Introduction: Autonomic and psychiatric symptoms occur in opioid withdrawal syndrome. We report a case in which a patient treated with hydromorphone for cancer pain showed psychiatric symptoms similar to withdrawal syndrome and improved with divided administration of an extended-release tablet formulation. Case: A 60-year-old woman who underwent surgery for left breast cancer. She had been treated with hydromorphone, non-opioid analgesics, analgesic adjuvants, and nerve blocks for pain due to recurrence of lumbar metastases. However, before regular oral administration of hydromorphone extended-release, symptoms of anxiety, irritability and restlessness began to appear. Since these symptoms improved a few hours after the regular administration, we suspected the effects of opioids on blood concentration and changed the dosage to twice-daily divided doses of the same drug. As a result, symptoms decreased dramatically. Conclusion: When patients experience withdrawal-like psychiatric symptoms while taking opioids, it may be possible to alleviate these symptoms by considering the effects of decreased blood levels and adjusting the dosage of the drug, such as divided dosing.