Download Psychosis

Psychosis
Schizophrenia = Disorder of thought resulting in
compromised function
DSM-IV Diagnostic Criteria
1) 2 or more of the following SSx for at least 1mo or
presence of voice commentary/multiple voice
conversation

Delusions (firmly held, false beliefs)

Hallucinations (olfactory, visual, tactile, gustatory,
audio)

Disorganized speech

Disorganized/catatonic behaviour

Negative SSx (flat/labile affect, social w/d,
apathy, isolation)
2) Social dysfunction
3) Disorder SSx for at least 6mo (including prodrome)
4) Rule out mood/medical disorder and substance abuse
5) If a Hx of a pervasive developmental disorder is
present, there must be symptoms of hallucinations or
delusions present for at least 1 month
Note: the above SSx are all “positive”; with the exception
of the explicitly stated “negative” SSx
Epidemiology

1% prevalence in general population, irrespective of
race, socioeconomic status etc.

starts when you are 15 20 yr old. More in males than
females.
Urgency

Psychotic episodes must be treated immediately

Important to gain control over psychosis, otherwise
health service utilization will be huge
Pathophysiology

Unknown pathophysiology

Mesolimbic (motivation, memory) and mesocortical
(cognition) dopaminergic tracts are implicated

Hypothesized DA receptor hypofunction in prefrontal
cortex(responsible for –ve symptoms) or DA receptor
hyperactivity (resp for +ve symptoms)

+ve symptoms: hallucinations, hearing voices, agitation,
delusions, fragmented thoughts ; crisis points (threat to
society)

-ve symptoms: flat, poor social interaction, isolation,
low physical activity, school participation

Cognitive : Confusion in thinking



Amantidine
Levodopa
Cocaine, LSD, Metamphetamine (psychosis can last up to
10 days with this), ecstasy, “pot”(more potent now than
it was 30-40 yrs ago, so can trigger schizo in someone
who had it before)
Why Treat?

May harm self

To increase ability to care for self
Clincial Outcomes

Eliminate psychotic SSx(+ve and –ve)

Reduce frequency/severity of future episodes

Increase function

Slow progress of disease

Prevent relapse
Pharmacotherapeutic Outcomes

The usual
Pharmacotherapeutic Endpoints

Reduce psychotic SSx within 48h and eliminate within a
few weeks

Reduce/eliminate # of future episodes

Increase patient’s ability to self-care within a few
weeks
Alternatives and Assessment
Non-pharmacological Options
ECT

Psych.
Rehab

Pharmacological Options
Atypicals
Typicals

Clozapine

Chlorpromazine

Olanzapine

Fluphenazine

Quetiapine

Haloperidol

Risperidone

Loxapine
*Only major options included; there are a lot more typicals,
but they are not commonly used (besides, they’re pretty
much all the same)
Use of antipsychotic medications

Risk Factors

Family Hx

If parent has psychosis, child has 10% chance
Drug Causes

Prednisone

Dopamine agonists (bromocriptine)
Last line or acute episode or Hx of good
response


In any illness that has psychotic features:
 Schizophrenia
 Reactive psychosis
 Substance induced psychosis
 Depression with psychotic features
 Manic disorders with psychotic
features
Impulse control disorder
Attention deficit disorder
1

Borderline personality disorder
Characteristic
Binds
Typicals

Primarily D2
(need 65% D2
occupancy for
these to work)

And D4
-just bind and
stay for 24hrs
SSx treated

+ve and –ve

Primarily +ve
EPS effects

Little

Significant
Unique SE**

None

Galactorrhea
- they simply bind

Increase
and leave
prolactin

Dystonia

Akathisia

Pseudoparkinsons

Tardive
dyskinesia
**Note: These SE are not “unique” in a literal sense, but
they are rarely caused by atypicals and hence are not usually
considered clinically

Atypicals
Primarily D4,
but also bind
D2
4)
5)

Thioridazine

Olanzapine

Chlorpromazine
Orthostatic HTN

Clozapine

Chlorpromazine

Thioridazine

Loxapine
Weight gain

Clozapine

Olanzapine
Side Effect Management

All of the antipsychotics can cause the following side
effects (to various degrees) with the exception of
those SE listed as “unique to typicals” in the previous
table
Anticholinergic

Dystonia

Akathisia

Pseudoparkins.
Typicals

All are equally efficacious for Tx of +ve SSx
Side Effects
Culprits of note:
1) Sedation

Chlorpromazine

Clozapine

Loxapine

Quetiapine

Thioridazine
2) Extrapyramidal

All typicals (esp. HPD, FPZ)
3) Anticholinergic

Clozapine



Risperidone

Behaves like typical AP when given in high doses
Quetiapine

Less efficacious than other atypicals



Clozapine

Excellent drug for Tx of resistant schizophrenia

1% agranulocytosis limits use

May manifest as throat infection

Requires CBC every week and d/c if < 2000/mm3
Olanzapine

Often the 1st choice due to good efficacy, relatively
good SE profile








Tardive
dyskinesia


Dry mouth, blurred vision,
constipation
Tx constipation with diet and stool
softener if necessary
Early after starting medication or
increase in dose (within 24-96 hrs)
Muscle spasm  neck spasm
Older agents more common than 2nd
generation
If occurs, can resolve with
benztropine and then can use on
regular basis to control
Resolves if stop medication
Motor Restlessness, agitation,
inability to sit still, inner restlessness
Risk is significantly reduced with 2nd
generation agents(may be seen on
occasion)
Clozapine and quetiapine appear to
have the lower rate
Reduce dose
Tremor(shaking hands), slow
movements, slowed speech, stiff,
stooped, rigidity
One or more of the 4 cardinal SSx
Due to DA receptor blockade
Risk is low with 2nd generation agents
Switch to atypical or use
benztropine(Cogentin)/amantadine(Sy
mmetrel) or
dimenhydramine(Benadryl)
See effect in 3-4 days and max in 2
weeks
Long term SE after an extended time
on meds.
Abnormal involuntary movements of
mouth (lip smacking), tongue
movements(often is the 1st sign),
face, trunk, hands or legs
2
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
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
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Sedation
Seizures
Neuroleptic
malignant
syndrome
Orthostatic
hypotension
Corneal
deposits
Effect on
thinking

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





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

(restlessness)
Worse with stress and may decrease
during sleep
No Tx; avoid by using atypicals
5% per year with first generation
agents
lower risk with 2nd generation
(risperidone and olanzapine)
Clozapine no reports
Rates higher if stop and start
medication
Related to length of time on
antipsychotic agents
May be reversible if catch early
If do not catch and remain on drug
may become irreversible
May abate over time
Try switching dose schedule
Lower seizure threshold
Switch to non-clozapine atypical or
haloperidol or fluphenazine
Autonomic dysfunction 
hyperthermia and altered
consciousness
Give bromocriptine or dantrolene
Tolerance may occur in 2-3mo
Get up slowly
Monitor for these
Initially may see problems with tasks
that require focusing, motor function,
care/precision.
See how initially responds
With continued use may see with
newer agents better attention and
visual-motor skills.
Treatment algorithm

See DiPiro p.1224

Summary:
1) Non-clozapine atypical (just pick one)
2) Try another
3) Try another or try typical depot if noncompliant
4) Typical (unless Hx of typical AP failure)
5) Clozapine
6) Add typical/atypical/antidepressant/ECT
7) Combinations + ECT
Principles of Therapy

Consider type of SSx (+ve vs. –ve)

Titrate dose until satisfactory response or
unacceptable SE develop

Consider changing Tx if unsatisfactory response in 612wk

Po route preferred, but can use liquids or depots for
noncompliant patients
Onset and Duration

Antipsychotic effects usually manifest in a 1-2 weeks,
and full effect should be seen within 4-6 weeks

Treat for at least 1y post-remission (or 5y in the case
of multiple episodes)

Lifetime Tx considered for multiple episodes or very
violent/aggressive cases
When can we see benefits:
First improvement in (days-weeks):
agitation
insomnia
Later we see improvements in (weeks-months)
hallucinations
Thought Disorders(paranoia)
Confusion in thinking
Last we see improvement(negative symptoms)
(Several months)
- Social interaction, isolation, physical activity, school
participation and gradual reintegration into the community
(this requires the combo of medication
+psychorehabilitation)
Haloperidol(atypical)
Efficacy: Good for +ve, poor for –ve symptoms
1st line for acute, but given iv or im
comes in Depo form (given every 3-4 weeks)
Onset: 1-2 weeks
SEs: EPS
CNS: Sedation, dizziness
Heart: Decr BP, tachycardia
Endocrine: weight gain, increase prolactin, impaired
glucose tolerance and hypercholesterolemia.
DIS: meds metabolized by 2D6 and 3A4
Risperidone
Efficacy: good for both +ve and –ve sx
given BID
Also 1st line
SEs  less EPS, hypotention, constipation, dry mouth, weight gain,
some increase in prolactin
Cost: 100-150/month
Clozapine
Efficacy: good for both +ve and –ve.
: good for tx of acute
: last line  mostly in resistant cases
SEs: Aggranulocytosis (1%), rapid dec WBC
DIs: SSRI, Carbamazepine, Grape fruit juice
Cost: 250/month
Olanzapine
Efficacy: +ve and –ve sx
Tx resistant: Resperidone, Olanzapine and quetiapine
for acute sx
givein IM
SEs  more weight gain, increases blood sugar and cholesterol
DIs SSRI, Grapefruit juice
Cost 200-250/month  covered by ODB
3
Quetiapine
Efficacy: for both +ve and –ve sx
: its not really used for resistant cases
: more for acute
: given IM
SEs: sedation, dizziness, h/a, tachycardia, hypotention, less wt gain
DIs: SSRI
Cost; 100-150/month
Monitoring Principles

Pharmacist should follow up in ~3d and 2wk to assess
tolerance and efficacy

MD should follow up at ~2wk and 6wk to assess
acceptability of response

Pt should constantly monitor for SE of whatever Tx is
chosen and notify Phm/MD if any become unacceptable
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