Intervenção Farmacológica

João Relvas

30 de Novembro de 2009
 Classification

• Most depressions have triggering life events – “Reactive Depression”

(especially in a first episode)

• Many patients present initially with physical symptoms (somatisation)

(some may show multiple symptoms of depression in the apparent

absence of low mood - “Masked Depression”)
Depression”)

• Some depression has no triggering cause - “Endogenous Depression”

Depression”

(more persistent and resistant to treatment)

 DEPRESSION - CLASSIFICATION

The three subgroups of depressive disorder according to DSM-IV are:

• 1. Major Depression

• 2. Dysthymia

• 3. Atypical Depression or depression not otherwise specified

(these need to be differentiated from grief and bereavement,

which are normal responses to a loss)

Seasonal Affective Disorder is not a separate mood disorder (it is

classified as a specifier to major depression)
 Grief and bereavement

• Normal responses to the loss of close relationship

• Depression, suicide, anxiety, and complicated grief
are most common adverse psychological sequelae of
loss
• Rates of depression during the first year after loss
of a spouse are 15-35% (figures that are 4-9 times
higher than the rate of general population)
• The risk of suicide also appears to be elevated
among individuals who have lost a spouse
(particularly in older men and in first year after a
death)
 P. MISTA ANSIEDADE / DEPRESSÃO
Sub-síndromal

Stress

P. A. G. Dep. Major
 Drug Effects
All drugs produce harmful as well as beneficial
effects.
• Main effects are related to desired therapeutic
effect.
• Side effects are unrelated to the desired effect.
• Placebo Effects are based upon an inert
substance's ability to elicit a significant
therapeutic response, independent of any
chemical property.
Routes of Administration
Pharmacokinetics
Drug Half-Life
Drug Action on Synaptic Transmission

Antagonist drugs are in red, Agonists are in blue

REGULAÇÃO DA EXPRESSÃO DOS GENES

Adapt. de S Hyman e R Malenka, 2001

FUNÇÕES BIOLÓGICAS
TRADUÇÃO CLÍNICA
 Antidepressivos
1950s 1980s SSRIs
IMAOs e ATCs 1982 zimeldina
imipramina 1957 1988 fluoxetina
iproniazida
1975
1964 NASSAs
Sugerido papel da
Sugerido papel da dopamina na
noradrenalina na depressão SNRIs
depressão
NARIs
1969
Sugerido papel da NDRI
serotonina na
depressão

1950s 1960s 1970s 1980s 1990s

Schildkraut JJ et al. J Psychiatr Res, 1964

Carlsson A et al. Eur J Pharmacol, 1969
Randrup A, Braestrup C. Psychopharmacology, 1977
ACÇÕES PRINCIPAIS DAS
BENZODIAZEPINAS

• Ansiolítica
• Hipnoindutora
• Miorrelaxante
• Anticonvulsivante
 Tyrosine

Tyrosine
Dopamine Synapse

L-DOPA

DA
VIAS DOPAMINÉRGICAS
 Typical and Atypical
Antipsychotic Drugs
• Typical APDs • “Old” Atypical APDs
– clozapine (binds to many receptors)
– risperidone (D2/5-HT2 antagonist)
– chlorpromazine
– haloperidol • “Newer” Atypicals (clozapine-
like)
– thiothixene – olanzepine
– sertindole
– ziprasidone
– Quetiapine

• “Newest” Atypical APD

– aripiprazole (D2 – functionally
selective or partial agonist)
 Antipsicóticos
Afinidades relativas, in vitro

Clozapina Amisulpride Risperidona

5HT2
5HT2 D2
D2 D2
M1 α1 α1/5HT2
α1
H1

Quetiapina Olanzapina Ziprasidona Haloperidol

5HT2 D2
M1 5HT2
5HT2 D2
H1 D2 D2 5HT1D
α1 α1
M1 5HT1A
H1
5HT2
 Escolha do Antipsicótico
Neurolépticos Convencionais
• Menos eficácia no tratamento de sintomas negativos
• Incidência de efeitos extra-piramidais nas dosagens
habituais
• Deteriorização da qualidade de vida
• Problemas de adesão à terapêutica

Novos Anti-psicóticos
• Menos efeitos secundários com doses terapêuticas
(ex: sedação, perturbações das funções cognitivas,
sintomas extra-piramidais)
• Maior eficácia sobre os sintomas negativos