Induction of Prolonged Mania During Ketamine Therapy for Reflex Sympathetic Dystrophy

Summary

A 42-year-old woman with chronic pain from reflex sympathetic dystrophy, who was high-functioning despite high-dose opioid use, underwent experimental IV ketamine therapy. Her antidepressant and sleep medications were initially held. She reported immediate pain relief, but pain returned by day 2. After restarting two of her medications on day 3, she reported significant relief by day 4. Starting on day 7, she exhibited over-sedation, admitted to self-administering opioids from a hidden supply, and became irritable and emotionally labile. She detailed past traumas without prompting. Despite restarting quetiapine and increasing duloxetine, her symptoms worsened, including pressured speech and tangential, disorganized communication. The case suggests ketamine therapy may unmask or trigger mania-like symptoms in vulnerable individuals.

Study at a glance

Abstract

Ms. M is a 42-year-old Caucasian married woman with a history of chronic left gluteal and left leg pain diagnosed as reflex sympathetic dystrophy. She was disabled by refractory symptoms that had failed a number of interventions and required high-dose opioids. Ms. M was otherwise high functioning and had completed a professional degree. The patient elected to undergo experimental IV ketamine therapy for her symptoms. An admission note documented a history of depression and insomnia, for which the patient had been prescribed duloxetine 20 mg daily, mirtazapine 45 mg qHS, and quetiapine 100 qHS. These medications were held on admission. On Day 1, ketamine was started and titrated from 10 to 20 mg/hour over a period of 5 days in the intensive care unit. The patient immediately reported that her pain was much better and it was a “miracle,” but by Day 2 she again complained of considerable pain. On Day 3, duloxetine 20 mg and mirtazapine 45 mg were restarted. By Day 4, Ms. M reported significant pain relief and continued to get better by Day 5 and Day 6. In these first 6 days, some subtle behavioral changes were seen (e.g., sometimes being too optimistic about the therapy), but nothing extraordinary was documented, and the therapy continued because Ms. M seemed to benefit considerably from it. On Day 7 of the ketamine protocol, Ms. M started exhibiting notable changes in her mental status. She appeared over-sedated and admitted to self-administering opioids from a supply she kept in her purse, but when asked to, she was reluctant to turn these over to her physicians. On Day 8, Ms. M was irritable and emotionally labile and expressed the feeling that the team was withholding pain medications from her. Without any prompting, she detailed a series of past traumas that she had experienced, including the deaths of her parents. Therefore, on Day 8, quetiapine 100 mg qHS was restarted, and duloxetine was increased to 60 mg. However, her mania like symptoms did not get better, and on Day 10 Ms. M demonstrated pressured speech and sent her physicians a lengthy e-mail that was tangential with loosening of associations. The communication included statements like “Dear Doctors and Heroes” and “If we could treat RSD like jazz we could treat individuals according to specific needs at specific times.” Given her symptoms, a decision was made to