Intrathecal and epidural drugs: ziconotide, baclofen, clonidine and morphine

Each neuraxial drug has a signature hazard: ziconotide causes neuropsychiatric toxicity but can be stopped abruptly, baclofen withdrawal can kill, clonidine must be tapered, and neuraxial morphine needs 24-hour monitoring and granuloma vigilance.

1. Ziconotide blocks N-type calcium channels. It binds channels on A-delta and C afferents in Rexed laminae I–II of the dorsal horn and is indicated for severe chronic pain when intrathecal therapy is warranted ¹.
2. Start low, titrate slowly. Begin at no more than 2.4 mcg/day (0.1 mcg/h), increasing by up to 2.4 mcg/day no more than 2–3 times a week, to a recommended maximum of 19.2 mcg/day by day 21 ¹.
3. Stop ziconotide for toxicity; no withdrawal. It carries a boxed warning for severe psychiatric symptoms and neurologic impairment, is contraindicated with a history of psychosis, and can be stopped abruptly without withdrawal effects ¹.
4. Baclofen withdrawal is an emergency. Abrupt discontinuation can cause high fever, altered mental status, rebound spasticity and rigidity, progressing to rhabdomyolysis, multi-organ failure and death; restore intrathecal baclofen at or near the previous dose ².
5. Epidural clonidine is for neuropathic cancer pain. It is indicated with opioids for severe cancer pain not relieved by opioids alone and is more likely effective for neuropathic than somatic or visceral pain ³.
6. Taper clonidine over 2–4 days. Abrupt withdrawal can cause rebound hypertension; excessive rises can be treated with clonidine or IV phentolamine ³.

Oral baclofen alone cannot be relied on to halt intrathecal baclofen withdrawal; it, or a benzodiazepine, is only a bridge that may prevent fatal sequelae until intrathecal delivery is restored ².

• Patients must not be abruptly withdrawn from intrathecal opioids when starting ziconotide; taper over a few weeks with equivalent oral opioid ¹.
• Ziconotide warnings include meningitis, reduced consciousness and creatine kinase elevation ¹.
• Intrathecal baclofen requires a positive screening dose before pump implantation ².
• Baclofen overdose causes drowsiness, respiratory depression, seizures and rostral progression of hypotonia to coma ².
• Epidural clonidine is not recommended for obstetric, postpartum or perioperative pain because of hypotension and bradycardia ³.
• Epidural clonidine is contraindicated with injection-site infection, anticoagulant therapy or a bleeding diathesis ³.
• Neuraxial morphine can cause delayed respiratory depression up to 24 hours; observe for at least 24 hours after the first dose ⁴.
• Monitor continuous intrathecal morphine for new neurologic signs suggesting an inflammatory mass ⁴.

• Continuing ziconotide through new hallucinations or confusion ¹.
• Treating baclofen withdrawal with oral baclofen alone ².
• Stopping epidural clonidine in one step ³.
• Stopping intrathecal opioids abruptly when switching a patient to ziconotide; taper over weeks with oral replacement ¹.