Nimodipine is indicated for the prophylaxis and treatment of ischemic neurologic deficits caused by cerebral vasospasm after subarachnoid hemorrhage that follows ruptured intracranial aneurysm. The patients should be in good neurologic condition postictus, eg, Hunt and Hess grades I to III.
Novel methods of administration of nimodipine for vasospasm. Besides oral administration, several novel methods for the delivery of nimodipine have been developed:
Intraarterial. Selective continuous intraarterial nimodipine treatment has been shown to be effective for refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage (32). Based on data collected from 42 patients, nimodipine has been recommended as an effective and safe intraarterial agent for the treatment of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage (04). Another retrospective study has shown beneficial effects in some patients with low-dose intraarterial nimodipine and the authors consider it as a valid adjunct for the endovascular treatment of cerebral vasospasm (05). A retrospective review from an institution where intraarterial nimodipine has been used since 2009 concluded that the treatment appears to be effective in reversing angiographic cerebral vasospasm, but it is not always effective in reversing clinical deterioration as several other factors, including treatment delay, affect the outcome (02). Results of another study showed that continuous intraarterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to hypertensive hypervolemic therapy and oral nimodipine alone, but emphasized that multimodal neuromonitoring should be done, and the dosage as well as the time of infusion should be determined, for each patient (03). A case control study concluded that angiographic reversal of vasospasm is seen in most patients following intraarterial nimodipine, but this does not always result in a long-lasting clinical response and is not a major advantage over the conventional hemodynamic therapy (07).
Intranasal administration. Lipid nanocapsules have been evaluated for particle size, drug payload, and in vitro drug release. In a study, the in vivo pharmacokinetic behavior of lipid nanoparticles loaded with nimodipine in blood and brain was compared with nimodipine solution after intravenous administration in rats (21). Results showed that they were capable of delivering the same amount of nimodipine to the brain with lower drug levels in blood. Lipid nanoparticles could provide an effective systemic delivery of nimodipine into the brain, with lower frequency of administration and minimal side effects.
Cisternal and intraventricular administration. Cisternal lavage with nimodipine by stereotactic catheter ventriculocisternostomy is a novel rescue therapy for the prevention of delayed cerebral infarction due to cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (22).
Stroke. Development of nimodipine for the indication of ischemic stroke was stopped after reaching phase III because the results revealed no evidence of efficacy of nimodipine in acute ischemic stroke.
Dementia. There is no convincing evidence to show that nimodipine is a useful treatment for unclassified dementia, Alzheimer disease, vascular dementia, or mixed Alzheimer and vascular dementia. A multicenter randomized clinical trial in China is evaluating the benefits and safety of nimodipine, administered within 1 week of onset of ischemic stroke, in preventing/treating mild cognitive impairment (31).
Epilepsy. Nimodipine was shown to have an anticonvulsive effect on penicillin-induced epileptiform activity in experimental animals. The explanation of this anticonvulsive effect is the calcium channel blocking effect of nimodipine to prevent excessive calcium influx into neurons, which is the initial step toward a seizure. A systematic review of randomized placebo-controlled add-on trials of calcium antagonists, including nimodipine in drug-resistant epilepsy, did not show efficacy (11).
Bipolar mood disorder. Nimodipine has been found to have a beneficial effect in ultrarapid-cycling bipolar depression.
Vestibular vertigo. Nimodipine has been reported to be effective in reducing the frequency of vestibular vertigo.
Urge incontinence. Treatment of geriatric urge incontinence with 30 mg nimodipine twice daily did not result in a significant improvement of incontinent episodes.
Call-Fleming syndrome. Calcium channel blockers such as nimodipine have been tried for the treatment of Call-Fleming syndrome, which is characterized by sudden onset of headache and focal neurologic deficits associated with segmental cerebral vasoconstriction.
Headache. Patients with primary thunderclap headache have been treated effectively with nimodipine. Intravenous nimodipine has been used for headache of reversible cerebral angiopathy. Responsiveness to nimodipine has been reported in a patient with thunderclap headache triggered by micturition (08).
Severe traumatic brain injury. In a study of patients with severe head trauma nimodipine was shown to improve cerebral metabolism and outcome, indicating a neuroprotective effect (01).
Vasospasm following traumatic subarachnoid hemorrhage. This can be successfully treated with intraarterial infusion of nimodipine.
Reversible cerebral vasoconstriction syndrome. Nimodipine relieves the headache component of this syndrome but has no definite effect on the hemorrhagic and ischemic complications.
Protection against iron toxicity of the brain. An experimental study has shown that nimodipine, as an L-type voltage-gated calcium channel blocker, may serve as a protective agent against iron overload, particularly in neuron cell types highly susceptible to iron toxicity (15).
Neuroprotection in whole brain radiation. An experimental study in rats exposed to brain radiation has shown that nimodipine alleviates delayed cognitive deficits due to neuron apoptosis likely by regulation of Bax/Bcl-2 and BDNF in the hippocampus (30).
A subtype of daily persistent headache starting with a thunderclap headache. This subtype responds to nimodipine, which decreases the CSF tumor necrosis factor alpha levels causing cerebral artery vasospasm (23).
Orgasmic headache. Nimodipine has been used to relieve as well as prevent the recurrence of headache during sexual activity accompanied by spasm of the middle cerebral arteries bilaterally (13).
Cranial nerve injuries. Nimodipine has been used for treatment of vocal fold (cord) paralysis, which is commonly due to recurrent laryngeal nerve injury. A retrospective study has shown that nimodipine treatment for acute vocal fold paralysis yielded equal recovery rates regardless of whether the medication was started within 15 days of onset or between 15 to 30 days or after 30 days (28). A systematic review and meta-analysis of open clinical studies supports the positive effect of nimodipine on vocal fold and facial motion recovery after injury (14).
Promotion of neuroregeneration. Nimodipine has been shown to attenuate spinal cord degeneration in experimental autoimmune encephalomyelitis and promote remyelination in a mouse model of multiple sclerosis (26). Because it combines features of immunomodulation with beneficial effects on neuroregeneration, nimodipine may have broad therapeutic implications for chronic neuroinflammatory diseases.