Severe orthostatic hypotension after adding low-dose aripiprazole to clozapine

Abstract

Lin YS et al. / Arch Clin Psychiatry. 2017;44(3):84 Dear Editor, Antipsychotics can cause orthostatic hypotension (OH) by blocking adrenergic receptors 1 . OH is easily under-recognized as it can be asymptomatic. In clinical practice, combination treatment of two or more antipsychotics is common; however, little attention has been paid to OH in this scenario. Here, we presented a patient who developed severe OH after adding aripiprazole 5 mg/d to clozapine 400 mg/d.A 33-year-old man with a 15-year history of schizophrenia presented because of severe auditory hallucination and persecutory delusion. After admission, the dose of clozapine was gradually increased to 400 mg/day, and the psychotic symptoms were improved. Over the following 4 weeks, the patient still exhibited negative symptoms, including alogia, avolition, asociality, and poor selfcare. Aripiprazole 5 mg/day was added, and the negative symptoms were improved. However, 2 weeks later, the patient fell down twice on a sudden rise from supine position. Physical and neurological examinations and the results of laboratory tests were negative. Notably, the lying-to-standing orthostatic test caused a remarkable change in blood pressure (BP). The patient showed 118/83 mmHg with pulse rate (PR) 90 beats per minute (bpm) in supine position and 70/36 mmHg with PR 122 bpm in standing position. Aripiprazole was discontinued, and the OH was relieved. After careful consideration of the risks and benefits, aripiprazole 5 mg/d was added again. However, OH recurred 2 weeks later. Therefore, aripiprazole was switched to escitalopram, and OH did not recur.OH is defined as a drop in BP (> 20/10 mmHg) within in 3 minutes of standing. The OH is associated with aripiprazole because of the temporal relationship between its occurrence and the commencement of aripiprazole, its resolution upon aripirazole discontinuation, and its recurrence with aripiprazole rechallenge. An animal study suggested that both clozapine and aripiprazole could block α 1 adrenoceptors, while the potential to cause OH is higher in clozapine 2 . There are few data addressing OH under the combination therapy of aripiprazole and clozapine. A review article reported no pharmacokinetic interaction between aripiprazole and clozapine 3 . Considering the pharmacodynamics, aripiprazole and clozapine might act together to antagonize the α 1 receptors, thereby increasing the risk of OH. Moreover, 5-hydroxytryptamine 2A (5-HT 2A ) antagonism could induce vasodilation 4 , and central 5-HT 1A stimulation could produce hypotension and bradycardia 5 . Being a 5-HT 2A antagonist and a 5-HT 1A partial agonist, aripiprazole may increase the risk of OH.In this case, the combination of aripiprazole and clozapine increased the risk of OH that was considered to be principally related to clozapine. However, the patient did not develop OH under high-dose clozapine treatment (400 mg/d). We suggest that the high-dose clozapine treatment have primed his vulnerability to OH. Therefore, even though the dose of add-on aripiprazole...

Effect of Antipsychotic Drugs and Orthostatic Hypotension on the Risk of Falling in Schizophrenic Patients

“…[21][22][23] It is because adverse drug reactions that are as unwanted effects of drug treatment, 24 with adrenergic receptors. 25 Furthermore, more on the dose of antipsychotic drugs or due to other physical conditions, tend to developed orthostatic hypotension. Prevention of orthostatic hypotension depends on the use of antipsychotics, 23,26 stepwise titration and doses distributed throughout the day (to minimize peak levels).…”

Safety and cardiovascular effects of multiple‐dose administration of aripiprazole and olanzapine in a randomised clinical trial

“…The BP lowering mechanism may be due to blocking the α1‐adrenergic receptors. Moreover, its 5‐HT2A antagonism could induce vasodilation and its 5‐HT1A agonism could produce hypotension and bradycardia (Lin, Ho, & Liang, 2017). Regarding OLA, SBP, DBP and HR significantly decreased after the first dose.…”

“…DBP decreased more in HTR2A rs6313 C allele carriers compared to T/T subjects during ARI treatment. Carriers of the wild‐type allele of HTR2A rs6313 could have induced vasodilatation, and therefore a decrease in BP (Lin et al, 2017).…”

Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial

“…The BP lowering mechanism may be due to blocking the α1-adrenergic receptors. Moreover, its 5-HT2A antagonism could induce vasodilation and its 5-HT1A agonism could produce hypotension and bradycardia (Lin et al, 2017). Regarding OLA, SBP, DBP and HR significantly decreased after the first dose.…”

“…DBP decreased more in HTR2A rs6313 C allele carriers compared to T/T subjects during ARI treatment. Carriers of the wild-type allele of HTR2A rs6313 could have induced vasodilatation, and therefore a decrease in blood pressure (Lin et al, 2017).…”