SUMMARY

• SPRAVATO is contraindicated in patients for whom an increase in blood pressure (BP) or intracranial pressure poses a serious risk (e.g., aneurysmal vascular disease, arteriovenous malformation, and history of intracerebral hemorrhage).¹
• Assess BP prior to administration of SPRAVATO. In patients whose BP is elevated prior to SPRAVATO administration (as a general guide: >140/90 mmHg) a decision to delay SPRAVATO therapy should take into account the balance of benefit and risk in individual patients.¹
• During the phase 3 clinical trials, patients who were already taking antihypertensive medications prior to the studies continued their concomitant antihypertensive medications at their regular schedule. If a patient was routinely taking the antihypertensive medications in the mornings, the morning dose was taken prior to intranasal dosing.^2,3
• During clinical trials, unless clinically indicated, it was recommended that transient increases in BP not be treated, as the BP typically returns to predose values within 2 hours following SPRAVATO nasal spray administration.^2,3 Refer patients experiencing symptoms of a hypertensive crisis immediately for emergency care. SPRAVATO should be used with caution in patients with hypertensive encephalopathy. The treatment with SPRAVATO should be initiated only if the benefit outweighs the risk.⁴
• Although not commonly required during the phase 3 long-term safety study (SUSTAIN-2), the following anti-hypertensive medications were used to treat elevated BP: bisoprolol, enalapril, captopril, metoprolol, amlodipine, bendroflumethiazide, hydrochlorothiazide, losartan, ramipril, and valsartan.⁵ These medications were either limited to use only on a dosing day or were newly initiated during the induction phase of the study. The proportion of SPRAVATO-treated patients receiving rescue medication for elevated BP in the study was 2.4% (8 out of 330 events).⁶
• An analysis of the short-term double-blind studies in TRD, evaluating a subset of patients without a prior history of hypertension, found that 2.1% of SPRAVATO+antidepressant (AD) and 1.2% of AD+placebo (PBO) patients initiated new antihypertensive medication. These included: amlodipine (0.7%), captopril (0.4%), losartan (0.4%), metoprolol (0.4%), and propranolol (0.4%) in the SPRAVATO+AD group, and hydrochlorothiazide (0.6%) and prazosin (0.6%) in the AD+PBO group.⁶
• Fua et al (2020)⁷ performed a post hoc analysis of patients with major depressive disorder and active suicidal ideation with intent (pooled data from the ASPIRE I and ASPIRE II trials),^8,9 which found that 15% of patients (34/227) who had received SPRAVATO+standard-of-care (SOC) and 4.9% of patients (11/225) who had received PBO+SOC experienced clinician-reported hypertension. Three patients in the SPRAVATO+SOC group received a single dose of captopril in response to a hypertensive adverse event. Two patients in the SPRAVATO+SOC group and 1 in the PBO+SOC group discontinued treatment due to hypertension. All severe hypertensive treatment-emergent adverse events resolved on the same day of dosing.
• BP should be monitored after SPRAVATO administration. Measure BP around 40 minutes post dose and subsequently as clinically warranted until values decline.¹ If BP remains high, promptly seek assistance from practitioners experienced in BP management.³

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 10 December 2024.