It appears to have comparable efficacy to olanzapine in the treatment of schizophrenia. Amisulpride augmentation, similarly to sulpiride augmentation, has been considered a viable treatment option (although, it is worth noting that the supporting evidence is limited to the theory, case reports, a small randomised double-blind placebo-controlled trial and a couple of open-label studies) in clozapine-resistant cases of schizophrenia. A randomised, double-blind, placebo-controlled clinical trial has been conducted to evaluate the efficacy of celecoxib as an adjunct to amisulpride, with significant success. Another recent study concluded that amisulpride is an appropriate first-line treatment for the management of acute psychosis.
Amisulpride has been tried as a treatment for acute mania in a few open-label studies. These findings should be interpreted with caution, not just due to the fact that these clinical trials were all open-label and hence low-quality but also because several case reports have been made documenting the precipitation of mania in schizophrenia patients that received amisulpride.
At low doses, it is also used to treat dysthymia where it appears to be at least as effective as conventional antidepressants according to a recent Cochrane review. In this indication, amisulpride is significantly more effective than:
Low-dose amisulpride has been found to be an effective treatment for postoperative emesis in a recent randomised, double-blind, placebo-controlled clinical trial. In a small (N=11) clinical trial amisulpride combined with either mirtazapine or citalopram was found an effective treatment for psychotic depression in elderly patients, although it should be noted that this trial was not placebo-controlled and hence the level of evidence it provides to amisulpride's efficacy in this indication is low. In a medium-sized (N=106) single-blind study it was found efficacious and well-tolerated in improving depressive symptoms in cancer patients undergoing chemotherapy.
Hyperprolactinaemia (which can lead to galactorrhoea, breast enlargement and tenderness, sexual dysfunction, etc.)
Weight gain (produces less weight gain than chlorpromazine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, zotepine and more (although not statistically significantly) weight gain than haloperidol, lurasidone, ziprasidone and approximately as much weight gain as aripiprazole and asenapine)
Anticholinergic side effects (although it does not bind to the muscarinic acetylcholine receptors and hence these side effects are usually quite mild) such as
- dry mouth
- disorder of accommodation
- Blurred vision
Extrapyramidal side effects (EPS; including dystonia, tremor, akathisia, parkinsonism). Produces a moderate degree of EPS; more than aripiprazole (not significantly, however), clozapine, iloperidone (not significantly), olanzapine (not significantly), quetiapine (not significantly) and sertindole; less than chlorpromazine (not significantly), haloperidol, lurasidone (not significantly), paliperidone (not significantly), risperidone (not significantly), ziprasidone (not significantly) and zotepine (not significantly).
Somnolence. It produces minimal sedation due to its absence of cholinergic, histaminergic and alpha adrenergic receptor antagonism. It is one of the least sedating antipsychotics.
QT interval prolongation (in a recent meta-analysis of the safety and efficacy of 15 antipsychotic drugs amisulpride was found to have the 2nd highest effect size for causing QT interval prolongation)
Hyperprolactinaemia results from antagonism of the D2 receptors located on the lactotrophic cells found in the anterior pituitary gland. Amisulpride has a high propensity for elevating plasma prolactin levels as a result of its poor blood-brain barrier penetrability and hence the resulting greater ratio of peripheral D2 occupancy to central D2 occupancy. This means that to achieve the sufficient occupancy (~60-80%) of the central D2 receptors in order to elicit its therapeutic effects a dose must be given that is enough to saturate peripheral D2 receptors including those in the anterior pituitary.
Amisulpride's use is contraindicated in the following disease states
Amisulpride and its relative sulpiride have been shown to bind to and activate the GHB receptor at doses that are used for therapeutic purposes.
Though it has long been widely assumed that dopaminergic modulation is solely responsible for the respective antidepressant and antipsychotic properties of amisulpride, it has recently been shown that it also acts as a potent antagonist at the 5-HT7 receptor. Several of the other atypical antipsychotics such as risperidone and ziprasidone are potent antagonists at the 5-HT7 receptor as well, and selective antagonists of the receptor show antidepressant properties themselves. To characterize the role of the 5-HT7 receptor in the antidepressant effects of amisulpride, a study prepared 5-HT7 receptor knockout mice. The study found that in two widely used rodent models of depression, the tail suspension test, and the forced swim test, those mice did not exhibit an antidepressant response upon treatment with amisulpride. These results strongly suggest that 5-HT7 receptor antagonism mediates the antidepressant effects of amisulpride.
Amisulpride also appears to bind quite strongly to the 5-HT2B receptor (see below table), though any implications of this are unclear.
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