Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Wilson, R. Search for Related Content PubMed Citation Articles by Wilson, R. Other Mood Disorders Syndromes Secondary to General Medical Disorders

Mania Associated With Dialysis

A Literature Review and New Patient Report

Received April 3, 1998; accepted June 3, 1998. From St. David's Hospital, Carmarthen, Wales, United Kingdom. Address reprint requests to Dr. Wilson, Specialist Registrar in Psychiatry, St. David's Hospital, Carmarthen, Wales, United Kingdom, SA31 3HB. e-mail: wilson9{at}which.net

Key Words: Case Report • Mania • Dialysis

Manic symptoms associated with hemodialysis have been described since the introduction of the technique; however, initial case reports were clearly linked with confusional states.¹ From 1967 onward, there have been 10 case reports of mania associated with hemodialysis, and 1 report of mania associated with peritoneal dialysis in which delirium was not obviously present (Table 1). Whether this connection is a causal or casual association has been questioned.² A case in which the onset of mania appeared to be related to renal failure and its treatment with hemodialysis is presented. The patient was assessed in 1997. Past literature on the subject is summarized.

View this table: [in this window] [in a new window]

TABLE 1.

Case Report

Case. A 67-year-old woman with chronic renal failure of unknown etiology developed fluid overload and was treated with emergency hemodialysis. Five sessions of hemodialysis were carried out uneventfully, which resulted in a marked improvement in her physical and biochemical parameters. Past medical history included secondary hypertension and anemia, gout, tertiary hyperparathyroidism, Type 2 diabetes mellitus, an inferior myocardial infarction, and left-ventricular failure. In her past psychiatric history, she had had a 2-month episode of postnatal depression at age 31, which had resolved without treatment. There was no family history of psychiatric illness.

Two days after finishing hemodialysis, a change in personality and behavior was noted. Over a 5-day period, she demonstrated increasing distractibility, irritability, restlessness, reduced sleep, and expressed the false idea that her husband was having an affair. She was readmitted with a provisional diagnosis of delirium, cause unknown.

Physical and neurological examination were unremarkable. Investigation results as follows: electrocardiogram unchanged to previous recordings, hemoglobin 11.6 g/dl, white cell count 13.1 x 10⁹ glucose 12.8 mmol/L, urea 38.8 mmol/L, creatinine 434 micromol/L, and corrected calcium 2.93 mmol/L. During her admission, there was no evidence of focal or systemic infection, subsequent white cell counts were normal, and her diabetes remained well controlled. The patient declined an electroencephalogram and neuroimaging.

Two hemodialysis sessions over 5 days improved her biochemical parameters (urea 27.1 mmol/L, creatinine 338 micromol/L, and corrected calcium 2.84 mmol/L), but her mental state worsened. She appeared episodically disorientated at night. She cooperated poorly with cognitive testing because of irritability, but one Mini-Mental State Exam elicited a score of 19/30—a score of less than 27 suggests delirium or dementia.³

Difficulties managing her behavior on the renal unit led to transfer to a psychiatric ward, where a 2-week assessment revealed the following: sustained elevation of mood with marked irritability, persecutory delusions that her husband was unfaithful and conspiring with the dialysis staff against her, grandiosity (e.g., stating she was planning to donate ;bp100,000 to start a dialysis unit in her home town), reduction of sleep, motor restlessness, distractibility, and lack of insight, in that she believed herself to be without any serious physical or psychological problems. Repeat cognitive testing elicited a normal Mini-Mental Exam State score of 27/30. Though specifically looked for, no fluctuations in conscious level or mental state were subsequently observed.

She met diagnostic criteria for mania with psychotic symptoms. The timing of onset in relation to uremia, hypercalcemia, and treatment with hemodialysis led to a diagnosis of organic mood disorder being made.⁴ Antipsychotic treatment (haloperidol 5 mg/day) was instituted, but noncompliance resulted in her detention under Section 2 of the United Kingdom's Mental Health Act. There was full resolution of mood disorder and psychotic symptoms after 10 days' compliance with antipsychotic treatment.

She was subsequently established on twice-weekly hemodialysis. Six weeks after initial presentation, there was a further episode of elevated mood and reduced sleep accompanied by grandiose and persecutory ideation. This episode occurred in clear consciousness. The relapse was attributed to her stopping haloperidol of her own accord because of extrapyramidal side effects. She was changed to risperidone (2 mg/day), an antipsychotic with fewer extrapyramidal side effects, and resumption of antipsychotic therapy abolished symptoms of relapse within 1 week.

It was decided to establish her on continuous ambulatory peritoneal dialysis (CAPD). She had an episode of heart block while a Tenchkoff catheter was being inserted, and as a result she was fitted with a permanent pacemaker. Ten weeks after initial presentation, the patient unexpectedly died of an acute myocardial infarction. Death occurred before CAPD had been commenced.

Discussion

Review of the literature suggests seven possible explanations for the association of dialysis and mania.

First, uremia by itself may cause a manic state. Case reports suggesting this effect date back to the 1870s, but there has been only one such report in recent times.⁵ A patient with mania due to end-stage renal failure may coincidentally be treated with dialysis.

Second, dialysis precipitates an acute confusional state that can be mistaken for mania. This presentation has been described from the early days of hemodialysis.¹

Third, dialysis can precipitate relapse or exacerbation of a preexisting bipolar disorder. Five cases in the literature document this occurring in association with hemodialysis. Manic relapse occurred at 1 week,⁶ 6 weeks,⁷ and 2 years⁸ after commencing hemodialysis. Major depression developed "within weeks" of beginning hemodialysis followed by manic relapse at 8 weeks.⁹ An active manic episode was exacerbated by having to start hemodialysis during it.¹⁰

One case report documents relapse of bipolar disorder in a patient treated with both hemodialysis and CAPD. A depressive relapse developed (time unspecified, but implication was within weeks) after starting hemodialysis. The patient was changed from hemodialysis to CAPD at 3 months, and then had a manic relapse after 5 months of CAPD.¹¹

In the cases^6–9,11 describing relapse of bipolar disorder, the patients were not on prophylactic psychotropic medication, so the association cannot be explained by dialysis reducing levels of mood-stabilizing medication. In the case describing exacerbation of an active manic episode by hemodialysis,¹⁰ reduction of medication levels by dialysis is a possible factor.

One case report is of a patient with bipolar disorder who had received hemodialysis for 5 years uneventfully while maintained on valproate and neuroleptics, but who had a relapse of mania 2 weeks after his psychotropic medication was stopped because of pancytopenia. In this case, hemodialysis appeared to have had no effect on the mood disorder in the presence of adequate maintenance therapy. Whether hemodialysis in the absence of maintenance treatment contributed to the manic relapse is unclear.¹²

Fourth, dialysis can precipitate the presentation of a latent bipolar disorder. Fifth, dialysis acts as a physiological/organic insult to precipitate a "secondary" mania. Sixth, bipolar disorder can emerge during a course of hemodialysis simply by chance association. Seventh, and finally, dialysis can cause cerebral damage that, in turn, can present with a manic syndrome. One case report suggests that dialysis encephalopathy can present initially with mania.¹³

Three cases^14–16 exist in which there was no personal or family psychiatric history, no suggestion of delirium, and no subsequent history of dementia or encephalopathy. Though it is not possible to state definitively whether these were cases of latent bipolar disorder, true secondary mania, or simply chance association, the timing of onset of mania after dialysis might help in deciding the more likely possibilities.

In two cases,^14,15 onset of mania after hemodialysis at 13 months and 9 years, respectively, suggests that initiation of hemodialysis was not a strong precipitant and that chance association is the likeliest explanation. In one of the cases of preexisting bipolar disorder described earlier, the onset of a manic episode 2 years after starting hemodialysis⁸ also suggests that the dialysis was not a major precipitant in the relapse and that the association could have been due to chance.

In one case,¹⁶ onset of mania at 9 days suggests that the initiation of hemodialysis was a strong precipitant and that secondary mania or the presentation of a latent bipolar disorder occurred in this case. All 11 existing case reports with the probable association between dialysis and manic presentation are summarized in Table 1.

The patient described in this case report had had severe uremia and hypercalcemia in the past (urea >50 mmol/L, creatinine >400 micromol/L, corrected calcium >2.90 mmol/L) without developing abnormalities of mental state. Hemodialysis, and the physiological and/or psychological stress associated with it, did appear to be the additional factor precipitating an abnormal mental state. Some features were consistent with delirium, and in view of the past medical history, the subsequent need for a permanent pacemaker, and the eventual death of the patient from a myocardial infarction, an undetected cardiac or cerebral ischemic event in the peridialysis period is a possibility. However, there were prolonged phases in which the patient appeared manic without evidence of delirium. Manic states that appear to evolve from delirious states but which are temporally and clinically separate have been described in "secondary mania."¹⁷

The patient had a history of depression 30 years earlier, and though the duration was brief, she may have had an underlying bipolar disorder. Therefore, this patient's presentation could fit with four of the seven possible etiologies listed before: delirium, presentation of latent bipolar disorder, chance association, or secondary mania.

Renal failure and dialysis are associated with a range of neuropsychiatric conditions: acute psychosis, adjustment reaction, depressive disorder, dialysis dementia, dialysis disequilibrium, and uremic encephalopathy.¹⁸ European and North American studies have suggested that the suicide rate in dialysis patients may be 15 times higher than in the general population.^19,20

Mania can complicate hemodialysis and CAPD, though the existing literature suggests there is more than one explanation for the association.

Previously successful treatment strategies for mania complicating dialysis have included the use of conventional antipsychotics,^13,14,16 benzodiazepines,¹⁵ oral lithium carbonate with careful blood monitoring,^6,8,9,12 and administration of lithium chloride via addition to the dialysate.^7,11 Case reports exist of patients with bipolar disorder on lithium prophylaxis not affected by initiating hemodialysis, perhaps due to careful lithium monitoring being observed.^21,22

ACKNOWLEDGMENTS

The author thanks Dr. Franco Benazzi for his help in the preparation of this paper.

REFERENCES

1. Locke S, Merrill JP, Tyler HR: Neurologic complications of acute uraemia. Arch Intern Med 1961; 108:519–528
2. Benazzi F: Mania during hemodialysis: causal or casual association? Am J Psychiatry 1992; 149:414
3. Folstein MF, Folstein SE, McHugh PR: "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189–198[Medline]
4. World Health Organization: ICD-10. Classification of Mental and Behavioural Disorders. Geneva, Switzerland, World Health Organization, 1992
5. El-Mallakh RS, Shrader SA, Widger E: Mania as a manifestation of end-stage renal disease. J Nerv Ment Dis 1987; 175:243–245[Medline]
6. Gruner JF, Dennert J, Schafer G: Lithium treatment in maintenance dialysis. Pharmacopsychiatry 1991; 24:13–16[Medline]
7. Oakley WF, Clarke WF, Parsons V: The use of dialysis bath fluid as a vehicle for a drug with a narrow therapeutic index—lithium chloride. Postgrad Med J 1974; 50:511–512[Abstract/Free Full Text]
8. Procci WR: Mania during maintenance hemodialysis successfully treated with oral lithium carbonate. J Nerv Ment Dis 1977; 164:355–358[Medline]
9. Port FK, Kroll PD, Rosenzweig J: Lithium therapy during maintenance hemodialysis. Psychosomatics 1979; 20:130–131[Abstract/Free Full Text]
10. Benazzi F: Uraemia and mania (letter). Br J Psychiatry 1991; 158:718
11. Flynn CT, Chandran PKJ, Taylor MJ, et al: Intraperitoneal lithium administration for bipolar affective disorder in a patient on continuous ambulatory peritoneal dialysis. Int J Artif Organs 1987; 10:105–107[Medline]
12. Quentzel SJ, Levine S: Aggressive lithium treatment for mania in a hemodialysis patient with end-stage renal disease. Psychosomatics 1997; 38:398–399[Free Full Text]
13. Jack RA, Rivers-Buckley NT, Rabin PL: Secondary mania as a presentation of progressive dialysis encephalopathy. J Nerv Ment Dis 1991; 171:193–195
14. Cooper AJ: Hypomanic psychosis precipitated by hemodialysis. Compr Psychiatry 1967; 8:168–174[Medline]
15. Jarecke RC, De Moya VF, Ware MR: A case of mania secondary to hemodialysis: successful treatment with clonazepam. J Clin Psychoparmacol 1990; 10:298–299
16. Thomas CS, Neale JT: Organic manic syndrome associated with advanced uraemia due to polycystic kidney disease. Br J Psychiatry 1991; 158:119–121[Abstract/Free Full Text]
17. Krauthammer C, Klerman GL: Secondary Mania—manic syndromes associated with antecedent physical illness or drugs. Arch Gen Psychiatry 1978; 35:1333–39[Abstract/Free Full Text]
18. Brown TM, Brown RLS: Neuropsychiatric consequences of renal failure (review). Psychosomatics 1995; 36:244–253[Abstract/Free Full Text]
19. Neu S, Kjellstrand C: Stopping long-term dialysis. N Engl J Med 1986; 314:14–20[Abstract]
20. Haenel Th, Brunner F, Battegay R: Renal dialysis and suicide: occurrence in Switzerland and in Europe. Compr Psychiatry 1980; 21:140–145[Medline]
21. Lippman SB, Manshadi MS, Gultekin AL: Lithium in a patient with renal failure on hemodialysis (letter). J Clin Psychiatry 1984; 45:444[Medline]
22. Koecheler JA, Canafax DM, Simmons RL, et al: Lithium dosing in renal allograft recipients with changing renal function. Drug Intelligence and Clinical Pharmacy 1986; 20:623–624

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Wilson, R. Search for Related Content PubMed Citation Articles by Wilson, R. Other Mood Disorders Syndromes Secondary to General Medical Disorders

Get information about faster international access.

Privacy Policy

Copyright © 1998 Academy of Psychosomatic Medicine. All rights reserved.

Home | Search | Current Issue | Past Issues | Subscribe | All APPI Journals | Help | Contact Us