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Cesare Turrina
La terapia con antidepressivi
nell’anziano
Brescia, maggio 2013
… depression is commonly seen in
primary care practices, and
interventions designed to address
this problem that fit within the
practice model are sorely needed …
Taylor & Murali 2004, Neuropsychopharmacology
A complete understanding of its
pathogenesis and treatment
response remains elusive
PATHOGENESIS
WHITE MATTER LESIONS AND DISRUPTION IN
CONNECTIVITY
HIPPOCAMPAL VOLUME (VASCULAR LESIONS) AND
MEMORY SPEED
GRAY MATTER?
HIPPOCAMPAL SHRINKING AFTER YEARS OF MULTIPLE
EPISODES (CORTISOL)
SYMPTOM PATTERN AND FREQUENCY
OF SPECIFIC DEPRESSIVE SUBTYPES
More somatic symptoms
Melancholic and delusional more frequent
Cognitive impairment is common
L/h
CLEARANCE DEL CITALOPRAM
Minimally, 50% of clinically used
medications are at least partly
dependent on CYP3A4 for their
clearance
In general, older patients are more
sensitive to adverse effects of
psychotropics at lower concentrations
CONVINZIONI
The pharmacological treatment of latelife depression has long been influenced
by three widely held beliefs about older
patients
1) They do not respond at the same rate
or as robustly as younger patients
2) They take longer to respond to
antidepressant medication, and
therefore a 12-week trial is
mandatory
3) They experience a higher rate of side
effects and adverse events
ANTIDEPRESSANT TRIALS
Some considerations
Diagnostic definition may be insufficient
Minor depression not captured
Comorbid medical illnesses
Cognitive impairment or dementia
TREATMENT MODERATORS
Subtype (melancholic or atypical)
Severity
Medical burden
Social support
Abnormalities on MRI indicating vascular disease
Neurocognitive abnormalities (executive dysfunction)
TRICICLICI
TRICICLICS SIDE EFFECTS AND SAFETY
ANTICHOLINERGIN EFFECTS
DRY MOUTH
CONSTIPATION
BLURRED VISION
URINARY RETENTION
CONFUSIONAL STATES
% remission
ACCUMULATED REMISSION RATE IN AN OPEN TREATMENT
TRIAL WITH NORTRIPTILINE ^
^ 75 MG END OF WEEK 1, THEN ADJUSTED TO ACHIEVE PLASMA LEVELS
SSRIs
SSRIs SIDE EFFECTS PROFILE
GASTROINTESTINAL DISTRESS
AGITATION
INSOMNIA
SEXUAL DYSFUNCTION
Discontinuation rates for SSRIs are not
statistically different from the
discontinuation rates reported for a
therapeutic level of nortriptiline in
geriatric samples
%
RESPONSE VS. REMISSION. VENLAFAXINE VS. CITALOPRAM
8-WEEK RCT
VENLAFAXINE
CITALOPRAM
DO PATIENTS WITH LATE-LIFE
DEPRESSION TAKE LONGER
TO RESPOND THAN YOUNGER
PATIENTS ?
Extending a nortriptiline trial from 7 to 9
weeks resulted in a higher response rate
(from 54 to 63%).
Slow responders had low plasma levels of
nortriptiline in the early weeks and
required a dosage increment
Georgotas et al., 1989
For both sertraline and fluoxetine, 95%
of the patients* who achieved a 50%
reduction in baseline Ham-D score did
so by the end of week 8
* 75 patients, mean age of 75
Newhouse et al., 2000
Neither the overall response or
remission rates nor the time to achieve
sustained remission supports the belief
that patients with late-life depression are
less responsive to antidepressant
medication or take longer to respond
However the “start low and go slow”
paradigm evolved in the era when
triciclics were the primary treatment for
depression … The utility of the “start
low and go slow” strategy for treatment
with SSRIs … is essentially untested
PROBABILITA’ DI REMISSIONE A 12 SETTIMANE
22%
MIGLIORAMENTO INFERIORE 30%
ALLA 2a SETTIMANA
7%
MIGLIORAMENTO INFERIORE 30%
ALLA 6a SETTIMANA
Rather, they can make informed
decisions about changing or continuing
treatment at the 4- and 6-week time
points made on the probability that
given the patient’s improvement to date,
he of she will or will not meet remission
criteria by week 12
The results suggest that if there is not a
moderate degree of symptomatic
improvement early in treatment,
clinicians can have a high level of
accuracy in predicting that the patient
will not adequately respond to this
treatment within 12 weeks
CAUTELE
FLUOXETINA E ANZIANI
… POSOLOGIA: adulti e anziani da 20 mg/die a
60 mg die …
SERTRALINA E ANZIANI
… negli anziani l’emivita di eliminazione può
essere prolungata, pertanto in questi pazienti
si deve somministrare il dosaggio più basso
possibile…
PAROXETINA E ANZIANI
… nei soggetti anziani si verifica un aumento
delle concentrazioni plasmatiche di paroxetina,
ma l’intervallo delle concentrazioni è
sovrapponibile a quello osservato nei soggetti
più giovani. La somministrazione dovrebbe
partire con la dose iniziale prevista negli adulti
…
VENLAFAXINA E ANZIANI
Non è necessario un adattamento specifico del
dosaggio … Tuttavia … richiede cautela …
sensibilità e affinità verso i neurotrasmettitori
che si verificano nell’invecchiamento … deve
essere impiegata sempre la dose minima
efficace … attentamente monitorati all’aumento
del dosaggio …
DULOXETINA E ANZIANI
Nei pazienti anziani non è raccomandato un
aggiustamento del dosaggio solamente in base
all’età. Tuttavia si deve osservare cautela nel
trattamento dei pazienti anziani
BUPROPIONE E ANZIANI
L’efficacia negli anziani non è stata dimostrata
in modo certo. Non si può escludere una
maggior sensibilità nei soggetti anziani
AGOMELATINA E ANZIANI
L’efficacia nei pazienti anziani non è stata
chiaramente dimostrata. Pertanto … deve
essere prescritto con cautela a questi pazienti
EVIDENZE
Inhibition of serotonin reuptake by
antidepressants and upper gastrointestinal
bleeding in elderly patients:
retrospective cohort study
van Walraven et al., BMJ 2001
FINDINGS
Risk of bleeding significantly increased by 10% with
increasing reuptake inhibition (overall rate 7.3 / 1000)
Risk was higher in octogenarians
Risk was higher in those with previous bleeding
- low inhibition 28.6
- high inhibition 40.3
DRUG INTERACTIONS IN THE
TREATMENT OF DEPRESSION IN
PATIENTS WITH ISCHEMIC HEART
DISEASE
C. Andrade, 2012, Journal of Clinical Psychiatry
Risk of abnormal bleeding
Absolute risk of bleeding appeared small
SSRIs + Aspirin vs. Aspirine alone: risk rised by 0.5 /
100 patients years
SSRIs + Aspirin + Clopidogrel vs. Aspiring +
Clopidogrel: risk rised by 1.5 / 100 patients years
Most cases of SSRIs related bleeding occur early
during treatment
CONCLUSIONI
La risposta alla terapia antidepressiva può essere frequente e rapida
come nell’età giovane adulta
La remissione è meno frequente, verosimilmente in relazione ad alcuni
fattori tipici dell’età avanzata
Va posta particolare attenzione alle interazioni farmacocinetiche
Il rischio di sanguinamento con gli SSRIs è di dimensioni contenute e
più prevedibile in alcune categorie di soggetti
Un atteggiamento eccessivamente attendista deve comunque
confrontarsi con l’elevato rischio di suicidio