Intrathecal Ziconotide May Increase Risk for Suicide

Allison Gandey

December 10, 2010

December 10, 2010 — A recent suicide has raised suspicion that intrathecal ziconotide may not only relieve pain but also alter impulse control. Investigators are calling for a comprehensive psychiatric evaluation in all patients before and during treatment. Researchers suggest ziconotide (Prialt, Elan) may pose a threat even in symptom-free patients with pain.

The new case of suicide is reported by a team led by Christoph Maier, MD, from the Department of Pain Management at Ruhr University in Bochum, Germany. Their work appears in the journal Pain.

The US label for ziconotide recommends that patients with a preexisting history of psychosis should not be treated with this product. "Severe psychiatric symptoms and neurological impairment may occur during treatment," the company points out. "All patients should be monitored frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness."

A similar explicit warning has to date not been issued by the European Medicines Agency.

Physicians must pay attention to the psychiatric side effects of this drug, Dr. Maier told Medscape Medical News. "Better monitoring of all patients on this medication is necessary," he said, and strict compliance to the contradictions such as a history of depression is key.

This case is particularly tragic.

His team reports that the patient who died showed no depressive symptoms at the start of treatment but went on to commit suicide 4 weeks later while receiving low-dose therapy. His cumulative dose was 779 μg, and the patient said he experienced sufficient pain relief.

"This case is particularly tragic," Dr. Maier said. The patient had pain in his feet for many years and had undergone numerous unsuccessful treatments. He experienced pain relief for the first time when treated with ziconotide. There were seemingly no adverse effects, Dr. Maier noted, until the unexpected suicide.

Ziconotide is a nonopioid used for severe and chronic pain. It acts as a selective N-type voltage-gated calcium channel blocker. The drug was developed from marine snail toxins. The active agent of ziconotide is the synthetic toxin of the cone snail.

Intrathecal ziconotide has been on the market in the United States since 2004 and is generally considered a safe alternative to morphine. Recently, the number of reports on the psychiatric adverse effects of ziconotide has increased. Some of these findings were reportedly never identified in the original clinical trials.

A Second Case

Dr. Maier and his team suspect there may be a causal relationship between ziconotide and suicide risk. A second patient, a 39-year-old woman with a history of depression but free of symptoms while taking antidepressants for more than 15 years, developed severe suicidal ideation while taking ziconotide. She had been taking the drug for 2 months for back pain, and her cumulative dose was about 2900 μg.

During treatment, the researchers report she complained of other psychiatric adverse effects, such as hallucinations, confusion, and partial amnesia, which resulted in 2 serious car accidents. The patient rapidly recovered after discontinuing use of the drug.

Dr. Maier says he is concerned ziconotide not only suppresses the transmission of pain stimuli but also affects the mind and could simultaneously reduce anxiety and impulse control. He warns this could promote suicidal tendencies in vulnerable patients.

His team recommends that all patients be evaluated for possible psychiatric disorders before treatment begins and during, irrespective of pain relief. They are calling on Elan and US and European regulatory authorities to revisit this issue.

The researchers have disclosed no relevant financial relationships.

Pain. Published online November 1, 2010.

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