Phase II, double-blind, randomised,

placebocontrolled study of adjunctive taurine

in firstepisode psychosis
Colin ODonnell1, Kelly Allott2,3, Hok Pan Yuen2,3 and Patrick McGorry2,3
Department of Psychiatry, Donegal Mental Health Service, Letterkenny, County Donegal, Republic of Ireland
2
Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia
3
Centre for Youth Mental Health, The University of Melbourne, Australia
1

Background
Symptomatic remission, including negative and cognitive symptoms, remain
suboptimal for many patients with psychosis.
Taurine is an inhibitory neuromodulatory amino-acid in the CNS and
activates GABA- and glycine-insensitive chloride channel and inhibits the
NMDA receptor. Taurine also functions as a neuroprotective agent and has a
role in neural development and neurogenesis.

Aim
To determine the efficacy of adjunctive taurine in improving
symptomatology and cognition among patients with a DSM-IV firstepisode
psychotic disorder.

Table 2. Demographic and clinical characteristics of the two treatment groups at baseline

Taurine
(n=47)

11 (28.2)

-2

Age, mean SD

21.42.3

21.32.3

-3

Years completed education, mean SD

12.12.2

12.62.3

-4

Race: non-white, n (%)

14 (29.8)

14 (35.9)

-5

Living with caregiver, n (%)

27 (57.4)

26 (66.7)

-6

Premorbid IQ, mean SD

Clinical Characteristics
Family history of psychiatric illness, n (%)

100.310.1

99.712.0

-7

34 (72.3)

26 (66.7)

Family of history of schizophrenia, n (%)

7 (14.9)

11 (28.2)

Duration of treatment (days), mean SD

296.5 221.2 274.8 261.5

300

Design

7 (14.9)

6 (15.4)

Schizoaffective disorder

3 (6.4)

4 (10.3)

Phase II, multi-centre, parallel, double-blind, randomised, placebo-controlled

trial (conducted between January 2007 and May 2009).

Mood disorder with psychotic features

1 (2.1)

0 (0.0)

Delusional disorder

2 (4.3)

1 (2.6)

Sample

Psychosis not otherwise specified

13 (27.7)

5 (12.8)

Treatment conditions and

assessment points
Participants were randomised to receive adjuvant taurine 4g or placebo for
12 weeks, plus low-dose antipsychotic medication as prescribed by their
treating doctor (no patient was prescribed a typical antipsychotic).
Assessments were conducted at baseline, 6-weeks and 12-weeks (Table 1).
Table 1. Outcome variables and measures used in the study

Outcome Variables

Assessment Instrument

Overall
symptomatology

Brief Psychiatric Rating Scale (BPRS) total

Cognition

MATRICS Consensus Cognitive Battery (MCCB)

composite

-9

SD=standard deviation; CPZ=chlorpromazine

(equivalence calculated using Gardner et al. 2010)

Taurine significantly improved symptomatology over 12 weeks on the

BPRS total score (95% CI 1.8-8.5; p=0.004, figure 2).
There was no group difference in the MCCB composite cognitive score
over 12 weeks (95% CI -1.7-1.0; p=.582, figure 3).
Improvements over 12 weeks in the taurine group compared to placebo
on secondary measures included: BRPS psychotic subscale (95% CI
0.1-1.5; p=0.026, figure 4), depression on the CDSS (95% CI 0.1-3.0;
p=.047, figure 5) and functioning on the GAF (95% CI 0.3-8.8; p=0.04,
figure 6) scores.
Side effects were low in both groups. A significant group difference was
found on one safety and tolerability item: Psychic item 2 (Asthenia/
Lassitude/Increased Fatigability) of the UKU, with the taurine group
showing a more favourable outcome (p=0.006).

12-weeks

*Not significant

2
1
0
Taurine

Placebo

Figure 4 Change from baseline in BPRS psychotic scale

0.0

6-weeks

12-weeks

p=.026

-0.5

-1.0

Discussion

-2.0

Adjunctive taurine is safe and appears to have clinical benefit in firstepisode psychosis.
While adjunctive taurine did not improve cognition, it improved total
symptomatology, psychotic symptoms, depression and functioning in
patients with first-episode psychosis.
The use of taurine warrants further investigation in larger randomised
studies, particularly early in the course of psychosis.

-2.5

Taurine

Placebo

Figure 5 Change from baseline in depression (CDSS)

0.0

6-weeks

12-weeks

p=.047

-0.5

-1.0

Assessed for
eligibility
N=252

Excluded
N=41
Declined
N=90

-1.5

-2.0

Udvalg for Kliniske Undersogelser (UKU)

Psychotic Symptoms

Positive and Negative Syndrome Scale (PANSS)

Negative Symptoms

Scale for the Assessment of Negative Symptoms

(SANS)

Depression

Calgary Depression Scale for Schizophrenia

(CDSS)

Clinical improvement

Clinical Global Impression (CGI)

Functioning

Global Assessment of Functioning (GAF)

Consented,
randomised
N=121

-2.5

Taurine

Placebo

Figure 6 Change in functioning (GAF) over 12 weeks

Allocated to Taurine
N=61

Allocated to Placebo
N=60

p=.04

5
4

Received Taurine
N=52

Received Placebo
N=45

At least 1 follow-up;
Included in analysis
N=47

At least 1 follow-up;
Included in analysis
N=39

Contact
Patrick McGorry
pat.mcgorry@orygen.org.au

3
2
1
0

35 Poplar Road
Parkville VIC 3052
1300 679 436

Taurine

Placebo

ABN 85 098 918 686 An initiative of The University

orygen.org.au
of Melbourne, Melbourne Health
and The Colonial Foundation

14234_ORYGEN_STUDIO_2016

Funding: This trial was supported by a Stanley Medical Research Institute grant 06T.
Clinical Trials Registration: This trial is registered with http://www.clinicaltrials.gov
trial number NCT00420823.

6-weeks

Tolerability and safety

One hundred and twenty-one participants were randomised to receive either

taurine 4g or placebo. Eighty six participants (n=47 taurine; n=39 placebo)
were included in the final analysis (Figure 1 and Table 2).

Placebo

-1.5

Secondary outcomes

Results

Taurine

Figure 1 Participant flow

Co-primary outcomes

p=.004

-8

Schizophreniform disorder

IQ<80, substance dependence, history of clinically significant physical

illness, brain surgery, infarction or neurological impairment (e.g., brain
tumour, epilepsy), and for women, being pregnant or lactating.

12-weeks

Figure 3 Change from baseline in cognition compostie

320
21 (53.8)

Exclusion criteria

6-weeks

-1

15 (31.9)

17 (36.2)

People aged 18-25 years of age with a DSM-IV diagnosis of first-episode

psychotic disorder (schizophreniform, schizophrenia, schizoaffective,
delusional, major depression or mania with psychotic features, psychosis
NOS) attending the Early Psychosis Prevention and Intervention Centre
(EPPIC), a subprogram of Orygen Youth Health, or the Recovery and
Prevention of Psychosis Service (RAPPS), a subprogram of Southern Health,
in Melbourne, Australia. Participants must have received a minimum of
3 months treatment prior to study entry and not be in the acute phase of
illness.

Demographic Characteristics
Female, n (%)

Dose of antipsychotic
(CPZ equivalence), median
Diagnosis, n (%)
Schizophrenia

Method

Placebo
(n=39)

Figure 2 Change from baseline in BPRS total