European Psychiatry - Volume 33 - March 2016

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24th European Congress of Psychiatry / European Psychiatry 33S (2016) S18–S55 S53
Towards personalized pharmacotherapy for
suicide prevention across the lifespan
S110
Using genomics to predict
antidepressant response in suicidal
depressed children
Maya Amitai (MD) , Alan Apter (MD) ∗
1 Department of Psychological Medicine, Schneider Children’s
Medical Center of Israel, Petach Tikva, Israel
2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
3 The Ruhman Family Laboratory for Research on the Neurobiology of
Stress, Department of Neurobiology, Weizmann Institute of Science,
Rehovot, Israel
∗ Corresponding author.
Background Depression and anxiety disorders are among the
most common childhood psychiatric disorders. Selective serotonin
reuptake inhibitors (SSRIs) are generally considered first-line treat-
ment for both depression and anxiety in this age group. However,
it has been reported that 30%–40% of all patients who receive a
sufficient dose and duration of treatment fail to respond. More-
over, SSRI use is frequently associated with serious adverse events
(SAE), including activation symptoms, manic switch and increased
suicidal behavior. These are particularly relevant in pediatric popu-
lations because of concerns about the suicide threat of SSRIs,
resulting in a black-boxwarning. Currently there is noway of know-
ing in advance who of the patients will respond. Identification of
biomarkers that would be early predictors of response and of the
occurrence of SAE could help to maximize the benefit–risk ratio for
the use of SSRIs, and speed up the matching of treatment to patient.
The main objective of this project is therefore to identify and vali-
date biomarkers predicting response and SAE in depressed children
and adolescents, thus improving treatment, enabling the develop-
ment of novel diagnostic tests and suggest novel therapeutic targets
for future related drug development.
Methods As a preliminary pilot, we already obtained blood sam-
ples from 80 depressed and anxious children and adolescents over
the last year before, during and after eight weeks of fluoxetine (FLU)
therapy. Genetic and epigenetic samples were collected from all
participants. The patients were treated with FLU 20–40mg/day for
8weeks. Clinical responsewasmeasuredwith several scales includ-
ing the Children’s Depression Rating Scale–Revised (CDRS-R), the
Beck Depression Inventory (BDI) and the Screen for Child Anxiety
Related Emotional Disorders (SCARED).
Results The participant’s age ranged from 6 to 18 (14.12 ±2.30)
years. The overall response rate was 56%. Ten percent responded
with SAE. Regarding Pharmacogenetics, The 5-HTTLPR ss geno-
type was associated with a poorer clinical response with regard to
depressive symptoms as well with fewer reports of agitation com-
pared to the ll genotype. Regarding immunemeasures, we analyzed
cytokine levels from 41 children. Plasma concentrations of TNF- ,
IL-6 and IL-1 were measured by enzyme linked immunosor-
bent assays (ELISA) before and after FLU treatment. Antidepressant
treatment significantly reduced TNF- levels (P= 0.037), with no
significant changes in the levels of IL-6 and IL-1 . All three
pro-inflammatory cytokines were significantly (P < 0.05) higher in
SSRI-refractory than SSRI-responsive patients, i.e.: higher levels of
TNF- , IL-6 and IL-1 might predict non-response to fluoxetine
treatment in children.
Future plans Out of the study sample we selected 13 remit-
ters and 13 non-responders and 10 children with SAE (activation
symptoms, manic/hypomanic switch, increased suicidality), and
analyzed expression profiles in peripheral blood at admission
and after 8 weeks of treatment using illumine Truseq technique.
Hopefully, we shall find significant differences in miRNA profiles
between the different groups which may serve as biomarkers indi-
cating AD treatment response and SAE. The differentially regulated
miRNA’s can be studied in depth in the future in animal models in
order to support the hypothesis that they may be involved in the
AD mechanism.
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.
S111
Large-scale suicide prevention by
pharmacological treatment of mood
disorders
E. Isometsa
University of Helsinki, Department of Psychiatry, Helsinki, Finland
Introduction In psychological autopsy studies, at least half of sui-
cides have suffered from depressive or bipolar disorders at time of
death. Improving access to care and provision of evidence-based
pharmacotherapies can be important preventive measures.
Objectives To examine suicide risk and pharmacoepidemiology
in mood disorders; evidence for efficacy of pharmacotherapies in
mood disorders and in preventing suicidal behaviour in them, and
limitations to effectiveness of treatment due to problems of adher-
ence.
Aims To evaluate potentials for suicide prevention in mood
disorders by improved access to treatment, improved quality of
treatment provision, improved adherence, or by specific pharma-
cotherapies.
Methods Selective review of literature.
Results Risk of suicide death and attempts in mood disorders
clusters intomajor depressive andmixed illness episodes, and time
spent in them is a major determinant of risk, but direct evidence for
preventive effects of effective pharmacotherapies remains limited.
Observational and randomized studies indicate lithium treatment
to reduce risk of suicide deaths and attempts. Ecological evidence
from Europe shows increasing sales of antidepressants to con-
sistently associate with declining regional suicide rates. Forensic
chemical studies still findmajority suicides negative for antidepres-
sants. Poor adherence is a central problem in treatment provision.
Conclusions Positive impact of increase in pharmacotherapy
provision in the last few decades on suicide mortality remains
uncertain. Lithium is the pharmacological agent with best evi-
dence for preventive utility, but underused. Providing treatments
for those at risk, improving quality and continuity of treatment,
and integrating them with psychosocial approaches is likely to be
beneficial for suicide prevention.
Disclosure of interest The author has not supplied his declaration
of competing interest.
S112
Brain imaging biomarkers in
personalizing pharmacotherapy of
suicidal depressed patients
J.J. Mann
Columbia University, New York, NY, USA
Background New knowledge has emerged about decision-
making, mood regulation, social distortions and learning that is
relevant for the diathesis for suicidal behavior. All four domains
have identified underlying neural circuits and for decision-making
and mood regulation also specific neurotransmitter systems.
Methods We have conducted PET studies of the serotonergic sys-
temandCSF studies of the serotonin, norepinephrine anddopamine
neurotransmitter systems in patients surviving suicide attempts
to determine whether they have neurotransmitter abnormalities
that resemble those found in the brain after suicide. We found