Manic and hypomanic states in cancer patients: A systematic review.

Introduction

There has been a considerable volume of literature addressing the intersection of cancer and mood disorders, particularly concerning the relationship between cancer and depression. It has been recognized as early as since the 1930s that depressive episodes may predispose an onset of cancer. Mood symptoms that emerge before cancer diagnosis have been known as “premonitory depression” (Lauter 1973 ; Cosci et al. 2015 ). A recent study demonstrated that 21% of patients with pancreatic cancer had a history of depression prior to their cancer diagnosis (Seoud et al. 2020 ; Michoglou et al. 2023 ). The argument has been continuing regarding whether depression arises as a psychological response to a cancer diagnosis, or a biological reaction to cancer. Recent research increasingly focuses on the biological mechanisms underlying the association between depression and cancer (Bortolato et al. 2017 ). Chronic exposure to elevated inflammatory cytokines due to cancer leads to alterations in neurotransmitter systems and can develop neuropsychiatric disorders such as depression (Felger and Lotrich 2013 ).

Bipolar disorder (BD) is a mental disorder that accompanies both depressive symptoms and manic symptoms. Its estimated prevalence rate is 2% and shows a gradual increase globally (Merikangas et al. 2011 ; He et al. 2020 ). In contrast with the research on depression and cancer, research on the relationship between BD or manic episodes and cancer has been relatively limited. Epidemiological data from large-scale cohort studies on breast cancer indicate that the incidence rate of breast cancer is 2.06 times higher in individuals with BD compared to the control group (Hung et al. 2013 ). Kanani et al. reported that breast cancer patients with comorbid mood disorders (depression or BD) experience poorer overall survival compared to those without such mood disorders (Kanani et al. 2016 ).

Literature to date suggests that the causes of manic states in patients with cancer have been categorized into three etiological perspectives: organic, drug-induced, and psychogenic. Krauthammer and Klerman ( 1978 ) introduced the concept of “secondary mania” in their seminal work on cancer and manic states. They reviewed various organic and pharmacological factors, such as drugs, infections, neoplasms, epilepsy, and metabolic disorders, that can induce manic states.

An increasing number of reports support the possibility of a pathophysiological link between cancer and BD (Asevedo et al. 2013 ). Cytokine-induced abnormalities in inflammation, hormones, and the immune system in individuals with cancer may represent a key pathophysiological pathway in the onset of manic episodes in BP (Goldberg and Schwertfeger 2010 ; Błogowski et al. 2014 ; Van den Ameele et al. 2016 ). Cytokine levels (such as TNF-α and IL-6), which rise in manic states, are known to increase in cancer patients as well. Hormonal abnormalities, specifically dysfunction of the hypothalamic-pituitary-adrenal axis, can cause impairments in neuroplasticity and brain dysfunction (Bauer et al. 2014 ; Rosenblat et al. 2014 ). The incidence of BP increases by 70% within five years following an autoimmune disease diagnosis (Eaton et al. 2010 ; Benros et al. 2014 ; León-Caballero et al. 2015 ).

Manic episodes may develop as a reaction to psychological stress (“psychogenic”) (Morgan et al. 2001 ), although the current diagnostic criteria, such as DSM-5 (American Psychiatric Association. 2013 ) and ICD-11 (World Health Organization 2019 ), do not formally recognize the term psychogenic mania. Studies have demonstrated the correlation between stressful life events and the onset or recurrence of manic episodes of BD (Kessing et al. 2004 ; Carmassi et al. 2020 ; Rodrigues Cordeiro et al. 2023 ).

BD remains a significant therapeutic challenge due to its symptom fluctuations and the resulting deterioration of patients’ functioning, heightened risk of suicide, and need for psychiatric hospitalization (Pompili et al. 2013 ; Harrison et al. 2018 ). Manic symptoms are particularly problematic due to patients’ heightened impulsiveness, aggression, irritability, and excitement (Gonçalves-Pinho et al. 2022 ). In cancer patients, manic episodes may hamper the initiation or continuation of cancer therapy due to the patients’ aggression and medication non-compliance. Typically, the treatment of psychiatric symptoms (including admission to psychiatric beds) is prioritized over cancer treatment, resulting in the postponement or cessation of cancer therapies, which can exacerbate the progression of cancer (Tohen and Grundy 1999 ). Additionally, patients with BD may refuse medication during their manic episodes, which also poses significant challenges for cancer treatment. Further, mistrust and aggression towards medical staff and family members prevent appropriate cancer treatment and care (Perlick et al. 1999 ; Osawa et al. 2013 ). Even after the manic episodes are remitted, the family may not be as emotionally supportive as before to the patient, which may lead to missed opportunity for the patient for appropriate cancer care. Also, psychological damage to family members may remain.

To the best of the authors’ knowledge, there are only sporadic studies of the emergence of manic states in the context of cancer, leaving a gap in understanding the etiology and the influence of manic episodes on cancer treatments. Therefore, in the current study, the authors conducted a systematic review to elucidate the characteristics of manic states in cancer patients. Once the review has been done, the authors expect that therapeutic strategies for manic episodes in patients with cancer would be made clearer.

Method

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline (Page et al. 2021 ) and the protocol for this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) of the National Institute for Health and Care Research, UK (CRD42020182372). The following studies were eligible: (1) cases of comorbid cancer and manic states (manic or hypomanic states), (2) without a history of mental illness prior to cancer diagnosis, (3) epidemiological studies or case reports, and (4) written in English or Japanese. The following reports were excluded: (1) cases of benign proliferative diseases, or (2) cases with a history of mental illness that were not attributable to cancer. We searched the following electronic databases: PubMed, Cochrane, CINAHL, and Igaku Chuo Zasshi, for the studies published between 1950 and 6 August 2021. Boolean searches were performed using the following Mesh terms: (“mania” OR “hypomania” OR “bipolar disorder”) AND (“cancer”). After removing duplicates, two authors (K.O. and D.F.) screened the titles and abstracts, then reviewed the full texts. References from the selected papers were manually searched. Any discrepancies between the two reviewers were discussed until agreement.

The following information was collected: the causes, timing of onset of manic states, their course and outcomes, including admissions to a psychiatric ward, pharmacotherapy and maintenance therapy for manic symptoms, duration until remission of manic states, recurrence of manic states, and the impact of manic states on cancer treatment. The flow diagram of the systematic literature search is presented in Figure 1 . Figure 1. Flow diagram of the systematic literature search.

Results

The search finally retrieved 56 papers (9 case series and 47 case reports), which included 67 cases in total (see Table 1 ). Table 1. Summary of reports on cancer patients presenting with manic state No. Author(s), year Age Sex Type of Cancer Cancer treatment status at the onset of mania Underlying factors of mania 1 Shen and Lee 2021 65 M Lung cancer Before cancer diagnosis Organic 2 El Hayek and El-Khoury 2020 57 M ACTH-producing small cell lung carcinoma Before cancer diagnosis Organic and Drug-induced 3 Mavrotas and Murray 2020 66 F Small cell lung cancer During cancer treatment Drug-induced 4 Garg et al. 2018 46 M Carcinoma colon During cancer treatment Drug-induced 5 Schillinger 2017 75 M Pancreas cancer Before cancer diagnosis Organic 6 Basterreche et al. 2017 66 M Pancreatic adenocarcinoma Before cancer diagnosis Organic 7 Reich et al. 2017 61 F Breast cancer During cancer treatment Organic and Drug-induced 8 Morosán Allo et al. 2015 62 F Papillary thyroid carcinoma During cancer treatment Organic 9 Asevedo et al. 2013 39 F Breast cancer After cancer diagnosis – before cancer treatment Organic 10 Brett et al. 2013 51 M Skin cancer (squamous cell carcinoma) During cancer treatment Drug-induced 11 Olde Engberink et al. 2013 74 F Large B-cell lymphoma Before cancer diagnosis Organic 12 Hechtman et al. 2013 14 M T-cell acute lymphocytic leukemia During cancer treatment Drug-induced 13 Shirata et al. 2013 70 M Gastric cancer During cancer treatment Psychogenic 14 Osawa et al. 2013 67 F Pancreas cancer During cancer treatment Organic 15 Matsunaga et al. 2012 66 F Gastric cancer During cancer treatment Psychogenic 16 Kimmel and Combs 2012 55 F Breast cancer During cancer treatment Drug-induced 17 Cassidy et al. 2012 17 M Acute lymphoblastic leukemia During cancer treatment Drug-induced 18 Roxanas and Hunt 2012 52 F Multiple myeloma unknown Drug-induced 19 Roxanas and Hunt 2012 54 F Multiple myeloma unknown Drug-induced 20 Roxanas and Hunt 2012 66 F Multiple myeloma unknown Drug-induced 21 Roxanas and Hunt 2012 69 F Breast cancer pulmonary infiltrates unknown Drug-induced 22 Roxanas and Hunt 2012 75 F B cell lymphoma unknown Drug-induced 23 Tutkunkardas and Mukaddes 2010 14 M T-cell acute lymphoblastic leukemia During cancer treatment Drug-induced 24 Ularntinon et al. 2010 8 M T-cell acute lymphoblastic leukemia During cancer treatment Drug-induced 25 Ularntinon et al. 2010 16 M Pre-B-cell acute lymphoblastic leukemia During cancer treatment Drug-induced 26 Enudi and Udolu 2009 30 M Malignant melanoma During cancer treatment Drug-induced 27 Murru et al. 2009 91 M Pancreas cancer Before cancer diagnosis Organic 28 Ni Mhaolain and Thakore 2007 54 M Malignant melanoma During cancer treatment Drug-induced 29 Mercadante et al. 2007 48 M myeloma IgG During cancer treatment Drug-induced 30 Mian et al. 2007 14 M Hodgkin’s Lymphoma During cancer treatment Drug-induced 31 Hochhauser et al. 2005 15 M B-lineage lymphoblastic lymphoma During cancer treatment Drug-induced 32 Hochhauser et al. 2005 6 M Acute lymphoblastic leukemia During cancer treatment Drug-induced 33 Ingram and Hagemann 2003 2 M Relapsed acute lymphoblastic leukemia During cancer treatment Drug-induced 34 Nakamura et al. 2003 74 M Gastric cancer During cancer treatment Drug-induced 35 Greenberg et al. 2000 53 F An acral lentiginous melanoma During cancer treatment Drug-induced 36 Greenberg et al. 2000 25 F Melanoma During cancer treatment Drug-induced 37 Greenberg et al. 2000 20 M Melanoma During cancer treatment Drug-induced 38 Onishi et al. 2000 66 M Lung cancer During cancer treatment Psychogenic 39 Mazure et al. 1999 61 M Glioblastoma Before cancer diagnosis Organic 40 Kramer and Cottingham 1999 14 F Pre B-cell acute lymphoblastic leukemia During cancer treatment Drug-induced 41 Iancu et al. 1997 47 M Chronic myeloid leukemia During cancer treatment Drug-induced 42 Strite et al. 1997 43 F Chronic myelogenous leukemia During cancer treatment Drug-induced 43 Strite et al. 1997 47 M Chronic myelogenous leukemia During cancer treatment Drug-induced 44 Morita et al. 1997 66 M Gastric cancer During palliative treatment Psychogenic 45 Morita et al. 1997 79 Unknown Tongue cancer During palliative treatment Drug-induced 46 Furutsuka et al. 1996 53 F Renal cell cancer During cancer treatment Drug-induced 47 Sirois 1995 67 M Unknown During palliative treatment Psychogenic 48 Watanabe et al. 1994 17 F Acute lymphoblastic leukemia (ALL) During cancer treatment Drug-induced 49 Khouzam et al. 1994 64 M Malignant melanoma During cancer treatment Drug-induced 50 Shinozaki et al. 1994 68 M Breast cancer During palliative treatment Psychogenic 51 Murata, 1994 39 M B cell lymphoma Before cancer diagnosis Organic 52 Stecker 1993 20 M Osteogenic sarcoma During palliative treatment Psychogenic 53 Fukue et al. 1993 62 M Hepatoma and laryngeal cancer During palliative treatment Psychogenic 54 Adams et al. 1988 52 M Chronic myelogenous leukemia During cancer treatment Drug-induced and cognitive decline 55 Venkatarangam et al. 1988 68 M Acute lymphoblastic leukemia (ALL) During cancer treatment Drug-induced 56 Collins and Oakley-Browne 1988 70 F ACTH-secreting small cell carcinoma of the lung Before cancer diagnosis Organic 57 Starkstein et al. 1988 28 M Astrocytoma During cancer treatment Organic 58 Motoyasu 1988 44 F Pancreatic cancer During palliative treatment Psychogenic 59 Lajeunesse et al. 1986 75 M Prostatic cancer During cancer treatment Drug-induced 60 Glynne-Jones et al. 1986 19 F Hodgkin’s disease During cancer treatment Drug-induced 61 Glynne-Jones et al. 1986 56 M Non-Hodgkin lymphoma During cancer treatment Drug-induced 62 Greenberg and Brown 1985 55 M Lung cancer (middle lobe epidermoid carcinoma) During cancer treatment Organic 63 Wamboldt et al. 1984 25 F Acute myelomonocytic leukemia During cancer treatment Drug-induced 64 Pickar et al. 1984 60 M Adenocarcinoma of the pancreas During cancer treatment Drug-induced 65 Oyewumi and Lapierre 1981 21 M Medulloblastoma During cancer treatment Organic 66 Jamieson and Wells 1979 45 M Unknown primary cancer Before cancer diagnosis Organic 67 Mann and Hutchison 1967 38 M Hodgkin’s disease During cancer treatment Drug-induced

Overview of the cases

The overview of the 67 cases is shown in Table 2 . The mean age of the cases was 47.9 years, with 64% of male patients. The most common cancer was leukemia (15 cases), followed by lymphoma (8 cases), lung cancer, pancreatic cancer, and malignant melanoma (6 cases each). Table 2. Manic states in 67 cancer patients All cases ( n = 67) Drug-induced cases ( n = 40) Organic cases ( n = 15) Psychogenic cases ( n = 9) Average age (years) 47.9 ± 22.2 41.2 ± 23.0 57.2 ± 18.5 58.8 ± 16.5 Gender Male: 43 (64.%) 24 (60%) 10 (66.7%) 7 (77.8%) Female: 23 (34.3%) 15 (37.5%) 5 (33.3%) 2 (22.2 %) Not stated: 1 (1.5%) 1 (2.5%) 0 (0%) 0 (0 %) Common types of cancer 1: Leukemia (15 cases) 1: Leukemia (14 cases) 1: Pancreatic cancer (4 cases) 1: Gastric cancer (3 cases) 2: Lymphoma (8 cases) 2: Lymphoma (6 cases) 2: Lung cancer (3 cases) 3: Lung cancer (6 cases) 2: Malignant melanoma (6 cases) 3: Lymphoma (2 cases) 3: Pancreatic cancer (6 cases) 4: Myeloma (4 cases) 3: Malignant melanoma (6 cases) 5: Breast cancer (2 cases) Cancer treatment status at the onset of mania Before cancer diagnosis 10 (15.0%) 0 (0%) 9 (60%) 0 (0%) After cancer diagnosis – before cancer treatment 1 (1.5 %) 0 (0%) 1 (6.7%) 0 (0%) Under cancer treatment 44 (65.7%) 34 (85%) 5 (33.3%) 3 (33.3%) Under palliative treatment (after active cancer treatment) 7 (10.4 %) 1 (2.5%) 0 (0%) 6 (66.7%) Unknown 5 (7.5 %) 5 (12.5%) 0 (0%) 0 (0%) Acute drug treatment for mania Yes: 52 (77.6%) 34 (85%) 11 (73.3%) 5 (55.6%) None: 13 (19.4%) 6 (15%) 1 (6.7%) 4 (44.4%) Not stated: 2 (1.5%) 0 (0%) 3 (20%) 0 (0%) Maintenance pharmacotherapy for mania Yes: 34 (50.7%) 24 (60%) 6 (40%) 2 (22.2%) None: 14 (20.9%) 7 (17.5%) 3 (20%) 4 (44.4%) Not stated: 19 (28.4%) 9 (22.5%) 6 (40%) 3 (33.3%) Brain imaging Yes: 37 (55.2%) 17 (42.5%) 14 (93.3%) 4 (44.4%) No or not stated: 30 (44.8%) 23 (57.5%) 1 (6.7%) 5 (55.6%) Duration of manic state until remission (days) Mean: 20.7 18.9 20.4 30.7 Median: 14 14 21 14 Admission to psychiatric wards Yes: 25 (37.3%) 11 (27.5%) 10 (66.7%) 3 (33.3%) None: 23 (34.3%) 13 (32.5%) 2 (13.3%) 6 (66.7%) Not stated: 19 (28.4%) 16 (40%) 3 (20%) 0 (0%) Continued or administration of cancer treatment after mania Yes: 35 (52.2%) 22 (55%) 9 (60%) 2 (22.2%) None: 13 (19.4%) 12 (30%) 2 (13.3%) 6 (66.6%) Not stated: 19 (28.4%) 6 (15%) 4 (26.7%) 1 (11.1%) Relapse of manic episodes Yes: 16 (23.9%) 12 (30%) 4 (26.7%) 0 (0%) None: 44 (65.7%) 22 (55%) 10 (66.7%) 9 (100%) Not stated: 7 (10.4%) 6 (15%) 1 (6.7%) 0 (0%)

Etiology of manic episodes

The etiology of manic states was documented in 64 cases, which were classified into organic, drug-induced, and psychogenic. Drug-induced factors were most common (40 cases), followed by organic (15 cases), and psychogenic (9 cases). Three cases were attributed to the overlapping of drug-induced and organic factors. In Table 3 , we presented the details of the organic cases. Table 3. Details of organic cases Correspondence with the criteria by Krauthammer and Klerman ( 1978 ) Association between the effectiveness of cancer treatment and the course of manic episodes Author (s) Publication year Onset of manic episodes prior to cancer diagnosis 1. Proximity between an organic cause and the onset of manic episodes 2. Negative medical history prior to the onset of the manic state 3. Negative family history 4. Late-onset (65 years or older) Shen and Lee 2021 Yes Two years before the cancer diagnosis Yes Not stated Aged (65yo) Yes Schillinger 2017 Yes Several months before the cancer diagnosis Yes Not stated Aged (75yo) Yes Basterreche et al. 2017 Yes Approximately four months before the cancer diagnosis Yes Not stated Aged (66yo) Unknown Morosán Allo et al. 2015 No Six weeks after surgery Yes Not stated 62yo Yes Asevedo et al. 2013 No Two months after the cancer diagnosis Yes Yes 39yo Unknown Olde Engberink et al. 2013 Yes Three weeks before the cancer diagnosis Yes Not stated Aged (74yo) No Osawa et al. 2013 No Three weeks after surgery Yes Yes Aged (67yo) Yes Murru et al. 2009 Yes Seven months before the cancer diagnosis Yes Not stated Aged (91yo) Unknown Mazure et al. 1999 Yes Several weeks before the cancer diagnosis Yes Not stated 61yo Unknown Murata 1994 Yes One month before the cancer diagnosis Yes Yes 39yo Yes Collins and Oakley-Browne 1988 Yes About 10 days before the cancer diagnosis Yes No Aged (70yo) Unknown Starkstein et al. 1988 No After recurrence and undergoing radiation therapy Yes Yes 28yo No Greenberg and Brown 1985 No Seven months after lung cancer treatment, a brainstem metastasis developed, leading to the onset of a manic state. Five months later, when the manic state recurred, the brain metastasis also expanded. Yes Yes 55yo Yes Oyewumi and Lapierre 1981 No After surgery and radiation therapy Yes Not stated 21yo Unknown Jamieson and Wells 1979 Yes Four months before the cancer diagnosis Yes No 45yo Unknown

Timing of the onset of manic episodes

Manic states predominantly occurred during cancer treatment (44 cases: 66%), followed by those that occurred before cancer diagnosis (10 cases: 15%). Of the 10 cases that exhibited the onset of manic episodes prior to the diagnosis of cancer, contributing factors for the manic episodes were identified in nine cases.

Clinical management of manic episodes

Pharmacotherapy for manic states was administered in 52 cases (78%). Maintenance pharmacotherapy after remission of manic states was administered in 34 cases (51%). The administered pharmacotherapy for manic states is summarized in Table 4 . Among the 52 cases where pharmacotherapy was administered, monotherapy with an antipsychotic or a mood stabilizer was most common, comprising 22 cases (40%). Combinations of antipsychotics and mood stabilizers, often accompanied by benzodiazepines, were also common. While benzodiazepines were frequently used for sleep, their daytime administration was also noted. In challenging cases, the first antipsychotic was switched to another or was augmented with other classes of medications. Table 4. Medications used to treat manic states Number of cases Maximum daily use (mg) Chlorpromazine equivalent (mg) Diazepam equivalent (mg) Antipsychotics Haloperidol 13 1.5–12 75–600 Risperidone 9 0.5–5 50–500 Olanzapine 8 5–20 200–800 Mood stabilizers Valproic acid 11 300–1000 Lithium 10 300–600 Benzodiazepines Lorazepam 6 1–4 10–40 Clonazepam 4 0.5–2 10–40 Multiple medications were used in some cases; therefore, the total number of cases in the table outweighs the actual number of cases.

Among the antipsychotics, haloperidol was predominantly used, followed by risperidone and olanzapine. Among mood stabilizers, both valproic acid and lithium were frequently used. In the cases of drug-induced manic states, reducing or discontinuing causative medications such as steroids or interferon while concurrently administering therapeutic agents for the manic state was often observed. The doses of medications were generally comparable to or lower than those used for common mood disorders (Marzani and Neff 2021 ).

Brain imaging was conducted in 37 cases (55%).

Clinical course of manic episodes and cancer treatment

The mean and median duration until remission of manic states were 21 and 14 days, respectively. Approximately one third of the cases required hospitalization to psychiatric wards (25 cases: 37%).

Cancer treatment was continued or initiated after the onset of manic states in 35 cases (52%). In a subset of 34 cases with complete relevant data, administration of maintenance pharmacotherapy, not in the palliative phase, and drug-induced or organic etiologies were significantly associated with continuation of cancer treatment. Administration of pharmacotherapy for acute-phase manic states showed a trend-level association with continued cancer treatment ( Table 5 ). The recurrence of manic states was observed in 16 cases (24%). Table 5. Comparison of cases who did and did not receive cancer treatment after a manic state Cases who received cancer treatment Cases who did not receive cancer treatment p -value n = 20 n = 14 Acute pharmacotherapy for mania 0.061 † Yes 20 (64.5%) 11 (35.5%) No 0(0.0%) 3(100.0%) Maintenance pharmacotherapy for mania 0.012 * Yes 19 (70.4%) 8 (29.6%) No 1 (14.3%) 6 (85.7%) Cancer treatment status at the onset of mania 0.010 * Before cancer treatment 5 (83.3%) 1 (16.7%) Under cancer treatment 15(65.2%) 8 (34.8%) Under palliative treatment 0 (0.0%) 5 (100.0%) Relapse of manic episodes 0.704 Yes 6 (66.7%) 3 (33.3%) No 14 (56.0%) 11 (44.0%) Admission to psychiatric wards 0.728 Yes 12 (20.0%) 7 (80.0%) No 8 (53.3%) 7 (46.7%) Underlying factors of mania 0.030 * Drug-induced 12 (60.0%) 8 (40.0%) Organic 7 (87.5%) 1 (12.5%) Psychogenic 1 (16.7%) 5 (83.3%) * P < 0.05, † P < 0.10

Discussion

To the best of the authors’ knowledge, this is the first systematic review that investigated manic states in cancer patients and their influence on cancer treatment.

Clinical characteristics of cancer patients presenting with manic states

The reported cases of cancer patients who developed manic episodes tended to be relatively young, predominantly male, and with hematological malignancies. The manic states most frequently occurred during cancer treatments; however, a substantial proportion of patients (15%) exhibited manic symptoms preceding the cancer diagnosis.

Only half of the cases were able to continue or commence cancer treatment, elucidating the substantial adverse impact of manic episodes on cancer therapy. Nearly 40% required admission to psychiatric wards, indicating the severity of their manic symptoms.

Etiology of manic episodes and their characteristics

Among the three categories of etiology of manic episodes, drug-induced manic states were the most frequent etiology, composing 60% of the cases. Steroid, which has been widely known a causative agent (Ismail et al. 2017 ), was the most common.

Organic cases were relatively few; however, since brain imaging was not performed in approximately half of the cases, there are chances of overlooked cases.

We compared the clinical characteristics of the three categories. As shown in Table 2 , drug-induced cases were relatively young (at 40s), compared with organic and psychogenic cases (late 50s). This can be attributed to the high incidence of leukemia cases in the drug-induced category, which frequently requires high-dose steroids.

A substantial proportion of the patients experienced recurrence of manic episodes in drug-induced and organic cases, while there was no case of recurrence in psychogenic cases. Psychogenic cases were more likely to be seen among patients at the terminal stage, where many patients deceased early in their clinical course.

Timing of the onset of manic episodes and their characteristics

The timing of the onset of manic states varied according to the causative factors: 85% of drug-induced cases occurred during cancer treatment, while many organic cases (60%) presented before the cancer diagnosis, and many psychogenic cases (67%) arose during palliative care.

A substantial proportion (15%) of patients exhibited manic episodes before the diagnosis of cancer. The mean age of onset for mania was 65, which is relatively higher than that of BD in general (Merikangas et al. 2011 ; Kroon et al. 2013 ). A few sporadic cases of manic episodes that preceded the diagnosis of pancreatic cancer (Pereira et al. 2022 ) have been reported. Sami et al. argued that the first hypomanic episode that occurred after the age of 50 is suggestive of organic factors (Sami et al. 2015 ).

In the current review, we collected the reports in which the authors of the report argued that patients’ manic state was associated with cancer; however, many reports lacked solid evidence to support their arguments. As shown in Table 3 , none of the reported cases satisfied the criteria of Krauthammer & Klerman. Further, in their criteria, no specific threshold has been proposed regarding the proximity between an organic cause and the onset of manic episodes.

It has long been known that depressive episodes can precede a diagnosis of cancer, which is known as “premonitory depression” (Lauter 1973 ). In terms of manic episodes, evidence does not appear sufficient to support a clinical entity of concept of “premonitory mania,” despite there are sporadic reports of manic episodes that precede a cancer diagnosis. Further investigation into the possibility of the concept of “premonitory mania” is warranted.

Clinical management of manic episodes

According to the practice guidelines for BD, pharmacotherapy is the standard approach for manic states (Tajika et al. 2022 ). Significant relief of manic symptoms is usually seen within two weeks (Li et al. 2017 ). Given the high relapse rate of BD (Keller et al. 1993 ), maintenance pharmacotherapy is recommended after remission of manic episodes (Kishi et al. 2022 ). However, in the current review, approximately 20% of the cases with manic episodes did not receive pharmacotherapy, and approximately half of the patients did not receive maintenance pharmacotherapy. The high rate of disrupted cancer therapy may be partly explained by the low rate of administering pharmacotherapy for the acute and maintenance phases of BD. No significant adverse effects have been reported in the use of mood stabilizers and/or antipsychotics in treating manic episodes. There was variability in the dosages of mood stabilizers, and even small doses were effective in many cases. Considering that the median duration to remission of manic states was as short as 14 days even in cancer patients, increasing the awareness of manic states could lead to better management that lead to better cancer treatment.

The current study revealed that brain imaging was conducted in only 55% of the cases. Since central nervous system (CNS) involvement of cancer, such as brain metastases and leptomeningeal metastases, can develop psychiatric symptoms, and the course of manic episodes differs depending on the underlying causes, CNS assessments, such as brain imaging, lumbar puncture, and electroencephalography, are recommended for cancer patients who exhibit psychiatric symptoms.

Clinical course of manic episodes and cancer treatment

After the onset of manic episodes, cancer treatment was provided in 55% of drug-induced cases and 60% of organic cases, but only in 22% of psychogenic cases, suggesting that manic episodes had a significant impact on cancer treatment.

The overall duration until the remission of manic states in drug-induced and organic cases was similar to that of patients in general psychiatric practice (Gonzalez-Pinto et al. 2010 ). The median duration until the remission of manic states is longer in organic causes than in drug-induced cases, suggesting that organic cases are likely to present with more likely to be treatment-resistant. The duration until remission was relatively long in psychogenic cases, which is attributable to the fact that psychogenic cases occurred in patients in the palliative-care phase, presenting with milder manic symptoms; therefore, no intense psychopharmacological treatment was provided to such patients.

Limitations and implications

The current review has a few limitations. First, this is a narrative review of cancer patients who had manic episodes. The association of manic episodes and cancer relied on the judgment of the reporting authors, and the evidence for the relationship between cancer and manic episodes has not been verified. Second, the classification of contributing factors to the onset of manic episodes (drug-induced, organic, and psychogenic) was based on the argument by the reporting authors. Further, these categories do not match the latest classification of mental illnesses, such as DSM-5 and ICD-11; therefore, the validity of the clinical entity is not established.

Despite these limitations, the current review is worth noting, since, to the best of the authors’ knowledge, it is the first comprehensive review of cancer and manic episodes. Further epidemiological and pathophysiological research is warranted to better understand the linkage between cancer and manic episodes.

Supporting information

Osawa and Fujisawa supplementary material 1

Osawa and Fujisawa supplementary material

Osawa and Fujisawa supplementary material 2

Osawa and Fujisawa supplementary material

Supplementary material

The supplementary material for this article can be found at https://doi.org/10.1017/S1478951526102466 .

Funding

This work was supported by JSPS KAKENHI Grant Number JP23K09528.

Competing interests

The authors declare none.

References

Adams F , Fernandez F and Mavligit G ( 1988 ) Interferon-induced organic mental disorders associated with unsuspected pre-existing neurologic abnormalities . Journal of Neuro-oncology 6 ( 4 ), 355 – 359 . doi: 10.1007/BF00177432 . 2464673

American Psychiatric Association (APA) . ( 2013 ) Diagnostic and Statistical Manual of Mental Disorders . Fifth edition (DSM-5) Washington, D.C : American Psychiatric Publication .

Asevedo E , Brietzke E and Chaves AC ( 2013 ) First manic episode in a patient with breast cancer . General Hospital Psychiatry 35 ( 6 ), 681 .e13–4. doi: 10.1016/j.genhosppsych.2013.05.002 . 23764349

Basterreche N , Arrúe A , Arnaiz A , et al. ( 2017 ) Mania preceding pancreatic cancer . Actas Espanolas de Psiquiatria 45 ( 1 ), 39 – 46 . Retrived from: https://actaspsiquiatria.es/index.php/actas/index . 28186320

Bauer IE , Pascoe MC , Wollenhaupt-Aguiar B , et al. ( 2014 ) Inflammatory mediators of cognitive impairment in bipolar disorder . Journal of Psychiatric Research 56 , 18 – 27 . doi: 10.1016/j.jpsychires.2014.04.017 . 24862657 PMC4167370

Benros ME , Eaton WW , Mortensen PB , et al. ( 2014 ) The epidemiologic evidence linking autoimmune diseases and psychosis . Biol Psychiat 75 , 300 – 306 . doi: 10.1016/j.biopsych.2013.09.023 . 24199668 PMC8797267

Błogowski W , Deskur A , Budkowska M , et al. ( 2014 ) Selected cytokines in patients with pancreatic cancer: A preliminary report . PloS One 9 ( 5 ), e97613 . doi: 10.1371/journal.pone.0097613 . 24849506 PMC4029741

Bortolato B , Hyphantis TN , Valpione S , et al. ( 2017 ) Depression in cancer: The many biobehavioral pathways driving tumor progression . Cancer Treatment Reviews 52 , 58 – 70 . doi: 10.1016/j.ctrv.2016.11.004 . 27894012

Brett AS , Voss T and Ridley EP ( 2013 ) Neuropsychiatric symptoms associated with topical imiquimod therapy: Report of 2 cases . JAMA Dermatology 149 ( 4 ), 500 – 501 . doi: 10.1001/jamadermatol.2013.1321 . 23715381

Carmassi C , Shear KM , Corsi M , et al. ( 2020 ) Mania following bereavement: State of the art and clinical evidence . Frontiers in psychiatry/Frontiers Research Foundation 11 , 366 . doi: 10.3389/fpsyt.2020.00366 . PMC7218050 32435209

Cassidy C , Sahay S and McNicholas F ( 2012 ) Steroid-induced mania: A case report . Irish Journal of Psychological Medicine 29 ( 3 ), 194 – 195 . doi: 10.1017/S0790966700017250 . 30200057

Collins C and Oakley-Browne M ( 1988 ) Mania associated with small cell carcinoma of the lung . The Australian and New Zealand Journal of Psychiatry 22 ( 2 ), 207 – 209 . doi: 10.3109/0004867880915896 . 2840887

Cosci F , Fava GA and Sonino N ( 2015 ) Mood and anxiety disorders as early manifestations of medical illness: a systematic review . Psychotherapy and Psychosomatics 84 ( 1 ), 22 – 29 . doi: 10.1159/000367913 . 25547421

Eaton WW , Pedersen MG , Nielsen PR , et al. ( 2010 ) Autoimmune diseases, bipolar disorder, and non-affective psychosis . Bipolar Disord 12 ( 6 ), 638 – 646 . doi: 10.1111/j.1399-5618.2010.00853.x . 20868462 PMC2950824

El Hayek S and El-Khoury J ( 2020 ) Late-onset mania associated with corticosteroids and small cell lung carcinoma . BMJ Case Reports 13 ( 2 ), e233403 . doi: 10.1136/bcr-2019-233403 . PMC7046414 32107258

Enudi W and Udolu OJ ( 2009 ) Neuropsychiatric complications associated with interferon - alpha −2b treatment of malignant melanoma . African Journal of Psychiatry 12 ( 3 ), 227 – 228 . doi: 10.4314/ajpsy.v12i3.48499 . 19750253

Felger JC and Lotrich FE ( 2013 ) Inflammatory cytokines in depression: Neurobiological mechanisms and therapeutic implications . Neuroscience 246 , 199 – 229 . doi: 10.1016/j.neuroscience.2013.04.060 . 23644052 PMC3741070

Fukue M , Uchitomi Y , Sugihara J , et al. ( 1993 ) 【A case of double cancer showing manic state】Sōjōtai o shimeshita jūfuku gan no 1 shōrei . Japanese Journal of General Hospital Psychiatry , 5 ( 1 ), 59 – 66 . Retrived from: https://square.umin.ac.jp/psy/ .

Furutsuka D , Kiriike N , Kuroda Y , et al. ( 1996 ) 【A case of renal cell carcinoma with persistent manic like symptoms and frontal hypoperfusion on SPECT induced by interferon】Intāferon no tōyo ni yori jizoku suru souyo shōjō to zentōyō no ketsuryūshōgai o teishita jinsaibō gan no 1-rei . Clinical Psychiatry , 38 ( 3 ), 310 – 312 . doi: 10.11477/mf.1405904069 .

Garg H , Prakash S , Deb KS , et al. ( 2018 ) Secondary mania following cancer chemotherapy with capecitabine . BMJ Case Reports CP 2018 , bcr - 2017 . doi: 10.1136/bcr-2017-220995 . PMC5878383 29599381

Glynne-Jones R , Vernon CC and Bell G ( 1986 ) Is steroid psychosis preventable by divided doses? The Lancet 2 ( 8520 ), 1404 . doi: 10.1016/s0140-6736(86)92051-9 . 2878267

Goldberg JE and Schwertfeger KL ( 2010 ) Proinflammatory cytokines in breast cancer: Mechanisms of action and potential targets for therapeutics . Current Drug Targets 11 ( 9 ), 1133 – 1146 . doi: 10.2174/138945010792006799 . 20545607

Gonçalves-Pinho M , Freitas A , von Doellinger O , et al. ( 2022 ) Bipolar disorder related hospitalizations - A descriptive nationwide study using a big data approach . The Psychiatric Quarterly 93 ( 1 ), 325 – 333 . doi: 10.1007/s11126-021-09951-6 . 34581934

Gonzalez-Pinto AM , Dardennes R , de Zélicourt M , et al. ( 2010 ) In-patient care costs of patients with bipolar I disorder: A comparison between two European centers . Journal of Affective Disorders 121 ( 1–2 ), 152 – 155 . doi: 10.1016/j.jad.2009.05.010 . 19482360

Greenberg DB and Brown GL ( 1985 ) Mania resulting from brain stem tumor . The Journal of Nervous and Mental Disease 173 ( 7 ), 434 – 436 . doi: 10.1097/00005053-198507000-00008 . 4009161

Greenberg DB , Jonasch E , Gadd MA , et al. ( 2000 ) Adjuvant therapy of melanoma with interferon-alpha-2b is associated with mania and bipolar syndromes . Cancer 89 ( 2 ), 356 – 362 . Retrived from: https://acsjournals.onlinelibrary.wiley.com/journal/10970142 . 10918166

Harrison PJ , Geddes JR and Tunbridge EM ( 2018 ) The emerging neurobiology of bipolar disorder . Trends in Neurosciences 41 ( 1 ), 18 – 30 . doi: 10.1016/j.tins.2017.10.006 . 29169634 PMC5755726

He H , Hu C , Ren Z , et al. ( 2020 ) Trends in the incidence and DALYs of bipolar disorder at global, regional, and national levels: results from the global burden of Disease Study 2017 . Journal of Psychiatric Research 125 , 96 – 105 . 32251918 10.1016/j.jpsychires.2020.03.015

Hechtman L , Russell RC and Young LJ ( 2013 ) Psychosis in a boy with ADHD treated with stimulants and acute lymphocytic leukemia treated with chemotherapy and steroids . Neuropsychiatry 3 ( 1 ), 17 – 21 . doi: 10.2217/npy.12.77 .

Hochhauser CJ , Lewis M , Kamen BA , et al. ( 2005 ) Steroid-induced alterations of mood and behavior in children during treatment for acute lymphoblastic leukemia . Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer 13 ( 12 ), 967 – 974 . doi: 10.1007/s00520-005-0882-8 . 16189647

Hung Y-P , Liu C-J , Tsai C-F , et al. ( 2013 ) Incidence and risk of mood disorders in patients with breast cancers in Taiwan: A nationwide population-based study . Psycho-oncology 22 ( 10 ), 2227 – 2234 . doi: 10.1002/pon.3277 . 23463734

Iancu I , Sverdlik A , Dannon PN , et al. ( 1997 ) Bipolar disorder associated with interferon-alpha treatment . Postgraduate Medical Journal 73 ( 866 ), 834 – 835 . doi: 10.1136/pgmj.73.866.834 . 9497963 PMC2431537

Ingram DG and Hagemann TM ( 2003 ) Promethazine treatment of steroid-induced psychosis in a child . The Annals of Pharmacotherapy 37 ( 7–8 ), 1036 – 1039 . doi: 10.1345/aph.1A271 . 12841815

Ismail MF , Lavelle C and Cassidy EM ( 2017 ) Steroid-induced mental disorders in cancer patients: A systematic review . Future Oncology 13 ( 29 ), 2719 – 2731 . doi: 10.2217/fon-2017-0306 . 29186986

Jamieson RC and Wells CE ( 1979 ) Manic psychosis in a patient with multiple metastatic brain tumors . The Journal of Clinical Psychiatry 40 ( 6 ), 280 – 283 . Retrived from: https://www.psychiatrist.com/jcp/ . 447611

Kanani R , Davies EA , Hanchett N , et al. ( 2016 ) The association of mood disorders with breast cancer survival: An investigation of linked cancer registration and hospital admission data for South East England . Psycho-oncology 25 ( 1 ), 19 – 27 . doi: 10.1002/pon.4037 . 26619290 PMC5096051

Keller MB , Lavori PW , Coryell W , et al. ( 1993 ) Bipolar I: A five-year prospective follow-up . The Journal of Nervous and Mental Disease 181 ( 4 ), 238 – 245 . doi: 10.1097/00005053-199304000-00005 . 8097229

Kessing LV , Agerbo E and Mortensen PB ( 2004 ) Major stressful life events and other risk factors for first admission with mania . Bipolar Disorders 6 ( 2 ), 122 – 129 . doi: 10.1111/j.1399-5618.2004.00102.x . 15005750

Khouzam HR , Emery PE and Reaves B ( 1994 ) Secondary mania in late life . Journal of the American Geriatrics Society 42 ( 1 ), 85 – 87 . doi: 10.1111/j.1532-5415.1994.tb06079.x . 8277121

Kimmel RJ and Combs H ( 2012 ) Steroid-induced mania treated with aripiprazole . Psychosomatics 53 ( 2 ), 181 – 183 . doi: 10.1016/j.psym.2011.03.002 . 22424166

Kishi T , Ikuta T , Matsuda Y , et al. ( 2022 ) Pharmacological treatment for bipolar mania: A systematic review and network meta-analysis of double-blind randomized controlled trials . Molecular Psychiatry 27 ( 2 ), 1136 – 1144 . doi: 10.1038/s41380-021-01334-4 . 34642461 PMC9054678

Kramer TM and Cottingham EM ( 1999 ) Risperidone in the treatment of steroid-induced psychosis . Journal of Child and Adolescent Psychopharmacology 9 ( 4 ), 315 – 316 . doi: 10.1089/cap.1999.9.315 . 10630463

Krauthammer C and Klerman GL ( 1978 ) Secondary mania: manic syndromes associated with antecedent physical illness or drugs . Archives of General Psychiatry 35 ( 11 ), 1333 – 1339 . doi: 10.1001/archpsyc.1978.01770350059005 . 757997

Kroon JS , Wohlfarth TD , Dieleman J , et al. ( 2013 ) Incidence rates and risk factors of bipolar disorder in the general population: A population-based cohort study . Bipolar Disorders 15 ( 3 ), 306 – 313 . doi: 10.1111/bdi.12058 . 23531096

Lajeunesse C , Parent R and Villeneuve A ( 1986 ) Manic-like episode following flutamide treatment . The American Journal of Psychiatry 143 ( 11 ), 1498 – 1499 . doi: 10.1176/ajp.143.11.1498 . 3777267

Lauter H ( 1973 ) Altersdepression-Ursachen, epidemiologie, nosologie . Aktuelle Gerontologie 3 , 247 – 252 . Retrived from: https://id.oclc.org/worldcat/entity/E39QH7JmpXckhHT4b6CqHgkM7R .

León-Caballero J , Pacchiarotti I , Murru A , et al. ( 2015 ) Bipolar disorder and antibodies against the N-methyl-d-aspartate receptor: A gate to the involvement of autoimmunity in the pathophysiology of bipolar illness . Neuroscience and Biobehavioral Reviews 55 , 403 – 412 . doi: 10.1016/j.neubiorev.2015.05.012 . 26014349

Li D-J , Lin C-H and Lu M-J ( 2017 ) Early improvement predicts treatment outcomes for patients with acute Mania: A naturalistic study in Taiwan . Journal of Clinical Psychopharmacology 37 ( 4 ), 435 – 440 . doi: 10.1097/JCP.0000000000000728 . 28590370

Mann AM and Hutchison JL ( 1967 ) Manic reaction associated with procarbazine hydrochloride therapy of Hodgkin’s disease . Canadian Medical Association Journal 97 ( 22 ), 1350 – 1353 . Retrived from: https://www.cmaj.ca/ . 6061601 PMC1923533

Marzani G and Neff AP ( 2021 ) Bipolar disorders: Evaluation and treatment . American Family Physician 103 ( 4 ), 227 – 239 . Retrived from: https://www.aafp.org/pubs/afp.html?cmpid=_van_188 . 33587568

Matsunaga M , Onishi H , Ishida M , et al. ( 2012 ) Hypomanic episode during recurrent gastric cancer treatment: report of a rare case and literature review . Japanese Journal of Clinical Oncology 42 ( 10 ), 961 – 964 . doi: 10.1093/jjco/hys127 . 22872746

Mavrotas M and Murray B ( 2020 ) Mania as a possible complication of immunotherapy . Progress in Neurology and Psychiatry 24 ( 1 ), 9 – 13 . doi: 10.1002/pnp.555 .

Mazure CM , Leibowitz K and Bowers MB, Jr ( 1999 ) Drug-responsive mania in a man with a brain tumor . The Journal of Neuropsychiatry and Clinical Neurosciences 11 ( 1 ), 114 – 115 . doi: 10.1176/jnp.11.1.114 . 9990567

Mercadante S , Villari P and Intravaia G ( 2007 ) Withdrawal acute psychosis after corticosteroid discontinuation . Journal of Pain and Symptom Management 34 ( 2 ), 118 – 119 . doi: 10.1016/j.jpainsymman.2007.03.005 . 17555921

Merikangas KR , Jin R , He J-P , et al. ( 2011 ) Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative . Archives of General Psychiatry 68 ( 3 ), 241 – 251 . doi: 10.1001/archgenpsychiatry.2011.12 . 21383262 PMC3486639

Mian I , Gearing R , DeSouza C , et al. ( 2007 ) Corticosteroid-related psychiatric complications in the treatment of Hodgkin’s lymphoma in an adolescent . Journal of the Canadian Academy of Child and Adolescent Psychiatry. Journal de l’Academie canadienne de psychiatrie de l’enfant et de l’adolescent , 16 ( 1 ), 27 – 29 . Retrived from: https://cacap-acpea.org/knowledge-share/journal/ . PMC2276163 18392176

Michoglou K , Ravinthiranathan A , San Ti S , et al. ( 2023 ) Pancreatic cancer and depression . World Journal of Clinical Cases 11 ( 12 ), 2631 – 2636 . doi: 10.12998/wjcc.v11.i12.2631 . 37214569 PMC10198113

Morgan JF , Beckett J and Zolese G ( 2001 ) Psychogenic mania and bereavement . Psychopathology 34 ( 5 ), 265 – 267 . doi: 10.1159/000049320 . 11799322

Morita T , Inoue S and Chihara S ( 1997 ) 【Manic state in terminal cancer patients】Shūmatsuki gan kanja no sōjōtai (in Japanese) . Seishin Igaku 39 ( 1 ), 59 – 65 . doi: 10.11477/mf.1405904252 .

Morosán Allo YJ , Rosmarin M , Urrutia A , et al. ( 2015 ) Myxedema madness complicating postoperative follow-up of thyroid cancer . Archives of Endocrinology and Metabolism 59 ( 4 ), 359 – 363 . doi: 10.1590/2359-3997000000090 . 26331326

Motoyasu A ( 1988 ) A case of terminal cancer which provoked manic state】Keika-chū ni sōjōtai o teishita makki gan no 1-rei . Japanese Journal of Clinical Psychiatry 17 ( 5 ), 667 – 672 . Retrived from: https://arcmedium.co.jp/products/list.php?category_id=1 .

Murata Y ( 1994 ) 【Manic state due to primary malignant lymphoma of the central nervous system: report of a case】Sōjōtai o teishita tōgainai genpatsu-sei akusei rinpashu no 1 shōrei . Iryo 48 ( 4 ), 309 – 312 . doi: 10.11261/iryo1946.48.309 .

Murru A , Castro P , Sanchez R , et al. ( 2009 ) Late-onset manic episode in a 91-year-old man without previous psychiatric history as a unique clinical manifestation of a pancreatic neoplasm . The Journal of Clinical Psychiatry 70 ( 2 ), 296 – 297 . doi: 10.4088/jcp.08l04577 . 19265648

Nakamura K , Nishiyama S , Sekida K , et al. ( 2003 ) A case of mania attributable to the administration of an anticancer agent】Kō gan-zai ni yori sōjōtai o teishita to omowa reru 1 shōrei . Hiroshima kenritsu byōin-i-shi , 35 ( 1 ), 67 – 71 . Retrived from: https://hiroshima.hpho.jp/about/journal-index/ .

Ni Mhaolain AM and Thakore JH ( 2007 ) Interferon-alpha induced mania during the adjuvant treatment of malignant melanoma . Irish Journal of Medical Science 176 ( 2 ), 137 – 139 . doi: 10.1007/s11845-007-0016-z . 17394037

Olde Engberink RHG , Knippels MCJ and Pijpers E ( 2013 ) Hypomanic episode as a first presentation of a large B-cell lymphoma . Japanese Journal of Clinical Oncology 43 ( 3 ), 318 – 320 . doi: 10.1093/jjco/hys238 . 23315385

Onishi H , Miyashita A and Kosaka K ( 2000 ) A manic episode associated with bereavement in a patient with lung cancer. A case report . Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer 8 ( 4 ), 339 – 340 . doi: 10.1007/s005209900109 . 10923776

Osawa K , Ukai S , Tsuji T , et al. ( 2013 ) mania in a patient with terminal pancreatic cancer】Jūdo no sōjōtai o teishita makki suizō gan no 1 shōrei . Psychiatry , 22 ( 4 ), 457 – 462 . Retrived from: https://www.kahyo.com/category/A1-SESN .

Oyewumi LK and Lapierre YD ( 1981 ) Efficacy of lithium in treating mood disorder occurring after brain stem injury . The American Journal of Psychiatry 138 ( 1 ), 110 – 112 . doi: 10.1176/ajp.138.1.110 . 7446761

Page MJ , McKenzie JE , Bossuyt PM , et al. ( 2021 ) The PRISMA 2020 statement: An updated guideline for reporting systematic reviews . BMJ 372 , n71 . doi: 10.1136/bmj.n71 . 33782057 PMC8005924

Pereira D , Wildenberg B , Oliveira P , et al. ( 2022 ) Manic syndrome as the presenting feature of pancreatic cancer . Revista Brasileira de Psiquiatria (Sao Paulo, Brazil: 1999) 44 ( 1 ), 111 – 112 . doi: 10.1590/1516-4446-2021-2384 . 35170675 PMC8827376

Perlick D , Clarkin JF , Sirey J , et al. ( 1999 ) Burden experienced by care-givers of persons with bipolar affective disorder . The British Journal of Psychiatry: the Journal of Mental Science 175 , 56 – 62 . doi: 10.1192/bjp.175.1.56 . 10621769

Pickar D , Dubois M and Cohen MR ( 1984 ) Behavioral change in a cancer patient following intrathecal beta-endorphin administration . The American Journal of Psychiatry 141 ( 1 ), 103 – 104 . doi: 10.1176/ajp.141.1.103 . 6197891

Pompili M , Gonda X , Serafini G , et al. ( 2013 ) Epidemiology of suicide in bipolar disorders: A systematic review of the literature . Bipolar Disorders 15 ( 5 ), 457 – 490 . doi: 10.1111/bdi.12087 . 23755739

Reich M , Girard E and Le Rhun E ( 2017 ) Breast leptomeningeal metastasis recurrence presenting as a manic episode . Palliative and Supportive Care 15 ( 2 ), 272 – 275 . doi: 10.1017/S1478951516000456 . 27346419

Rodrigues Cordeiro C , Côrte-Real BR , Saraiva R , et al. ( 2023 ) Triggers for acute mood episodes in bipolar disorder: A systematic review . Journal of Psychiatric Research 161 , 237 – 260 . doi: 10.1016/j.jpsychires.2023.03.008 . 36940629

Rosenblat JD , Cha DS , Mansur RB , et al. ( 2014 ) Inflamed moods: A review of the interactions between inflammation and mood disorders . Progress in Neuro-Psychopharmacology & Biological Psychiatry 53 , 23 – 34 . doi: 10.1016/j.pnpbp.2014.01.013 . 24468642

Roxanas MG and Hunt GE ( 2012 ) Rapid reversal of corticosteroid-induced mania with sodium valproate: A case series of 20 patients . Psychosomatics 53 ( 6 ), 575 – 581 . doi: 10.1016/j.psym.2012.06.006 . 23157995

Sami M , Khan H and Nilforooshan R ( 2015 ) Late onset mania as an organic syndrome: A review of case reports in the literature . Journal of Affective Disorders 188 , 226 – 231 . doi: 10.1016/j.jad.2015.08.027 . 26368947

Schillinger D ( 2017 ) The living donor: A Tale of money, Mania, and clinical mastery . JAMA: the Journal of the American Medical Association 317 ( 15 ), 1531 – 1532 . doi: 10.1001/jama.2016.17221 . 28418485

Seoud T , Syed A , Carleton N , et al. ( 2020 ) Depression before and after a diagnosis of pancreatic cancer: Results from a national, population-based study . Pancreas 49 ( 8 ), 1117 – 1122 . doi: 10.1097/MPA.0000000000001635 . 32833946 PMC7450395

Shen S-H and Lee S-H ( 2021 ) A case of lung cancer with brain metastasis following late-onset bipolar disorder . Behavioural Neurology 2021 , 8880539 . doi: 10.1155/2021/8880539 . 33868511 PMC8034995

Shinozaki T , Shima Y , Nishimura H , et al. ( 1994 ) Manic defence of terminal cancer patients】Gan makki kanja no souteki bōei ni tsuite . Tāminarukea 4 , 170 – 172 . Retrived from: https://www.seikaisha.blue/palliative-care/about/ .

Shirata T , Akiba D , Tobizawa T , et al. ( 2013 ) 【A case of advanced gastric cancer presenting with mania】Sōjōtai o teishita shinkō igan no shōrei . Yonezawa Shiritsubyōin seishin igaku , 33 ( 1 ), 21 – 24 . Retrived from: https://ci.nii.ac.jp/ncid/AN00358544 .

Sirois F ( 1995 ) Rehearsing one’s death . Journal of Palliative Care 11 ( 3 ), 50 – 52 . Retrived from: https://journals.sagepub.com/home/pal . 7472795

Starkstein SE , Boston JD and Robinson RG ( 1988 ) Mechanisms of mania after brain injury. 12 case reports and review of the literature . The Journal of Nervous and Mental Disease 176 ( 2 ), 87 – 100 . doi: 10.1097/00005053-198802000-00004 . 3276815

Stecker E ( 1993 ) The terminally ill patient on an acute psychiatric unit. A case study . Journal of Psychosocial Nursing and Mental Health Services 31 ( 5 ), 13 – 15 . doi: 10.3928/0279-3695-19930501-05 . 8355226

Strite D , Valentine AD and Meyers CA ( 1997 ) Manic episodes in two patients treated with interferon alpha . The Journal of Neuropsychiatry and Clinical Neurosciences 9 ( 2 ), 273 – 276 . doi: 10.1176/jnp.9.2.273 . 9144108

Tajika A , Hori H , Iga J-I , et al. ( 2022 ) Mood stabilizers and antipsychotics for acute mania: Systematic review and meta-analysis of augmentation therapy vs monotherapy from the perspective of time to the onset of treatment effects . The International Journal of Neuropsychopharmacology/official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum 25 ( 10 ), 839 – 852 . doi: 10.1093/ijnp/pyac050 . PMC9593220 35932466

Tohen M and Grundy S ( 1999 ) Management of acute mania . The Journal of Clinical Psychiatry 60 ( Suppl 5 ), 31 – 34 . Retrived from: https://www.psychiatrist.com/jcp/ . discussion 35-6 10192405

Tutkunkardas MD and Mukaddes NM ( 2010 ) Drug induced mania in a boy with high functioning autism . Psychopharmacology Bulletin 43 ( 2 ), 82 – 85 . Retrived from: https://medworksmedia.com/psychopharmacology-bulletin/ . 21052044

Ularntinon S , Tzuang D , Dahl G , et al. ( 2010 ) Concurrent treatment of steroid-related mood and psychotic symptoms with risperidone . Pediatrics 125 ( 5 ), e1241 – 5 . doi: 10.1542/peds.2009-1815 . 20385646

Van den Ameele S , van Diermen L , Staels W , et al. ( 2016 ) The effect of mood-stabilizing drugs on cytokine levels in bipolar disorder: A systematic review . Journal of Affective Disorders 203 , 364 – 373 . doi: 10.1016/j.jad.2016.06.016 . 27344047

Venkatarangam SH , Kutcher SP and Notkin RM ( 1988 ) Secondary mania with steroid withdrawal . Canadian Journal of Psychiatry Revue Canadienne de Psychiatrie 33 ( 7 ), 631 – 632 . doi: 10.1177/070674378803300711 . 3197019

Wamboldt FW , Weiler SJ and Kalin NH ( 1984 ) Cyclosporin-associated mania . Biological Psychiatry 19 ( 7 ), 1161 – 1162 . Retrived from: https://www.biologicalpsychiatryjournal.com/ . 6383485

Watanabe TK , Sylvester CE and Manaligod JM ( 1994 ) Mania or panic associated with dexamethasone chemotherapy in adolescents . The Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine 15 ( 4 ), 345 – 347 . doi: 10.1016/1054-139x(94)90609-2 . 7918509

World Health Organization . ( 2019 ) International Statistical Classification of Diseases and Related Health Problems . 11th Revision .