AP agent, AC agent
Anticholinergic Drugs to Treat Dystonia
(3)
- Benztropine
(Cogentin) - Trihexyphenidyl
(Artane) - Diphenhydramine
(Benadryl)
Oral side effect – dry mouth
EPS - Pseudoparkinsonism
- four cardinal symptoms
– akinesia, bradykinesia or decreased motor activity
– tremor
– cogwheel rigidity
– postural abnormalities - incidence: 15-36%
- pathophysiology: decrease in DA activity
- onset: 1-2 weeks after AP initiation or increase in dose
- risk factors: high potency AP, increased AP doses, age > 40,
female - treatment: decrease dose, change AP agent, AC agents
[benztropine (Cogentin)], DA agonist [amantadine
(Symmetrel)]
Anticholinergic Drugs to Treat
Pseudoparkinsonism
(2)
- Benztropine
(Cogentin) - Trihexyphenidyl
(Artane)
Oral side effect – dry mouth
EPS - Akathisia
- extreme motor restlessness/inability to sit still
– patient can not typically control akathisia for even a short time period - incidence: 25-36%
- pathophysiology: unknown
- onset: 2-4 weeks
- difficult to distinguish from anxiety/agitation/psychosis
– akathisia made worse with increased AP doses - risk factors: high potency AP, large AP dose
- treatment: decrease dose, change AP agent, beta blocker
[propranolol (Inderal)] , or a benzodiazepine
– No oral side effects associated with propranolol
Propranolol (Inderal)
* MOA -
* Common Side Effects
(5)
nonselective
beta-adrenergic
receptor blocking
agent
– Dizziness, weakness
and fatigue
* No life-threatening side
effects
* No oral side effects
* Overdose –
hypotension and
bradycardia
* High risk for drug
interactions
EPS - Tardive Dyskinesia
- syndrome characterized by involuntary movements
– buccal-lingual-masticatory syndrome (BLM)
– orofacial movements
– writhing movements of face, neck, back, trunk and extremities - incidence: 20%
- pathophysiology: (1) increase in DA receptor sensitivity (2)
neuronal degeneration - onset: usually late (years)
- risk factors: increased age, female, concurrent diagnosis of
mood d/o, long duration of AP use - AIMS (Abnormal Involuntary Movement Scale)
EPS - Tardive Dyskinesia
Treatment
- prevention
- reduce dose of AP – always use lowest effective
dose - change AP to second generation antipsychotic (SGA)
– clozapine – treatment option - 2 drugs recently FDA approved for TD
– MOA – vesicular monoamine transporter 2 inhibitor
(VMAT2)
» Valbenazine (Ingrezza) - Oral side effect – dry mouth
» Deutetrabenazine (Austedo) - Oral side effect – dry mouth
Oral Side Effects
* FGA
(7)
* Medications to treat
side effects of FGA
– Dry Mouth
(5)
– Chlorpromazine
(Thorazine)
» Dry mouth
» Hypersalivation (EPS)
» Sialorrhea (EPS)
– Haloperidol (Haldol)
» Hypersalivation (EPS)
» Sialorrhea (EPS)
» Benztropine (Cogentin)
» Trihexyphenidyl
(Artane)
» Diphenhydramine
(Benadryl)
» Valbenazine (Ingrezza)
» Deutetrabenazine
(Austedo)
Summary – First Generation
Antipsychotics
* Advantages
(3)
* Disadvantages
(6)
– effective for positive
symptoms
– multiple dosage
formulations available
– decreased cost
– not effective in 30% of
patients
– minimal efficacy for negative
symptoms
– minimal efficacy for cognitive
symptoms
– high side effect burden
(EPS)
– risk of tardive dyskinesia
– nonadherence
Clozapine (Clozaril or Fazaclo)
* Indications
(2)
* Additional Information
(5)
– Treatment refractory schizophrenia
» Lack of efficacy
» Intolerable side effects (i.e. TD)
– ↓ risk of recurrent suicidal behavior in schizophrenia and schizoaffective
disorder
– agranulocytosis
– dose related seizure risk
– myocarditis
– oral side effects
» dry mouth, sialorrhea, hypersalivation
Risperidone (Risperdal)
* Indications
(3)
– Schizophrenia
» Acute treatment
* Adults + adolescents 13-17 years
» Maintenance treatment
– Bipolar I Disorder
» Acute Manic or Mixed Episodes – monotherapy or in combination with
lithium or VPA
* Adults + children and adolescents 10-17 years
– Autism
» Treatment of irritability associated with autistic disorder in children and
adolescents (ages 5-16 years)
» Symptoms of aggression towards others, deliberate self-injuriousness,
temper tantrums, and quickly changing moods
Risperidone
* Additional information
(3)
– doses > 6 mg/day = increase risk of EPS
– ↑ prolactin - not dose related
– no oral side effects
Olanzapine (Zyprexa)
* Indications
(2)
– Schizophrenia
» Acute treatment
* Adults and adolescents 13-17 years
» Maintenance treatment
– Bipolar I Disorder
» Acute Manic or Mixed Episode – monotherapy or combination with
lithium or VPA
* Adults and adolescents 13-17 years
» Maintenance treatment – monotherapy
» Depressed Episodes - combination product only (Symbyax - olanzapine
+ fluoxetine)
Olanzapine
* Indications
(2)
– Treatment Resistant Major Depressive Disorder –
combination product only (Symbyax – olanzapine + fluoxetine)
» Defined as nonresponse to 2 separate trials of different
antidepressants of adequate dose and duration in the
current episode
– Acute agitation associated with schizophrenia or Bipolar I
mania (IM formulation only)
- Other Information
– oral side effect – dry mouth
Quetiapine (Seroquel and Seroquel XR)
* Indications
(3)
* Additional Information
(2)
– Schizophrenia
» Acute treatment
» Maintenance Treatment
– Bipolar I Disorder
» Acute Manic of Mixed Episodes – monotherapy or in combination with
lithium or VPA
» Depression (Bipolar I and II disorder)
» Maintenance
– Adjunctive Treatment of Major Depressive Disorder (inadequate response to
antidepressant monotherapy)
– Oral side effect – dry mouth
– Commonly used off-label as a sedative hypnotic and anxiolytic
Aripiprazole (Abilify)
* Mechanism of
action
(2)
– D2 partial agonist
– 5HT2a antagonist
Aripiprazole
* Indications
(4)
– Schizophrenia (Adults + adolescents 13-17 years)
» Acute treatment
» Maintenance treatment
– Bipolar Disorder I (Adults + children/adolescents 10-17 years)
» Acute Manic or Mixed Episodes – monotherapy or in combination with
VPA or lithium
» Maintenance treatment
– Adjunctive treatment of Major Depressive Disorder (inadequate
response to antidepressant monotherapy)
– Autism
» Treatment of irritability associated with autistic disorder in children and
adolescents (ages 5-16 years)
» Symptoms of aggression towards others, deliberate self-injuriousness,
temper tantrums, and quickly changing moods
Aripiprazole
* Other Information
(2)
– akathisia is more common than other types of EPS
– no oral side effects
Lurasidone (Latuda)
* Indications
(3)
* Additional Information
(2)
– Schizophrenia
» Acute treatment
– Depressive episodes associated with Bipolar I disorder
– Must be taken with food (at least 350 kcal)
– No oral side effects
Oral Side Effects
of SGA
* Sialorrhea,
Hypersalivation
(1)
* Dry Mouth
(3)
– Clozapine (Clozaril)
– Clozapine (Clozaril)
– Olanzapine (Zyprexa)
– Quetiapine (Seroquel)
Summary – SGA
* Advantages
(4)
* Disadvantages
(1)
– effective for positive symptoms
– may be effective for negative
symptoms
– clozapine effective in treatment
refractory schizophrenia
– improved side effect profile as
compared with FGA
» decreased risk of TD
» decreased incidence of EPS
» minimal to no prolactin elevation
(except RIS)
– risk of metabolic side
effects
Selection of Antipsychotic Therapy
- Second Generation Antipsychotics (with the
exception of clozapine, olanzapine, and iloperidone)
have become the agents of first choice for the
treatment of schizophrenia.
– Practice guidelines and consensus statements support this
recommendation.
Maintenance Antipsychotic Therapy
- Relapse rates are extremely high
– 60-80% relapse rate within 1 year with no antipsychotic therapy
– 20% relapse rate within 1 year with continued antipsychotic therapy
- Treatment duration:
1st episode - treat x – year
2nd episode - treat x – years
> 2 episodes - treat for —
1
5
lifetime
Response to
Antipsychotic Therapy
*decreased: agitation/
hostility/aggression/
combativeness/anxiety
*normalization of sleep
and eating patterns
*improvement in
socialization/
self-care habits/
mood
*improvement in
thought disorder/
mood
*decrease in
delusions/
hallucinations
*appropriate
conversation
potentially
persistent symptoms
*impaired insight/
judgment
*inappropriate affect
*fixed delusions/
hallucinations
Expect to see initial improvement
in symptoms within 2 weeks of
starting antipsychotic therapy.
Maximum response make take up
to 6-8 weeks.
