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Published: April 2003
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Atypical Antipsychotics May Cause Hypertension

Prescriber Update 24(1): 4
April 2003

Dr David Coulter, IMMP Director,
New Zealand Pharmacovigilance Centre, Dunedin

Acute hypertension may occur soon after the commencement of atypical antipsychotic treatment and can be severe, with collapse and altered consciousness. There may be an increased risk if selective serotonin reuptake inhibitors (SSRIs) are administered concomitantly. This adverse reaction appears to be dose-related and it is recommended that blood pressure be monitored during the early stages of atypical antipsychotic therapy, particularly in the presence of SSRIs.

Adverse reaction identified through IMMP monitoring
Case 1
Case 2
Other cases had similar features
Concomitant use of SSRIs may increase risk of hypertension
Monitor BP when commencing atypical antipsychotics or adding in SSRIs
References

Adverse reaction identified through IMMP monitoring

All of the atypical antipsychotics currently available in New Zealand (i.e. clozapine, olanzapine, quetiapine and risperidone) are monitored in the Intensive Medicines Monitoring Programme (IMMP). From the 572 case reports analysed, hypertension has been identified as a possible adverse reaction. Routine screening of the data revealed this unexpected association.

Hypotension with atypical antipsychotics is a known effect and for all four medicines a total of 19 reports of hypotension, or symptoms suggesting hypotension (e.g. faintness) have been received. In comparison, 13 reports of hypertension have been received; 10 with clozapine, two with risperidone and one with quetiapine. At this stage of monitoring more data have been collected for clozapine and so the actual numbers of reports of hypertension are not a guide to comparative risk. The two most severe cases occurred with risperidone and these are described below.

Case 1

A woman aged 53 had been on risperidone 1mg daily for three days when she collapsed with diminished consciousness (unresponsive to voice) and was found to have a blood pressure (BP) of 190/110 and a tachycardia of 140. The risperidone was withdrawn and by the following day she had recovered. The patient had a history of hypertension and was on treatment with enalapril 2.5mg daily, but the BP had been "normal" prior to taking risperidone. She was also taking paroxetine 40mg and thioridazine 25mg daily.

Case 2

A woman aged 54 was commenced on risperidone 0.5mg daily and after the third dose developed rigidity and a BP of 210/110. Her level of consciousness was reduced. There was no fever, and her creatine kinase and renal function test results were normal. Risperidone was withdrawn and the symptoms resolved within six hours of admission to hospital. She advised that her usual BP was around 145/100 and she was on treatment with cilazapril 5mg daily for hypertension. Other medicines were paroxetine 30mg daily and pantoprazole 40mg daily.

Other cases had similar features

In the other 11 cases of hypertension occurring during atypical antipsychotic treatment, the ages ranged from 15 to 66 years, with eight patients being under 35 years of age. There was a marked rise in BP in each case with the systolic ranging from 140 to 170 and diastolic pressures ranging from 95 to 120. In all but one case, the elevated BP was noted within a month of atypical antipsychotic treatment commencing. Concomitant medicines were recorded for five patients, two of whom were taking the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram. In three patients the antipsychotic was withdrawn and recovery was rapid, and in two the BP returned to normal with dose reduction.

It seems likely that the hypertensive reaction to atypical antipsychotics is dose-related because it was noted that the BP rose during upward titration of the dose in several patients and two patients recovered with dose reduction. Hypertension resolved in one patient while continuing on treatment, and in two others the BP was controlled with ACE inhibitors while continuing on the atypical antipsychotic. The outcome is unknown for three patients.

Concomitant use of SSRIs may increase risk of hypertension

Of note is that four of the 13 patients were also taking SSRIs, including the two patients with the most severe hypertension, both of whom were taking paroxetine. The atypical antipsychotics and the SSRIs share some common CYP450 enzymes in their metabolism and there is potential for an increase in blood levels of the antipsychotic through competitive inhibition.

Monitor BP when commencing atypical antipsychotics or adding in SSRIs

The evidence from these case reports is sufficient to establish a signal of a reaction that seems little known.  Only a few case reports in the literature describe hypertension, all with clozapine.1,2,3  The hypertensive reaction to the atypical antipsychotics is generally of early onset and may be more likely to occur with the concomitant administration of SSRIs. At this stage, it is unclear whether pre-existing hypertension is a risk factor. It would seem prudent to monitor blood pressure during early stages of therapy with atypical antipsychotics, particularly when SSRIs are prescribed concomitantly.

Competing interests (author): Novartis has provided research grants for the IMMP. Novartis is the sponsor of Clozaril® (clozapine).

Correspondence to Dr David Coulter, NZ Pharmacovigilance Centre, PO Box 913, Dunedin.

References
  1. Gupta S. Paradoxical hypertension associated with clozapine. Am J Psychiatry 1994;151:148.
  2. George TP, Winther LC. Hypertension associated with clozapine. Am J Psychiatry 1996;153:1368-1369.
  3. Ennis LM, Parker RM. Paradoxical hypertension associated with clozapine. Med J Aust 1997;166:278.

 

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