185 - References

References

184 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 1 dopamine receptor antagonism.9 All five dopamine receptor subtypes (D1–5) are known to be involved in renal sodium excretion and blood pressure regulation.9 Antipsychotics vary in their affinity for these dopamine receptor subtypes, and the relative importance of each receptor subtype is unclear. Other suggested mechanisms include α2 antagonism leading to prolonged noradrenaline release, hypertension through renal potassium loss, and sodium and fluid retention, possibly owing to D4 receptor antagonism.10 Some antipsychotics are more commonly implicated than others, although individual patient factors are also likely to be important. Most case reports involve clozapine,11,12 with some clearly describing normal blood pressure before clozapine was introduced, a sharp rise during treatment and return to normal when clozapine was discontinued or doses were decreased.12 Blood pressure has also been reported to rise again on rechallenge and increased urinary catecholamines mimicking phaeochromocytoma have been noted in some cases. Clozapine can usually be continued with antihypertensive drugs.12 Case reports also implicate aripiprazole,13–16 sulpiride,17,18 risperidone,19 quetiapine20 and ziprasidone.21 Olanzapine has been linked to water retention and hypertension in a pregnant woman22 and intracranial hypertension in an adolescent.23 Data available through the UK Medicines and Healthcare products Regulatory Authority yellow card system indicate that clozapine is the antipsychotic drug most associated with hypertension. There are substantially fewer reports with aripiprazole, olanzapine, quetiapine and risperidone.24 The timing of the onset of hypertension in these reports with respect to antipsychotic initiation is unknown. In long-­term treatment, hypertension is seen in around 30–40% of patients regardless of antipsychotic prescribed.25 A cross-­sectional study found an increased risk of hypertension only for perphenazine,26 a finding not readily explained by its pharmacology. No antipsychotic is contraindicated in essential hypertension, but extreme care is needed when clozapine is prescribed. Concomitant treatment with SSRIs may increase risk of hypertension, possibly via inhibition of the metabolism of the co-­prescribed antipsychotic.20 It is also theoretically possible that α2 antagonism may be at least partially responsible for clozapine-­induced tachycardia and nausea.27 Treatment of antipsychotic-­associated hypertension should follow standard protocols. Switching to alternative antipsychotics with a lower cardiometabolic risk should be considered where possible. There is specific evidence for the efficacy of valsartan and telmisartan in antipsychotic-­related hypertension.28 References

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