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Flashcards in Psychiatric disorders Deck (92):
1

What are the major psychiatric disorders we will be focusing on

Bipolar disorder
Schizophrenia

2

Life time prevalence of schizophrenia in the US

1%

3

Lifetime prevalence of suicide among schizophrenic patients

10%

4

Genetic risks of schizophrenia

3% if 2nd degree relative has it
10% if first degree relative has it
40% if both parents have it
Mono-zygotic twin risk 48%

5

Presentation of schizophrenia

NOT split personality
Chronic diagnosis of thought and affect

6

Acute schizophrenic psychotic episodes

Auditory hallucinations (especially voices)
Delusions (fixed false beliefs)
Ideas of influence (outside forces control their actions)

7

Positive schizophrenic symtoms

Most obvious/dramatic
Suspiciousness, unusual thought content, hallucinations, etc.

8

Negative schizophrenic sx

Functional impairments
Affect flattening, alogia, anhedonia

9

Cognitive schizophrenic sx

Impaired attention, working memory, executive function

10

Schizophrenia tx overview

Pharmacotherapy = mainstay

11

Nonpharmacological tx for schizophrenia

Psychosocial rehab = mainstay

12

What measurements should you be looking at when getting ready to start treatment for schizophrenia to establish a baseline?

**Doing so to rule out medical or substance abuse causes**
Vitals
EKG
CBC (fasting glucose)
Electrolytes
Lipid studies
LFTs
Thyroid functions
Renal fx
Urine drug screen

13

Original rationale for pharmacotherapy of schizophrenia

Acute psychotic episodes increase DA neurotransmission
Results in hypersensitivity to stimuli
(this is the original dopamine hypothesis)

14

Current rationale for pharmacotherapy of schizophrenia

Since inhibitory neurons are modulated by DA 5-HT, Ach and NE, these become targets for new Aps
Newer dysregulation hypothesis

15

Neurochemistry associated with schizophrenia

AP efficacy is proportional to D2 affinity
Non-D2 receptors are associated with SEs/AEs

16

First generation antipsychotics (FGAs)

DA antagonism = MOA
MOA characterizes "typical" anti-psychotics

17

Neuroleptic

Prominent D2-dopamine receptor antagonism
Typical anti psychotic
Contrasted with atypical mechanism of action of second generation anti-psychotics
Preferred term = First Generation Antipsychotic (FGA)

18

Examples of First Generation Antipsychotics

Fluphenazine 2-20 mg/day
Haloperidol 2-25 mg/day

19

Traditional Equivalent dose of FGAs

2 for both
allows for switching to equivalent dose of another FGA

20

Efficacy of FGA

Immediate D2 receptor blockaged
Theraputic effect develops over 6-8 weeks

21

Percentages of decreased presynaptic release of DA

>60% D2 blockade = clinical response
>70% D2 blockade = hyperprolactinemia
> 80% D2 blockage = increased risk of EPS

22

Adverse effects FGAs

Sedation
Dystonias/Parkinsonian movement disorders (EPS)
Anticholinergic effects
Orthostatic hypotension
Seizures
Hyperprolactinemia
Moderate weight gain
Prolonged QT interval (incidence of sudden death 0.015% only about twice that of the healthy population)

23

Anticholinergic effects of antipsychotic drugs

constipation
Urinary retention
blurry vision
tachycardia
dry eyes, mouth, and throat

24

Antipsychotics (APs) that increase QT interval

Thioridazine
Ziprasidone
Haloperidol

25

QT interval inn crease in milliseconds for Thioridazine

35.8

26

QT interval inn crease in milliseconds for Ziprasidone

20.6

27

QT interval inn crease in milliseconds for Haloperidol

4.7

28

Early neurological adverse effects of FGAs

Acute dystonia
Akathisia
Parkinsonism

29

Acute dystonia w/ FGAs

1-5 days = maximal risk
Treat with:
biphenhydramine IM
benztropin IM

30

Akathisia w/ FGAs

5-60 days
Usual treatment for agitation is more drugs -> not in this case

31

Parkinsonism w/ FGAs

5-30 days

32

Late neurological adverse effects of FGAs

Neuroleptic malignant syndrome (weeks; 10% mortality; antiparkinson agents not effective)
Tardive dyskinesia (after months - years of treatment)
Perioral tremor (rabbit sundrome; months -> years)

33

Neuroleptic malignant syndrome (NMS)

more common in pts on high potency FGAs, depot FGAs, deyhydrated, or exhausted pts

34

NMS Tx

DISCONTINUE antipsychotic
DA agonist bromocriptine reduces rigidity, fever, and CK in up to 94% of pts
Amantadine (another DA agonist) works up to 63% of the time

35

NMS follow up

Use only SGAs for rechallenge post-NMS

36

Early Second Generation Antipsychotic agents (SGAs)

Clozapine
Risperidone
Olanzapine
Quetiapine
Ziprasidone
Arpiprazole

37

Later SGA agents

Paliperidone
Iloperidone
Asenapine
Lurasidone

38

What additional therapeutic mechanisms do SGAs have

D1, D4 antagonism
NE, 5-HT (serotonin) antagonism

39

Why are SGAs atypical APs

Due to their non-D2 antagonism
Significantly less risk of extrapyramidal effects

40

Tradeoff of SGAs

Increased risk of metabolic effects like weight gain

41

Atypical APs

ability to produce antipsychotic responses with few or no acutely occurring extrapyramidal effects
Enhanced efficacy
Absence of tardive dyskinesia
Ex: clozapine (only SGA to fulfill all criteria)

42

SGA SE

Mod-severe weight gain
DM
Clozapine:
1) Seizures
2) Nocturnal salivation
3) Agranulocytosis
4) Myocarditis
5) Lens opacities

43

Clozapine

FDA approved despite risk of agranulocytosis (.39%)
Risk of death = 0.013%
Weekly CBCs for 6 months; then q2 weeks
Reserved for pts who fail other methods

44

Early SGAs

Virtually no extrapyramidal sx
Greatly reduced risk of tardive dyskinesia
Good for negative sx
Significantly less relapse than with FGAs (25% w/ Risperidone vs 40% with haloperidol)

45

Paliperidone (late SGA)

9-OH metabolite of risperidone

46

Iloperidne (late SGA)

Increased risk of orthostatic hypotension

47

Asenapine (late SGA)

ODT SL tabs
don't chew or swallow
increased risk of anaphylaxis and angioedema

48

Schizophrenia tx

3 phases:
1) Acute
2) Stabilization
3) Maintenance

49

Tx of first acute psychotic episode

First goal: calm agitated pt
Immediate treatment improves long term outcomes
Most psychiatrists will prescribe SGA (not clozapine; decreased anger and anxiety seen in 24-48 hours)

50

Suicide risk ______ as other sx improve

Increases!!!!!!!

51

When do we use clozapine

Lack of response with other SGAs
Intolerable SE from other APs

52

Role of FGAs

Typically not first line
May be used before a SGA if chronically ill pts have a previously satisfactory response

53

Stage 1 pharmacotherapeutic algorithm

Only for pts w/ first schizophrenic episode
SGAs = FIRST LINE

54

Stage 2
pharmacotherapeutic algorithm

Chronically ill pts recently started on APs
Or new onset pt with poor response to Stage 1
Monotherapy w/ FGA or SGA
Chose different AP than used in stage 1

55

Stage 3 pharmacotherapeutic algorithm

Switch to clozapine (monotherapy)
Increased efficacy for suicidal behavior
Consider earlier use in suicidal pts
Monitor CBC pts (Look for agranulocytosis)

56

Stage 4 pharmacotherapeutic algorithm

Continue clozapine
Add additional AP (combination therapy)

57

Stage 5 pharmacotherapeutic algorithm

Trial of monotherapy AP
Use FGA or SGA not previously used

58

Stage 6 pharmacotherapeutic algorithm

Consider combination therapy
When switching APs -> overlap 2nd agent for 1-2 weeks
Taper and DC first agent (taper clozapine SLOWLY)

59

Combination treatment of schizophrenia

Using 2 APs simultaneously

60

Augmentation treatment of schizophrenia

Addition of non-AP drug to an AP
Use only in inadequately responding pts
Augmentation agents are rarely effective for schizophrenia used alone
Responders will usually improve rapidly
If no sx improvement -> DC augmentation agent

61

Augmentation Agents

Mood stabelizers
SSRIS
Beta blockers

62

Mood stabilizers as augmentation agent

Lithium
Valproic acid
Carbamazepine

63

Beta blockers as augmentation agents

Antiaggressive effect
Propranolol
Pindolol
Nadolol

64

Combination of therapy (step 4-6)

Multiple MOAs
Combos should be time limited (12 weeks)
If no improvement -> taper one and discontinue
Series of monotherapies preferred over AP combination

65

Maintenance tx of schizophrenia

1st presentation may respond sooner
Meds may reduce sx -> None are curative
All sx may not abate
Prevents relapse (18-32% on drugs vs. 60-80% on placebo)
Continue at least 12 months past remission

66

Long acting depot injectable APs

Recommended in unreliable pts
Not 1st line
Look for SE as a cause for nonadherence

67

Depot APs

Haloperidol decanoate (FGA)
Fluphenazine decanoate (FGA)
Risperidone microspheres (SGA)

68

Haldol lactate vs haldol decanoate

immediate vs sustained release

69

Haloperidol decanoate

Use 10-15xs the oral daily dose
Round dose up to nearest 50 mg
Give dose via deep IM (not IV) injection once a month
Overlap with PO haloperidol for first month

70

Fluphenazine decanoate

Use 1.2 times oral daily dose
Use 1.6 times PO dose for more acutely ill pts
Round up dose to nearest 12.5 mg interval
Overlap w/ PO fluphenazine for 1 week

71

Risperidone micropsheres

Only SGA depot agent; needs reconstitution
Optimum dose is 25-50 mg
Higher doses have no more benefit, but more EPS

72

Bipolar disorder

1 disorder: mania
2 disorder: hypomania
Must rule out amphetamine use and pheochromocytoma
Most distinctive syndromes in psychiatry

73

What did bipolar disorder used to be called

Manic depression

74

Bipolar disorder (BP) characterizations

Elevated mood
Overactivity
Lack of need for sleep
Increased optimism

75

Unique hallmark of bipolar disorder

Mania

76

BP mania

Different from usual behavior
Single episode significant for diagnosis
Types: one, alternating, every few year episodes

77

Classic bipolar disorder

Bipolar 1
manic phase-usually requires hospitalization

78

Major depression + hypomania

bipolar 2

79

Rapid cyclers and BP disorder

>4 manic or depressive cycles per year

80

Genetics of BP disorder

50% of pts have family hx of BP disorder
Risk -> 10% in siblings of affected parients

81

Acute mania tx

Medical emergency
Marriage, job, and life of pt at risk
AP drugs = effective in acute mania
Rapid onset may be lifesaving in violent pts
Newere atypical AP (SGAs) are they effective in complaining pts

82

More tx for acute mania

Lithium
Valproic acid
Carbamazepine

83

DX for bipolar depression

Depressive episodes respond to: SSRIs, TCAs, MAOIS
Note: antidepressants may induce switch from depression to mania
Dont use AD in pts w/ hx of dangerous mania episodes

84

Mood stabilizers:Lithium

Classic
Good for: mania, bipolar disorder; bipolar deressin

85

Lithium therapeutic index

Therapuetic (acute mania) =0.6-1.2%
Tremor
Seizures/sudden death >2.5 mEq/L

86

Tx of bipolar depression

Depressive episodes need a response
will give SSRIs then,
Tricyclic antidepressants (TCAs)
Monoamine oxidasing inhibitors

87

Caution with use of antidepressants with BP disorder

Induce switch from depression to mania
Don't use w/ h/o mania episodes

88

Lithium for BP disorder

Classic mood stabilizer
Good for mania, bipolar disorder, and bipolar depression (last 2 = prophylactically)

89

Narrow therapeutic index of Lithium

Acute mania: 0.6-1.2 mEq/L
Tremor: 1.5-2 mEq/L
Seizures/death: >2,5 mEq/L

90

Remember w/ lithium

Draw blood levels twice/week until stable
Collect trough samples just prior to next dose

91

Cabamazepine

Anticonvulsant found useful in the 80s
.5 of all doses were for bipolar illness
Weekly dosing

92

Valproic acid

Recent study found Li prophylaxis much more effective than valproate for suicide prevention (JAMA 2003; 290(11): 1467-73)