Date post: | 26-Oct-2014 |
Category: |
Documents |
Upload: | konark-dinkar |
View: | 111 times |
Download: | 3 times |
AMAZEOAMAZEO AMISULPRIDE AMISULPRIDE
((50,100,200,400mg)50,100,200,400mg)
Neurotransmitter ProfileNeurotransmitter Profile
• Low dose – Works presynaptically– Blocks D2 and D3 in frontal cortex – Increases Dopaminergic transmission– Relieves negative symptoms
• High Dose – Works post-synaptically– Blocks D2 and D3 in the limibic system– Reduces Dopaminergic transmission– No action on any other neurotransmitter
including 5HT2
Mechanism of actionMechanism of action• Amisulpride is a unique atypical antipsychotic that selectively
blocks D2 and D3 receptors presynaptically in the frontal
cortex, possibly enhancing dopaminergic transmission
• D2 and D3 subtypes blocked in limbic system (cortical) but
not in Basal Ganglia (Striatum)
• Postsynaptically blocks D2 and D3 in the limbic areas,
possibly reducing it.
• Thus dopaminergic over-activity in the frontal cortex, and
under-activity in the limbic areas, can be treated
simultaneously, alleviating both positive and negative
symptoms of schizophrenia, respectively.
Dosage guidelinesDosage guidelines• Acute Schizophrenia
– 400 to 800mg/day divided BD
• Patients with predominant negative symptoms– 50 to 300mg/day given OD or BD
• No titrations required• Preferably given before meals• Administered BID over 400mg/day• Renal insufficiency – Adjustments reqd• Hepatic insufficiency – No dosage adjustment
as weakly metabolised
Simple Dose – response Simple Dose – response relationshiprelationship
PRE-SYNAPTIC
POST-SYNAPTIC
PRE-SYNAPTIC
POST-SYNAPTIC
PROMINENTNEGATIVE
SYMPTOMS
OPTIMAL CONTROLBOTH POSITIVE &
NEGATIVE SYMPTOMS
POSITIVE SYMPTOMS
400 mg/day
800 mg/day
300 mg/day
50 mg/day
400 mg/day
800 mg/day
300 mg/day
50 mg/dayPROMINENTNEGATIVE
SYMPTOMS
MAINTENENACEPERIOD
ACUTE PHASE
PRE-SYNAPTIC
POST-SYNAPTIC
PRE-SYNAPTIC
POST-SYNAPTIC
PROMINENTNEGATIVE
SYMPTOMS
OPTIMAL CONTROLBOTH POSITIVE &
NEGATIVE SYMPTOMS
POSITIVE SYMPTOMS
400 mg/day
800 mg/day
300 mg/day
50 mg/day
400 mg/day
800 mg/day
300 mg/day
50 mg/dayPROMINENTNEGATIVE
SYMPTOMS
MAINTENENACEPERIOD
ACUTE PHASE
How different from How different from other atypicalsother atypicals
• It acts primarily on dopaminergic D2 and D3 receptors of the limbic system and spares the striatal dopamine– Therefore least likely to cause EPS
• Atypicals generally have greater 5HT2A affinity than D2/D3. Amisulpride is an exception
Major uses of amisulprideMajor uses of amisulpride• MAJOR
– 1st Episode Psychosis – For treatment of both positive and negative symptoms
– Schizophrenia with prominent negative symptoms
– Schizophrenia with associated depression– Comorbid or standalone dysthymia
• POTENTIAL – Augmentation to clozapine / olanzapine
• Resistant schizophrenia• Inorder to reduce the side effects of first lines
– Augmentation to SSRIs• Treatment resistant MDD
Weight gainWeight gain
Mortimer A, et al. A double-blind randomized comparative trial of amisulpride versus olanzapine
for six months in the treatment of schizophrenia. Int Clin Psychopharmacol 2004
Amazeo Olanzapine (n=188) (n=188)
Ave
rag
e in
crea
se in
w
eig
ht
at t
he
end
of
6 m
on
ths
Significantly lower weight gainPotential than Olanzapine or risperidone
Rapid cross taperingRapid cross tapering
• Reduce the old treatment by 30-50% every 3-7 days
• Introduce Amazeo– 400-800mg for positive symptoms– 50-300mg for negative symptoms
• No dose titrations required as there is a low risk of drug interactions with other drugs
• Maintain anticholinergic medication for 2-4 weeks
Summary : Amazing binding Summary : Amazing binding profileprofile
• Its clean, its distinct• Focus on D2 / D3• Low doses – Pre-synaptic• High doses – Post-synaptic• Limbic selective thus low EPS• No action on 5HT2 unlike other atypicals
• BENEFITS– Negative symptoms and depressive symptoms– Low EPS
Summary : Amazing Summary : Amazing superioritysuperiority
• Compared to other atypical drugs– Similar efficacy as measured thru BPRS
or PANS score– Weight gain– EPS– Diabetes / other metabolic side effects
Summary : Amazing benefits Summary : Amazing benefits to patientsto patients
• Persisting symptoms of depression or negative symptoms even under treatment cause emotional flattening and avolition apathy– Amazeo achieves amazing results
• Return of the patients into societal activities like friends, family, outdoor activity
• Change of emotions from one of depression to that of happiness
CompetitorsCompetitors
• SULPITAC Sun Pharma• SOLTUS Intas• AMIGOLD Lupin• AMIPRIDE Talent• ZULPRIDE Unichem