Treatment Principles Schizophrenia - PowerPoint Presentation

Slide1

Treatment Principles

SchizophreniaSlide2

Treatment should be optimized for each individual in order to improve the outcome

Tandon

R et al.

J Psychiatr Pract. 2006;12(6):348–363.

Treatment and other services

Reduces disease burden

Rehabilitation (enhance adaptive skills)Social skills training

Supports (environmental changes)

Supported housingSupported employment

Treatment (reduce symptoms and prevent relapse)

MedicationsPsychosocial interventions (e.g. cognitive behavioral therapy)

Costs and unintended adverse consequences

Side effectsDiscrimination

Adds to treatment burden

RECOVERY

Health and wellnessVocational and/or educational functioningIndependent livingBetter physical healthInstrumental competenceSocial integrationImproved quality of life

Direct and indirect costs

Related health risks Slide3

Psychosocial interventions should be tailored to the goals, needs, abilities and circumstances of individuals

Canadian Psychiatric Association.

Can J Psychiatry

. 2005;50(13

Suppl

1):7S–57S. [CPA Guidelines].

Patient

Vocational training and support

Integrated substance use programme

Psychoeducation

Family

psychoeducation

Peer support, self-help and recovery

Cognitive behavioral therapy (CBT)

Social skills training

Ability and interest in workingSubstance use issues

Medication treatment adherence and relapse prevention

- Family members available

- Ongoing treatment, monitoring of recovery, and support

Consumer involvement (empowerment) in setting rehabilitation goals

Social interaction skills

- Dysphoria and/or depression

- Stress and relapse prevention

Patient needs help with:

Patient has:Slide4

Continuous maintenance treatment may decrease deterioration in symptoms during the second year following diagnosis

*Increase from baseline in the sum of

PANSS

positive and negative scores ≥25% or ≥10 points (if baseline value ≤40) or a CGI-C score ≥6.

CGI-C=Clinical Global Impression-Change scale; PANSS=Positive and Negative Syndrome ScaleGaebel W, et al. J Clin Psychiatry. 2011;72(2):205–218.

Maintenance treatment is more effective than targeted intermittent treatment in preventing relapseSurvival analysis for clinical deterioration* for patients receiving maintenance antipsychotic treatment versus intermittent treatment: Slide5

Only a small proportion of patients with schizophrenia achieve recovery

CGI-

SCH

=Clinical Global Impression-Schizophrenia scale. *Defined as <4 in the CGI-

SCH positive, negative, cognitive, and overall severity score, plus no inpatient admission for ≥24 months. †Defined as ≥70 on the EuroQoL5 dimensions visual analogue scale (EQ-5D VAS) for ≥24 months. ‡Defined as employed/student, plus independent living, plus active social interactions for ≥24 months.

Novick D, et al. Schizophr Res. 2009;108(1–3):223–230.

Employment, independent

living, social activity

, and medication adherence were important predictors of recovery

In a 3-year observational study, adults with schizophrenia (N=6642) achieved:Slide6

How do medication side effects exacerbate functional impairment?Slide7

Take home points

Treatment side effects (such as EPS, activating, sedating, sexual/endocrine, cardiovascular or metabolic side effects) can impose a significant burden on patients

, with activating and sedating side effects among the most ‘bothersome’

Antipsychotic-induced sedation may impair functional capacity and quality of life, and impact caregiver burdenActivating side effects (i.e., akathisia, anxiety, insomnia, agitation, restlessness) may also may impair functional capacity and quality of life, and impact caregiver burdenSlide8

Side effects of treatments for schizophrenia can impose a significant burden on patients

1. Morgan VA, et al

.

Aust N Z J Psychiatry. 2012;46(8):735

52. 2. Awad AG , et al. Acta Psychiatr Scand Suppl. 1994;380:27–32. 3. Barnes TR, et al. J Psychopharmacol. 2011;25(5):567–6203.

77%

61%

30%

reported medication side

effects

1reported

impairment intheir daily life as a result of medication

side effects1reported moderate or severe impairment1

Side effects impair

ability to interact with others, reducing quality of life

2 If not addressed, antipsychotic side effects can cause long-term distress and contribute to chronic health complications3A

small shift in functional status may have marked effects on an individual’s quality of life

2

In a study of 1,825 participants with psychosis: Slide9

Side effects can be classified into different groups

1.

Jibson

MD. Second-generation antipsychotic medications: pharmacology, administration, and comparative side effects. In:

UpToDate, Stephen Marder (Ed), UpToDate, Waltham, MA. Accessed March 13, 2015. 2. Lehman AF, et al. [APA Practice Guidelines] 2010. 3. Lieberman JA, et al.

N Engl J Med. 2005;353(12):1209–23. 4. Kane JM, et al. Schizophr Res

. 2016 pii: S0920-9964(16)30162–1. 5. Cheng-Shannon J et al. J Child Adolesc Psychopharmacol

. 2004;14(3):372-94

MetabolicHyperglycaemia

Weight gain

HyperlipidaemiaDiabetes mellitus

Metabolic syndrome

Sedating

Somnolence Hypersomnia

Sedation

CardiovascularQT interval prolongationCardiac arrhythmias

Sexual / endocrine

Sexual dysfunction

Hyperprolactinemia

Extrapyramidal symptoms

Dyskinesia

Dystonia

Parkinsonism

Activating

Akathisia

Agitation

Insomnia

Anxiety

Restlessness

Antipsychotic-

induced side

effects

1

–4

FatigueSlide10

There are multiple clinical benefits of a low risk of extrapyramidal symptoms

Tandon

R,

Jibson

MD.

Ann Clin Psychiatry. 2002;14(2):123–9.

Enhanced

compliance

d

Lower tardive

dyskinesia riskb

Fewer motor

side effectsa

Less dysphoriac

Less impaired

cognitionbReduced negative symptomsb

Reduced extrapyramidal symptoms

Strength of evidence:

a

very

strong, almost certain;

b

moderately

strong, probable;

c

mild

to moderate, possible;

d

some

suggestion, little or no hard data.

Note:

all antipsychotic drugs carry a significant risk for extrapyramidal symptoms for which active management is recommended. While all of the drugs in the class have been shown to contribute to the these side effects, each drug has its own specific risk profile.Slide11

Akathisia is associated with emotional symptoms and cognitive impairment

1. Hofer A, et al.

J

Clin Psychiatry. 2004;65(7):932–9. 2. Kim JH, Byun HJ. J

Clin Pharm Ther. 2007;32:461–467. 3. Kim et al. Compr Psychiatry. 2002;43(6):456–462.

Emotional symptoms

Cognitive impairment

Depression

3

Anxiety

2

Somatization

3

Obsessive–

compulsive3

Paranoid ideation3Reduced self-esteem1

Severe subjective

distress

3

Mental

control

3

Associate

learning

3

Discrimination

2

Perception

2

Coping

responses

2

Selective

attention

2Slide12

Some antipsychotics are associated with high rates of sedating side effects, which can worsen outcomes

1.

Loebel

AD et al. CNS Spectr

2014;19(2):197–205. 2. DiBonaventura M et al. BMC Psychiatry 2012;12:20. 3. Said Q et al. Pharmacoepidemiol Drug Saf 2008;17(4):354–364. 4. Seeman MV. Psychiatr Q

2012;83(1):83–89; 5. Lindberg N et al. Int Clin Psychopharmacol 2002;17(4):177–184. 6. Miller DD. Curr Psychiatr. 2007;1;6(8):38. 7. Miller DD, et al. Prim Care Companion J

Clin Psychiatry. 2004; 6(suppl 2): 3–7.

Medication non-

adherence2

Concerns over the safety of dependants,

4 particularly as women are more sensitive to sedative effects

5

Risk of unintentional injury3

Reduced cognitive performance and functional capacity

1

For agitated patients, sedating side effects and true antipsychotic effects are sometimes incorrectly thought to be the same

6

Sedation may be considered necessary for controlling positive symptoms; however, selecting a less sedating antipsychotic for patients who experience excessive sleeping can improve outcomes

7

Antipsychotic-induced sedating side effects have been associated with:Slide13

Sedation can have a severe impact on many aspects of patient life

1. Miller DD.

Curr

Psychiatr. 2007;1;6(8):38. 2. Kane JM, Sharif ZA. J

Clin Psychiatry. 2008;69(suppl 1):18–31. 3. Lehman AF, et al. [APA Practice Guidelines] 2010. 4. Loebel AD, et al. CNS Spectr. 2014;19(2):197–205. 5. Millier A, et al. J Med Econ. 2014;17(12):853–61. 6. Said Q, et al. Pharmacoepidemiol Drug

Saf. 2008;17(4):354–64. 7. DiBonaventura M, et al. BMC Psychiatry. 2012;12:20.

Long-term sedation may prevent patients from gaining improvement from psychosocial training, psychiatric rehabilitation and other treatments1

Persistent sedation can interfere with social, academic, recreational and vocational functioning, and with quality of life, often leading to treatment dissatisfaction

2–6 Sedation/cognition side effects (e.g., sedation, difficulty thinking/ concentrating, sleepiness, dizziness) are associated with medication non-

adherence7Slide14

Sedation impacts both patient functioning and caregiver burden

Kane JM, Sharif

ZA

. J Clin Psychiatry. 2008;69)s Suppl. 1):18–31.

Persistent sedation

or somnolence

Impacts on patient’s quality of life

Functional impairments in vocational, academic, social and recreational activities

Dissatisfaction with medication

Discontinues

treatment/becomes non-adherent

Constantly feel tired

No energy

Cannot think clearly

They do not want to get out of bed or participate in activities

PatientCaregiver

Effects of patient sedation can

increase

caregiver

burden

Patients may also have impaired

cognitive

and

motor

performance and

increased risk of injury Slide15

Activating***

†

Sedating*

†

Prolactin/endocrine*

Metabolic**

GI

Activating and sedating effects are among the most ‘bothersome’ antipsychotic side effects

*p<0.05,

**p<0.01, ***p<0.001

for the association with a lower likelihood of adherence;

†

study authors grouped activating side effects under the category ‘EPS/agitation’ and sedating side effects under the category 'sedation/cognition’.

EPS=extrapyramidal symptoms;

GI=gastrointestinal.

DiBonaventura

M, et al.

BMC Psychiatry

. 2012;12:20.

86.2% of patients with schizophrenia reported the presence of any medication

side effect in this cross-sectional study (N=876)Slide16

Gastrointestinal side-effects can occur with antipsychotics

Dyspepsia

Vomiting

NauseaEsophageal

dysmotility HypersalivationDry mouthConstipation

1. MHRA Antipsychotics learning module 2015. Available at http://www.mhra.gov.uk/antipsychotics-learning-module/con155606?useSecondary=&showpage=8 Last accessed July 2016. 2. De Hert M et al. BMC Gastroenterol. 2011:8;11:17.

In a retrospective study of 273 patients with schizophrenia, over a period of 22 months:2

36.3% had at least 1 pharmacological intervention for constipation

Gastrointestinal side-effects associated with antipsychotics

1 Slide17

Are medication side effects a necessary compromise for continued symptom control?Slide18

Take home points

A key challenge for physicians is to choose an antipsychotic that effectively controls symptoms, while minimizing side effects

The limitations of current treatments can lead to a frustrating experience for everyone impacted

Treatment of schizophrenia needs a rational approach with minimal tolerability issues to optimize patient functioning Slide19

Selecting suitable treatments for schizophrenia can pose a dilemma for psychiatrists

An ‘ideal’ medication is one that

can:

2

treat psychosis

lead to symptom resolution

lead to remission overcome treatment resistanceeffectively prevent against relapsehave a benign side-effect profile

(with minimal sedation and akathisia)have efficacy for symptoms of anxiety and depression1. Kane JM, et al. Dialogues

Clin Neurosci. 2010;12(3):345–357. 2. Correll CU. J Clin Psychiatry. 2011;72(suppl. 1):9–13. 3. Abidi S, et al. Can J Psychiatry. 2003;48(11):749‒755. 4. Leucht S, et al

Lancet. 2013;382(9896):951‒962. 5. Ucok et al. World Psychiatry. 2008;7(1):58‒62. 6. Barnes TR, et al. J Psychopharmacol

. 2011;25(2):567‒620.In selecting treatments for schizophrenia, physicians consider variables related to the:1,2

Patient

Illness

Medication

Environment

The long-term nature of side effects, including

metabolic

,

endocrine

and

cardiac

complications, can pose a dilemma for physicians in providing

effective

treatment

while

avoiding side

effects

3

Physicians have to consider how side effects interact with the patient’s health and lifestyle

(e.g.,

age

,

weight

,

cardiovascular

health, co-prescribed

medications

,

previously experienced

side effects)

4–6 Slide20

Ongoing collaboration with patient in decision-

making

1

Careful assessment of possible adverse effects of

treatment

1,3

Protocols for health monitoring

1Guidelines for good practice are measurement-based and individualized 1. Canadian Psychiatric Association.

Can J Psychiatry. 2005;50(13;s uppl 1):7S–57S. [CPA Guidelines]. 2. Lehman AF, et al. [APA Practice Guidelines] 2010. 3. Hasan A, et al. World J Biol Psychiatry. 2013;14(1):2–44 [WFSBP guidelines]. Ongoing, careful monitoring is critical

1

Reliable and repeated assessment of the efficacy of treatment using defined treatment targets1,2

Using standard rating scales like BPRS and PANSS will facilitate this goal

Standard protocols should be customized in response to individual vulnerabilities/needs and specific agent1Slide21

Shared decision-making and patient centered

care lead

to better

health outcomes

When patients are involved in decisions about health and care, the decisions are better, health and health outcomes improve, and resources are allocated more efficiently11. Foot C et al. The Kings Fund, 2014; 2. Coulter & Collins. The King’s Fund, 2011

A central part of shared decision-making is the recognition that patients and clinicians bring different, but equally important, knowledge and expertise to the process:1,2

Shared decision-making is a process in which clinicians and patients work together to make decisions about care and treatment based on both clinical evidence and the patient’s informed preferences1

Clinician's expertise

Diagnosis Disease etiology Prognosis

Treatment options

Outcome probabilities Patient’s

expertise

Experience of illnessSocial circumstances

Values

Preferences Attitude to riskSlide22

Efficacy for positive and negative symptoms are higher priorities than tolerability for physicians when choosing a treatment

Lecrubier

Y, et al.

Eur

Psychiatry. 2007;22(6):371–379.

Percentage of patients (n=6,523)Most common reasons for selecting an antipsychotic reported by 872 European and US physicians Slide23

Treatment of schizophrenia needs a rational approach with minimal tolerability issues to optimize patient functioning

1. Lehman AF, et al. [APA Practice Guidelines] 2010. 2.

Kuipers

E, et al. NICE Guideline. 2014

Antipsychotics that

minimize EPS, cardiovascular risk, and activating and sedating adverse effects may optimize the physical

health and social functioning of patients with schizophrenia

APA guidelines recommend choosing a medication that offers

good clinical response without intolerable side effects1

NICE guidelines recommend regular monitoring of side effects based on the side-effect profile of the prescribed

antipsychotic2Patients who experience

serious side effects may decide that the adverse effects outweigh the benefits of medication

1Slide24

Medication side effects can impair workplace performance and act as a barrier to entering or returning to work

1. Novak L,

Švab

V.

Psychiatr Danub. 2009;21(1):99–102. 2. Steadman K, et al. Working with Schizophrenia: Employment, recovery and inclusion in Germany. The Work Foundation. 2015.

In a focus group of patients with schizophrenia, stigma of side effects was most felt in employment and occupation and had led to some reducing their dose or skipping regular medication

1*

‘Lazy’

‘Pretending’‘Addiction problems’

Flight of ideas

Lack of concentration

Tiredness

Muscle rigidity and clumsiness

Ridicule

The onset of schizophrenia during the

teens and early twenties can interrupt:EducationEarly careersTransition to independent livingEmployers and colleagues may be wary

of working with someone with schizophrenia due to negative

misconceptions of their ability and/or nature

Treatment side effects, symptoms and risk of relapse may make entering or returning to work difficult

2

Consequence of schizophrenia

Perception by othersSlide25

Negative feelings towards medication are associated with lower scores in both affect and self-esteem

Hofer A, et al.

J

Clin Psychiatry

. 2004;65(7):932–939.

Lancashire QoL

subscaleIndependent variableDirection of effect

Partial correlation*P-value

General life satisfactionWork↑

0.330.005

Cognitive symptoms (PANSS)↑

0.41<0.001

Depression/anxiety (PANSS)↓

–0.230.045

Parkinsonism

↓–0.270.021AffectWork

↑

0.42

<0.001

Negative feelings and effects (DAI)

↓

–0.33

0.003

Self-esteem

Depression/anxiety (

PANSS

)

↓

–0.34

0.003

Parkinsonism

↓

–0.36

<0.001

Negative feelings and

effects (DAI)

↓

–0.25

0.026

Multiple linear regression analysis of various factors on quality of life

*

Partial correlation of independent variable with the dependent (quality of life) variable, adjusting for other independent variables in the model. DAI, Drug Attitude Inventory; PANSS, Positive and Negative Syndrome Scale, QOL, quality of life; ↑ higher values of independent variable were associated with higher

QoL

scores; ↓ higher values of independent variable were associated with lower

QoL

scoresSlide26

Side effects of antipsychotic medications are

significantly associated with lower adherence

Odds ratios based on multivariable logistic regression with adherence as dependent variable. Adherence defined as a score of zero on the

Morisky Medication. Adherence Scale. 95% Confidence Intervals are indicated. †study authors grouped activating side effects under the category ‘EPS/agitation’ and sedating side effects under the category 'sedation/cognition’. DiBonaventura M, et al. BMC Psychiatry

. 2012;12:20.

Adjusted odds ratios for the impact of each side effect on complete adherence (N=876):

Restlessness/feeling jittery

Insomnia (difficulty sleeping)

Tremors

Agitation

Difficulty thinking or concentrating

Sleepiness

Sedation

Dizziness

Decreased interest in sex

Sexual dysfunction

Difficult or painful menstrual periods

Male breast enlargement or secretions

Weight gain

Increase in blood glucose level

Nausea/vomiting

Constipation

Activating†

Sedating

†

Prolactin/

endocrine

Metabolic

GI

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50Slide27

Emotional and practical burdens of schizophrenia on families are intertwined

Tsang

HW

, et al. Int J

Rehabil Res. 2003;26(2):123–130.

The subjective burden of social stigma for relatives of patients includes feelings of frustration, anxiety, low self-esteem and helplessness

E.g., financial burden

E.g., frustration

E.g., anxiety

Further attempts to e.g., find employment are more difficult

Difficulties meeting practical demands

Patient symptoms aggravated

Negative emotional responseSlide28

Take home points

A key challenge for physicians is to choose an antipsychotic that effectively controls symptoms, while minimizing side effects

The limitations of current treatments can lead to a frustrating experience for everyone impacted

Treatment of schizophrenia needs a rational approach with minimal tolerability issues to optimize patient functioning Slide29

Can advances in the understanding of receptor

pharmacology avoid the current treatment compromises? Slide30

Take home points

Antipsychotics have a rich receptor pharmacology which contributes to efficacy as well as side effects

Level of sedation is affected by histamine H1 affinity and the amount of drug reaching the H1 receptors

Partial agonists often avoid the development of adverse effects associated with overstimulation of receptors by full agonistsSlide31

Antipsychotics have a rich receptor pharmacology, which contributes to efficacy as well as side effects

Receptor

1

Effects of blockade

D

2

Antipsychotic,

antimanic

, antiagression

EPS/akathisia, tardive dyskinesia, increased prolactin

ɑ

1

-adrenergic (peripheral)

Postural hypotension, dizziness, syncope

ɑ

2-adrenergic(peripheral)Antidepressant, increased alertness

Increased blood pressure

H

1

Anxiolytic, sleep induction, anti-EPS/akathisia

Sedation, weight gain

M

1

(central)

Memory, cognition, anti-EPS/akathisia

Dry mouth

M

2

-4

(peripheral)

Blurred vision, constipation, urinary retention, tachycardia, hypertension

5-

HT

1A

(partial

agonism

)

Anxiolytic, antidepressant, anti-EPS/akathisia

5-

HT

2A

Anti-EPS/akathisia, antipsychotic

5-

HT

2C

Increased appetite/weight(?)

1.

Correll

CU.

Eur

Psychiatry.

2010;25(

suppl

2):S12–S21. 2. Stahl SM.

CNS

Spectr

. 2013;18(6):285‒288. 3.

Leucht

S et al.

Lancet

. 2013;382(9896):951‒962.

Antipsychotics with a

stronger relative affinity

for a particular receptor system

over the

D

2

receptor

are likely to induce

side effects

associated with the blockade of that receptor

system

1

Newer antipsychotics, which act as

partial agonists at the

D

2

receptor

, regulate dopamine activity and

reduce the risk

of

extrapyramidal symptoms

and

prolactin

elevation

2,3

Efficacy

Side effectsSlide32

A key factor for

D2

partial

agonism is the determination of the optimal level of intrinsic activity at the receptor Citrome L, et al.

Expert Rev Neurother 2015;15(10):1219–1229.

Too high:1

Activity closer to that of an agonistPotential lack of antipsychotic effect

Side effects such as nausea, vomiting, insomnia and motor effects

Too low:1 Activity closer to that of an antagonist

Potential increased risk of extrapyramidal symptoms and raised prolactin levels

Advances in the understanding of receptor pharmacology support the development of new agents that offer efficacy with improved tolerability profiles Slide33

Take home points

Antipsychotics have a rich receptor pharmacology which contributes to efficacy as well as side effects

Level of sedation is affected by histamine H1 affinity and the amount of drug reaching the H1 receptors

Partial agonists often avoid the development of adverse effects associated with overstimulation of receptors by full agonistsSlide34

SummarySlide35

Summary

For references please see slide notes

Optimal

patient functioning

and

improved quality of life

are important treatment goals at

all stages

of schizophrenia management

Functional impairment may result from an

insufficient treatment effect

Sedating or activating side effects can prevent patients from functioning at their optimal level and negatively impact their quality of life

The side effects associated with current treatments are often seen as a necessary compromise

for continued symptom control

The limitations of current treatments, especially the

side-effect burden, and the impact on different domains of functioning can be frustrating for everyone and decrease quality of life Agents with different pharmacological profiles may avoid the current treatment compromises, and help patients with schizophrenia to function at their optimal level