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G o o d reasons t o be reluctant
Movements
Antipsychotics for t h e Reluctant
Primary Care Physician
disorders
Extrapyramidal symptoms
Tardive dyskinesias
Hyperproiactinemia
IVIetabolic side effects
A m y Burns,
M D
Providence Family M e d i c i n e Flesidency Consulting
Psychiatrist
obesity
diabetes
hyperlipidemia
A p p r o p r i a t e situations in w h i c h t o
consider prescribing an antipsychotic
• w h e n t h e r e is n o s p e c i a l i s t a v a i l a b l e
• W h e n y o u f e e l c o n f i d e n t in y o u r skills/know/ledge
base
• Taking over maintenance meds f r o m a
psychiatrist after t h e m e d s have been idealized
• Emergently, until t h e y can see a specialist:
- Acutely agitated patient
- Psychotic patient
- Manic patient
Dopamine pathways
- M e s o l i m b i c — d o p a m i n e hyperactivity in this
region t h o u g h t t o cause positive s y m p t o m s of
psychosis
- M e s o c o r t i c a l — d o p a m i n e hypo-activity in this
region t h o u g h t to give negative and cognitive
s y m p t o m s of psychosis
- T u b u l o i n f i d i b u l a r — 0 2 blockade in this p a t h w a y
gives hyperproiactinemia
- Nigrostriatal—D2 blockade in this p a t h w a y gives
extra-pyramidal symptoms
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Tubuloinfundibular Pathway
• D o p a m i n e continuously inhibits t h e release of
prolactin
• D 2 antagonists result in hyperproiactinemia
- Galactorrhea, breast development
- Infertility
- Osteoporosis
- Risperidone (Risperdal) a n d its m e t a b o l i t e ,
paliperidone (Invega) are i n f a m o u s for this
- T r e a t m e n t : c h a n g e a n t i p s y c h o t i c s t o o n e w i t h less D 2
a n t a g o n i s m , add Ability, add bromocriptine....
Extrapyramidal side effects
•
Dystonia
- I n t e r m i t t a n tcontractures of tongue, face, neck
a n d back, torticollis, retrocolllis, o c u l o g y r i c crisis
and e x t r e m e hyperextension. Rare laryngospasm
can be life t h r e a t e n i n g
- A c u t e dystonia have rapid o n s e t in t h e first five
days of t r e a t m e n t and highly disturbing
- Risk factors for acute dystonia: y o u n g age, m a l e ,
use of cocaine, history of acute dystonic reaction.
Extrapyramidal side effects
• Akathisia
- M o s t c o m m o n f o r m o f EPS
- M o t o r restlessness w i t h a compelling urge t o
m o v e a n d a n i n a b i l i t y t o sit still
- These patients do a lot of pacing
Akathisia could exacerbate agitation t h a t y o u had
intended to treat
Akathisia video o n Y o u T u b e : T o m S t u a r t (1)
Treatments for akathisia
Dystonia
• stop
t h e a g e n t o r low/er t h e d o s e w i t h close
monitoring for exacerbation of symptoms
• Add a benzodiazepine
BID
(2) L o r a z e p a m
• If a b o v e a r e n ' t e f f e c t i v e o r i n d i c a t e d
consider
O.Smg
could
- Betablocker (3-5) (Example: propranolol l O m g
BID-20mg TID)
- B e n z t r o p i n e ( C o g e n t i n ) (6) I m g B I D - 2 m g BID
• Treatment:
• B e n z t r o p i n e ( C o g e n t i n ) l - 2 m g BID,
• D i p h e n h y d r a m i n e ( B e n a d r y l ) 2 5 - 5 0 m g BID
• W h e n s e v e r e g i v e IV o r I M , if m i l d can g i v e l o w e r d o s e P O
• C h a n g e a n t i p s y c h o t i c t o o n e w i t h less p r o p e n s i t y f o r EPS
• A n t i c i p a t e , especially in y o u n g m e n by g i v i n g H a l d o l I M
with benztropine
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3/31/2014
Extra-pyramidal side effects
• Parkinsonism
- Masl^ed fades
- R e s t i n g t r e m o r (pill rolling)
- Cogwheel rigidity
- Shuffling gait
- Reduced a r m swing
-
Tardive Dyskinesia
• S u c k i n g , s m a c k i n g o f lips
• Choreoathetoid movements o f tongue,
extremities, o r truncal areas
• Facial g r i m a c i n g
• Lateral j a w m o v e m e n t s
Bradykinesia
• YouTube:
Tardive Dyskinesia
Video.avi
- YouTube search for: Parkinsonian Gait D e m o n s t r a t i o n
Parkinsonism Treatments
A I M S f o r m (10)
- Lower dose o fcausative agent
- Cogentin (benztropine) I m g BID
- Artane (trihexyphenidly) 5 m g TID
side effects: cognitive i m p a i r m e n t , d e l i r i u m ,
hyperthermia, dry m o u t h , blurred vision,
glaucoma, constipation, urinary retention
- S y m m e t r e l (amantadine) lOOmg BID-TID
Tardive Dyskinesia (TD)
• Higher incidence i nolder, first generation
antipsychotics w h e n used a thigh doses, b u t
also frequent w i t h the n e w atypical
antipsychotics.
• U p t o 5 % risk o f incidence per year o f
exposure, s y m p t o m s arise late i nt r e a t m e n t ,
after more than 6 months
• Screen w i t h a nA b n o r m a l Involuntary
M o v e m e n t S c a l e ( A I M S e x a m ) 6 - 1 2 m o n t h s (9)
W l i a t t o d o about Tardive Dyskinesia
• C h a n g e antipsychotic t o o n e w i t h less
propensity for T D such as
quetiapine(Seroquel) o r aripiprazole
• Lower the
(Abilify)
dose
• Add V i t a m i n B6 6 0 0 m g BID
|J Clin Psychiatry. 2 0 0 7 N o v ; 6 8 ( l l ) : 1 6 4 8 S4VlumtaB6lrcMinratfortwcHvcdvihlnMla:ar«ndornlz»idouble4>lfn(tplK«b^
nu<tv.)
• Discuss t h e situation w i t h t h e patient t o
d e c i d e o n a p l a n t h a t is r i g h t f o r t h e m .
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3/31/2014
W h a t to do w h e n you spot a growing
metabolic syndrome
M e t a b o l i c side effects
• A n u m b e r of the antipsychotic medications are
k n o w n t ocause weight gain, hyperlipidemia,
hyperglycemia and hypertension (11)
• Switch t oa different antipsychotic that has a
l o w e r liability for w e i g h t gain/dyslipidemia
• "Metabolic adverse effects have overtaken
neurological adverse effects as a m a j o r c o n c e r n i n
treating psychosis" (12)
• S h o r t e n e d life e x p e c t a n c y a m o n g c h r o n i c a l l y
m e n t a l l y ill p a t i e n t s a t t r i b u t e d p r i m a r i l y t o
physical health complications rather t h a n suicide
(13)
(14)
- For e x a m p l e change f r o m Zyprexa t o Abilify
- Gradual cross titration o v e r t h r e e w e e k s usually
protects patients against an exacerbation o f
psychosis.
- Monitor and document resolution of metabolic
problems
Treatment options for metabolic
s y n d r o m e in context of antipsychotic
Monitoring Guidelines
M o i t t t o r i i H i f o r i n e t a b o b c s i d e r f t e t t s o f a n t i p s y t i i o t u ; ctriH)«
1
A1
A
B
12
Wf«k«
•x
X
X
every
S
Quarterty
1
• Treat problems symptomatically
- Antihypertensives for hypertension
- Statins for dyslipidemia
- T r e a t diabetes
X
X
X
X
Monitoring challenges
• Difficult t o get fasting labs f r o m t h e s e patients
- In 2 0 1 0 A D A a d d e d H g A l c as a diagnostic t e s t f o r
diabetes
- S o m e clinicians are getting just t o t a l cholesterol and
HDL in o r d e r t o calculate N O N - H D L lipids w h e n t h e y
can't get a fasting sample.
Treatment options for metabolic
s y n d r o m e in c o n t e x t o f antipsychotic
• Diet m a n a g e m e n t and exercise can b e helpful
for some patients with
antipsychotic-induced
weight gain and mild o r m o d e r a t e
dyslipidemias (14, 15, 16)
• Responsibility o fm o n i t o r i n g and m a n a g e m e n t
• P M D v s Psychiatrist
• D e v e l o p i n g a s y s t e m t om a k e s u r e y o u r get t h i s
done.
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3/31/2014
Treatment options for metabolic
s y n d r o m e in context of antipsychotic
• Metformin 1000-2000
mg/day
• R a n d o m i z e d trials have show^n t h a t after 1 2 16 weeks of metformin treatment (concurrent
w i t h antipsychotic), patients have lost 5 0 % of
the weight gain induced by the
antipyschotic
treatment. (17-20)
John
2 3 year old m a l e b r o u g h t in by his f r i e n d s w i t h
c o m p l a i n t s o f n o t sleeping, w e i g h t loss, a n d
feeling convinced t h a t e v e r y o n e in S p o k a n e
hates him, hearing people m u m b l e under
t h e i r b r e a t h , " Y o u ' r e a n idiot" U r i n e d r u g
screen c o m e s back positive for m e t h . You are
u n c o m f o r t a b l e being in t h e r o o m w i t h h i m as
h e is s t a r i n g s u s p i c i o u s l y a t y o u .
W h i c h antipsychotics would you
H o w t o pick a n a n t i p s y c h o t i c ?
•
Efficacy
• Side effect profile
consider?
Mr. Gardner
• 4 5 year old Caucasian m a l e w i t h
Schizophrenia w h o has gained 7 5 pounds on
Zyprexa 2 0 m g CiHS a n d n o w has borderline
diabetes
- T r i a l of Abilify.
•
•
•
•
W e e k 1 : Abilify l O m g Q A M ; Zyprexa 2 0 m g QHS
W e e k 2: Abilify 2 0 m g Q A M ; Zyprexa l O m g QHS
W e e k 3: Abilify 3 0 m g Q A M ; Zyprexa 5 m g QHS
Thereafter: Abilify 3 0 m g Q A M ; no Zyprexa
- Add m e t f o r m i n ,m a n a g e diabetes
Mrs. Schollnneyer
• 5 2 year old f e m a l e b r o u g h t in by her
husband.
S h e s e e m s t o be h a v i n g t h e t i m e o f h e r life in
your office, very talkative, flirting w i t h you
hasn't felt t h e need t o sleep in a couple
days.
Her husband tells you t h a t she
$20K on lawn o r n a m e n t s yesterday.
and
of
spent
She
was
hospitalized for a similar episode in her 30's.
She isn't taking any medications currently.
5
References
•• 1 ) Y o u T u b e v i d e o o f A k a t h i s i a : T o m S t u a r t
• 2 ) L i m a A R , S o a r e s - W e i s e r K, B a c a l t c h u k J , B a r n e s T R . B e n z o d i a z e p i n e s for
neuroleptic-induced acute akathisia. Cochrane Database Sysl Rev 2002;
:CDQ01950.
• 3 ) I n w i n M , S u l l i v a n G , Van P u t t e n T. P r o p r a n o l o l a s a p r i m a r y t r e a t m e n t o f
n e u r o l e p t i c - i n d u c e d a k a t h i s i a . H i l l s i d e J Clin P s y c h i a t r y 1 9 8 8 ; 1 0 : 2 4 4 .
• 4 ) A d l e r L, D u n c a n E, A n s r i s t B . e t a l . E f f e c t s o f a s p e c i f i c b e t a 2 - r e c e p t o r b l o c k e r i n
neuroleptic-induced akathisia. Psychiatry Res 1 9 8 9 : 2 7 : 1 ,
• 5 ) K r a m e r M S , G o r k i n R, D i J o h n s o n C. T r e a t m e n t o f n e u r o l e p t i c - i n d u c e d a k a t h i s i a
w i t h p r o p r a n o i o i : a c o n t r o l l e d r e p l i c a t i o n s t u d y . H i l l s i d e J Clin P s y c h i a t r y 1 9 8 9 ;
•
6 ) A d l e r L A , P e s e l o w E, R o s e n t h a l M , A n g r i s t B. A c o n t r o l l e d c o m p a r i s o n o f t h e
effects o f propranolol, benztropine, a n d placebo o n akathisia: a n i n t e r i m analysis.
P s v c h o p h a r m a c o l Bull 1 9 9 3 ; 2 9 : 2 8 3 .
• 7)YouTube: Parkinsonian Gait Video
• 8 ) M a r d e r SR, Essock S M , M i l l e r AL, e t a l . Physical healtti m o n i t o r i n a o f p a t i e n t s
w i t h schizophrenia. A m J Psychiatry 2004; 161:1334.o.avi
References continued
9| Y o u T u b e ; T a i d H e D y s k i n e s i a V i d e o . a v i
l O l A I I V I S f o r m . R u i h J A J R - , H a n d b o o k o f P ^ h u l r k M e a s u i P i , A r n e r x a n PivchialckAsjoc>^>on,2000,166-16a
111 M a r d e r S , S l r o u p T S U p T o D a l e ' P h a r m a c o l h e r a w f u r S c h u o p h i e F i i d : Side ERecl M a n a g e m e m ' , Last
updatedApril4,2013.
1 2 ) C o h n , T o n y . ' ' M e t a b f J I c M o n r r o r i n g t o f Pilient5onAn(ipsvchoticM«)icaliom" Psych i a u i c T i m g i I > c e m b e t
2 0 U VolXXDC N o . 1 2 , p g 3 i - J S .
l-it B, J Psychialry. 2 0 n ; t 9 9 : 4 S 3 . l i S , ^ 4 1 - 1 4 2 .
14^ L i e b | e r m a n J A . S t r p u ^ S . ^ l g k F r o y J P j t ^ t f f e c t i w n e i - i o f a M i p s y c h o l i c d n i H s m patier.liwlthchron«:
I S j ^ G a n w I i K B ^ h a v i o r a l t h e r a p y f o i w c i n h t l o « in p a t i e n t s w i t h i c h i ; o p h r e n i 3 . ] C t i n P ! i v d i i a l r Y 2 O 0 7 ; 6 e S u p p I
16) D a u m r t G L
j^g'jg^^"^' ^'
^ ''^''avionil weinht-loii inicrvernioniii personswith ierioui mental