Abstract
We would like to call attention to the possibility that aripiprazole could induce a severe hypertensive crisis in adolescents. We report the case of a 14-year-old girl admitted to the hospital for a first psychotic episode. Upon admission, auditory hallucinations, paranoid delusions, disorganized speech, and bizarre behavior were present. The medical history and the physical examination revealed no somatic disorder. Routine blood tests, including complete blood cell count, and liver and renal functions were normal. No illicit drugs or alcohol were detected in blood or urine. Also, no specific abnormalities were observed on the electroencephalogram or on the brain magnetic resonance imaging (MRI). Aripiprazole was initiated at 10 mg/day. Thirty-three hours after the first dose, the patient complained of headache and palpitations. The physical examination revealed that the patient had developed a hypertensive crisis combining arterial hypertension (190/100 mmHg) and tachycardia (125 beats per minute [bpm]). An electrocardiogram revealed sinusal tachycardia with no other significant abnormalities. Ariprazole was interrupted and the malignant hypertension successfully treated with nifedipine. Twenty-four hours later, we interrupted the calcium channel blocker and changed to an alternative second-generation antipsychotic (risperidone). Additional clinical and paraclinical investigations excluded the main endocrine and renovascular disorders that could explain this hypertensive crisis. The patient's blood pressure returned to normal for her remaining 2 weeks of hospitalization.
Although we are unable to prove that aripiprazole is causally related to this hypertensive crisis, a similar case was reported in a 56-year-old schizophrenic patient (Borras et al. 2005). These case reports contrast with the lack of occurrence of blood pressure abnormalities reported in most studies exploring the efficacy and tolerability of aripiprazole in adolescents and adults (Findling et al. 2008; Kane et al. 2009). However, some studies have reported a relatively high incidence of hypertension in patients treated with aripiprazole versus placebo (respectively 7.8%, n = 73 and 3.6%, n = 77) (Keck et al. 2007). These discrepancies could be explained by the length of follow-up of the studies, because longer periods of follow-up correlate with an increased incidence of metabolic syndrome, i.e., weight gain, dyslipidemia, hyperglycemia, and hypertension.
The mechanisms implied in the development of hypertension in patients suffering from a metabolic syndrome are probably not the same as those leading to the occurrence of a hypertensive crisis 24 hours after the introduction of aripiprazole. Aripiprazole is known to display high affinity for dopamine (D3) and serotonin (5-HT1A, 5-HT2A) receptors and functionally, to act as an inverse agonist at 5-HT2B receptors and as a partial agonist at 5-HT2A, 5-HT2C, D3, and D4 receptors (Shapiro et al. 2003). It also displays high affinity for the α-1A adrenergic receptors and to a less degree to the α-1B, -2A, -2B, -2C and β-1, -2 adrenergic receptors (Shapiro et al. 2003). Many studies underline the role of the α-1A adrenergic receptors in malignant hypertension (Fu et al. 1994) and also in hypertensive crisis due to pheochromocytoma (Kobal et al. 2008). Further investigations are needed to understand the mechanisms involved, but individual sensitivity is probably an important factor.
This important side effect, although seemingly of rare occurrence, is too significant to be disregarded, and any prescription of aripiprazole should be carefully monitored, specifically in adolescents. Aripiprazole is now widely prescribed since it becomes the second atypical antipsychotic to receive Food and Drug Administration (FDA) approval for the treatment of schizophrenia in teens.