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Case report Suicide and suicidal ideation after marrow transplantation A Molassiotis and PJ Morris Haematology Department, Hammersmith Hospital, London, UK

Summary: Two cases of patients who attempted suicide following BMT and one case of a patient with suicidal ideation during his isolation period for BMT are reviewed. The factors which contributed to this situation are investigated. Finally, issues relating to psychological interventions are briefly discussed Keywords: suicide; bone marrow transplantation

Although there has been increasing interest in the emotional aspects of bone marrow transplantation (BMT) in the last decade or so,1 suicide has not been investigated thoroughly in the BMT literature. BMT involves numerous stresses such as the decision to undergo marrow transplantation, aggressive pre-transplant conditioning, immunosuppression, isolation for a prolonged period of time, the ‘waiting’ period for the marrow engraftment, numerous treatment complications, and finally the long period of adjustment.2 All these stressors, combined with the diagnosis of a lifethreatening illness may overshadow the value, meaning or quality of life, and patients can become vulnerable to suicide or suicidal ideation. Suicidal behaviour after BMT has been reported in a case study by Jenkins and Roberts.3 The authors drew attention to the need of the transplant teams to be vigilant in assessing the emotional state of BMT patients. Also, major depression has been associated with suicide or thoughts of death,4,5 and depression is a common problem in cancer patients.6 Depression may be the result of either a recurrence of a severe depressive illness which pre-dates the diagnosis, a psychotic depression usually secondary to ongoing steroid medication, or a reactive depression in response to a life-threatening disease.4 Other risk factors for suicide include severe insomnia, chronic illness, organic brain syndrome, undiagnosed mental illness (besides depression), substance/alcohol abuse, male gender, race/ethnicity, and age.7–9 Suicide rate (including suicidal ideation) is highest in adults over 65 years of age,10 followed by adolescents and young adults (15–25 years old), where the estimated rate appears to be around 2% in the USA.8 The exact rate of Correspondence: Dr A Molassiotis, University of Malta, Institute of Health Care, G’Mangia, MSD 07, Malta Received 15 May 1996; accepted 29 August 1996

suicide among cancer patients is unknown.5 Cancer patients, due to the multiplicity of stressors that they experience, may believe that suicide offers the only escape from the unendurable pain, depression or unrelenting symptoms of the disease. We report three cases of suicidal behaviour in BMT patients, of which one was successful. The three cases received their BMT in two UK centres. Two of these cases were long-term survivors and the third was a patient in isolation immediately after receiving a marrow transplant. These cases occurred over a period of 3 years. Two more cases demonstrated suicidal behaviour during the same 3year period, but are not detailed here. About 312 transplants were carried out during this period in these two BMT centres. The aims of the current case study are as follows: (1) to increase awareness of the issue of suicide during BMT; (2) to identify patient characteristics that may contribute to suicide/suicidal ideation; and (3) to offer suggestions for the management of potentially suicidal BMT patients.

Case reports Case 1 A 33-year-old nursing sister presented in July 1991 with symptoms indicative of paroxysmal nocturnal haemoglobinuria. She did not respond to therapy with prednisolone and had been transfusion-dependent since diagnosis. She was offered a BMT from her HLA-matched sister and given an 80% chance of cure. As she had no children, fertility strategies were discussed. However, she and her husband decided against cryopreservation of fertilised ova due to the risks involved. She underwent allogeneic BMT in March 1993 as she had become neutropenic and her transfusion requirements had increased. She was discharged a month later with no graft-versus-host disease (GVHD), no significant infective complications and mildly elevated creatinine levels due to cyclosporin A toxicity. Towards the end of April she was admitted to hospital with an itchy rash and high temperature. During this admission she became unwell with fever, weight and appetite loss, abnormal liver function tests (LFTs) (she was on steroids and intravenous amphotericin) and jaundiced. Several diagnoses were possible, including GVHD, and fungal or viral infection. She was complaining of short-term memory loss and was referred to the Psychological Medicine

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Department for assessment. However, she did not keep the appointment with the psychiatrist. She was also in tears at times and suffered from insomnia. She did not have a sustained depressive affect and refused antidepressants, which were anyway contraindicated due to her liver dysfunction (creatinine 1.25 mg/dl, increased bilirubin and hepatic haematoma). She was discharged on a low dose of steroids. Ten days later she arrived at the hospital for an outpatient visit and on getting out of the car she was unable to walk. She was admitted to hospital and appeared to be slightly confused overnight, but was discharged the next day. Seven days later, on day 123 post-BMT she was admitted to hospital with an acute psychotic episode. Her mental state had severely deteriorated. She was agitated, disturbed by paranoid fantasies, constant repetitive movements and pacing, attempts to damage herself (she had burned herself and was found putting an electrical flex around her neck) and suicidal thoughts. This appeared to be a mixture of organic brain reaction, psychotic state and depressive reaction. Insight was difficult to assess. Contributory factors included profound hepatic failure, steroid reaction and anxiety/depression about her plight. Psychiatric nursing was provided on a 24 h basis and she was reviewed regularly. Medication was difficult to prescribe due to her hepatic dysfunction. She had no recollection of recent events, and she complained of difficulty sleeping and nightmares. Reactive depression was the diagnosis established after a psychiatric assessment later the same week. The patient was complaining of nightmares and reactivation of bad memories of past events. It was not clear whether these memories were real. She was treated with low doses of chlorpromazine and temazepam. Prior to discharge she stated that she no longer felt suicidal or depressed, but complained of daytime drowsiness. She was also able to joke about the memories which pre-occupied her. She demonstrated an overall improvement in her mental state, with no sustained depressive affect or anhedonia. It appeared that her depression was resolving. On day 130 she developed mild exertional dyspnoea related to a persisting pleural effusion. A month later (day 155) she was reviewed in the outpatient clinic and was found to still have a poor short-term memory. She was still suffering from hepatic dysfunction due to liver GVHD and liver haematoma, a right pleural effusion, and poor bone marrow function. The impaired short-term memory was probably associated with her poor state of health. She continued to receive prednisolone for the next few months to control her GVHD (range of dose 40–100 mg on alternate days) and more therapies for her liver and renal dysfunction. All this time she had short periods of improvement and long periods of hospitalisation and treatment. There were no psychiatric symptoms reported for the next 9 months, but the family were concerned about her poor state of health. She also started working part-time as a nurse teacher and a month later started working full-time. However, she had problems coping with work, possibly related to her short-term memory loss and was referred to the hospital psychiatrist. Before this appointment she cut her femoral artery with a carving knife at home, about 12 months after her transplant.

Case 2 A 44-year-old woman was diagnosed in June 1990 with chronic myeloid leukaemia. She was an articulate and intelligent school teacher, married, with two daughters aged 10 and 11 years. The discovery of her leukaemia proved to be a bitter blow for the family. She commenced treatment with hydroxyurea. The only significant previous medical problem was that in 1982 she developed a lump in her right breast which turned out to be a ductal adenocarcinoma. This was treated with radiotherapy and there were no signs of recurrence. She received a volunteer unrelated donor BMT at the beginning of February 1992. On day 5 she developed severe mucositis and required intravenous diamorphine and parenteral nutrition for some time. On day 15 she developed melaena probably related to mucositis and was given platelets. High doses of steroids were commenced to control erythema and redness of her knuckles, as well as the diarrhoea. She was discharged on day 40. On discharge she had GVHD grade 2 of the gut and skin and was taking prednisolone 100 mg on alternate days. GVHD continued for the next few months, and she was hospitalised on several occasions with problems related to nausea, vomiting, clostridium difficile diarrhoea, toxicity to clofazamine which was given as an additional treatment for GVHD, hyponatraemia, febrile illness of unknown aetiological origin and renal impairment. Seventeen months post-BMT, after a few months of relatively good health she was admitted to hospital with problems resulting from a decrease in her prednisolone dose. She also started treatment again for renal dysfunction. Later she was hospitalised twice more with severe haemoptysis (self-limiting). Her skin had completely peeled. At this point it was the first time she talked about her appearance. Her body image was very important to her and she felt unattractive and ugly. A psychologist saw her twice to discuss with her issues of altered body image, which were of major concern to her, but no further interventions were planned. Over the next few months she developed more complications and needed repeated admissions to hospital. During February 1994 she was admitted to hospital with cyclosporin toxicity. At the same time she had to deal with her cutaneous and pulmonary GVHD, renal impairment, sicca syndrome of the eyes and mouth, onycholysis, and bronchiolitis. Prednisolone was increased to 200 mg for a few days and then reduced to 50 mg on alternate days. A few days after returning home she attempted suicide taking a paracetamol overdose, exactly 2 years after her BMT (possibly an ‘anniversary reaction’ in the light of her ongoing problems). Following this, she received hospice care at home (due to her physical complications) and died soon after. Case 3 A successful 50-year-old solicitor was admitted in July 1994 for allogeneic BMT (from his HLA-identical sister). He had a 7-year history of essential thrombocythaemia, treated with oral chemotherapy to control the platelet count.

Suicidal ideation after BMT A Molassiotis and PJ Morris

The disease progressed after 1992 when his marrow became mildly hypocellular, probably secondary to longterm chemotherapy. In April 1993 he had a blast cell count of 5% and a year later had a fibrotic trephine and 17% blasts. He gradually transformed through myelodysplasia to acute myeloid leukaemia (AML) with myelofibrosis. In June 1994 he suffered cough, shortness of breath, pallor, tiredness, nausea, anorexia, night sweats, bone pain, poor concentration and a feeling of being generally ‘stressed out’. A month before the BMT his BM aspirate contained 50% blast cells with an extremely fibrotic trephine. Taking into account his age, CMV status and female donor, the risks of BMT mortality were high. Equally, there was a high chance of relapse even if the BMT was technically satisfactory. His chance of long-term survival following BMT was estimated at 10–20%. His social situation was of some interest. He was divorced and had a 16-year-old daughter who was living with her mother. There was no social support system for him, except for his daughter. His father had died from AML and he was adamant that he did not want ‘to go the same way’. A psychological assessment on day 2 revealed severe depressive symptomatology, low self-esteem, feelings of worthlessness and understandable anxiety. He also suffered badly from feelings of lack of control brought about by the disease transformation (considering that his career was going well and that he was very independent). On day 3 he communicated suicidal plans. He could not cope with his illness anymore and was very often in tears. The third week post-BMT he commenced methylprednisolone to control his GVHD. On day 19 he developed an acute psychotic episode with visual hallucinations and paranoid thoughts. This episode was attributed to steroids. On day 20 he was still disorientated and frustrated and on day 22 was very confused. Steroids were reduced and his psychotic symptoms settled within a week. On day 30 the patient was assessed again but there were no changes in his depression and anxiety levels from the previous assessment on day 2. He felt extremely bored, fearful, and was more sure of his decision to commit suicide. He had decided exactly how and when to do it. He did not complete

Table 1

his plans however, as he died 12 weeks after the transplant from severe bowel GVHD. Discussion A number of possible reasons underlying suicidal ideation in BMT patients can be seen from examination of these case studies (Table 1). High doses of steroids often produce psychotic reactions. Sometimes these reactions can be masked by the presence of systemic organ failure, as in case 2. Severe complications for prolonged periods of time with difficulty in controlling symptomatology and repeated admissions to hospital (cases 1 and 2) or poor prognosis (case 3) can give rise to suicidal ideation. Impaired organ function (liver, kidney, lung) can also affect the patient’s emotional state, as illustrated in case 1. Isolation can be perceived as a stressful experience by some patients, but its effects cannot be clearly separated from the treatment itself or coping with a life-threatening illness.11 Lack of immediate family and friends (social support) in case 3 might have contributed to suicidal thoughts, as the literature has shown that strong family relationships are associated with better emotional adjustment in BMT patients.12 Abnormal liver function tests (case 1, possibly due to hepatic GVHD or fungal/viral infection) were a contraindication to the use of antidepressants. Such a situation can complicate the management of potentially suicidal patients. Most antidepressants, especially tricyclics and related drugs, are well known to be a cause of hepatic problems (abnormal LFTs). Monoamine oxidase inhibitors, less commonly used, have been associated with jaundice and on rare occasions fatal progressive hepatocellular necrosis. Similarly, serotonin uptake inhibitors (ie Prozac) can rarely cause an increase in LFTs, necessitating discontinuation of the drugs. Thus, psychopharmacological management of depressed BMT patients with abnormal liver function has many obstacles. Psychiatric symptoms, especially depression and delirium or psychotic episodes, can develop at any point during steroid treatment.4 Chemotherapy (eg vincristine,

Risk factors underlying suicidal ideation in BMT patients

Risk factors Use of high doses of steroids Major depression (not reactive) Abnormal metabolic status and impaired physical functioning Weak family relationships/social support Poor disease prognosis Drug toxicity affecting CNS Disturbed body image (especially in adolescents and young adults) Insomnia Chronic illness Organic brain syndrome Undiagnosed mental illness (besides depression) Substance/alcohol abuse Asking for better management of physical symptoms Prior psychiatric history P = present; A = absent; NA = could not be/was not assessed.

Present/Absent P P P P P P P P — ?P NA A NA NA

All cases Cases 1 and 2 Case 1 Case 3 Case 3 Case 1 Case 2 Case 1 — Case 1

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asparaginase, etc), opioid analgesics, fever and infection, and metabolic abnormalities can alter the psychological state of a patient which, in turn, can lead to depression and delirium.4 Because depression and suicide are linked, treating depression and reducing physical symptom distress may often reduce suicide risk.5 It is important to note that physicians and nurses often fail to ask their cancer patients about depression, and depressed patients often report only physical symptoms and minimise their depression or suicidal ideas. Furthermore, eight out of 10 suicidal people ask for better management of their physical symptoms, but the suicide risk factor is not usually detected.9 Although a prior psychiatric history can be a risk factor for suicide, none of the patients in this series of case studies had a comprehensive psychiatric assessment prior to BMT. A pre-BMT psychosocial evaluation that includes prior psychiatric history, quality of social support, prior history of coping and coping with disease/treatment, quality of affect, mental status and proneness to anticipatory anxiety,13 and regular routine psychological assessment thereafter, even in the absence of obvious problems, should be offered to all BMT patients. Training of staff in the recognition of psychiatric morbidity can benefit patients and improve their quality of life. Training is necessary, as it has been shown that health professionals, especially nurses, can underestimate suicide risk, or misidentify worries and fears as suicide risk factors.9 Many patients do well from a psychological perspective and are not interested in psychological intervention,14 but intervention should be offered as necessary. Every intervention with BMT patients must be characterised by flexibility to meet each patient’s needs, 4 and it should be a combination of psychopharmacology and psychotherapeutic techniques. Teaching alternative coping techniques can also be beneficial for the patient, and may reduce suicide attempts and considerably decrease psychiatric morbidity among BMT survivors. Post-prevention strategies could be directed toward sharing information, expressing feelings and identifying those who are most vulnerable for suicidal actions. 15 Further research should be directed towards quantifying the problem of suicide among marrow transplant patients and comparing it with data from other cancer populations and the general adult population in the appropriate age range. This will assist in recognising how often suicide among marrow transplant patients is a problem. Suicide prevalence over a 3-year period in these two institutions was broadly speaking 2.5–3.0%. This percentage is much higher compared to adults in the same age range. A point of concern in relation to these cases is that other factors, besides the ones identified, may be responsible for suicidal ideation and suicide. These factors may include personal history prior to BMT, coping with stresses or a life-threatening disease or relationship between the patient and the donor. Further, the depression in cases 1 and 3

may be related to personality characteristics. Unfortunately, these important issues were not assessed before the death of these patients. In conclusion, suicidal ideation may be much more common in BMT patients than is generally recognised, and attempts should be made prior to BMT to identify patients particularly at risk. Acknowledgements The authors would like to express their appreciation to Professor JM Goldman and Dr DW Milligan for their kind permission to review their cases.

References 1 Andrykowski MA. Psychosocial factors in bone marrow transplantation: a review and recommendations for research. Bone Marrow Transplant 1994; 13: 357–375. 2 Brown HN, Kelly MJ. Stages of bone marrow transplantation: a psychiatric perspective. Psychosom Med 1976; 38: 439–446. 3 Jenkins PL, Roberts DJ. Suicidal behaviour after bone marrow transplantation. Bone Marrow Transplant 1991; 7: 159–161. 4 Levenson JA, Lesko LM. Psychiatric aspects of adult leukemia. Semin Oncol Nurs 1990; 6: 76–83. 5 Saunders JM, Valente SM. Cancer and suicide. Oncol Nurs Forum 1988; 15: 575–581. 6 Derogatis LR, Morrow GR, Fetting J et al. The presence of psychiatric disorders among cancer patients. JAMA 1983; 249: 751–757. 7 Garden FH, Garrison SJ, Jain A. Assessing suicide risk in stroke patients: review of two cases. Arch Phys Med Rehabil 1990; 71: 1003–1005. 8 Shaffer D. Preventing suicide in young people. Innov Res 1993; 2: 3–9. 9 Valente SM, Saunders JM, Grant M. Oncology nurses knowledge and misconceptions about suicide. Cancer Pract 1994; 2: 209–216. 10 Buchanan D, Farran C, Clark D. Suicidal thought and selftranscendence in older adults. J Psychosoc Nurs Ment Health Serv 1995; 33: 31–34. 11 Molassiotis A, Van den Akker OBA, Milligan DW et al. Psychological adaptation and symptom distress in bone marrow transplant recipients. Psycho-Oncology 1996; 5: 9–22. 12 Molassiotis A, Van den Akker OBA, Boughton BJ. Perceived social support, family environment, and psychosocial recovery in bone marrow transplant long-term survivors. Soc Sci Med (in press). 13 Futterman AD, Wellisch DK, Bond G, Carr CR. The Psychosocial Levels System: a new rating scale to identify and assess emotional difficulties during bone marrow transplantation. Psychosomatics 1991; 32: 177–186. 14 Maguire P. Doctor patient skills. In: Argyll M (ed.). Social Skills and Health. Methuen: London, 1981, pp 56–81. 15 Norton RD. Adolescent suicide: risk factors and countermeasures. J Health Educ 1994; 25: 358–361.