One of the side effects of opioid administration is opioid-induced constipation (OIC). To address this side effect, the oral peripheral μ opioid receptor antagonist naldemedine was developed. As this drug does not cross the blood–brain barrier, it is thought that it does not lead to opioid withdrawal syndrome (OWS) with central nervous system symptoms.

Here, we report a cancer patient who presented with symptoms centered round anxiety and irritation 4 months after administration of naldemedine for OIC and who was diagnosed with OWS after close investigation.

The patient was a 65-year-old female who had surgery for stage IB endometrial cancer 4 years previously, but experienced recurrence involving the pelvis 2 years later. Medical narcotics were used to control pain, but naldemedine was started to control subsequent constipation. When naldemedine-related OWS was suspected and the administration of naldemedine discontinued, the above symptoms disappeared within two days, and no recurrence was observed thereafter.

For patients receiving naldemedine, it is necessary to consider the possibility of OWS regardless of the period of administration in order to maintain patient quality of life.

Naldemedine, an oral peripheral μ-opioid receptor antagonist, was developed for the treatment of constipation, a side effect of opioid use. Naldemedine is not generally recognized as causing opioid withdrawal in which associated symptoms affecting the central nervous system.

From the series of cancer patients undergoing symptom management, we report a case treated with naldemedine for constipation in relation to the use of opioids for cancer pain and who displayed severe psychological symptoms associated with withdrawal immediately after the use of naldemedine.

The patient was a 36-year-old woman diagnosed with cervical cancer Stage IIB, PS3. When the patient, who was using oxycodone hydrochloride hydrate (80 mg/day) for ileal pain, was started on naldemedine for constipation, she complained of sweating after just 5 min and hallucinations after 1 h. The patient also displayed physical/behavioral abnormalities such as diarrhea and hyperactivity, and psychological abnormalities such as aggression toward staff.

Despite the psychiatric symptoms worsening over time, there were no abnormalities in terms of blood biochemical data, and no brain metastasis was observed on MRI. Based on the Clinical Opiate Withdrawal Scale, these symptoms were judged to indicate opioid withdrawal. Naldemedine was discontinued due to naldemedine-related opioid withdrawal syndrome and, thereafter, the psychiatric symptoms diminished, with no recurrence of similar symptoms observed to date.

If mental and behavioral abnormalities occur in patients receiving naldemedine, it is necessary to consider the possibility of opioid withdrawal syndrome as a differential diagnosis.

It is well known that the burden on the families of cancer patient extends across many aspects, but there have been no reports of family members developing delirium due to the burden of caring for a cancer patient.

We reported a caregiver who developed Wernicke encephalopathy (WE) while caring for a family member with advanced cancer.

The subject was a 71-year-old woman who had been caring for her husband, diagnosed with gastric cancer and liver metastases, for 5 months. She visited the “caregivers’ clinic” after referral by an oncologist who was worried about a deterioration in her mental condition that had appeared several weeks previously. The woman had a history of diabetes mellitus. Some giddiness was observed and, based on her inability to answer questions, her level of consciousness was checked and some disorientation was observed. She was diagnosed with delirium. A blood sample was collected to investigate the cause of the delirium, but the test data showed no hypoglycemia. Her appetite had declined since her husband was diagnosed with cancer. Thiamine deficiency was suspected as thiamine stores in the body are depleted within about 18 days and her loss of appetite had continued for 5 months. On intravenous injection of 100 mg of thiamine, her consciousness level was returned to normal in 1 h. A diagnosis of WE was supported by the patient's abnormally low serum thiamine level.

The family members of cancer patients may develop a loss of appetite due to the burden of caring, resulting in WE. When providing care for signs of distress in family members, it is necessary to pay attention not only to the psychological aspects but also to their level of consciousness and physical aspects, particularly the possibility of serious illness resulting from reduced nutritional status.

Cancer patients often want to spend their final days at home, and it is essential that general practitioners have knowledge of and technical skills related to cancer medicine and symptom relief. Recent clinical studies have revealed that Wernicke encephalopathy (WE) is quite common in cancer patients. However, there have been no reports to date on WE in cancer patients undergoing home medical care.

From a series of cancer patient undergoing home medical care, we reported a patient with lung cancer who developed WE.

An 84-year-old female with lung cancer undergoing home medical care developed an impaired mental state and an attention deficit. Her symptoms fulfilled the diagnostic criteria for delirium. WE was suspected as the patient's food intake had fallen from normal a month previously to somewhere between 50% or just a few mouthfuls. This diagnosis was supported by abnormal serum thiamine and the disappearance of delirium after thiamine administration.

When delirium occurs in cancer patients undergoing home treatment, it is necessary to suspect thiamine deficiency as a potential cause, as appropriate diagnosis and treatment can prevent irreversible brain-related sequelae.

Cognitive dysfunction has a negative effect on cancer treatment; however, in a cancer setting, specific treatments can restore cognitive function. Such conditions are known as reversible dementia, with one of these being vitamin B12 (VB12) deficiency. However, there have been no reports of VB12 deficiency identified by preoperative evaluation in cancer patients.

We studied a patient who was referred to the Department of Psycho-oncology on suspicion of cognitive decline prior to lung cancer surgery. Preoperative evaluation revealed VB12 deficiency.

The patient was an 82-year-old woman diagnosed with lung cancer. She also presented with cognitive decline and, therefore, was referred to the Department of Psycho-oncology for preoperative evaluation. The patient scored 19 points on a Mini-Mental State Examination (MMSE), which is indicative of cognitive decline. As the onset of symptoms occurred several months previously and they were subacute, the possibility of reversible dementia was considered. Extensive examination revealed VB12 deficiency, and VB12 replacement therapy normalized the MMSE score to 25 points before surgery.

When cognitive decline is observed in cancer patients, it is necessary to actively evaluate the serum levels of some B vitamins, including VB12.

The symptoms of thiamine deficiency vary considerably and asymptomatic cases; i.e., subclinical thiamine deficiency (SCTD), are known to exist. However, there is no information available on the treatment of SCTD.

We report a patient who underwent intravenous thiamine replacement therapy for about a month after being diagnosed with SCTD, but who developed SCTD again about three weeks after finishing the treatment.

The patient was a 64-year-old woman who, after starting treatment for cervical cancer, complained of anxiety and underwent an initial psychiatric examination. The psychiatric diagnosis was an adjustment disorder. Based on the possibility of SCTD complications due to her decreased appetite and weight loss, her serum thiamine concentration was measured and found to be low. Therefore, thiamine was administered intravenously for 29 days. At the end of treatment, thiamine administration was discontinued as there were no apparent neuropsychiatric symptoms or problems with appetite. Twenty-three days later, there were still no problems with appetite or neuropsychiatric symptoms, but a follow-up blood sample revealed that her serum thiamine was again below the normal range.

Currently, there is no information available regarding the diagnosis and treatment of SCTD in cancer patients. In some cases, such as this case, the deficiency recurs without any symptoms indicative of SCTD; therefore, further examination for diagnosis and treatment is necessary.

Nivolumab has become an effective treatment option for cancer in various sites; however, this drug may cause immune-related adverse effects due to its mechanism of action. Furthermore, little has been reported on thiamine deficiency (TD) in patients receiving nivolumab treatment.

From a series of cancer patients, we reported a patient with recurrent renal cell carcinoma who developed TD after the start of nivolumab treatment.

A 74-year-old man with recurrent renal cell carcinoma was referred to the psycho-oncology department as he had lost about 4 kg and displayed a loss of energy after four cycles of nivolumab treatment. Psychiatric interviews revealed a decrease in energy. Neurological examination did not reveal any impairment in consciousness, ataxia, or ocular symptoms. He did not develop appetite loss. The malabsorption or overconsumption of some nutrients is thought to occur due to the rapid loss of weight; thus, a reduction in vitamin B1, which has a short storage period in the body and is often deficient in cancer patients, was suspected. The diagnosis of TD was supported by the patient's abnormally low serum thiamine level.

In patients treated with nivolumab, it is necessary to pay careful attention to TD when proceeding with the treatment. It is hoped that future research may reveal the link between nivolumab administration and TD.

Thiamine deficiency (TD) is recognized in various kinds of disease with associated loss of appetite including cancer. However, it has not been recognized to date in bereaved partners after spousal loss from cancer.

From a series of bereaved partners who lost a spouse to cancer, we report on those who developed TD after bereavement.

Case 1 was a 57-year-old woman who sought consultation at our “bereavement clinic.” Her husband had been diagnosed with pancreatic cancer one year earlier and had died one month previously. At the first visit, she was observed to suffer depression, anxiety, and decreased appetite. Neurological, blood, and biochemical examinations did not reveal any noteworthy findings. She was diagnosed with uncomplicated bereavement. Detailed examination revealed that her appetite had been markedly decreased for approximately five weeks. The diagnosis of TD was supported by her abnormally low serum thiamine level. Case 2 was a bereaved 73-year-old male who had lost his wife to hypopharyngeal cancer one month previously after a five-year illness. He had shown a lack of energy for the month preceding his wife's death, but because there was no improvement after her death, his family recommended he seek consultation at our “bereavement clinic.” He was suffering from major depressive disorder. Detailed examination revealed that his appetite had been decreased for more than two weeks. Again, the diagnosis of TD was supported by his abnormally low serum thiamine level.

These reports demonstrate that there is a possibility that bereaved could develop TD after the loss of a loved one. TD should be considered whenever there is a loss of appetite lasting for more than 2 weeks, and medical staff should pay careful attention to the physical condition of the bereaved to prevent complications because of TD.

Thiamine deficiency (TD) is recognized in various kinds of disease with associated loss of appetite including cancer; however, TD has not been recognized in the family caregivers of cancer patients to date.

From a series of cancer patient caregivers, we reported an aged family caregiver who developed TD while caring for the cancer patient.

The caregiver was a 90-year-old male. He had been accompanying his wife, who was diagnosed with colon cancer 4 years previously, on hospital visits as the primary caregiver, but because of psychological issues, he was recommended to visit the psycho-oncology department's “caregiver's clinic” for a consultation. Detailed examination revealed that his appetite had been only about 50% of usual from about one year before, and he had lost 12 kg in weight in one year. The diagnosis of TD was supported by his abnormally low serum thiamine level.

This report demonstrates that there is a possibility that care providers could develop TD from the burdens associated with caregiving. TD should be considered whenever there is a loss of appetite lasting for more than 2 weeks, and medical staff should pay careful attention to the physical condition of care providers to prevent complications resulting from TD.

Although thiamine deficiency (TD) and Wernicke encephalopathy (WE) are not rare in cancer patients, the cases reported to date developed TD and/or WE after treatment had started.

From a series of cancer patients, we report a patient diagnosed with TD without the typical clinical symptoms of WE at the preoperative psychiatric examination.

A 43-year-old woman with ovarian cancer was referred by her oncologist to the psycho-oncology outpatient clinic for preoperative psychiatric evaluation. Her tumor had been growing rapidly before the referral. Although she did not develop delirium, cerebellar signs, or eye symptoms, we suspected she might have developed TD because of her 2-month loss of appetite as the storage capacity of thiamine in the body is approximately 18 days. The diagnosis of TD was supported by abnormally low serum thiamine levels.

Cancer therapists need to be aware that thiamine deficiency may occur even before the start of cancer treatment. In cases with a loss of appetite of more than 2 weeks’ duration, in particular, thiamine deficiency should be considered if the tumor is rapidly increasing, regardless of the presence or absence of delirium.

Wernicke encephalopathy (WE) is a neuropsychiatric disorder caused by thiamine deficiency. It is recognized in various stages of the cancer trajectory but has not previously been recognized during nivolumab treatment.

From a series of WE patients with cancer, we report a lung cancer patient who developed WE during treatment with nivolumab.

A 78-year-old woman with lung cancer was referred to our psycho-oncology clinic because of depressed mood. Psychiatric examination revealed disorientation to time, date, and place, which had not been recognized 1 month previously. Her symptoms fulfilled the diagnostic criteria for delirium. No laboratory findings or drugs explaining her delirium were identified. WE was suspected as she experienced a loss of appetite lasting 4 weeks. This diagnosis was supported by abnormal serum thiamine and the disappearance of delirium after intravenous thiamine administration.

We found WE in an advanced lung cancer patient receiving treatment with nivolumab. Further study revealed the association between nivolumab and thiamine deficiency. Oncologists should consider thiamine deficiency when a patient experiences a loss of appetite of more than 2 weeks regardless of the presence or absence of delirium.

Wernicke encephalopathy (WE) is a neuropsychiatric disorder caused by thiamine deficiency, and is sometimes overlooked because of the diversity of clinical symptoms.

From a series of WE patients with cancer, we report a lung cancer patient who developed WE, the main symptom of which was agitation.

A 50-year-old woman with lung cancer was referred to our psycho-oncology clinic because of agitation lasting for three days. No laboratory findings or drugs explaining her agitation were identified. Although the patient did not develop delirium, ophthalmoplegia, or ataxia, WE was suspected because she experienced a loss of appetite loss lasting 5 weeks. This diagnosis was supported by abnormal serum thiamine and disappearance of agitation one hour after intravenous thiamine administration.

This report emphasizes the clinical diversity of WE and indicates the limits of the ability to diagnose WE from typical clinical symptoms. The presence of a loss of appetite for more than two weeks may be the key to the accurate diagnosis of WE.

Wernicke's encephalopathy (WE) is a neuropsychiatric disorder caused by a thiamine deficiency. Although WE has been recognized in cancer patients, it can be overlooked because many patients do not exhibit symptoms that are typical of WE, such as delirium, ataxia, or ocular palsy. Furthermore, outpatients with WE who intermittently present at psycho-oncology clinics have not been described as far as we can ascertain.

This report describes two patients who did not exhibit the complete classic triad of symptoms among a series with cancer and WE, and who attended a psycho-oncology outpatient clinic.

Case 1, a 76-year-old woman with pancreatic cancer and liver metastasis, periodically attended a psycho-oncology outpatient clinic. She presented with delirium and ataxia as well as appetite loss that had persisted for 8 weeks. We suspected WE, which was confirmed by low serum thiamine levels and the disappearance of delirium after thiamine administration. Case 2, a 79-year-old man with advanced stomach cancer, was referred to a psycho-oncology outpatient clinic with depression that had persisted for about 1 month. He also had appetite loss that had persisted for several weeks. He became delirious during the first visit to the outpatient clinic. Our initial suspicion of WE was confirmed by low serum thiamine levels and the disappearance of delirium after thiamine administration. The key indicator of a diagnosis of WE in both patients was appetite loss.

This report emphasizes awareness of WE in the outpatient setting, even when patients do not exhibit the classical triad of WE. Appetite loss might be the key to a diagnosis of WE in the absence of other causes of delirium.

Thiamine is an essential coenzyme for oxidative metabolisms; however, it is not synthesized in the human body, and the average thiamine storage capacity is approximately 18 days. Therefore, thiamine deficiency (TD) can occur in any condition of unbalanced nutrition. If TD is left untreated, it causes the neuropsychiatric disorder Wernicke encephalopathy (WE). Although WE is a medical emergency, it is sometimes overlooked because most patients with WE do not exhibit all of the typical symptoms, including delirium, ataxia, and ophthalmoplegia. If all of the typical clinical symptoms of WE are absent, diagnosis of TD or WE becomes more difficult.

From a series of cancer patients, we reported three patients who developed TD without the typical clinical symptoms of WE.

A 69-year-old woman with pancreatic body cancer receiving chemotherapy with paclitaxel and gemcitabine for six months. Her performance status (PS) was 1. A detailed interview revealed that she had appetite loss for six months. Another 69-year-old woman with ovarian cancer received nedaplatin; her PS was 0. A detailed interview revealed that she had appetite loss for three months. A 67-year-old woman with colon cancer receiving ramucirumab in combination with second-line fluorouracil with folinic acid and irinotecan. Her PS was 1. A detailed interview revealed that she had appetite loss for three weeks. None exhibited typical clinical signs of WE, but they developed appetite loss for six months, three months, and three weeks, respectively. The diagnosis of TD was supported by abnormally low serum thiamine levels.

This report emphasizes the possibility of TD in cancer patients even when patients do not develop typical clinical signs of WE. The presence of appetite loss for more than two weeks may aid in diagnosing TD. Patients receiving chemotherapy may be at greater risk for developing TD.

Wernicke encephalopathy (WE) is a neuropsychiatric disorder caused by thiamine deficiency. Several reports of WE in cancer patients are known. WE is sometimes overlooked because most patients do not exhibit its typical symptoms (e.g., delirium, ataxia, ocular palsy). If delirium is not present, a diagnosis of WE is difficult because delirium is the hallmark symptom of WE.

Taken from a series on WE in cancer, we report two patients who developed WE without delirium during periodic psycho-oncology outpatient visits.

Case 1. A 61-year-old woman with non-Hodgkin lymphoma who was periodically attending a psycho-oncology outpatient clinic developed an unsteady gait. WE was suspected because she also developed appetite loss for two weeks, and we could find no other laboratory findings to explain her unsteady gait. Our diagnosis was supported by abnormal serum thiamine and disappearance of the gait disturbance after intravenous thiamine administration. Case 2. A 50-year-old woman with breast carcinoma with bone metastasis developed an unsteady gait. WE was suspected because she also developed loss of appetite for two weeks, and no other laboratory findings could explain her unsteady gait. The diagnosis was supported by abnormal serum thiamine and disappearance of the gait disturbance after administration of intravenous thiamine.

Our report emphasizes the importance of being aware of WE, even when patients do not present with delirium. The presence of loss of appetite for more than two weeks may be the key to a diagnosis of WE.

Few reports of Wernicke encephalopathy in oncological settings have been published. Some cases of Wernicke encephalopathy are related to appetite loss; however, the degree to which loss of appetite leads to thiamine deficiency is not known.

A 63-year-old female with advanced cancer of the external genitalia was referred for psychiatric consultation because of disorientation, insomnia, and bizarre behaviors. Her symptoms fulfilled the diagnostic criteria for delirium. Routine laboratory examinations did not reveal the cause of the delirium. Thiamine deficiency was suspected because appetite loss had continued for 19 days since she had been admitted to hospital.

Intravenous administration of thiamine resulted in recovery from the delirium within three days. Serum thiamine level was found to be 16 ng/ml (normal range: 24–66 ng/ml). The clinical findings, the low level of thiamine in the serum, and the effective alleviation of delirious symptoms after thiamine administration fulfilled Francis's criteria for delirium induced by thiamine deficiency.

Clinicians must be aware of the possibility of Wernicke encephalopathy in cancer patients, especially in those with loss of appetite for longer than 18 days. The degree of appetite loss in such patients might serve as a reference. Early detection and intervention may alleviate the symptoms of delirium and prevent irreversible brain damage.

The death of a loved one is one of the most stressful events of life, and such stress affects the physical and psychological well-being of the bereaved. Dissociative amnesia is characterized by an inability to recall important autobiographical information. Dissociative amnesia in the bereaved who have lost a loved one to cancer has not been previously reported. We discuss herein the case of a patient who developed dissociative amnesia the day after the death of here beloved husband.

A 38-year-old woman was referred for psychiatric consultation because of restlessness and abnormal behavior. Her 44-year-old husband had died of pancreatic cancer the day before the consultation. On the day of the death, she looked upset and began to hyperventilate. The next day, she behaved as if the deceased were still alive, which embarrassed her family. At her initial psychiatric consultation, she talked and behaved as if her husband was still alive and in the hospital.

Her psychiatric features fulfilled the DSM–V criteria for dissociative amnesia. The death of her husband had been very traumatic for her and was considered to have been one of the causes of this dissociation.

This report adds to the list of psychiatric symptoms in the bereaved who have lost a loved one to cancer. In an oncology setting, we should consider the impact of death, the concomitant defense mechanisms, and the background of the families.

Family caregivers of cancer patients suffer from physical, psychological, and social distress and therefore are often referred to as second order patients. Akathisia is a common side effect of antipsychotics and antidepressants that causes great discomfort and even agitation and is often described by patients administered these drugs as the most distressing side effect of their treatment. Several studies of akathisia as a cause of distress in cancer patients have been reported. However, akathisia has not been reported as a cause of distress in family caregivers of cancer patients.

A 74-year-old spouse caregiver who was under treatment for major depressive disorder was not able to visit the hospital where her husband, a terminally ill cancer patient, was being treated. Initially, the spouse caregiver thought that she could not visit the hospital because of the symptoms of her depression and her grief about losing her husband. However, careful clinical examination revealed that she was suffering from akathisia in addition to her grief.

Discontinuation of her sulpiride treatment resulted in the disappearance of her akathisia symptoms, and therefore she became able to visit the hospital and care for her terminally ill husband.

Drug induced akathisia is a cause of distress in spouse caregivers taking certain drugs. It is important for clinicians to realize that family caregivers might suffer from not only socioeconomic, physical, and psychological problems but also side effects of medication.