first generation antipsychotics along with amisulpride , risperidone , paliperidone , and zotepine have been consistently reported to be associated with the high rates of hyperprolactinemia and termed as  prolactin - raising ,  whereas clozapine , olanzapine , quetiapine , ziprasidone , and aripiprazole , which have a more favorable profile , have been termed as  prolactin - sparing .  switching over to aripiprazole or adjunctive aripiprazole , has been advocated for the optimal management of antipsychotic - induced hyperprolactinemia .
adjunctive treatment with aripiprazole has been shown to normalize prolactin levels without affecting improvements in the psychotic symptoms that had already been achieved with the previous antipsychotic treatment . however
, a literature search shows the case reports of paradoxical hyperprolactinemic symptoms such as galactorrhea associated with aripiprazole use .
saraf et al . in a case report of a female , who developed hyperprolactinemia , while on aripiprazole , postulated that aripiprazole could have dopamine antagonistic properties at higher doses as the partial d2 agonistic activity could be dose - related .
recent research has also shown that the beneficial effect of aripiprazole on other antipsychotic - induced hyperprolactinemia is seen at lower doses and plateaus off at higher doses . however , here , we present the case of a female with the delusional disorder who developed symptomatic hyperprolactinemia even while on a low dose ( 10 mg / day ) of aripiprazole .
a 36-year - old married female was presented to the psychiatry outpatient services with 2 years of delusion of infidelity and significant sociooccupational dysfunction in the absence of any impairment in sleep or appetite .
vitals were stable , body mass index ( bmi ) was calculated to be 26 and systemic examinations revealed no abnormality .
baseline prolactin level was 14 ng / ml . in view of the high bmi and poor insight , she was started on aripiprazole .
it was expected that the favorable side effect profile of aripiprazole with relatively less weight gain and extrapyramidal symptoms would ensure compliance .
aripiprazole was started at an initial dose of 5 mg at night and was increased to 10 mg and later 15 mg after 4 days each and 15 mg was continued as maintenance .
however , 3 weeks later , she was presented with galactorrhea and a missed menstrual period .
the possibility of aripiprazole - induced hyperprolactinemia was considered and aripiprazole was stopped . as she was otherwise asymptomatic ,
no other medication was started and she was sent home . at follow - up , 1-month later , galactorrhea had subsided , she had menstruated , and repeat prolactin levels were 18 ng / ml . her psychotic symptoms continued to be in remission , and she returned home medication - free .
aripiprazole was restarted as previously , but was maintained at 10 mg owing to the previous history of hyperprolactinemia .
she reported back within a month with the complaints of galactorrhea and amenorrhea at which time her psychotic symptoms were in complete remission .
serum prolactin levels were repeated and found to be elevated ( 84 ng / ml ) .
serum prolactin levels were normalized ( 19 ng / ml ) and hyperprolactinemia symptoms were subsided within 1-month .
peptides , steroids , and neurotransmitters regulate the synthesis and release of the hormone prolactin from the lactotrophs of the anterior pituitary .
dopamine acts as a tonic inhibitor of prolactin secretion through the tuberoinfundibular and the tuberohypophysial dopaminergic systems .
the binding of dopamine to the d2 receptors on the membrane of the lactotroph cells inhibits the prolactin gene transcription , synthesis and release of prolactin , and lactotroph proliferation . on the other hand , d2 receptor blockade by antipsychotics counteracts the tonic inhibitory effect of dopamine on prolactin secretion , thus elevating serum prolactin levels .
the degree of hyperprolactinemia caused correlates with the penetrability of the blood - brain barrier and the strength of the dopamine blockade .
the quicker the drug dissociation from the receptor , the lesser is the increase in plasma prolactin .
the functional activity of a partial agonist at the specific receptor depends on the presence or absence of other full agonists and antagonists in the surrounding milieu .
they bind to the receptor to produce the physiological response seen , when the receptor is activated .
however , if a full agonist is simultaneously present , the partial agonist shows functional antagonist activity .
it competes with the full agonist for receptor occupancy and when bound , the response is lesser than that seen with the full agonist alone .
aripiprazole has a lower intrinsic activity at the d2 receptor than dopamine , allowing it to act as both , a functional agonist and antagonist , depending on the surrounding levels of dopamine . in the presence of a prolactin - raising antipsychotic ,
adjunctive aripiprazole competes with it to possibly act as an agonist in the tuberoinfundibular pathway , thus bringing down the elevated prolactin levels .
however , as a stand - alone treatment , the functional activity of aripiprazole in this pathway would be dependent solely on the dopamine levels .
hence , it is possible that in the absence of a competing d2 antagonist and the presence of dopamine ( the natural agonist ) , aripiprazole could act as a functional antagonist at lower doses also , and thus , elevate prolactin levels .
 hyperprolactinemia is a common adverse effect of antipsychotic medication . 
 switching over to aripiprazole or adjunctive aripiprazole has been advocated for optimal management of antipsychotic - induced hyperprolactinemia . adjunctive treatment with aripiprazole has been shown to normalize prolactin levels without affecting already achieved improvements in psychotic symptoms . 
 however , here , we present the case of a 36 year old female with delusional disorder who developed symptomatic hyperprolactinemia while on aripiprazole treatment . 
 dopamine acts as a tonic inhibitor of prolactin secretion through the tubero - infundibular dopaminergic system . 
 aripiprazole being a partial agonist has a lower intrinsic activity at the d2 receptor than dopamine , allowing it to act as both , a functional agonist and antagonist , depending on the surrounding levels of dopamine . 
 hence , in the absence of a competing d2 antagonist and the presence of dopamine ( the natural agonist ) , aripiprazole could act as a functional antagonist and thus elevate prolactin levels . 
INTRODUCTION
CASE REPORT
DISCUSSION
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