For citation: Olexenko L.V., Vybornykh D.E. Zhurnal Nevrologii i Psikhiatrii Imeni S. S. Korsakova. 2017;117(8):124-131. doi: 10.17116/jnevro201711781124-131.
Mental disorders in Hodgkin's lymphoma
Olexenko L.V., Vybornykh D.E.
National Research Center for Hematology, Moscow, Russia
In the presented review of the literature, the mental disorders observed in patients with Hodgkin's lymphoma (LH) are described differentially with the isolation of psychotic states, affective nonpsychotic disorders and adjustment disorders. Psychotic disorders include affective, delusional states, delirious obscuration of consciousness. Among adjustment disorders, states of different psychopathological structures are distinguished. Attention is drawn to the frequency of anxious, depressed and mixed states. In addition, cases of development of conversion disorders are described in the framework of adjustment disorders. Behavioral disorders that lead to a violation of therapeutic compliance are also considered. In the nosological aspect, mental disorders in LH are treated as adjustment disorders.
Key words: Hodgkin's lymphoma, mental disorders, psychoses, adjustment disorders, violations of therapeutic compliance.
This literature review differently describes mental disorders in patients with Hodgkin's lymphoma (HL) with an emphasis on psychotic disorders, affective states and adjustment disorders. Psychotic disorders observed in patients with HL include affective, delusional conditions, delirium. There are different psychogenic states among the adjustments. Attention is drawn to the frequency of anxious, depressive or mixed states. Conversion disorders and behavioral disorders that lead to non-compliance inpatients with HL are described as well. In nosologic aspect, mental disorders in HL are classified as somatogenic and adjustement disorders.
Keywords: Hodgkin's lymphoma, mental disorders, psychoses, adjustment disorders, noncompliance.
In 1832 Th. Hodgkin, a British physician and pathologist, described 7 patients who had an enlarged lymph node and spleen, a general exhaustion and a decline in strength (asthenia). After 23 years, S.Wilks called this condition his name - Hodgkin's disease. He not only studied the cases described by Hodgkin, but added 11 own observations to them. However, only in 1944 the first morphological classification of Hodgkin's lymphoma (LH) was proposed, which allowed establishing a certain correlation between the severity of the course of the disease and morphological changes.
Descriptions of psychiatric disorders in patients with Hodgkin's disease (Hodgkin's disease, lymphogranulomatosis) of patients concern mainly individual patients or are included in descriptions of samples of patients with other oncological / oncohematological diseases. Therefore, until now in the scientific literature there is no systematic analysis and generalization of such violations. Meanwhile, this contingent is of interest to psychiatrists, since among patients with lymphoproliferative diseases, especially with LH, a high proportion of patients with personal and behavioral characteristics are described by psychologists as "strangeness of character", "inadequacy of behavior" .
Among the mental disorders observed in patients with LH, there are mental disorders of various registers. The psychotic states were described in the most detail. In addition, there are descriptions of affective disorders, disorders of the neurotic level, personality changes and mental pathology, formed against the background of organic changes in the central nervous system.
The prevalence of mental disorders in LH
The prevalence of mental pathology in patients with LH is estimated by different authors from 17 to 54%.
J. Devlen et al.  63 patients with LH were examined on average 32 months after the diagnosis of the disease. As a result of psychiatric examination, 34 (54%) patients were diagnosed with anxiety and depressive disorders, as well as their combination. In 8 (23.5%) patients there were syndromically completed disorders, in 10 (29.4%) - sub-syndromal, borderline level. M. dos Santos et al.  summarized the results of psychiatric consultations for 1 year in the hematology unit of one of the general hospitals. The prevalence of depressive and / or anxiety disorders (according to the DSM-III-R criteria) was determined at 20-40%.
D. Stark et al.  studied a group of 178 patients with different diseases - LH and other lymphomas, plasma cell hemoblastoses and malignant melanoma. Anxiety disorder was detected in 48% of cases with a share of anxiety disorders in patients with LH of 0.33.
S. Oerlemans et al.  also studied the prevalence of anxiety and depressive disorders in patients with LH. They found that the latter have such psychiatric disorders more often than in healthy people (17% versus 11%).
L. Daniels et al.  41% of patients had asthenic disorders, 23% had anxiety, and 18% had depressive disorders.
Among psychotic disorders with LH, affective disorders, delusional states and delirious confusion of consciousness were described.
Affective psychoses in LH are represented by mental disorders of the psychotic level of both manic and depressive poles.
It should be noted that the relevant descriptions include observations of psychoses arising from the use of nitrogen mustard, which was used to treat LH at the dawn of the chemotherapy era of this disease [7, 8]. So, B. Roswit and J. Pisetsky  brought the medical history of a 25-year-old man who, for 4 years suffered LH and passed several courses of radiation therapy. Due to the therapeutic resistance, he was treated with a course of nitrogenous mustard gas (intravenous administration at a dose of 5 mg every 4th day). Five days after completion of the treatment, the patient became agitated, euphoric; episodes of confusion were also noted. During the examination, the patient was verbose and extremely active. His speech was accelerated; there was a tendency to confabulation. There were no hallucinations. Expressed fragmentary ideas of jealousy towards his wife. He did not keep within the bed and wandered all day around the department. The described mental disorders persisted for 3 weeks and then completely disappeared. At repeated, second and third courses of treatment with nitrogenous mustard of psychic disorders was not observed. Somatic reactions to the drug being administered were limited to the development of thrombocyto-, leukopenia and anemia, which was interpreted by the authors as a reflection of the development of tolerance of the organism to nitrogen mustard gas. A diagnosis of toxic psychosis was established due to the use of nitrogen mustard gas.
A. Mann et al.  described maniacal psychosis in the treatment with procarbazine (a drug having a weak inhibitory effect on monoamine oxidase activity in a patient with LH). Starting from the 15th day of treatment with procarbazine at a dose of 100 mg twice a day, the patient felt a mood lift, a burst of energy. By the 21st day, he noted that "energy abnormally increased", felt "like drugs". Soon the patient became talkative, the content of his speech became more and more "strange". He began to draw meaningless diagrams, wrote and sent ridiculous letters to business partners, spoke about the grandeur and importance of his plans. He was noted for motor anxiety and a sharp disturbance of a night's sleep. After the removal of three teeth during this period under the anesthesia of xylocaine, the patient became even more active. I identified myself with a senior doctor, considered the hospital staff as my subordinates, promised to help them in their careers. In a state of psychomotor arousal he was hospitalized; therapy with procarbazine was discontinued and aminazine was administered in the form of intramuscular injections, and then per os at a dose of 250 mg 4 times a day. The patient's condition improved significantly after 2 days of such therapy. The authors concluded that the occurrence of a manic state in the patient was promoted by procarbazine as an inhibitor of monoamine oxidase. In addition, a role could play a role and adrenaline, which is part of the anesthetic of xylocaine. They did not exclude the influence of the somatic disease, which was a great stress for the patient.
There is another description of manic psychosis associated with taking procarbazine in a 20-year-old woman with LH. It belongs to M. Carney et al. . The psychosis arose against the background of polychemotherapy (nitrogen mustard, vincristine, procarbazine, prednisolone). The patient became agitated, screamed, swore, did erotic suggestions, reasoned how she would spend her big money. The psychosis was stopped with antipsychotics therapy phenothiazine series and lithium carbonate.
I. Rosenberg et al.  gave an example of successful treatment of a patient with LH with a long history of bipolar affective disorder (BAP I) in a state of psychotic mania. In this case, clozapine was used for treatment in combination with lithium and lorazepam. It is known that clozapine can cause agranulocytosis . In this regard, the authors expressed their opinion on the admissibility of the use of clozapine in patients with diseases of the blood system, in particular with LH, but under the condition of constant control of the leukocyte formula.
D. Folks et al.  led the observation of a 22-year-old man with LH, who noted the development of psychotic symptoms and suicidal tendencies. At the time of his hospitalization in a psychiatric hospital, he underwent three cycles of chemotherapy in the combined mode of "Mustargen, Vincristine, Procarbazine and Prednisolone (MOPP)" and underwent a second course of radiation therapy. Upon examination, the patient complained of insomnia with an early awakening, depression with suicidal thoughts and fear of death; tried to hang himself.
Upon examination, the patient looked exhausted, while he showed motor excitement and speech pressure. There was a dysphoria with an affect of anger. Nortriptyline was prescribed in a daily dose of 75 mg and loxapine 75 mg per day. As a result of such therapy for 2 weeks, motor excitement became less pronounced, suicidal thoughts were disactualized, night sleep improved. The authors characterized the patient's psychotic state as a major depressive episode.
The psychotic disorders of the delusional register with LH in the literature are presented by depressive and hallucinatory-delusional states.
H. Braun and W. Eicke  led the observation of a 40-year-old patient from a family burdened with mental disorders. After the diagnosis of LH, treatment with chloromethine was started (a compound of nitrogen mustard gas). Treatment patient first carried well, but after 1 month suddenly became restless, for no reason refused injection. Psychomotor arousal increased so much that she was transferred to a psychiatric clinic. On examination, the patient made an impression very frightened, stood with her eyes wide open, and always mournfully and incoherently repeated that she should repent that she would not lie and would acknowledge everything. Asked what exactly was oppressing her, the patient answered that she had all the witnesses, but she could not say anything concrete. In a strong excitement she suddenly shouted: "If everything is taken too seriously, then you can go crazy ... I constantly struggle with this, I throw silly thoughts out of my head, but they come back." She said that she was afraid of an imminent death. Questions about suicide rejected. The night after arrival in the hospital, anxiety increased, the next day the patient began to do rhythmic movements with her hands; she bent and stretched her arms, often knocking with her teeth. Two weeks after the onset of psychosis, the picture of the disease continued to remain unchanged, although the patient became a little calmer. After 1 week, improvement was noted in connection with the therapy. The patient began to help to restore order in the ward, but still the predominance of confusion over her was still noticeable. At times she was again seized by fear, she refused to take medicine. After 1 month after the onset of psychosis, the patient's behavior stabilized, she began to feel better. Amnesized the details of what happened to her during the psychosis. The authors diagnosed the patient "symptomatic psychosis with a paranoid color." They also noted that psychosis began when, after long-term treatment with LH with the use of chloromethin, the manifestations of lymphoma began to decrease. After cessation of therapy using this highly toxic substance, the manifestations of psychosis relatively quickly stopped.
BA Tseleibeev et al.  published 2 observations of somatogenic psychoses in patients with LH. In one case, there was a delusion of poisoning that ended in the terminal stage of the disease with amenia, in the other - psychomotor agitation with fragmentary delusions, auditory and visual hallucinations in periods of worsening of the somatic state.
Symptomatic psychosis was also described by P. Salles  in the ethno-psychiatric aspect. They were followed by a man of 26 years, an indigenous of the Republic of the Congo. The patient was hospitalized in a psychiatric hospital due to severe psychomotor agitation that developed against pain in the left abdomen and lower back, increase in the liver and increase in body temperature to 38 ° C. At the first psychiatric examination he was anxious, verbose, presented numerous somatic complaints; there was also a low mood. He spent many hours lying still in the bed, closing his eyes. However, sometimes he took uncomfortable poses, even theatrical and acrobatic (on all fours, in the pose of the knotted knot); did not respond to speech. Long periods of mutism were interrupted by groans and complaints, especially when visiting staff and family members. When trying to make comments to him excited, shouted, gesticulated, left his bed to go to sleep "under the tree," grazing the orderlies. This behavior, which was partially induced by others, disappeared when the patient remained alone. The psychosis therapy included the use of chlorpromazine in doses of 150-300 mg / day. During the treatment, a clear positive dynamic in the patient's condition was revealed, and he was discharged from the hospital. After 4 months, he again went to the clinic, with an increase in subclavian lymph nodes on the left, hepatosplenomegaly, an array of enlarged lymph nodes in the abdominal region squeezing the internal organs; In the study of biopsy of lymph nodes, Sternberg cells were found. The diagnosis of LH was established. When treating corticosteroids, the patient showed asthenia "euphorizing effect of therapy". The ethnic coloring of the observation was manifested in the interpretation of the patient's mental pathology by local physicians (manifestation of the state as a "zombie"). The authors diagnosed "symptomatic psychosis (depressive-paranoid state) with catatonic disorders."
I. Mian et al.  described the manic state of a teenager suffering from LH. The psychosis manifested in the period of the 4th course of chemotherapy, which included prednisolone, cyclophosphamide, vincristine, dapsone and procarbazine. The patient expressed a delirium of greatness: he represented himself as God, who produces computer programs for reading other people's thoughts. In addition, he considered himself the owner of billions of dollars. He believed that he could cure sick people, resurrect the dead and force thoughts to move people in space. The patient had visual hallucinations: "saw" the fire in his hands, which he called "infernal fire." Therapy of the described condition consisted in the appointment of sequentially olanzapine and haloperidol, which required the introduction of a corrector, the anticholinergic drug benztropine, into the treatment regimen. The authors expressed the opinion that the etiology of psychosis in this case is likely mixed, but great importance was attached to treatment with steroids.
D.E.Vybornykh  observed the patient suffering from LH, in whom the recurrence of the disease coincided with a hallucinatory-delusional attack with Kandinsky-Clerambo syndrome and catatonia phenomena within the framework of a schuboid (schizophrenic-progestive) schizophrenia. The patient indifferently agreed with the fact that she had a relapse of a potentially fatal disease, even considered it (with directed questioning) as "a test of faith in God," but in delusional experiences the theme of the disease was not reflected. Both in the history of the patient and in the clinical picture during the examination period, hallucinatory-delusional disorders dominated with the phenomena of mental automatism and signs of catatonia, changes in the personality of the schizophrenic type with the growth of negative disorders (social seclusion with a decrease in the need for communication, and lack of emotional responses). In a study carried out by the same author later , it was shown that a higher proportion of psychoses of the schizophrenic spectrum (endogenomorphic psychoses - hallucinatory and depressive-delirious states and schizophrenic attacks) is noted in lymphoproliferative diseases, especially lymphosarcomas and LH. And in the case of LH, these forms of psychosis occur much more often than delirium, in contrast to other diseases of the blood system, in which the opposite tendencies are revealed. In addition, LH is the only disease in the blood system, in which somatogenically induced schizophrenia attacks are detected.
In the literature there are also descriptions of delirious and onyroid occultation of consciousness, comparable to such states in other severe somatic diseases. J. Tuchel  described a patient of 53 years with LH, about which she was assigned mitomene (a derivative of nitrogenous mustard gas). She entered the hospital in a state of "excitement," but without violations in time and space. After 2 weeks the patient had a dream. There were fears of being alone in the bathroom and one sleeping. She "saw" the hedge and behind her the field, from where come some men. It used to happen that the patient called for nurses to drive out the "men at the window". Sometimes it was not oriented in time. Violations of attention and failures in memory were noted. She did not remember her fears, experienced in a dream. During the survey, it could give unrelated answers to questions. For example, when she was asked about a violation of sensitivity in her legs, the patient replied: "I have not written a letter to my husband yet." During 1 month of hospitalization, the patient began to show periods of disorientation and a "sleepy" state, during which speech was disrupted, sometimes becoming incoherent, with perseverations. In response to the questions asked, she sometimes produced a number of syllables without clear meaning and meaning; was often seen aimlessly swarming on the floor. With a very strong psychomotor agitation, the patient had to fix on the bed. At morning rounds of doctors the patient complained that her husband wants a divorce, and she needs to go home urgently, since he already lives there with another woman, which he wrote to her yesterday in a letter; while the patient was crying, refused to talk, then, on the contrary, behaved inadequately fun, said that she was feeling great. Because of the signs of mitomin intolerance, therapy with the use of this drug was discontinued. The author regarded the patient's mental disorders as delirium - a toxic psychosis with elements of catatonic disorders.
IN AND. Maksimenko  observed 2 cases of somatogenic psychoses in patients with LH. In one case, a patient with a somatogenic asthenia, accompanied by anxiety and depression, developed a fantastically illusory onyroid. In another observation, psychopathological symptoms fit into the picture of hypoactive delirium (asthenic disorders, to which disorientation phenomena, hypnagogic hallucinations were attached).
Thus, the psychotic states described in LH are quite diverse in clinical manifestations. At the same time, there is a tendency to develop disorders typical of endogenous disorders (presence of catatonic disorders in their structure, as well as affective disorders of the manic pole). It is also important that, in most cases, the psychoses described in LH are manifested on the background of "aggressive" chemotherapy.
Mental pathology, formed against the background of organic changes in the brain
Among the CNS lesions that can cause mental disorders in patients with diseases of the blood system, paraneoplastic limbic encephalitis is mentioned with the development of the so-called "Ophelia syndrome" described in patients with LH [21-27]. This syndrome is characterized by impaired memory and other cognitive functions, affective and behavioral disorders. In addition, in the majority of patients complex partial (focal) and generalized epileptic seizures are observed. Against this background, the development of the delirious confusion of consciousness is possible .
D. Sohn et al.  described auditory and visual hallucinations in a patient whose hypothalamus, vault, transparent septum, optic nerves, visual cross-section, left branch of the trigeminal nerve, oblong and spinal cord were involved in the lymphogranulomatous process.
C. Slattery et al.  led the observation of a cerebellar cognitive syndrome with an affective component in a 19-year-old girl with LH and paraneoplastic degeneration of the cerebellum. Such a syndrome includes affective disorders, volitional control, control of arbitrary actions, orientation in space and speech. The patient was found to have decreased mood, tearfulness, irritability, apathy, asthenia, sleep disturbances (early awakening). However, there were also periods when she felt a recovery, showed an inadequate optimism, accompanied by an increase in alcohol consumption. She was diagnosed with bipolar affective disorder type II, imipramine and lithium were prescribed, which had a positive therapeutic effect. The authors believe that mental disorders in this case are a direct consequence of organic CNS damage. The presence of paraneoplastic degeneration of the cerebellum gave them reason to assume its special role in the genesis of affective disorder.
With a certain degree of probability, we can also speak about the involvement of organic brain pathology in previously described psychoses in patients with LH.
Adjustment disorders and post-traumatic stress disorder
Among the psychiatric disorders detected in patients with LH, many authors point to the likelihood of developing mental disorders caused by reactions to events related to the circumstances of LH diagnosis. They refer to them as adjustment disorders, or adaptation disorders. Among the latter, states of different psychopathological structures are distinguished, but more often anxious, depressed and mixed states are encountered.
J. Loge et al.  459 patients with LH were examined using questionnaires to assess the level of psychological stress and identify predictors of anxiety and depression. In 27% of patients, anxious and depressive conditions were detected (14.5% anxiety, 4% depression, 8.5% anxiety and depression). The use of multiple logistic regression techniques by these authors showed that anxiety was associated with a low level of education, duration of observation (more than 7 years), irradiation in combination with chemotherapy and the presence of mental disorders prior to LH disease or during treatment. Depression was associated with age and mental disorders, detected before the disease of LH. It was noted that anxiety is most pronounced after 7-10 years of treatment, and intensive treatment with LH was associated with an increased risk of manifestation of anxiety. In addition, the same authors  conducted a similar study of asthenia in patients with LH and established the conjugation of its elevated level with the severity of anxiety and depression.
J. Lavoie et al. , in 7 (13.2%) cases, anxiety and depressive disorders were noted in the posttransplant period in a study of 53 patients who underwent autologous stem cell transplantation for primary resistance or recurrence of LH.
B. Kawiecka-Dziembowska et al.  conducted a survey of 50 patients diagnosed with LH at the age of 20-65 years, dedicated to personality characteristics, depression and quality of life in patients with LH during the diagnosis of the disease, active treatment and remission. According to the authors, the results confirm the possibility of personal changes in patients with LH at different stages of the disease, associated with increased symptoms of depression, as well as the connection between the depth of depression and quality of life. Differences between the results obtained in men and women with LH allowed the authors to assume the existence of different mechanisms of survival and adaptation to the disease in patients of different sexes.
In the study of D.E. Elective  described a schizophrenic dissociative adjustment disorder in a patient with LH. The patient, despite the verified diagnosis of hemato-oncologic disease, for a long time refused official treatment, relying on the means of traditional medicine, healers and herbalists. And it was only when he had difficulty breathing due to compression of the trachea with a conglomerate of enlarged cervical lymph nodes, he turned for help and passed the necessary chemotherapy courses. However, with the slightest relief of the state, I tried to avoid another injection of chemotherapy drugs, returning to folk medicine. The patient's condition was qualified as a pseudomodulation syndrome in the context of a dissociative reaction with a slow-paced psychopath-like schizophrenia. In the clinical picture of the disease, the phenomenon of his alienation dominated, with complete denial of the very fact of the presence of LH. Attention was drawn to the complete denial of the malignant nature of the disease with pronounced disturbances of behavior, up to passive resistance to adequate care (non-attendance at examinations, non-compliance with recommendations). Such reactions, according to the author, are the most resistant to psychopharmacotherapy.
In single publications, cases of somatoform disorders development are considered in connection with side effects of polychemotherapy of depressive adjustment disorders.
W. Weddington  drew attention to the fact that patients with lymphogranulomatosis receiving polychemotherapy often experience psychogenic nausea, sometimes with vomiting. The author explains this phenomenon from the point of view of elaborating a conditioned reflex, but interprets it from psychodynamic positions ("use" by patients of psychogenic symptoms to explain the avoidance of chemotherapy). Other authors [36-38], describing the same phenomenon, connect it with anxiety-phobic disorders, conditioned by the procedure and real unpleasant sensations from chemotherapy.
R. Nesse et al.  led 6 observations of the appearance of unusual taste and olfactory sensations ("the smell of the clinic, drugs," "something chemical") in patients suffering from LH. Despite the fact that such sensations arose on the background of chemotherapy, the authors called these sensations "pseudo-hallucinations", arguing that this interpretation was possible with the absence of external stimuli, although they recognized the "learning" due to the long experience of taking medications, their odor and associated nausea. Summarizing all the features of the described observations, they tend to attribute them to stress reactions.
P. Davidson  leads the observation of a patient who was diagnosed with LH 1 year before the development of psychosis, and she underwent a course of radiation therapy. In addition, she had an unsuccessful family situation (alcoholism and aggression from her husband). All this led to the development of stuttering. The patient was assigned a librium of 10 mg every 6 hours, and psychotherapy (psychodrama, group and individual psychotherapy) was conducted with her. After 3 months of treatment, the patient's stammering occurred only in moments of desperation, anger at her husband. Lengthened periods of normal speech, she began to make attempts to restore the financial well-being of the family. In another 1 month the stammering has completely passed. The authors designated the described condition as "hysterical dysfemia" (speech disturbance caused by psychological factors).
It is known that the diagnosis of cancer, including LH, is a stressful event for the patient [41-43]. A number of patients with LH in this situation may develop posttraumatic stress disorder (PTSD), characterized by repeated experience of the event and avoiding behavior .
V. Varela et al.  studied PTSD in patients with LH. They examined 105 patients suffering from LH, and 101 healthy (control). The prevalence of PTSD was slightly higher in patients with LH compared with control (13% vs. 6.9%, p = 0.098). Nevertheless, a significantly larger number (35.2%) of patients met the criteria for "partial PTSD" compared with the control (17.8%, _p = 0.004). The majority of patients with LH (86.5%) with partial PTSD reported experiencing noticeable difficulties in daily functioning characteristic of PTSD.
One of the key factors for the success of specific therapy for hematological patients is the establishment and maintenance of therapeutic cooperation between the doctor and the patient (compliance). The problem of the violation of therapeutic co-operation by oncological patients, their insufficient compliance (non-compliance) are widely discussed in the psycho-oncological literature. At the same time, violations of compliance, including the delay in applying for medical help, the refusal of recommended restrictions on physical activity, non-compliance with diet, arbitrary manipulation of dosage of drugs, drug withdrawal, transition to methods of self-medication and alternative medicine, etc., are considered as forms of pathological behavior, associated with mental disorders [44, 45]. Information about incompetence in patients with LH is meager and is considered in the context of various mental disorders, including schizophrenia and schizophrenia disorder, affective pathology, personality disorders. Among the features associated with such patients with noncompliance, a high level of negation, a low threshold of pain sensitivity and a relatively high share of refusals are highlighted [46-49].
In the work of R. Tsang et al.  presented the case of the refusal of the patient suffering from LH with autism from vital diagnostic and treatment procedures in connection with the pathological sensations arising during their performance. The authors report that in this observation, medical manipulations were possible only after the application of anesthesia.
D. Lerner et al.  described a 42-year-old man with LH who had several relapses of the disease. He underwent bone marrow transplantation (TCM), but refused maintenance therapy. The new hospitalization was associated with the need for a repeat BMT and the patient agreed to it. The behavior of the patient in the department was characterized by anger, demonstrativeness and aggressiveness towards the nurses and treating physicians. The patient rudely told the staff that he was irritated not only in relation to the health workers, but also to himself. Noted the loss of appetite for sleep disturbance. The doctors intended even to stop the preparation for TCM due to patient's incompetence. The patient then agreed to treatment with risperidone (0.5 mg 2 times / day), which caused excessive drowsiness, and the dose was reduced to 0.5 mg at bedtime. After 2 days the patient became calmer. Staff noted improvement in the patient's mood and compliance.
In the studies of D.E. Elected and co-workers. [49, 51], in patients with LH, two types of conditions were identified, leading to the development of violations of therapeutic cooperation between the doctor and the patient: 1) paranoic adjustment disorder accompanied by self-treatment, 2) adjustment disorders accompanied by partial refusal of treatment. In paranoic adjustment disorder accompanied by self-medication, the central position in their clinical picture is occupied by the supercaluated ideas , which dominate the patients' minds, associated with catalytic affect: confidence in the possibility of self-treatment is accompanied by persistent positive emotions with a sense of hope and "vital" well-being. The content of the supra-valuable ideas under consideration is not of a gross pathological character, but reflects the structure of the real situation associated with overcoming the symptoms of severe oncohematological disease (the so-called subjective supervalued ideas) . Thus, patients are considering the possibility of "optimizing" pharmacotherapy. Although the overvalued ideas of self-treatment are not accompanied by a denial of medical care, patients have signs of "pathological behavior in the disease" . In particular, medical recommendations that do not coincide with the pathological ideas of patients about the treatment process are not observed. In patients with the type of reactions studied, both pathocharacterological traits observed in paranoid prone to the formation of supervalued ideas and signs of schizoid personality disorder (expansive schizoidia) are revealed .
In the second type of considered states - adjustment disorders by refusal of treatment, three subtypes are distinguished: schizophrenic adjustment disorders with the phenomena of negation of the disease, dissociative reactions with the phenomena of alienation of some aspects of the oncological disease and anxious-hypochondriacal reactions. In schizophrenic adjustment disorders, the clinical signs of "autistic separation from reality" dominate . In the light of these ideas, a dangerous or even life-threatening disease either does not appear to be a hindrance that can impede the implementation of "creative intentions," or, contrary to the diagnosis established by specialists, is associated with less significant bodily pathology. The characteristics of the reaction include gross behavioral disorders: in the face of severe physical suffering, there is an unreasonable refusal to seek medical help or hospitalization, and non-compliance with medical recommendations. In patients with the type of reactions studied, signs characteristic of schizotypal personality disorder are revealed. With dissociative reactions with the phenomena of alienation of some aspects of oncohematological disease, there is a tendency to minimize the severity of manifestations of somatic pathology. Patients deny not the disease as such, but only its threatening nature. So, the possibility of a lethal outcome is excluded. The patient knows that with the ailment that he suffers, death is possible, but he is convinced that it will not affect him. Denial of the disease acquires the character of persistent overvalued formations, which is accompanied by disadaptive behavior .
Despite the limited data presented in this review, they indicate the relevance of further study of psychiatric disorders in LH, which significantly affect the course and prognosis of this disease. The urgency of the problem in question is also related to the lack of development of its clinical aspects, including psychosomatic correlations and optimization of psychopharmacotherapy.
1. Schklovsky-Kordi N, Kalmikova M, Ivaschkina M, Pivnik A. Psychological portret of HD-patient. Leuk Lymphoma. 1998;29:1:38.https://doi.org/10.3109/10428199809066342
2. Devlen J, Maguire P, Phillips P, Crowther D, Chambers H. Psychological problems associated with diagnosis and treatment of lymphomas. II: Prospective study. Br Med J. 1987;295:17:955-957.https://doi.org/10.1136/bmj.295.6604.955
3. dos Santos MJ, Pimentel P, Monteiro JM, Cardoso G, de Oliveira JJ, Almiro M, Santos JM, de Lacerda JM. Psychiatric disorders in hospitalized patients with hematologic neoplasms. Acta Med Port. 1991;4:1:5-8.
4. Stark D, Kiely M, Smith A, Velikova G, House A, Selby P. Anxiety disorders in cancer patients: Their nature, associations, and relation to quality oflife. J Clin Oncol. 2002;20:3137-3148. https://doi.org/10.1200/JCO.2002.08.549
5. Oerlemans S, Mols F, Nijziel MR, Zijlstra WP, Coebergh JWW, van de Poll-Franse L V. The course of anxiety and depression for patients withHodgkin's lymphoma or diffuse large B cell lymphoma: a longitudinal studyof the PROFILES registry. J Cancer Surviv. 2014;8(4):555-564. https://doi.org/10.1007/s11764-014-0367-1
6. Daniels LA, Oerlemans S, Krol ADG, Creutzberg CL, van de Poll-FransLV. Chronic fatigue in Hodgkin lymphoma survivors and associations with anxiety, depression and comorbidity. Br J Cancer. 2014;110:868-874. https://doi.org/10.1038/bjc.2013.779
7. Roswit B, Pisetsky JE. Toxic psychosis following nitrogen mustard therapy. J Nerv Ment Dis. 1952;115(4):356-359.https://doi.org/10.1097/00005053-195201000-00029
8. Braun H, Eicke WJ. Symptomatic psychosis in nitrogen-mustard treatment of a lymphogranulomatosis. Nervenarzt. 1955;26(2):71-73.
9. Mann AM, Hutchinson JL. Manic Reaction Associated with Procarbazine Hydrochloride Therapy of Hodgkin's Disease. Canad Med Ass J. 1967;97(25):1350-1353.
10. Carney MW, Ravindran A, Lewis DS. Manic psychosis associated with procarbazine. BMJ. 1982;284(6309):82-83.https://doi.org/10.1136/bmj.284.6309.82-a
11. Rosenberg I, Mekinulov B, Cohen LJ, Galynker I. Restarting clozapinetreatment during ablation chemotherapy and stem cell transplant for Hodgkin's lymphoma. Am J Psychiatry. 2007;164(9):1438-1439. https://doi.org/10.1176/appi.ajp.2007.06122021
12. Выборных Д.Э. Влияние психотропных препаратов на систему кроветворения. Социальная и клиническая психиатрия. 2002;12(4):71-79. [Vybornykh DE. Vliyanie psikhotropnykh preparatov na sistemu krovetvoreniya. Sotsial'naya i klinicheskaya psikhiatriya. 2002;12(4):71-79. (InRuss.)].
13. Folks DG, Alexander AI, Rabin PL. Psychiatric Disturbance in Hodgkin's Disease. The Southern medical journal. 1984;76:1094-1095:1100. https://doi.org/10.1097/00007611-198309000-00006
14. Целибеев Б.А., Яшиш И.Л., Окунев В.Н. Психические нарушения при гематологических заболеваниях. Журнал невропатологии и психиатрии им. С.С. Корсакова. 1964;64(8):1192-1197. [Tselibeev BA,Yashish IL, Okunev VN. Psikhicheskie narusheniya pri gematologicheskikh zabolevaniyakh. Zhurnal nevropatologii i psikhiatrii im. S.S. Korsakova. 1964;64(8):1192-1197. (In Russ.)].
15. Salles P. Hodgkin's disease: an ethno-psychiatric aspect (Apropos of a casein an African). Ann Med Psychol (Paris). 1960;118(2):728-733.
16. Mian I, Gearing R, DeSouza C, Solomon L. 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.
17. Выборных Д.Э. Психические расстройства у больных с заболеваниями системы крови (типология, эпидемиология, терапия): Дис. ... д-ра мед.наук. М. 2012. Ссылка активна на 03.03.17. Доступно по: http://www.psychiatry.ru/cond/0/diss/2012/191 [Vybornykh DE. Psikhicheskie rasstroistva u bol'nykh s zabolevaniyami sistemy krovi (tipologiya, epidemiologiya, terapiya): Dis... dokt. med. nauk. M. 2012. (In Russ.). Ссылкаактивна на 03.03.17. Доступно по: http://www.psychiatry.ru/cond/0/diss/2012/191 (In Russ.)].
18. Выборных Д.Э. Психогематология. М.: Практическая медицина; 2014.[Vybornykh D.E. Psikhogematologiya. M.: Prakticheskaya meditsina; 2014. (In Russ.)].
19. Tuchel J. Neurologic-psychiatric changes in lymphogranulomatosis. Psychiatr Neurol Med Psychol (Leipz). 1957;9(11):338-348.
20. Максименко В.И. Психические и нервные изменения при лимфогранулематозе. Материалы Второго всероссийского съезда невропатологов и психиатров. 1967;443-445. [Maksimenko VI. Psikhicheskie i nervnyeizmeneniya pri limfogranulematoze. In: Materialy Vtorogo Vserossiiskogo S"ezda Nevropatologov I Psikhiatrov. 1967;443-445. (In Russ.)].
21. Carr I. The Ophelia syndrome: memory loss in Hodgkin's disease. Lancet (London, England). 1982;1(8276):844-845. http://www.ncbi.nlm.nih.gov/pubmed/6122069. https://doi.org/10.1016/s0140-6736(82)91887-6
22. Pfliegler G, Posan E, Glaub D, Telek B, Rak K. Hodgkin's disease and memory loss: another case of the Ophelia syndrome. Br J Haematol. 1990;74(2):232. http://www.ncbi.nlm.nih.gov/pubmed/2317460.https://doi.org/10.1111/j.1365-2141.1990.tb02571.x
23. Bernard P, Vinzio S, Talarmin F, Kadouri A, Flocard F. Encephalite limbique revelatrice d'une maladie de Hodgkin. Rev Med Interne. 2003;24(4):257-260. https://doi.org/10.1016/S0248-8663(03)00053-5
24. Fassin D. De l'invention du traumatisme a la reconnaissance des victimes. Vingtieme Siecle Rev d'histoire. 2014;123(3):161. https://doi.org/10.3917/vin.123.0161
25. de Bot ST, Dorresteijn LDA, Haaxma CA, Kappelle AC, van de Warrenburg BPC. From psychiatric symptoms to paraneoplastic syndrome. Tijdschr Psychiatr. 2008;50(9):603-609. http://www.ncbi.nlm.nih.gov/pubmed/18785107.
26. Mat A, Adler H, Merwick A, Chadwick G, Giuseppe GF, Dalmau JO, Tubridy N. Ophelia syndrome with metabotrophic glutamat receptor 5 antibodies in CSF. Neurology. 2013;2:1349-1350.https://doi.org/10.1212/wnl.0b013e31828ab325
27. Olmos D, Rueda A, Jurado JM, Alba E. Presentation of Hodgkin's lymphoma with ophelia syndrome. J Clin Oncol. 2007;25(13):1802-1803. https://doi.org/10.1200/JCO.2006.10.0578
28. Kung S, Mueller PS, Geda YE, Krahn LE. Delirium resulting from paraneoplastic limbic encephalitis caused by Hodgkin's disease. Psychosomatics. 2002;43(6):498-501. https://doi.org/10.1176/appi.psy.43.6.498
29. Sohn D, Valensi Q, Miller SP. Neurologic manifestations of Hodgkin's disease. Intracerebral Hodgkin's granuloma. Arch Neurol. 1967;17(4):429-436.http://www.ncbi.nlm.nih.gov/pubmed/4292676 https://doi.org/10.1001/archneur.1967.00470280095011
30. Slattery C, Agius M, Zaman R. Bipolar disorder associated with paraneoplastic cerebellar degeneration: a case report. Psychiatr Danub. 2010;22(suppl 1):137-138. http://www.ncbi.nlm.nih.gov/pubmed/21057423.https://doi.org/10.1016/j.eurpsy.2008.01.398
31. Loge JH, Abrahamsen AF, Ekeberg O, Hannisdal E, Kaasa S. Psychological distress after cancer cure: a survey of 459 Hodgkin's disease survivors. BrJ Cancer. 1997;76(6):791-796. https://doi.org/10.1038/bjc.1997.464
32. Loge JH, Foss Abrahamsen A, Ekeberg 0, Kaasa S. Fatigue and Psychiatric Morbidity Among Hodgkin's Disease Survivors. J Pain Symptom Manage. 2000;19(2):91-99. https://doi.org/10.1016/s0885-3924(99)00148-7
33. Lavoie JC, Connors JM, Phillips GL, Reece DE, Barnett MJ, Forrest DL, Gascoyne RD, Hogge DE, Nantel SH, Shepherd JD, Smith CA, Song KW, Sutherland HJ, Toze CL, Voss NJS, Nevill TJ. High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: Long-term outcome in the first 100 patients treated in Vancouver. Blood. 2005;106:1473-1478.https://doi.org/10.1182/blood-2004-12-4689
34. Kawiecka-Dziembowska B, Borkowska A, Zurawski B, Paiaszynska R,Makarewicz R. Ocena temperamentu, jakosci zycia i nasilenia cech depresji u pacjentow z choroba Hodgkina w jej ronych fazach. Psychiatr Pol. 2005;39(4):679-690. http://www.psychiatriapolska.pl/uploads/PPt39n4s679Kawiecka.pdf
35. Weddington WW. Psychogenic Nausea and Vomiting Associated with Termination of Cancer Chemotherapy. Psychotherapy and psychosomatics. 1982;37:129-136. https://doi.org/10.1159/000287565
36. Reesal RT, Bajramovic H, Mai F. Anticipatory nausea and vomiting: a form of chemotherapy phobia? Can J Psychiatry. 1990;35(1):80-82. http://www.ncbi.nlm.nih.gov/pubmed/1969324
37. Cella DF, Pratt A, Holland JC. Persistent anticipatory nausea, vomiting, and anxiety in cured Hodgkin's disease patients after completion of chemotherapy. Am J Psychiatry. 1986;143(5):641-643.https://doi.org/10.1176/ajp.143.5.641
38. Nerenz DR, Leventhal H, Easterling D V, Love RR. Anxiety and drug taste as predictors of anticipatory nausea in cancer chemotherapy. J Clin Oncol. 1986;4(2):224-233. https://doi.org/10.1200/jco.19220.127.116.11
39. Nesse RM, Carli T, Curtis GC, Kleinman PD. Pseudohallucinations in cancer chemotherapy patients. Am J Psychiatry. 1983;140:483-485. https://doi.org/10.1176/ajp.140.4.483
40. Davidson PW. Hysterical dysphemia. Am J Psychiatry. 1964;121:395-397.https://doi.Org/10.1176/ajp.121.4.395
41. Diagnostic and Statistical Manual of Mental Disorders (4th Ed. Text Revision). Washington DC: American Psychiatric Association; 2000.https://doi.org/10.1176/appi.books.9780890423349
42. Geffen DB, Blaustein A, Amir MC, Cohen Y. Post-traumatic stress disorder and quality of life in long-term survivors of Hodgkin's disease and non-Hodgkin's lymphoma in Israel. Leuk Lymphoma. 2003;44(11):1925-1929. https://doi.org/10.1080/1042819031000123573
43. Varela VS, Ng A, Mauch P, Recklitis CJ. Posttraumatic stress disorder (PTSD) in survivors of Hodgkin's lymphoma: Prevalence of PTSD and partial PTSD compared with sibling controls. Psycho-Oncology. 2013;22(2):434-440. https://doi.org/10.1002/pon.2109
44. Akaho R, Sasaki T, Yoshino M, Hagiya K, Akiyama H, Sakamaki H. Bone marrow transplantation in subjects with mental disorders. Psychiatry Clin Neurosci. 2003;57(3):311-315. https://doi.org/10.1046/j.1440-1819.2003.01122.x
45. Strauss DH, Spitzer RL, Muskin PR. Maladaptive denial of physical illness: A proposal for DSM-IV. Am J Psychiatry. 1990;147:1168-1172. https://doi.org/10.1176/ajp.147.9.1168
46. Risko A, Fleischmann T, Molnar Z, Schneider T, Varady E. Influence of the pathological psychological state of cancer patients on their decisions. Support Care Cancer. 1996;4(1):51-55. http://www.ncbi.nlm.nih.gov/pubmed/8771295 https://doi.org/10.1007/BF01769876
47. Olweny CL, Juttner CA, Rofe P, et al. Long-term effects of cancer treatment and consequences of cure: cancer survivors enjoy quality of life similar to their neighbours. Eur J Cancer. 1993;29A(6):826-830. http://www.ncbi.nlm.nih.gov/pubmed/8484971 https://doi.org/10.1016/s0959-8049(05)80418-6
48. Tsang RW, Solow HL, Ananthanarayan C, Haley S. Daily general anaesthesia for radiotherapy in uncooperative patients: ingredients for successful management. Clin Oncol (R Coll Radiol). 2001;13(6):416-421. http://www.ncbi.nlm.nih.gov/pubmed/11824877 https://doi.org/10.1007/s001740170004
49. Выборных ДЭ, Моисеева ТН, Габеева НВ, Савченко ВГ. Нарушения терапевтического сотрудничества (non-compliance) у пациентов с лимфогранулематозом. Под ред Смулевича А.Б. Психические расстройства в общей медицине. 2009;(1):32-34. [Vybornykh DE, Moiseeva TN, Gabeeva NV, Savchenko VG. Narusheniya terapevticheskogosotrudnichestva (non-compliance) u patsientov s limfogranulematozom.Psikhicheskie rasstroistva v obshchei meditsine (pod red A.B.Smulevicha).2009;(1):32-34. (In Russ.)].
50. Lerner DM, Schuetz L, Holland S, Rubinow DR, Rosenstein DL. Low-dose risperidone for the irritable medically ill patient. Psychosomatics.2000;41(1):69-71. https://doi.org/10.1016/S0033-3182(00)71177-7
51. Vybornykh DE, Savchenko VG, Moiseeva TN, Gabeeva NG. Noncompliance in the patients with Hodgkin's disease. Psycho-Oncology. 2006;15(2 suppl):449. https://doi.org/10.1002/pon.1092
52. Stransky E. Die paranoiden Erkrankungen. Z ges Neurol Psychiat. 1913;(18):386-416. https://doi.org/10.1007/bf02869654
53. Stransky E. Schizophrenie und intrapsychische Ataxie. Jb Psychiat. 1914;(36):485.
54. Pilowsky I. Abnormal illness behavior (dysnosognosia). Psychother Psychosom. 1986;46(1-2):76-84. https://doi.org/10.1159/000287964
55. Смулевич А.Б. Малопрогредиентная шизофрения и пограничные состояния. 1987. [Smulevich AB. Maloprogredientnaya shizofreniya i pogranichnye sostoyaniya. 1987. (In Russ.)].
56. Кемпинский А. Психология шизофрении. М.: Ювента; 1998. [Kempinskii A. Psikhologiya shizofrenii. M.: Yuventa; 1998. (In Russ.)]