In the rare cases of infants who survive their first year of life, severe developmental and motor delays are seen; neither of two infants studied in 2019, both aged around two years, had achieved head control, and both required a ventilator to breathe.Type II is also known as the "lethal perinatal" form of OI, and is not compatible with survival into adulthood. Due to similarly severely deformed bones, sometimes infants with severe type III are wrongly initially classified as type II; once long-term survival is shown, they are considered as having type III instead. : 1511

Type III
Collagen quantity is sufficient, but is not of a high enough quality. : 1512  Clinical differentiation between types III and IV is not always simple, and is further confounded by the fact that an untreated adult with type IV may have worse symptoms than a treated adult with type III;: 1511  features only found in type III are its progressively deforming nature: 1511–1512  and the presence of a face with a "triangular" appearance.
This action inhibits the release of pro-nociceptive neurochemicals like glutamate, calcitonin gene-related peptide (CGRP), and substance P in the brain and spinal cord, resulting in pain relief. Therapeutic use
Due to the profound side effects or lack of efficacy when delivered through more common routes, such as orally or intravenously, ziconotide must be administered intrathecally (i.e. directly into the spinal fluid). As this is the most expensive and invasive method of drug delivery and involves additional risks of its own, ziconotide therapy is generally considered appropriate (as evidenced by the range of use approved by the FDA in the US) only for “management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies or IT morphine”. Research is ongoing to determine whether ziconotide can be formulated in a way that would allow it to be administered by less invasive means.However, this must be weighed against the high level of pain management, both in terms of degree and length, and the apparent lack of tolerance and other signs of dependence even after extended treatment along with the need for alternatives to other therapies that have not worked for the patient. Ziconotide is also contraindicated for patients with certain preexisting mental disorders (e.g. psychosis) due to evidence that they are more susceptible to certain severe side effects. Adverse reactions
The most common side effects are dizziness, nausea, confusion, nystagmus, and headache.