assessing & management of side effects: part 1 and managing side effects.pdf · potential side...

Assessing & Management of side effects: Part 1

medicationmanagement

What side effects of antipsychotic medication do you see in you clinical practice?

How do you routinely assess for side effects of medication?

Potential side effects Central nervous system Movement disorders [EPSEs] Thermoregulatory effects [NMS] Central anticholinergic toxicity Sedation Cardiovascular Hypotension Tachycardia EGC changes

Haematological Neutropenia Leukopenia Agranularcytosis Gastrointestinal effects Sialorrhoea Constipation Opthalmological Neuroendocrine Hyperprolactineamia Sexual dysfunction Weight gain Glucose and lipid metabolism Genitourinary [incontinence] Dermatological [rashes]

Mechanism of Action Dopamine hypothesis of schizophrenia

Schizophrenia is associated with impaired dopaminergic neurotransmission in the brain

Hyperactivity: Positive symptoms

Hypoactivity: Negative symptoms

Mesocortical pathway - Learning and memory

Mesolimbic pathway - Emotions

Nigrostriatal pathway - Movement regulation

Tuberoinfundibular pathway - Prolactin regulation

Stahl SM. Essential Psychopharmacology of antipsychotics and mood stabilizers. 1st ed. Cambridge: Cambridge University Press; 2002

Clozapine Olanzapine Haloperidol Risperidone

Hist. H1

α1-adren. α2-adren.

Musc 5-HT2C 5-HT2A D4 D2

Sertindole Quetiapine Ziprasidone Zotepine

D1 Broad receptor binding profile

Chlorpromazine

Data from Bymaster et al., 1996, unpublished observations; Schotte et al., 1996,

Increase in negative

symptoms

Mesocortical pathway

Stahl, Essential Psychopharmacology;Cambridge University Press 2000

EPSs Nigrostriatal pathway


Prolactin levels rise

Tuberoinfundibular pathway


drowsiness

decreased blood pressure

dizziness

1 INSERTED


constipation

LAXATIVE

blurred vision

dry mouth drowsiness

M1 INSERTED


H1 INSERTED

drowsiness

weight gain


5HT7

1

2 5HT2A

D2 risperidone


5HT7

5HT6

H1 1

2 5HT2A

D2 quetiapine


5HT7

5HT6

5HT3

5HT2C

5HT1A

M1 H1 1

2

D1

D3 D4

5HT2A

D2

clozapine

5HT6

5HT3

5HT2C

M1 H1 1

D1

D3 D4

5HT2A

D2 olanzapine


5HT1D SRI

NRI

5HT7

5HT2C

5HT1A

1

D3

5HT2A

D2 ziprasidone


Current practice Survey of 250 CPNs/Thorn graduates CPNs report that medication management is

part of their role Routinely monitor psychopathology; side effects

Very high priority for training Measures infrequently used (KGV 5%;

LUNSERS 25%) 25% ask about sexual dysfunction Thorn training improves reported practice

Gray R. et al (2001) JP&MHN, 7, 4, 12-18

Use of measures

0

10

20

30

40

50

60

LUNSERS

SIMPSON

AIMSOW

N

Perc

enta

ge

CPNsThorn graduates

General side effect assessment tools

LUNSERS Based on the UKU Self-report Symptom experienced in

the last month 51-items rated on a five

point scale Red herrings Sub-scales Some validity/reliability

data available

Advantages Easy to use Comprehensive Allows side effects to be

prioritised

Disadvantages Side effects will be missed Time consuming to score Dubious red herrings Some patients are unable

to complete

LUNSERS sub-scales Extrapyramidal symptoms Anticholinergic effects Other autonomic

Dizziness; feeling sick; palpitations; etc

Allergic reactions Psychic side effects

Sedation; tension; depression; etc

Hormonal side effects Miscellaneous Red herrings

Example items from the LUNSERS Each item is rated on a five point scale

Not at all; very little; a little; quite a lot; very much Rash Difficulty staying awake Runny nose Increased dreaming Headaches Dry mouth Swollen or tender chest

What are EPSEs?

Dystonia Signs & symptoms Muscle spasm in any part of the body. Trismus (contraction of

the masculatory muscles);Blepharospasm (sustained forceful eye closure); Facial grimacing; Oculogyric spasm (eyes rolling back) Tortocolis (head and neck twisted to the side); Retrocolis (head and neck forced back): laryngeal spasm Patient may be unable to speak or swallow

How common is it? Approx 10%. Associated with typicals. More common in young men, drug naïve, high potency meds

How long does it take to develop?

Minutes after administering IM, hours after oral (acute) months- years (tardive)

Assessment observation

Treatment Administration of anticholinergic meds Oral (patient may not be able to swallow) IM (response 20 minutes) IV ( response 5 minutes)

Pseudo-parkinsonism Signs & symptoms Motor symptoms: Rigidity (limbs resistive to passive

movements); tremor; postural abnormalities; Bradykinesia or akinesia (characterised by a reduction in spontaneous facial movements); decreased facial expression, flat monotone voice, decreased arm swing, inability to initiate movement Mental effects: Bradyphrenia (slow thinking), mental clouding salivation

How common is it? Approx 20% more common in elderly females, pre existing head injury, stroke


Days to weeks

Assessment Simpson & Angus EPSE rating scale. Observation. Patient report

Treatment Reduce dose Change to atypical Prescribe anticholinergic

Simpson-Angus Scale (SAS) Reference: Simpson GN and Angus JWS (1970) Acta Psych Scand,

212 (sup 44), 11-19 10 item measure for drug induced parkinsonism Facilitates standardised clinical assessment of

Rigidity, tremor and salivation Has validity Ten items rated on a five point scale (0=complete absence of the

condition, 4=presence of the condition in extreme form) 7/10 items measure rigidity

Shoulder shaking, arm dropping, and elbow and wrist rigidity Items from tremor and pooling of saliva in the mouth The global score in the summation of all the items divided by the

number of items Scores of up to 0.3 are considered within the normal range

Model for assessing side effects


LUNSERS+observation every six months

Management: consult Maudsley prescribing guidelines

Observe or pt reports stiffness: Simpson/Angus scale

Discussion with multi-disciplinary team

Feedback to the patient


Review and re assess

akathesia Signs & symptoms “Can’t sit still”; Subjective inner restless; foot stamping when

sitting down; rocking from foot to foot; pacing; mental unease, unrest or dysphoria

How common is it? Approx 25%


Hours to weeks

Assessment Barnes Akathisia Scale. Observation, patient report

Treatment Reduce dose Switch to atypical (clozapine, quetiapine) Antimuscarinic (benzatropine) Propranalol/diazepam/clonazepam

* Anticholinergics not useful for akathesia

Barnes akathesia rating scale (BAS or BARS) Reference

Barnes TRE (1989) Br J Psych 154, 672-676 Measures Objective features of motor restlessness Subjective complaints of restlessness

And associated distress Rated on a scale of 0-3

Operational definitions for each scale point Also a global severity rating on a six-point scale (0=absent, 5=severe) Diagnostic for mild moderate and severe akathisia Scale should be completed after observation of the patient for five

minutes




Observe or pt reports restlessness: Barnes akathisia scale





Tardive Dyskinesia Signs & symptoms Involuntary repetitive movements. Perioral movements (lip

smacking, sucking, darting, twisting tongue, chewing, lip puckering, puffing cheeks) facial and eye (grimacing, tics, blinking, brow arching) extremities and trunk (choriform movements) noisy breathing

How common is it? 5% after first year of exposure. More common in females, people with negative symptoms, co morbidity – dementia, mood disorder, diabetes). The longer the exposure the greater the risk


Months to years

Assessment Abnormal Involuntary movement Scale (AIMS) Observation, patient report

Treatment Stop anticholinergic medication. Switch to an atypical (clozapine, olanzapine, quetiapine). Tetrabenazine, clonazepam, vitamin E

Treatment outcome Parkinsonism and dystonia not associated

with a worse outcome Akathisia associated with a worse outcome

Suicide/violence

The course of EPS Fig 1. The time course of acute extrapyramidal

symptoms (Casey 1996)

0

5

10

15

20

25

30

7 14 30

Time (days)

EPS

(% o

f pat

ient

s)

AkathisiaDystoniaParkinsonism

Overview of the AIMS Introduced by US National Institute of Mental Health (NIMH)

- Guy (1976) Global instrument Divided into seven body regions Each item rated on a five point scale Additionally global ratings of

Overall severity Incapacitation Patient awareness

Dental status can be recorded Tremor is excluded Total score of 0-40 Detailed examination protocol

AIMS rating scale 0= None/normal 1= Minimal 2= Mild 3= Moderate 4= Severe








Observe unusual movements (not rhythmic): AIMS

Problem solving Formulation

Brief summary of assessments agreed by interviewer and patient

Problem identification (SM) Target (SMART)

Evidence based intervention Agree plan review

Single case study design

010203040506070

Baselin

e

Evaluati

on

Durabilit

y

LUNSERS Baseline assessment Formulation/problems

and targets Specific problems Design intervention Implement intervention Evaluation Durability

Rating scales General - LUNSERS Parkinsonism – Simpson-Angus

Akathisia – Barnes Akathisia Scale

Tardive Dyskinesia – Abnormal

Involuntary Movement Scale (AIMS)

Role play exercise In pairs: Practice: Introducing the LUNSERS to the patient Work through the assessment (guided completion

notion..) For any side effect identified rate the associated

distress… if you have time consider the grouping of SE’s experienced (how may their prescription be contributing to this?)

FEEDBACK TO GROUP

assessing & management of side effects: part 1 and managing side effects.pdf · potential side...

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