Intrathecal Therapy for Chronic Pain: A Review of Morphine and Ziconotide as Firstline Options

Pain Med. 2019 Apr 1;20(4):784-798. doi: 10.1093/pm/pny132.


Objectives: To evaluate the evidence for morphine and ziconotide as firstline intrathecal (IT) analgesia agents for patients with chronic pain.

Methods: Medline was searched (through July 2017) for "ziconotide" or "morphine" AND "intrathecal" AND "chronic pain," with results limited to studies in human populations.

Results: The literature supports the use of morphine (based primarily on noncontrolled, prospective, and retrospective studies) and ziconotide (based on randomized controlled trials and prospective observational studies) as first-choice IT therapies. The 2016 Polyanalgesic Consensus Conference (PACC) guidelines recommended both morphine and ziconotide as firstline IT monotherapy for localized and diffuse chronic pain of cancer-related and non-cancer-related etiologies; however, one consensus point emphasized ziconotide use, unless contraindicated, as firstline IT therapy in patients with chronic non-cancer-related pain. Initial IT therapy choice should take into consideration individual patient characteristics (e.g., pain location, response to previous therapies, comorbid medical conditions, psychiatric history). Trialing is recommended to assess medication efficacy and tolerability. For both morphine and ziconotide, the PACC guidelines recommend conservative initial dosing strategies. Due to its narrow therapeutic window, ziconotide requires careful dose titration. Ziconotide is contraindicated in patients with a history of psychosis. IT morphine administration may be associated with serious side effects (e.g., respiratory depression, catheter tip granuloma), require dose increases, and cause dependence over time.

Conclusion: Based on the available evidence, morphine and ziconotide are recommended as firstline IT monotherapy for cancer-related and non-cancer-related pain. The choice of first-in-pump therapy should take into consideration patient characteristics and the advantages and disadvantages of each medication.

Keywords: Cancer Pain; Firstline Intrathecal Therapy; Morphine; Noncancer Pain; Polyanalgesic Consensus Conference; Ziconotide.

Publication types

  • Review

MeSH terms

  • Analgesics, Non-Narcotic / administration & dosage*
  • Analgesics, Opioid / administration & dosage*
  • Chronic Pain / drug therapy*
  • Humans
  • Injections, Spinal
  • Morphine / administration & dosage*
  • Pain Management / methods*
  • omega-Conotoxins / administration & dosage*


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • omega-Conotoxins
  • Morphine
  • ziconotide