ABSTRACTS - World Psychiatric Association

SPS5.2.
SCIENTIFIC RATIONALE FOR WHAT WE OBSERVE
IN THE CLINIC
G. Gründer
Department of Psychiatry and Psychotherapy, University
of Aachen, Germany
Knowledge of the receptor-binding profiles of antipsychotics can help
optimise the efficacy and safety of treatment. For example, activity at
dopamine receptors plays a role in psychosis, while activity at serotonin
receptors is associated with impact on mood, cognition and anxiety
symptoms. High-affinity dopamine D 2
receptor binding and slow
dissociation, however, may lead to extrapyramidal symptoms and
hyperprolactinaemia. Activity at other receptors, such as histamine H 1
,
muscarinic and a-adrenergic receptors, may also be associated with
adverse events. Attention should be paid to the pharmacokinetic implications
of the route and mode of administration (oral, intramuscular or
long-acting). While short-term adverse events may be associated with
mode of administration, there is no evidence for different long-term tolerability
profiles. In patients who experience side effects, appropriate
short- or long-term co-medications should be added. Switching from
one antipsychotic to another may be desirable, such as in the event of
insufficient efficacy or unacceptable safety issues, such as weight gain.
Switching medication may, however, be associated with amplified or
muted treatment effects, hangover effects relating to the half-life of the
previous agent, and adverse events relating to receptor up-regulation.
Switching must therefore be carried out according to appropriate psychopharmacological
principles, with a clear understanding of the pharmacokinetic
profiles of the agents involved (e.g., by cross-titration with
appropriate titration strategies). Balancing efficacy and tolerability is
essential in patients receiving antipsychotic medication, and careful
attention to the receptor-binding and pharmacokinetic profiles of the
different agents can minimise adverse events and improve outcomes.
SPS5.3.
THINKING LONG-TERM FROM THE START
M. De Hert
University Psychiatric Centre, Leuven Catholic University,
Kortenberg, Belgium
Compliance with antipsychotic therapies in patients with severe mental
disorders is a major concern for clinicians. The need for long-term
antipsychotic treatment may be challenged if a patient has difficulty
accepting the prospect of life-long administration or has concerns
over the potential adverse events (AEs) associated with antipsychotic
drugs. The early onset of AEs, such as akathisia or agitation, may
increase the likelihood of poor long-term compliance by encouraging
patients to self-manage. This can lead to treatment discontinuation
and/or poor adherence, which may result in reduced efficacy and
negatively impact the long-term prognosis. People with severe mental
disorders often have impaired physical health. This may be related to
their lifestyle, their difficulty accessing healthcare services or to side
effects of antipsychotic medication. Reduced physical health is linked
to drug-induced hyperprolactinaemia, and to an increased prevalence
of weight gain, diabetes and dyslipidaemia. These latter metabolic disturbances
have been shown to increase a patient’s risk of developing
cardiovascular disease, with potentially serious consequences. The
propensity to cause metabolic disturbances varies between antipsychotic
agents and data suggest that the unwanted metabolic effects of
some antipsychotics may be reversed by switching to an agent with a
more favourable side effect profile. Considering the concern over
compliance with antipsychotic therapies and the risk of metabolic
disturbances, it is important to provide a therapeutic agent that is
effective at treating the symptoms of the mental disease and does not
further impact on the physical health of the patient from the outset of
the illness.
SPS6.
AGOMELATINE: OPTIMIZE THERAPY FOR ALL
DEPRESSED PATIENTS
(organized by Servier)
SPS6.1.
CIRCADIAN RHYTHMS: STRONG EVIDENCE
ON HOW TO APPROACH DEPRESSION
E. Frank
Western Psychiatric Institute and Clinic, University of Pittsburgh
School of Medicine, Pittsburgh, PA, USA
Although life in industrialized society masks endogenous circadian
rhythms that were more apparent centuries ago, circadian rhythm regularity
and synchrony have great importance for all aspects of human
health and well-being. Indeed, our knowledge of this relationship
grows almost daily, with evidence that everything from organ systems
to gene products benefit from circadian integrity. Our research group
has focused on the relationship of circadian regulation and psychiatric
illness, particularly mood disorders. Nearly 20 years ago we articulated
a “social zeitgeber” hypothesis concerning the way in which
life events that disrupt an individual’s normal routines could initiate a
cascade that, in vulnerable individuals, might lead to an episode of
depression or mania. Since that time we have developed two lines of
evidence in support of this hypothesis. First, we demonstrated that life
events characterized by social rhythm disruption are temporally associated
with onset of mood episodes. We subsequently demonstrated
that a psychotherapeutic intervention which specifically targets regularizing
of daily routines is associated with the prevention of both
manic and depressive episodes and that the protective effect of the
treatment is directly related to the extent to which patients increase
the regularity of their social rhythms. More recently, this same intervention
has been shown to be associated with recovery from bipolar
depression and significant improvement in occupational function. We
discuss the implications of these findings for the treatment of all
depressions.
SPS6.2.
PHARMACOLOGICAL PROFILE OF AGOMELATINE:
THE FIRST MELATONERGIC ANTIDEPRESSANT
G. Racagni
Center for the Study of Neuropharmacology, University
of Milan, Italy
Beyond the classical monoamine hypothesis, which has limitations, a
variety of research approaches have been followed to obtain more
effective treatments for depression, with better safety profile and more
rapid symptoms relief. Among these approaches, the regulation of circadian
rhythms in mammals has attracted growing interest, because
the disruption of circadian rhythms is now well described in
depressed patients, suggesting that the human circadian system is a
key player in the etiology and in the treatment of mood disorders. This
led to the synthesis of agomelatine, an agonist with high affinity for
melatonergic MT 1
and MT 2
receptors, and antagonist at 5-HT 2C
receptors. As expected from its pharmacological profile, agomelatine
was able to synchronize circadian rhythm patterns in several animal
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