AMAZEO

AMISULPRIDE (50,100,200,400mg)

Neurotransmitter 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 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 underactivity in the limbic areas, can be treated simultaneously, alleviating both positive and negative symptoms of schizophrenia, respectively.

Dosage 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 relationship

POST-SYNAPTIC

POSITIVE SYMPTOMS

ACUTE PHASE

800 mg/day

OPTIMAL CONTROL BOTH POSITIVE & NEGATIVE SYMPTOMS

MAINTENENACE PERIOD

400 mg/day

300 mg/day
PRE-SYNAPTIC

PROMINENT NEGATIVE SYMPTOMS

PROMINENT NEGATIVE SYMPTOMS

50 mg/day

How different from other 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 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 gain
Average increase in weight at the end of 6 months

Significantly lower weight gain Potential than Olanzapine or risperidone

Amazeo (n=188)

Olanzapine (n=188)

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

Rapid 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

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

Summary : Amazing binding profile

BENEFITS
Negative symptoms and depressive symptoms Low EPS

Summary : Amazing superiority

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 to 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

Competitors
SULPITAC SOLTUS AMIGOLD AMIPRIDE ZULPRIDE Sun Pharma Intas Lupin Talent Unichem