Up to now, no reliable biological markers
for risk and relapse among cocaine-dependent
patients have been identified. Apomorphine is a
D2>D1 nonselective dopamine-receptor agonist.
Apomorphine produces yawning and hormonal
changes. It has been suggested that addicts
present an enhanced sensitivity of the dopamine
neurotransmitter system (Casas
et al, 1995).
The Apomorphine Test may be useful in
assessing central dopamine system alterations
associated with chronic heroin consumption
(Guardia et
al, 2002). The yawn-inducing Apomorphine
Test has been proposed as a marker for
predicting relapse during the withdrawal period
in cocaine-dependent patients (Roncero et al,
2010). Also, the Complete Apomorphine Test,
which includes an Apomorphine Test plus a
Placebo Test or viceversa, has been proposed as
a biological marker for predicting early relapse
(Roncero et al, 2012).
OBJECTIVE
To study the Apomorphine Test as a
biological marker for relapse in
cocaine-dependent patients as performed on the
first day and on day 11 or 12 of
abstinence.
MATERIAL & METHOD
39 (35 men) 31.94 (20-48) y.o. cocaine
addicts were recruited and included in an
addiction program involving 2 weeks of
detoxification as in-patients and a 23-week
follow-up period.
Dependence was diagnosed according to
DSM-IV-TR criteria. Other principal Axis I
comorbid diagnoses were excluded (schizophrenia,
bipolar disorders, major depression, OCD, etc).
We used SCID I and SCID II to evaluate Axis I
and II disorders. Patients were evaluated using:
Analogic Visual Scale (AVS) for cocaine Craving,
CCQ, CSSA, WURS, ADHD-RS, BDI, STAI-R/S
scales.
We performed a double-blind clinical trial
using the Complete Apomorphine Test at the
beginning (day 1) and end (day 11 or 12) of a
in-patient detoxification program.
Each patient received 0.005 mg/kg of
apomorphine and 0.005 mg/kg of placebo
subcutaneously in each test. There was a 45-
minute break between the Apomorphine Test and
the placebo test.
Yawning was monitored and noted by
independent observers for periods of 45 minutes
following administration of the apomorphine or
placebo.
We defined relapse as 3 consecutive positive
urinoanalyses for cocaine or 5 positive ones in
4 weeks. Also, if the patient did not submit to
the urinoanalysis control, it was considered to
be positive.
Results
Patients (n = 22) who relapsed within the
first 4 weeks showed higher yawn count in the
combined Apomorphine Test performed on days 1and
day 11 or 12 than patients (n = 17) who did not
relapse within this period of time 18.85 (SD
=13.12) vs. 10.71 (SD =12.40 ), Z -1.89, (p
<0.05).
There were no differences between the two
groups in the AVS, CCQ, CSSA, WURS, ADHD-RS,
BDI, STAI-R/S mesures.
CONCLUSIONS
The increased number of yawns in
early-relapse patients could be evidence of the
usefulness of the combining of the yawn-inducing
Apomorphine Test performed on the first and last
days of the detoxification process.
The Apomorphine Test could be a biological
marker for predicting early relapse in
cocaine-dependent patients. It can give
clinicians indirectly information of how
affected is the dopaminergic
neurotransmission.
References
Casas M, Guardia J, Prat G, Trujols J. The
apomorphine test in heroin addicts. Addiction.
1995; 90(6):831-835
Casas M, Prat G, Guardia J, Duro P. Yawning
induced by low doses of apomorphine as posible
biological marker for studying the effects of
CNS active compounds on the dopamine system. In:
Palomo T et al., editors. Strategies for
studying Brain disorders.Vol 2. London: Farrand
Press;1994.p.55-70.
Guardia J, Casas M, Prat G, Trujols J,
Segura L, Sanchez-Turet M.The apomorphine test:
a biological marker for heroin dependence
disorder? Addict Biol. 2002; 7(4): 421-426.
Roncero C, López-Ortíz C,
Rodríguez-Pascual M , Corominas M,
Castells X, Grau-López L, Daigre C,
Gómez-Baeza S, Castrillo E, Valero S,
Casas M. The apomorphine test as a biological
marker for relapse in cocaine-dependent
patients. Presented at 18th meeting European
Psychiatric Association (AEP). Munich (Germany)
21 February -2 March 2010.
Roncero C, Grau-López L, Daigre C,
Gonzalvo B, Corominas M, Egido A, Castells X,
Gómez-Baeza S Esteve O, Casas M. A new
model for the apomorphine test as a biological
marker for cocaine-dependent patients. Presented
at 20th meeting European Psychiatric Association
(AEP). Prague (Czech Republic) 3-6 March
2012.
