Updates on amisulpride in psychotic illnesses

1. Role of Amisulpride
in the management
of psychotic illnesses
S.K. Kar

2. Thedancers
Amisulpride
Levosulpiride
Sulpiride

3. Amisulpride Levosulpiride Sulpiride

4. Theaudience
Schizophrenia
Bipolar disorder
Other mood disorder (Dysthymia)

5. Thestoryis
about……
Amisulpride
Psychotic
disorders

6. History
 1990s: Introduced to market by Sanofi-Aventis (A
French company)
 2008s: Patent with Sanofi-Aventis expired and it was
available in generic formulations

7. How
Amisulpride
works?
 Dopamine partial agonist; Dopamine
stabilizer
 Dose dependent action & state
dependent action
Facilitates dopamine
transmission
Low doses
Blocks dopaminergic
transmission
High doses
High
dopaminergic
state
Reduces
dopaminergic
output
Low
dopaminergic
state
Increases
dopaminergic
output
Receptor Agonist Antagonist
D2 + (low doses) + (high doses)
D3 - +
H1, 5-HT7, 5-
HT2B
- +

8. How long?
Actions may start as early as by 1 week
Wait for 4-6 weeks to see the efficacy
Looking for cognitive functions: Wait for
16-20 weeks
Continue till complete remission / plateau
First episode psychosis: At least 1 year
after reaching plateau
Second & subsequent episodes: Indefinite
period of treatment

9. Amisulpride
Positive Negative Aggressive Affective
Target symptoms
Cognitive

10. Using
Amisulpride?
 Baseline investigation: Metabolic parameters
 Specific situation: ECG, Electrolytes, Blood counts
 If it does not work: Trying another antipsychotic
drug
 After 2 failed trials of antipsychotics : Clozapine can
be tried
 Augmentation of amisulpride: Valproate,
Lamotrigene, Carbamazepine, Oxcarb., Lithium,
BZDs
 Reduces positive symptoms; Unable to eliminate the
symptoms completely (also valid for other
antipsychotics)
 Monitoring for side effects:
 EPS, Galactorrhoes, Amenorrhoea, Sleep disturbances,
Agitation, Anxiety, Constipation, Wt. gain
Dosing tips:
Negative symptom : 50 – 300mg/day
Positive symptoms: 400-800mg/day
Dysthymia : 50mg/day
Beyond 400mg/day, to be given in divided doses
Maximum recommended dose: 1200mg/day
Beyond 400mg/day@ Risk of agitation
Beyond 800mg/day @ Risk of QTc prolongation
Renal insufficiency needs cautious use

11. No(Avoid)
Amisulpride,
if…..
 Pheochromocytoma
 Prolactin-dependent tumors
 Pregnancy & lactation
 Children (below 18yrs: Safety & efficacy not
studied)
 Concomitantly with drugs that prolongs QTc
 Allergy to amisulpride
 Severe renal impairment

12. Why
Amisulpride?
Evidences
so far…….

13. Amisulpride
versusother
atypical
antipsychotics for
schizophrenia
 Trials comparing oral amisulpride with oral
forms of aripiprazole, clozapine, olanzapine,
quetiapine, risperidone, sertindole, ziprasidone or
zotepine in people with schizophrenia or
schizophrenia-like psychoses.
 Amisulpride was similarly effective as olanzapine
and risperidone and more effective than ziprasidone
 Amisulpride induced weight gain less than
risperidone
 Conclusion:
 Amisulpride may be somewhat more effective than
ziprasidone, and more tolerable in terms of weight gain
and other associated problems than olanzapine and
risperidone
Cochrane Database Syst Rev. 2010 Jan 20;(1):CD006624. doi: 10.1002/14651858.CD006624.pub2.

14. Comparativeefficacyand
tolerabilityof32oral
antipsychoticsfortheacute
treatmentofadultswith
multi-episodeschizophrenia:
asystematicreviewand
networkmeta-analysis
Lancet. 2019 Sep 14; 394(10202): 939–951.
doi: 10.1016/S0140-6736(19)31135-3

15. Comparativeefficacyand
tolerabilityof32oral
antipsychoticsfortheacute
treatmentofadultswith
multi-episodeschizophrenia:
asystematicreviewand
networkmeta-analysis
Lancet. 2019 Sep 14; 394(10202): 939–951.
doi: 10.1016/S0140-6736(19)31135-3
--- Favors Antipsychotic---- Favors Placebo ---
Efficacy

16. Comparativeefficacyand
tolerabilityof32oral
antipsychoticsfortheacute
treatmentofadultswith
multi-episodeschizophrenia:
asystematicreviewand
networkmeta-analysis
Lancet. 2019 Sep 14; 394(10202): 939–951.
doi: 10.1016/S0140-6736(19)31135-3
Efficacy

17. Comparativeefficacyand
tolerabilityof32oral
antipsychoticsfortheacute
treatmentofadultswith
multi-episodeschizophrenia:
asystematicreviewand
networkmeta-analysis
Tolerability
Lancet. 2019 Sep 14; 394(10202): 939–
951.

18. Comparativeefficacyand
tolerabilityof32oral
antipsychoticsfortheacute
treatmentofadultswith
multi-episodeschizophrenia:
asystematicreviewand
networkmeta-analysis
Tolerability
Lancet. 2019 Sep 14; 394(10202): 939–
951.

21. Conclusion
 Efficacy
 Comparable to olanzapine & risperidone
 Tolerability
 Metabolic friendly
 Higher risk of prolactinemia
 Cost
 For negative symptoms: Reasonable cost
 Positive symptoms: Higher cost
 Availability
 Not an issue
 Evidences
 Less number of head to head trials

22. Lancet. 2019
Lancet. 2013
Comparative efficacy of ……..
32 antipsychotics

23. Amisulpride
Becomes Choice:
Negative symptoms
Depressive symptoms
Sedation not required
Augmentation of clozapine
Low risk of diabetes
Low risk of dyslipidemia
Low risk of weight gain

24. Amisulpride says …