Usually it can be used lower dosage as antidepressant in erderly for short period. 

Thanks for your answer. However, as clinical pharmacist i do not agree with amisulpride as first choice in elderly in depression (MDD), however i agree when we have depression with psychotic symptoms and maybe Alzheimer's dementia, because of its low impact on EPS (after risperidone and quetiapine; because D3 activity). In these view this drug can substitute tricyclic antidepressants and antipsychotics, which are not recommended acordnig to the Beers criteria and Priscus List. This drug has almost no sedative potential, which is also positive in long term trial. If a combination of amisulpride and antidepressant is under question, then SSRI (especially escitalopram) could be combined if we have an onset but not a remmision of MDD after 12 long term trial with monotherapy. Very positive is that this drug could be stopped immediately, because its low discontinuation potential (bcs. without H1, M3, alpha-1 activity).. Regards Matej

i do not write that this drug was the first choise in depression.

Amisulpride might indeed be very effective in the elderly patients. However, to my experience, the potential of inducing EPS is not that small. I have seen parkinsonism even after very low doses and if dose goes up to 200 mg and a patient is older than 75... Well, the drug becomes problematic. On the other hand, the use as an augmentation in MDD could be bigger. Low doses (usually up to 100 mg/day) are quite effective, particularly in cases with lack of energy / apathy / anhedonia. 

Thanks for the answers of all of you. Yes, i agree that efficacy has been showed in real clinical practice, especially because of its pharmacological profile. I agree that doses higher than 150 mg are problematic and I also agree that this drug must not be used as first line tratment for MDD. In most cases we can combine SSRIs with bupropion, because of its mechanism of action, althouh some trials has been negative (combination with duloxetine for example). However, this is very optimistic drug, which has very low consumption (too low for my opinion).

As clinical pharmacist i often has been involved at the old age departments. QTc prolongation is a problem, although often dose dependent (same like quetiapine). The biggest plus of amisulpriude is that has NO pharmacokinetic interactions! which is very important when we plan pharmacotherapy in elderly patients, because they are often treated with polypharmacy. The next important reason is a lack of pharmagenetic impacts on drug's pharmacokinetics, which is seen in other antipsychotics. In many patients a so called pharmacogenomic failure should be considered when a drug is prescribed (e.g. especially risperidone and quetiapine and also olanzapine). With amisulpride we do not have these problems and often when we do not have good outcomes (many failures) with other antipsychotics we can try with amisulpride because of pharmagenetic/impact on CYP sytems.

After all that has been written, my greatest concern about prescribing amisupride in the elderly is the prolongation of QTc.  According  a recent article in Lancet, among all first and second generation antipsychotics, amisulpride causes the highest QTc prolongation.

Dear Amar. This is completely true, however this is only one issue. In metaanalysis published by Cipriani and Leucht et al. in 2013 in the Lancet a multiple-treatment metaanalysis has been done. In the case of amisulpride the OR was 0,66, (QTc prolongation) which means that this is true. However, in the terms of all cause discontinuations amisulpruide was almost the best among (OR=0.44) together with clozapine. If I turn this story with overall efficacy of amisulpride was again 'among the best' with SMD -0,66 (clozapine had only higher SMD). This means that amisulpride is very good antipsychotic and QTc is one of the most problematic value. If I sum up, with prudent and careful selection we can protect our patients from QTc prolongation and ECG can be made before and after treatment with amisulpride. Also if we have patients with atrial fibrillation, heart failure and arrhythmias we should avoid the use of amisulpride. Next important issues are pharmacodynamic interactions (QTc-QTc drug), which could be very problematic again for amisulpride. For example elderly people are often treated with ciprofloxacin, moxifloxacin, amiodarone etc... and when these drugs are selected the use of amisulpride should be avoided (or we should change other medications). When I work as clinical pharmacist consultant in primary care setting I usually suggest GPs and psychiatrists which antibiotic should be chosen in patients treated with amisulpride (e.g. nitrofurantoin) to avoid serious important pharmacodynamic interactions with amisulpride. Another important drug is metoclopamide which should be avoided with amisulpride, because of serious possible EPS (also domperidone is not a great option because of QTc prolongatio). The best approach in these patients is to involve clinical pharmacist to protect patients and payers from serious important drug-drug interactions and minimize drug discontinuation, which is often seen in the patients treated with antipsychotics.

Amisulpride has dose dependent action on D2 receptors and in low (small) doses its actions is primarily via D2 autoreceptors and in high doses as antagonist on D2 receptors and small action on D1 receptors. Because of this mode of actions in small doses we can use Amisulpride as antidepressants and in higher doses as antipsychotic drug (potency towards D2 heteroreceptors is higher than autoreceptors). This is very specific mode (mechanism) of action and consequently we have specific so called 'dose-dependent' action.

The Second example of Amisulpride is its action via D3 receptors. Because of this activity (potency and efficacy) on D3 receptors there is very few possibility of serious adverse events in form of dyskinesia tardive and tremor in compare to haloperidol. Its D3 activity and small D1 activity (high doses) is key mode of action in ensuring the safety pharmacotherapy.

The third important feature of Amisulpride is connected with agonism/antagonism. Often named as partial agonist Amisulpride has similarities than partial agonists. In the case of low concentration acts on presynaptic autoreceptors. In the case of many combinations of antipsychotics there is a place for Amisulpride. With its special activity there are some positive trials where the antipsychotic polypharmacy has been used and proven. Especially interesting is its combination with clozapine, however there is special caution required, because of possible prolongation with QTc.

The fourth important thing is its use for negative symptoms of schizophrenia, for which sulpiride is better than 'typical' antipsychotics.

Taken together there are many features, which are connected with atypical antipsychotic and therefore it is more atypical antipsychotic than typical, although potency towards D2 receptors is very high compared to atypical antipsychotics.

If i conclude, this is very interesting agent for pharmacologists and psychiatrists and according to the trials, where polypharmacy was tasted, supiride/amisulpiride is underprescribed. In real clinical practice there is high prevalence of haloperidol and risperidone use in combinations with other antipsychotics, although we do not have evidence to do it (or contra evidence Lancet 2012 risperidone-clozapine or clozapine alone). On the another hand, there are positive trials of sulpiride/amisulpiride use especially with clozapine and olanzapine. As clinical pharmacist specialist within psychiatry i often suggest to add the Amisulpride or combine, when antipsychotic polypharmacy is under question.

Sulpiride and amisulpiride are DEFINITELY underutilized in the USA because neither is available!

Article Amisulpride treatment of clozapine-induced hypersalivation i...

Article Influence of chronic hyperprolactinemia induced by sulpiride...

Above are papers from Israel and Japan

I competely agree with you! Maybe you know why are not available in U.S.? This is maybe another story why there are not so many papers about those drugs, athough their efficacy has been proven many times.

It probably has to do with marketing because so much does in the USA, including:

McNeil not wanting to release pimozide because it was making huge profits off Haldol.

Sandoz trying to monopolize Clozaril by making it an antipsychotic for "treatment refractory schizophrenia" only.

But the specifics re: Sulpiride/amisulpiride I do not know.

Article The role of pimozide in clinical psychiatry: A review

Article Hematologic Impact of Antibiotic Administration on Patients ...

Article Exploring the Potential Effect of Polypharmacy on the Hemato...

Article Maximizing clozapine utilization while minimizing blood dysc...

Hey Matej - I am late to the debate. Amisulpride is effective and useful in low dose for negative symptoms. It has a useful dose range too, e.g. for 1st episode cases. Its augmentation of clozapine has been superseded by aripiprazole in recent years. 

To answer your question, I too believe its lack of profile / penetration is due to lack of marketing rather than lack of effect. Demonstrating the power of commercialism!