The normal vascular response with assumption of the upright posture is pooling of blood in lower extremities → decreased venous return to the heart → reduced cardiac output → compensatory increase in sympathetic outflow → increased peripheral resistance, venous return, cardiac output → limit the fall in BP to 5–10 mmHg SBP .

A disruption in the compensatory mechanism results in a greater fall in BP when the body assumes an upright posture.

Orthostatic hypotension is caused by disease conditions that impair autonomic reflexes resulting in a failure to increase peripheral resistance and venous return to the heart. It can also occur when there is significant intravascular volume depletion. Medications cause orthostatic hypotension by multiple mechanisms including vasodilation, volume depletion , and autonomic dysfunction. Major etiologies are listed in the table.

Orthostatic hypotension is a common side effect of antipsychotics and causes syncope in a small proportion of patients. Both the hypotension and syncope are most commonly reported with clozapine [1]. It is thought to result mainly from blockade of alpha-1 receptors in peripheral blood vessels thus interfering with the vasoconstrictor response to peripheral pooling of blood. Other mechanisms are vasodilation from cholinergic blockade and central effect on autonomic regulation and baroreceptor reflexes [2]. In general, lower potency agents are more likely to cause orthostatic hypotension. The hypotension occurs early in treatment and often patients develop tolerance to this side effect. It is reversible on stopping the offending medication.

Among antidepressants, tricyclic antidepressants (TCAs) and older monoamine oxidase inhibitors (MAOIs) can cause orthostatic hypotension by alpha-adrenergic blockade. Selective serotonergic reuptake inhibitors (SSRIs) are only rarely associated with orthostatic hypotension [3]. Mirtazapine has moderate alpha-adrenergic blockade and occasionally causes orthostatic hypotension. Trazodone is also associated with this side effect. Wellbutrin is not associated with orthostatic hypotension .

Mood stabilizers are not associated with orthostatic hypotension.

Risk factors for developing orthostatic hypotension include polypharmacy, older age, preexisting cardiac, or metabolic disease.