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)

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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