Amazeo (amisulpride) 1w6a5x

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

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No titrations required Preferably given before meals istered 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

OPTIMAL CONTROL BOTH POSITIVE & NEGATIVE SYMPTOMS

MAINTENENACE PERIOD

800 mg/day

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

Average increase in weight at the end of 6 months

Weight gain

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

• • • • • •

Summary : Amazing binding profile

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 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