Successful Treatments for Early Psychosis: Consistent Antipsychotic

Use, Supportive Education/Employment, Cognitive Training, and Aerobic Exercise

Keith H. Nuechterlein, Ph.D.

Distinguished Professor UCLA Departments of Psychiatry and Psychology,

Semel Institute for Neuroscience & Human Behavior Director, UCLA Center for Neurocognition

and Emotion in Schizophrenia

Principles of Individual Placement and Support (IPS) Model

(Robert Drake & Deborah Becker) •  Work rehabilitation is integral

component of mental health treatment, not separate (job specialist w/in clinical team)

•  Goal is competitive employment in typical work settings

•  Emphasis is on obtaining jobs directly, rather than after lengthy pre-employment training

Principles of Individual Placement and Support (IPS) Model

(Robert Drake & Deborah Becker)

•  Continuous vocational rehabilitation services based in real work experiences

•  Follow-along support to sustain employment

•  Services based on consumers’ preferences and choices

•  Outreach into community

Percentage Returning to Competitive Work or Regular School (N = 69)

44

83 92

22

41

60

0 10 20 30 40 50 60 70 80 90

100

Baseline First 6 months 7 to 18 months

Perc

enta

ge o

f Gro

up

IPS-WFM

Separate VR

Adjusting for non-significant baseline differences, Wald x2 = 7.73, p < .0054 for 1st 6 mos.; Wald x2 = 4.73, p < .03 for next year

Total Number of Weeks in Competitive Work or Regular School Over 18 Months (N = 69)

0

10

20

30

40

50

Treatment Group

41.8

25.9

Tota

l Wee

ks a

t Wor

k or

Sc

hool

IPS-WFM

Separate VR

F = 8.43, p < .005

Premorbid Adjustment

Environmental Stress

Schizophrenic Negative Symptoms

Disorganized Symptoms Coping by the

Patient and Significant

Others

Attention and

Perceptual Processing

Neurocognitive Factors

Working Memory

Verbal Memory &

Processing Speed Learning of

Work Skills

Three cognitive factors account for 52% of variance in return to

work or school 9 months later in recent-onset schizophrenia

Return to Work or School

Nuechterlein et al., Schiz Bull, 2011

Medication Non-Adherence (from Peter Weiden)

•  50% of patients have significant non-adherence within one year of beginning treatment.

•  75% within two years. •  50% of the direct medical costs of

psychiatric hospitalization attributed to non-adherence.

UCLA Study Design •  12-month randomized controlled trial with first-

episode schizophrenia patients at the UCLA Aftercare Research Program

•  Patients received Individual Placement and Support, a form of supported education and supported employment, to provide a context of active work rehabilitation

•  After stabilization, patients were randomly

assigned to the medication condition and the psychosocial treatment condition (2 X 2 design)

UCLA First-Episode Randomized Controlled Trial of LAI vs. Oral Risperidone: Time to 1st Relapse

Kaplan Meier: χ2 (1) = 9.9, p = .002

Correlations between Antipsychotic Medication Adherence and Cognitive Gains in First-Episode Schizophrenia

(n = 57 at 6 months)

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

Overall Composite*

Working Memory*

Visual Lrng* Social Cognition

Cor

rela

tion

MCCB Gain in 6 Mo.

* p < .05; + p < .10

MCCB Overall Composite Score Covarying for Medication Adherence and Finishing

Full 1-Year Protocol (n = 46)

26

28

30

32

34

36

38

Baseline 12 Months

T Sc

ore

Cog Trng Healthy Beh Trng

Group X Time interaction, p = .025

Global Functioning Scale: Role Effect in 12 Months (n = 53)

3

3.5

4

4.5

5

5.5

6

Baseline 12 Months

Wor

k/Sc

hool

Fun

ctio

ning

Cog Trng Healthy Beh Trng

Group X Time interaction, p = .03, Cohen’s d = .62

Pilot Study of Adding Aerobic Exercise to Cognitive Training

•  Increasing evidence that aerobic exercise releases neurotrophic factors (e.g., brain-derived neurotrophic factor) that stimulate synaptic plasticity and enhance learning

•  We hypothesize that adding regular aerobic exercise to neuroplasticity-based cognitive training will increase cognitive gains

Cognitive Training & Exercise (CT&E) Might Enhance Impact on Global

Cognition (MCCB Overall Composite Score) (n = 14)

25

27

29

31

33

35

37

39

Baseline 10 Weeks

MC

CB

Ove

rall

Com

posi

te

T Sc

ore CT&E

CT

Estimated effect size, Cohen’s f = 0.48

Cognitive Training & Exercise (CT&E) Might Enhance Impact on Social

Cognition (n = 16)

30

32

34

36

38

40

42

44

Baseline 10 Weeks

MC

CB

Ove

rall

Com

posi

te T

Sco

re

CT&E CT

Estimated effect size, Cohen’s f = 0.65

Overall Conclusions •  Supported education/employment can

strikingly increase the proportion of patients who return to school or a job after an initial psychotic episode.

•  Long-acting injectable antipsychotic medication is a promising strategy for reducing relapses and improving cognition and everyday functioning in recent-onset schizophrenia.

Overall Conclusions •  Systematic cognitive training can impact

cognitive functioning and everyday functioning in the early course of schizophrenia.

•  Aerobic exercise and cognitive training might have synergistic effects on learning and overall cognitive functioning that enhance the impact of cognitive training alone.

Investigators Keith H. Nuechterlein, Ph.D. (P.I.) Kenneth Subotnik, Ph.D. Joseph Ventura, Ph.D. George Bartzokis, M.D. Sarah McEwen, Ph.D. Denise Gretchen-Doorly, Ph.D. Treating Psychiatrists Michael Gitlin, M.D. Laurie Casaus, M.D. John Luo, M.D. Michael Boucher, M.D. Case Managers/Therapists Nicole R. DeTore, M.A. Luana Turner, Psy.D. Yurika Sturdevant, Psy.D.

Statistical Consultation Gerhard S. Hellmann, Ph.D. Catherine Sugar, Ph.D. Sun Hwang, M.P.H.

Research Assistants Craig Childress, M.A. Kimberle Kelly, M.A. Robin Kite, M.A. Jacqueline Hayata, B.A. Lilian Medina, B.A. Rachel Wood, M.A. Arielle Ered, B.A. Research Center Administrator Fe Asuan, B.A.

UCLA Aftercare Research Program Staff