hypotension is a known effect of atypical antipsychotics . in addition , the prevalence of orthostatic hypotension in the elderly is estimated to be between 5% and 33% and increases with age.1 orthostatic hypotension is a common side effect of a number of medications , including antipsychotic drugs , and a major contributing factor to the occurrence of falls with adverse consequences , such as bone fractures , injuries , functional decline , dependency , and death .
furthermore , the extent to which antipsychotic drugs cause hypotension differs , and low - potency conventional antipsychotics and clozapine are among the more problematic . however , there is little information on acute hypertension resulting from antipsychotic drugs .
aripiprazole is a potent ( high - affinity ) partial dopamine d2 agonist , a serotonin 5-ht1a agonist and a 5-ht2a antagonist.2 it acts as a functional antagonist of d2 receptors under hyperdopaminergic conditions but exhibits functional agonistic properties under hypodopaminergic conditions.3 here , two cases of acute hypertension during the switch from other antipsychotics to aripiprazole are reported .
her mental condition had been maintained with 2 mg / day of risperidone or 816 mg / day of perospirone for several years .
hypertension ( systolic blood pressure > 180 mmhg ) had developed 2 years previously and had been treated with a salt reduction policy and amlodipine at 5 mg / day . as a result
, her blood pressure was controlled , and amlodipine was discontinued after 1 year . due to akathisia , perospirone at 8 mg / day was changed to quetiapine at 100 mg / day or olanzapine at 5 mg / day ; however , these drugs were withdrawn because of sedation .
thus , aripiprazole was initiated , but she suffered from dizziness , headache , and anacatesthesia as well as hypertension ( 200/110 mmhg ) .
thus , aripiprazole was changed to risperidone at 2 mg / day , and her blood pressure immediately dropped to 130/80 mmhg .
this patient was a 63-year - old man with a 9-year history of bipolar disorders .
his primary symptoms included depressed mood , insomnia , appetite loss , concentration difficulty , and suicidal ideation .
he was diagnosed with hypertension ( systolic blood pressure > 180 mmhg ) 1 year previously and treated with a salt reduction policy and nifedipine at 10 mg / day .
consequently , his blood pressure was controlled , and nifedipine was discontinued after 3 months of treatment .
his mental status was depressed with lithium treatment at 600 mg / day , paroxetine at 30 mg / day and olanzapine at 5 mg / day .
because of persistent depressive episodes , olanzapine at 5 mg / day was switched to aripiprazole at 3 mg / day . when the dose of aripiprazole escalated to 24 mg / day
, his blood pressure increased to 180/90 mmhg with headache , and he was inarticulate . although his hypertension was treated with amlodipine at 5 mg / day and propranolol at 60 mg / day , his blood pressure did not change .
in the two cases presented here , hypertension after aripiprazole initiation but recovery after aripiprazole discontinuation was observed .
based on these clinical courses , it was concluded that the hypertension worsened due to aripiprazole , although withdrawal effects of previous antipsychotics can not be ruled out .
antipsychotics are known to cause the metabolic syndrome of insulin resistance , hyperlipidemia , and hypertension .
thus , addressing blood pressure as well as glycemia and lipid levels is an important step in the management of patients taking aripiprazole .
in addition , according to the product information , the most frequently reported adverse reaction in clinical trials was headache ( otsuka pharmaceutical co , ltd , tokyo , japan ) .
the dopamine receptor in vascular smooth muscle participates in vasodilatation , but the possibility that aripiprazole causes vascular smooth muscle to shrink as an antagonist under conditions in which dopamine is superabundant and high blood pressure is induced has been hypothesized . however , there is no d2 receptor in vascular smooth muscle , although there are d1 receptors .
because aripiprazole has extremely low affinity for the d1 receptor , it is unlikely that the high blood pressure observed with aripiprazole was mediated through the d1 receptor .
although hirose et al reported that aripiprazole acts as an antagonist for the 5-ht2a receptor,4 davies et al indicated that aripiprazole is a partial agonist for 5-ht2a.5 because the 5-ht2a receptor participates in the contraction of vascular smooth muscle , the possibility that vascular smooth muscle shrank as a result of aripiprazole acting as an agonist for 5-ht2a and inducing a rise in blood pressure has been hypothesized .
the involvement of -1a adrenergic receptors can not be ruled out because aripiprazole has high affinity for -1a adrenergic receptors,6 which is related to malignant hypertension.7 in addition , nitric oxide is known to suppress blood pressure .
an in vitro study using brain macrophages has suggested that aripiprazole inhibits nitric oxide production from microglial cells.8 therefore , suppression of nitric oxide by aripiprazole may result in the patient s hypertension .
however , only four reports have demonstrated high blood pressure induced by aripiprazole . borras et al reported hypertension ( 220/110 mmhg ) and tachycardia during aripiprazole treatment at 30 mg / day in a schizophrenic patient , which disappeared after aripiprazole discontinuation and propranolol
administration.9 pitchot and ansseau indicated that the addition of 5 mg of aripiprazole to 150 mg of venlafaxine in a patient with major depressive disorder led to hypertension ( 200/110 mmhg ) and that aripiprazole discontinuation led to normalized blood pressure within 48 hours.10 hsiao et al showed high blood pressure ( 220/110 mmhg ) , headache , and dizziness after treatment with 90 mg of duloxetine and 5 mg / day of aripiprazole in a depressed patient.11 moreover , the administration of nifedipine and ramipril did not have an antihypertensive effect , and blood pressures were normalized with a reduction in aripiprazole from 5 mg / day to 2.5 mg / day .
in addition , bat - pitault and delorme reported hypertension ( 190/110 mmhg ) in an adolescent patient , which was most likely induced by aripiprazole.12 although pitchot and ansseau and hsiao et al discussed the influence of a concomitant drug,10,11 case one in the current report received aripiprazole only , and high blood pressure developed after aripiprazole .
therefore , it is not likely that the influence of the concomitant drug induced hypertension .
pitchot and ansseau suggested the association with a prior history of cardiovascular disease , including coronary disease,10 and the two cases in the current report also revealed a history of hypertension .
therefore , blood pressure variation must be carefully monitored when administering aripiprazole to patients with a previous history of cardiovascular disease .
this report presented two cases demonstrating high blood pressure after aripiprazole initiation , although blood pressures were normalized following aripiprazole interruption .
although the mechanism underlying the rise in blood pressure remains unclear , careful monitoring of blood pressure variations when administering aripiprazole to patients previously treated for high blood pressure is necessary .
 aripiprazole is widely used in the treatment of schizophrenia and bipolar disorders . 
 although antipsychotics generally have hypotensive effects , two cases were identified that demonstrated hypertension during the switch from other antipsychotics to aripiprazole . 
 the hypertensive state of these patients recovered after switching back to other antipsychotics , and these cases suggest that aripiprazole may lead to hypertension . 
Introduction
Case one
Case two
Discussion
Conclusion