On 2017 Apr 12, Konstantinos Fountoulakis commented:

This is a paper on the efficacy of adjunctive aripiprazole on the reduction of prolactin levels in patients with antipsychotic-induced hyperprolactinaemia (1). In that particular study, adding aripiprazole in stabilized patients with schizophrenia already under haloperidol (mean dosage around 20 mg daily) was not accompanied by an increase in side-effects or destabilization of the patients. However, the unusually low Simpson Angus scale scores for haloperidol treated patients, implies the use of anticholinergics; this could have masked an increase in EPS. If on the contrary no anticholinergics were used, then this could be a special population of patients. The Simpson Angus scale does not rate akathisia, (a major problem with aripiprazole) thus it is rather inadequate for that study. A crude explanation of the lowering of prolactin levels could be that adding aripiprazole reduced the overall antidopaminergic effect of haloperidol but this could had been achieved just by lowering the haloperidol dosage. Another explanation suggests that aripiprazole as a partial dopamine agonist leads to internalization of dopamine receptors (2). However, when spared activated receptors are not available, it is unlikely that aripiprazole could exert its ‘partial agonist’ properties and manifest a more artidopaminergic effect, thus leading to more EPS (3). A preferential agonist action of aripiprazole in the pituitary implies also the presence of spare D2 receptors in the pituitary and it is in contrast with the literature (4). The only remaining explanation is that since it has been consistently shown that aripiprazole possesses a higher affinity to D2 receptors than haloperidol, it also completely replaced haloperidol on the D2 receptor. Shim et al discuss it however they do not follow it explicitly. The magnitude of this replacement should be considered to be almost complete since it has been suggested that aripiprazole is effective when >90% of D2 receptors are occupied (5). Thus it does not seem that the conclusions of Shim et al are justified. In essence what their trial showed is that it is needless to add aripiprazole; the therapist should either reduce the dosage of the original antipsychotic or switch to aripiprazole or to another appropriate agent

References

1. Shim JC, Shin JG, Kelly DL, Jung DU, Seo YS, Liu KH, Shon JH, Conley RR: Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial. Am J Psychiatry 2007; 164(9):1404-10
2. Laruelle M: Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 2000; 20(3):423-51
3. Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, Yocca FD, Molinoff PB: Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 2002; 302(1):381-9
4. Dean B, Pavey G, Scarr E, Goeringer K, Copolov DL: Measurement of dopamine D2-like receptors in postmortem CNS and pituitary: differential regional changes in schizophrenia. Life Sci 2004; 74(25):3115-31
5. Hamamura T, Harada T: Unique pharmacological profile of aripiprazole as the phasic component buster. Psychopharmacology (Berl) 2007; 191(3):741-3

On 2017 Apr 12, Konstantinos Fountoulakis commented:

This is a paper on the efficacy of adjunctive aripiprazole on the reduction of prolactin levels in patients with antipsychotic-induced hyperprolactinaemia (1). In that particular study, adding aripiprazole in stabilized patients with schizophrenia already under haloperidol (mean dosage around 20 mg daily) was not accompanied by an increase in side-effects or destabilization of the patients. However, the unusually low Simpson Angus scale scores for haloperidol treated patients, implies the use of anticholinergics; this could have masked an increase in EPS. If on the contrary no anticholinergics were used, then this could be a special population of patients. The Simpson Angus scale does not rate akathisia, (a major problem with aripiprazole) thus it is rather inadequate for that study. A crude explanation of the lowering of prolactin levels could be that adding aripiprazole reduced the overall antidopaminergic effect of haloperidol but this could had been achieved just by lowering the haloperidol dosage. Another explanation suggests that aripiprazole as a partial dopamine agonist leads to internalization of dopamine receptors (2). However, when spared activated receptors are not available, it is unlikely that aripiprazole could exert its ‘partial agonist’ properties and manifest a more artidopaminergic effect, thus leading to more EPS (3). A preferential agonist action of aripiprazole in the pituitary implies also the presence of spare D2 receptors in the pituitary and it is in contrast with the literature (4). The only remaining explanation is that since it has been consistently shown that aripiprazole possesses a higher affinity to D2 receptors than haloperidol, it also completely replaced haloperidol on the D2 receptor. Shim et al discuss it however they do not follow it explicitly. The magnitude of this replacement should be considered to be almost complete since it has been suggested that aripiprazole is effective when >90% of D2 receptors are occupied (5). Thus it does not seem that the conclusions of Shim et al are justified. In essence what their trial showed is that it is needless to add aripiprazole; the therapist should either reduce the dosage of the original antipsychotic or switch to aripiprazole or to another appropriate agent

References

1. Shim JC, Shin JG, Kelly DL, Jung DU, Seo YS, Liu KH, Shon JH, Conley RR: Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial. Am J Psychiatry 2007; 164(9):1404-10
2. Laruelle M: Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 2000; 20(3):423-51
3. Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, Yocca FD, Molinoff PB: Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 2002; 302(1):381-9
4. Dean B, Pavey G, Scarr E, Goeringer K, Copolov DL: Measurement of dopamine D2-like receptors in postmortem CNS and pituitary: differential regional changes in schizophrenia. Life Sci 2004; 74(25):3115-31
5. Hamamura T, Harada T: Unique pharmacological profile of aripiprazole as the phasic component buster. Psychopharmacology (Berl) 2007; 191(3):741-3