© Borgis - Postępy Nauk Medycznych 9/2013, s. 609-614
*Marzena Samardakiewicz1, Jakub Litak2, Aneta Szudy2, Agata Makarewicz3
Zaburzenia psychiczne indukowane steroidami u adolescentów w przebiegu leczenia ostrej białaczki limfoblastycznej
Mental disorders induced by steroids in the course of treatment for acute lymphoblastic leukemia in adolescents
1Department of Pediatric Hematology, Oncology and Transplantology, Medical University, Lublin
Head of Department: prof. Jerzy R. Kowalczyk, MD, PhD
2Medical Students’ Research Association, Department of Pediatric Hematology, Oncology and Transplantology, Medical University, Lublin
Head of Department: prof. Jerzy R. Kowalczyk MD, PhD
3Chair and Department of Psychiatry, Independent Public Teaching Hospital No 1 in Lublin, Lublin
Head of Department: prof. Andrzej Czernikiewicz, MD, PhD
Streszczenie
Wstęp. Kortykosteroidy/GKS stanowią ważny element w leczeniu wielu chorób nowotworowych wieku dziecięcego. Mogą prowadzić jednak do wystąpienia wielu niepożądanych objawów somatycznych i behawioralnych, w tym zaburzeń psychicznych, także jakościowych. Szczególnie narażeni są pacjenci z ostrą białaczką limfoblastyczną/ALL otrzymujący w protokołach terapeutycznych wysokie dawki prednizonu/PRED i deksametazonu/DEXA i pacjenci z chorobą Hodkina/HD wielokrotnie otrzymujący cykle z DEXA.
Cel pracy. Analiza przypadków zaburzeń psychicznych indukowanych przyjmowaniem steroidów w przebiegu leczenia ostrej białaczki limfoblastycznej u dzieci powyżej 12 roku życia.
Materiał i metody. Przedmiotem analizy był przebieg epizodów przejściowych zaburzeń psychicznych u dwóch pacjentów z ALL oraz ocena stanu psychicznego w określonych momentach czasowych w trakcie intensywnej terapii oraz podczas długofalowej obserwacji po zakończeniu leczenia podtrzymującego remisję. Epizody zaburzeń funkcji psychicznych wystąpiły dwukrotnie, w obu protokołach leczenia, w momencie redukcji steroidów.
Wyniki. Pacjent A (chłopiec, 14,9 at) z ALL (BFM 97; Prot I: 37 dni x 100mg PRED/dzień: 28 dni maks. dawka, 9 dni redukcja; Prot. II: 30 dni x 16 mg DEXA: 21 dni dawka max, 9 dni redukcja). W trakcie redukcji PRED (od 29. do 37. dnia) zaobserwowano u pacjenta spowolnienie psychoruchowe, pogorszenie kontaktu słownego, utratę zainteresowania otoczeniem i osobami, przygnębienie, izolację, ęk i płaczliwość. W trakcie pierwszego dnia redukcji DEXA (22. dzień terapii) chłopiec podjął zamiar próby samobójczej, przy próbie interwencji stawiał opór, był pobudzony, wyrażał głośno myśli samobójcze. Pacjent B (chłopiec, 15,2 at) z ALL (ALL-IC 2002; Prot. I: 37 dni x 115mg PRED/dzień:28 dni maks. dawka, 9 dni redukcja; Prot. II: 31 dni x 20 mg DEXA: 22 dni maks. dawka, 9 dni redukcja). 10 dni po rozpoczęciu PRED, po osiągnięciu maks. dawki, chłopiec stał się mało aktywny, izolujący się, w obniżonym nastroju. Objawy utrzymywały się na tym samym poziomie od 10. do 37. dnia. W pierwszym dniu redukcji dawki DEXA zaobserwowano u pacjenta niepokój, ęk, a behawioralne przesłanki wskazywały na intensywne doznania omamowe.
Wnioski. 1. Dzieci i młodzież otrzymujący wysokie dawki steroidów (PRED i /lub DEXA) w przebiegu leczenia nowotworów są narażone na wystąpienie zaburzeń psychicznych. 2. Epizody zaburzeń psychicznych u nastoletnich chłopców z ALL każdorazowo wystąpiły w momencie redukcji steroidów, w obrazie psychopatologicznym miały podobne elementy, ale różniły się w zakresie zastosowanej farmakoterapii i przebiegu późniejszego funkcjonowania pacjentów. 3. Rozpoznawanie i leczenie epizodów psychiatrycznych u dzieci z chorobami nowotworowymi wymaga wypracowania standardu postępowania w warunkach polskich ośrodków onkologii i hematologii dziecięcej, także po zakończeniu leczenia.
Summary
Introduction. Glicokorticosteroids/GKS are an important element in children’s cancer treatment. However, they can lead to many adverse somatic and behavioral symptoms, including psychic disorders, also quality ones. Especially exposed are the patients with acute lymphoblastic leukemia/ALL treated with high doses of Prednisone/PRED and Dexamethasone/DEXA, as well as patients with Hodgkin Disease/HD treated with multiple DEXA cycles.
Aim. Analysis of cases of mental disorders induced by taking steroids during treatment of acute lymphoblastic leukemia in children over 12 years of age.
Material and methods. The subject of analysis was the course of transient episodes of mental disorders in two patients with ALL and evaluation of mental state at certain points in time during intensive care and during long-term follow-up after completion of maintenance therapy. Episodes of mental dysfunction occurred twice, in both treatment protocols, at the time of reduction of steroids.
Results. Patient A (14.9 year-old boy) with ALL (BFM 97; Prot I: 37 days x 100mg of PRED daily: 28 days of max dose, 9 days of dose reduction; Prot. II: 30 days x 16 mg of DEXA: 21 days of the max dose, 9 days of reduction). During PRED dose reduction (on 29th-37th days) the patient was observed with psychomotor retardation, impaired verbal contact, oss of interest in surroundings and people, depression, isolation, anxiety and crying. During the first day of DEXA reduction (the 22th day) the boy attempted suicide, resisted to an attempt to intervene, he was excited, he expressed suicidal thoughts aloud. Patient B (15.2 year-old boy) with ALL (ALL-IC 2002; Prot. I: 37 days x 115mg of PRED daily: 28 days of max dose, 9 days of dose reduction; Prot. II: 31 days x 20 mg of DEXA: 22 days of full dose, 9 days of reduction). 10 days after the start of PRED therapy, after reaching the maximum dose, the boy has become very ittle active, secluded and in ow mood. Symptoms remained at the same evel from 10th to 37th day. And during the first day of DEXA dose reduction anxiety and fear were observed in the patient, and behavioral indications pointed to intense hallucinatory experience.
Conclusions. 1. Children and adolescents receiving high-dose steroids (PRED and/or DEXA) in the course of cancer treatment are at risk of developing mental disorders. 2. Episodes of mental disorders in adolescent boys with ALL occurred at the time of the reduction of steroids and had similar elements in the psychopathological image, but differed in the field of applied medication and course of the subsequent functioning of patients. 3. Diagnosis and treatment of psychiatric episodes in children with cancer requires the development of standards of procedure in conditions of Polish centers of pediatric oncology and hematology, also after the completion of treatment.
Introduction
Corticoids as widely available and used drugs are becoming an important weapon in the fight against many diseases encountered in pediatric practice. They also play a key role in the treatment of acute lymphoblastic leukemia (ALL). The effectiveness of these drugs seems to be unquestionable, playing fundamental role in the long-term treatment of ALL. Long-term use of glicocorticoids (GCS) causes serious side effects such as abnormal fat distribution, obesity, hypertension, diabetes, myopathy, osteopenia, hepatomegaly, or immunosuppression manifested as a tendency to infections. In addition to somatic changes corticosteroids may cause a number of mental disorders in the form of mood disorder. Among them we can highlight problems such as anxiety, agitation, insomnia, mania and depression, and even psychotic states with delusions and hallucinations (1, 2). Data from the literature estimate the incidence of these disorders in the 5 to 75% of patients treated for various reasons with doses of corticosteroids (3). A series of studies conducted in adult patients suggests that acute psychiatric states correlate with the amount of the dose. Severe psychiatric symptoms occurred in 1.3% of patients receiving < 40 mg prednisolone daily (or equivalent of the dose), in 4.6% of patients treated with prednisolone dose from 41 to 80 mg, and in 18.4% of patients treated with doses exceeding 80 mg per day. There are also other relevant factors, including family predisposition (4). Further studies show an increased incidence of psychiatric disorders in patients treated with doses of 40 mg of prednisone a day (5). Pediatric studies have confirmed that the dose of 40 mg/m2 of prednisone a day increased risk of psychotic disorders (6). Thus, the data coming from the publications and numerous studies describes pediatric patients with the diagnosis of ALL as a group of the highest risk of psychiatric disorders in connection with the intake of high doses of corticosteroids (7, 8). These disorders may occur at different times from the beginning of treatment with steroids. Lewis and Smith estimate 11.5 days as the average time from the start of treatment to the first symptoms of psychotic disorders, 39% of disorders occur in the first week, 62% within two weeks, 83% within 6 weeks (9). Mental disorders can also occur during dose reduction and withdrawal of the drug, most often manifesting as depression, anxiety, and fatigue (10) as well as mania and disorders of consciousness (11, 12).
The mechanism of function of corticosteroids triggering psychiatric conditions in patients is not fully known. The likely effects are impaired synthesis of monoamines (such as serotonin, dopamine, catecholamines) which is caused by exogenous corticosteroids, or disturbance in the economy neuropeptide transmitters. Corticosteroids increase the level of dopaminergic activity, and also reduce the central and peripheral serotonin secretion which may lead to psychotic states (13, 14). Another probable mechanism of steroids’ function is hippocampal nerve damage, which in the process of additive synergism with used chemotherapeutic drugs and cytostatics can increase the psychiatric side effects of treatment of ALL (15). In patients with episodes of steroid-induced psychiatric disorders elevated levels of corticosteroid receptor mRNA were stated, which may also indicate a genetic determinants of these processes (16). Elevated levels of endogenous corticosteroids (neurotransmitter) of tetrahydrodeoxycorticosteone (THDOC) induces a reduction in the level of allopregnanolone and can be found in many models of acute depression (17).
Aim
Analysis of cases of mental disorders induced by taking steroids during treatment of acute lymphoblastic leukemia in children over 12 years of age.
Material and methods
The subject of analysis was the course of transient episodes of mental disorders in two patients with ALL and evaluation of mental state at certain points in time during intensive care and during long-term follow-up after completion of maintenance therapy. The average age of patients at diagnosis was 14.9 years. Episodes of mental dysfunction occurred twice, in both treatment protocols, at the time of reduction of steroids.
Medical records of two patients treated for acute lymphoblastic leukemia in oncology and hematology ward for children at Pediatric Hospital in Lublin were analyzed. Criteria for selection of patients for analysis: identification of ALL, the age at diagnosis over 12 years, the occurrence of an episode of mental dysfunction during intensive treatment, temporal association of the episode with the intake of steroids, the ability to conduct follow-up. The patients were treated according to therapeutic protocols in force at the time of diagnosis (BFM 97 and ALL-IC 2002). These protocols treatment of acute lymphoblastic leukemia in children are composed of several stages, and during intensive treatment (induction of remission/Protocol I and the consolidation of remission/Protocol II) request similar doses of steroids. Patients receive in Protocol I prednisone (1-28 days 60 mg/m2/day and 3 x 3 days at a dose reduced), and in Protocol II dexamethasone (1-21 days 10 mg/m2/day and 3 x 3 days at a dose reduced). Between these protocols patients receive protocol M not containing steroids.
During the treatment, patients are supported by a planned psychological care. In the first month of treatment were assessed: intellectual functioning (WISC-R), emotional functioning (“How are you” Choynowski, Skrzypek), personality functioning (16PF Cattell) and the functioning of the family system (interview). In addition, the mental state of patients were analyzed on the basis of interview and psychiatric examination at certain points in time during the intensive care (T0 – at the beginning of treatment, E1 – during the first episode, E2 – during the second episode), and during long-term follow-up after the completion of maintenance therapy (T1 – after intensive treatment, T2 – 3 months after the end of treatment, T3 – 6 months after treatment).
Results
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Piśmiennictwo
1. Stuart FA, Segal TY, Keady S: Adverse psychological effects of corticosteroids in children and adolescents. Arch Dis Child 2005; 90: 500-506.
2. Dubovsky AN, Arvikar S, Stern TA, Axelrod L: The Neuropsychiatric Complications of Glucocorticoid Use: Steroid Psychosis Revisited. Psychosomatics 2012: 53: 103-115.
3. Ularntinon S, Tzuang D, Dahl G, Shaw RJL: Concurrent Treatment of Steroid-Related Mood and Psychotic Symptoms With Risperidone. Pediatrics 2010; 125: 12.
4. The Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther 1972; 13: 694-698.
5. Hall RCW, Popkin MK, Stickney SK, Gardner ER: Presentation of the steroid psychoses. J Nerv Ment Dis 1979; 167: 229-236.
6. Drigan R, Spirito A, Gelber RD: Behavioral effects of corticosteroids in children with acute lymphoblastic leukemia. Med Pediatr Oncol 1992; 20(1): 13-21.
7. Harris JC, Carel CA, Rosenberg LA et al.: Intermittent high dose corticosteroid treatment in childhood cancer: behavioral and emotional consequences. J Am Acad Child Psychiatr 1986; 25(1): 120-124.
8. Felder-Puig R, Scherzer C, Baumgartner M et al.: Glucocorticoids in the treatment of children with acute lymphoblastic leukemia and Hodgkin’s disease: a pilot study on the adverse psychological reactions and possible associations with neurobiological, endocrine, and genetic markers. Clin Cancer Res 2007; 13(23): 7093-7100.
9. Lewis DA, Smith RE: Steroid-induced psychiatric syndromes: a report of 14 cases and a review of the literature. J Affect Disord 1983; 5: 319-332.
10. Fricchione G, Ayyala M, Holmes VF: Steroid withdrawal psychiatric syndrome. Ann Clin Psychiatry 1989; 1: 99-108.
11. Venkatarangam SH, Kutcher SP, Notkin RM: Secondary mania with steroid withdrawal. Can J Psychiatry 1988; 33: 631-632.
12. Campbell KM, Schubert DS: Delirium after cessation of glucocorticoid therapy. Gen Hosp Psychiatry 1991; 13: 270-272.
13. Ingram DG, Hagemann TM: Promethazine treatment of steroid-induced psychosis in a child. Ann Pharmacother 2003; 37(7-8): 1036-1039.
14. Schatzberg AF, Rothschild AJ, Langlais PJ et al.: A corticosteroid/dopamine hypothesis for psychotic depression and related states. J Psychiatr Res 1985; 19(1): 57-64.
15. Riccardi R, Riccardi A, Lasorella A et al.: Cranial irradiation and permeability of blood-brain barrier to cytosine arabinoside in children with acute leukemia. Clin Cancer Res 1998; 4(1): 69-73.
16. Dietrich J, Monje M, Wefel J, Meyers C: Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 2008; 13(12): 1285-1295.
17. Mellon SH, Griffin LD, Compagnone NA: Biosynthesis and action of neuroactive steroids. Brain Research Reviews 2001; 37: 3-12.
18. Shad AT: Late Effects of Childhood Cancer and Treatment 2010. http://emedicine.medscape.com/article/990815 – overview on December 21, 2011.
19. Hudson MM, Mertens AC, Yasui Y et al.: Health status of adult long-term survivors of childhood cancer. A report from the childhood cancer survivor study. JAMA 2003; 290(12): 1583-1592.
20. Ducore JM, Waller DA, Emslie G et al.: Acute psychosis complicated induction therapy for acute lymphoblastic leukemia. J Pediatr 1983; 103: 477-480.
21. Watanabe TK, Sylwester CE, Manaligad JM: Mania or panic associated with dexamethasone chemotherapy in adolescents. J Adolesc Health 1994; 15: 345-347.
22. Kramer TM, Cottinghan EM: Risperidone in the treatment of steroid-induced psychosis. J Child Adolesc Psychopharmacol 1999; 9: 315-316.
23. Ularntinon S, Tzuang D, Dahl G, Shaw RJ: Concurrent treatment of steroid-related mood and psychotic symptoms with risperidone. Pediatrics 2010; 125(5): 1241-1245; DOI:10.1542/peds.2009-1815.
24. Mian I, Gearing R, DeSouza C et al.: Clinical rounds in child and adolescent psychiatry. Corticosteroid-related psychiatric complications in the treatment of Hodgkin’s lymphoma in an adolescent. J Can Acad Child Adolesc Psychiatry 2007; 16(1): 27-29.
25. Warrington TP, Bostwick JM: Psychiatric adverse effects of corticosteroids. Mayo Clin Proc 2006; 81(10): 1361-1367.
26. Samardakiewicz M, Mitura-Lesiuk M, Kowalczyk JR: Acute psychiatric episodes during intensive treatment course in adolescent cancer patients. Pediatr Blood Cancer 2011; 57(5): 750.
27. Samardakiewicz M, Mitura-Lesiuk M, Kowalczyk JR: Acute psychiatric episodes during intensive treatment course in pediatric cancer patients aged 8-12 and 12-18 years. Psychooncology 2011; 20 (suppl. 2): 188-189.
28. Samardakiewicz M, Mitura-Lesiuk M, Kowalczyk JR: Epizody neuropsychiatryczne wyindukowane kortykosteroidami u nastoletnich pacjentów z ostrą białaczką limfoblastyczną. Onkol Pol 2012; 135 (suppl. 1): 57.
29. Wienier LS, Pao M, Kazak A et al.: Quick Reference for Pediatric Oncology Clinicians: The Psychiatric and Psychological Dimentions of Pediatric Cancer Symptom. Charlottesville APOS/IPOS, 2009.
30. Rymaszewska J, Podolak-Dawidziak M, Kiejna A: Zaburzenia psychiczne w przebiegu nowotworów. [W:] Krzakowski M (red.): Zalecenia postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych. VM Media, Warszawa 2009: 465-471.
31. Deyell R, Lorenzi M, Ma S et al.: Antidepressant use among survivors of childhood, adolescent and young adult cancer: A report of The Childhood, Adolescent and Young Adult Cancer Survivors (CAYACS) Research Program. Pediatr Blood Cancer 2013; 60: 816-822.
32. Thompson AL, Steacy K: Young adult Hodgkin’s lymphoma survivors develops panic disorder during early survivorship. Psychitric Ann 2012; 42(3): 78-81.
