ISDN Cream and Insomnia
Isosorbide dinitrate (ISDN) cream does not cause insomnia when applied topically for anal fissures. The documented side effects of topical ISDN are limited to headache, which occurs in a minority of patients and is typically mild and transient.
Evidence from Clinical Studies
The most comprehensive evidence comes from multiple prospective studies specifically evaluating topical ISDN for anal fissures:
Headache is the only consistently reported side effect across all studies, occurring in approximately 7-50% of patients, and is described as mild and transient 1, 2, 3.
In a study of 100 patients treated with ISDN ointment, the only complication observed was temporary headache in 7 patients (7%), with no mention of insomnia or sleep disturbances 1.
A prospective study of 16 patients using intra-anal ISDN application every 3 hours (except during the night) reported that all patients experienced mild and transient headache, but no sleep-related adverse effects were documented 2.
A larger study of 34 patients treated with topical ISDN for up to 12 weeks reported no insomnia or sleep disturbances among the documented side effects 3.
Mechanism and Systemic Absorption
The local application of ISDN for anal fissures results in minimal systemic absorption, which explains the absence of systemic side effects like insomnia:
ISDN works locally by reducing internal anal sphincter pressure and increasing anodermal blood flow through nitric oxide-mediated vasodilation 3, 4.
The doses used topically (1.25-2.5 mg applied three times daily) are substantially lower than systemic doses used for cardiovascular conditions 4.
Important Clinical Distinction
It is critical to distinguish between topical ISDN for anal fissures and systemic nitrate formulations used for cardiac conditions:
Systemic isosorbide mononitrate (used for angina) can cause dizziness and hypotension, which might indirectly affect sleep quality, but insomnia is not listed as a documented side effect even for systemic formulations 5.
The documented side effects of systemic nitrates include headaches, hypotension, dizziness, and reflex tachycardia—but not insomnia 5.
Clinical Recommendations
If a patient using ISDN cream reports insomnia, consider alternative explanations:
Pain from the anal fissure itself commonly disrupts sleep, and this typically improves within 6-10 days of starting ISDN treatment as pain resolves 2, 3.
Anxiety about the condition or other concurrent medications should be evaluated as potential causes of sleep disturbance.
The headache associated with ISDN, while common, is mild and transient and does not typically interfere with sleep 1, 2.
Continue ISDN treatment as prescribed (typically for 6-12 weeks) unless other contraindications arise, as the healing rate is excellent (83-93%) and the side effect profile is limited to mild, transient headache 1, 3, 4.