ABSTRACTS - World Psychiatric Association

US19.
ADVANCES IN THE MANAGEMENT
OF TREATMENT-RESISTANT PSYCHOTIC
DISORDERS
US19.1.
NEW APPROACHES IN THE TREATMENT
OF REFRACTORY SCHIZOPHRENIA
H.-J. Möller
Department of Psychiatry, University of Munich, Germany
About 10-30% of patients with schizophrenia have little or no
response to antipsychotic medication and up to an additional 30%
have partial response. Reasons for treatment resistance are amongst
others wrong diagnosis, suboptimal dose and duration of antipsychotic
treatment, poor or non-adherence, unresponsiveness to a special
antipsychotic in the individual case, neurobiological factors,
comorbidity. Since long time clozapine has been the treatment of
choice for patients with drug refractory schizophrenia. Other second
generation antipsychotics (SGAs) have not proved to be as effective
in refractory patients as clozapine, a view which was also supported
by the respective phase of the CATIE trial. There is very limited evidence
for the efficacy of combining antipsychotics in refractory schizophrenia,
although this seems to be theoretically meaningful under
certain pharmacological considerations: e.g., the combination of a
multi-receptor SGA with a soft D2 receptor blocker. There is also limited
evidence of the usefulness of augmentation with mood stabilizers.
Possibly the best data are available for lamotrigine as an adjunctive
treatment. Patients with excited, anxious and catatonic features
might profit from the adjunctive use of benzodiazepines. Patients
with persistent negative symptoms may benefit by a comedication
with antidepressants. Also glutamatergic drugs have proven, however
inconsistently, to be beneficial. As far as cognitive disturbances are
concerned, comedication with cognitive enhancers/antidementia
drugs appears meaningful. However, the results of several randomised
studies are inconsistent. In very severe cases of drug refractory
schizophrenia, electroconvulsive therapy is applied in some clinical
settings, although there is only limited evidence in this respect.
Based on the available evidence, the treatment programme has to be
tailored to the needs of the individual patient. Pharmacogenetics
might support this individual tailoring in the future. Although there
are several new antipsychotics in the pipeline, there are currently no
hints whether this problem will be overcome.
US19.2.
POTENTIAL FOR ENHANCING OUTCOMES
IN TREATMENT-RESISTANT SCHIZOPHRENIA
PATIENTS: THE ROLE OF ADJUNCTIVE
MEDICATIONS
W.W. Fleischhacker
Department of Biological Psychiatry, Medical University
of Innsbruck, Austria
Managing treatment-resistant schizophrenia patients remains a huge
challenge to the field. Among the various treatment options,
polypharmacy is the most commonly used and least well researched
strategy. The choice of adjunctive medication will depend on the target:
patients whose positive symptoms do not adequately respond to
antipsychotic monotherapy will most likely be managed differently
than those for whom additional improvement in negative symptoms
or cognitive function is sought. The spectrum of add-on medications
ranges from adding benzodiazepines, antidepressants and mood stabilizers
to combining two or three different antipsychotics. The available
evidence supporting any of these options is very weak. Recently
experimental agents, such as glutamatergic and nicotinergic drugs,
have been explored in an attempt to establish a rational polypharmacy.
As major breakthroughs have not been made, the clinician is still
left with the responsibility to choose among the available options,
often on a trial and error basis.
US19.3.
RELEVANCE AND TREATMENT OF NEGATIVE
SYMPTOMS IN SCHIZOPHRENIA
A.C. Altamura, G. Colombini, B. Dell’Osso
Department of Psychiatry, University of Milan, Italy
Among the different dimensions of schizophrenia, negative symptoms
represent core features of the illness and reflect a reduction or
loss of normal cognitive and emotional functioning that includes flattened
affect, impoverished speech, apathy, avolition, anhedonia, asociality,
psychomotor retardation and impaired attention. Biopathogenetic
hypotheses in relation to negative symptoms stem from neuromorphological,
neurochemical, neuroendocrinological and neuroimmune
data. Even though positive symptoms of schizophrenia
may be expected to improve with optimal medication management,
this may not be the case for negative symptoms, that have historically
been less responsive to pharmacological treatment and associated
with a great impact on functional outcome. With respect to the pharmacological
treatment of negative symptoms in schizophrenia, the
efficacy of standard antipsychotics has been frequently reported, but
these compounds have several limitations in term of side effects. The
introduction of novel antipsychotics has been accompanied by
reports suggesting their great efficacy in reducing negative symptoms.
However, it has been suggested that improvements may be related to
decreases in positive symptoms and reduced sedation or extrapyramidal
side effects. In addition, most studies with novel antipsychotics
have been focused on the acute treatment and short-term outcome
and reliable data on the long-term outcome are lacking. Besides atypical
antipsychotics, other classes of compounds have been assessed
for negative symptoms, including selective serotonin reuptake
inhibitors (SSRIs) and other antidepressants, NMDA agonists and
anticholinergic agents. However, with respect to the use of augmentative
antidepressants, published studies yielded inconclusive results,
being characterized by small samples and methodological limitations
(e.g., no control for change in secondary negative symptoms). Preliminary
studies with the NMDA agonist glycine and D-serine, in augmentation
to an antipsychotic, found significant reduction in persistent
negative symptoms. Positive results, however, have not been replicated
in larger subsequent studies. Novel agents such as selegiline,
naltrexone, dehydro-epiandrosterone, galantamine, nitric oxide, L-
deprenyl and pergolide have recently shown positive effects on general
negative symptoms but remain untested against primary negative
symptoms. The perspective to rationalize the pharmacological treatment
of negative symptoms of schizophrenia needs a specific diagnostic
preliminary approach and a particular attention in considering
atypical antipsychotics and novel compounds as specific effective
treatments.
22 World Psychiatry 8:S1 - February 2009