Electroconvulsive therapy as a treatment for refractory neuropsychiatric lupus with catatonia: three case studies and literature review

Abstract

Neuropsychiatric disorders associated with systemic lupus erythematosus are very common. Treatment generally consists of glucocorticoids and immunosuppressive therapy; however, some cases are unresponsive. Electroconvulsive therapy (ECT) is a recognized treatment modality in psychiatry and is an option for refractory cases of neuropsychiatric lupus. This report describes three cases of neuropsychiatric lupus that improved with ECT after failure of antipsychotics and immunosuppressive therapy. All cases met DSM-5 criteria for catatonia (case 1: agitation, stereotypies, and grimacing; case 2: stupor, mutism, and grimacing; case 3: agitation, mutism, and stereotypies); therefore, ECT was indicated. This case series shows that ECT can be a therapeutic option in patients with neuropsychiatric lupus, especially when associated with catatonia and unresponsive to conventional treatment.

Keywords

Electroconvulsive therapy systemic lupus erythematosus neuropsychiatric lupus catatonia

Introduction

Neuropsychiatric disorders are reported in 14–75% of patients with systemic lupus erythematosus (SLE). This wide variability in the prevalence of central nervous system involvement in SLE is partly due to the absence of a gold standard for diagnosis. Psychosis is one of the neuropsychiatric manifestations associated with SLE and generally occurs in the context of multisystemic active disease, associated mainly with cutaneous and hematological manifestations.¹ Diagnosis and management of neuropsychiatric lupus remains a challenge for rheumatologists. Therapy is empirical and based on clinical experience.

Electroconvulsive therapy (ECT) is a psychiatric treatment modality that uses electricity applied via electrodes to the scalp to induce controlled convulsions. It is used for management of severe depression, schizophrenia, mania, and refractory catatonia. In patients with neuropsychiatric lupus, ECT has shown promising results in cases of catatonia, mania, and severe depression, with or without psychotic symptoms.²

The present report describes three cases of severe neuropsychiatric lupus with catatonia that responded to ECT after failure of antipsychotic and immunosuppressive therapy.

Methods

We report three cases from hospitalized patients with refractory neuropsychiatric lupus with catatonia who received ECT with improvement of symptoms. The patients were from two different centers, one from Hospital de Clínicas de Porto Alegre and the others from Hospital Universitário Clementino Fraga Filho in Rio de Janeiro, both in the division of rheumatology. Subsequently, we conducted an extensive review of the scientific literature about the use of ECT in patients with lupus using the MEDLINE (PubMed), EMBASE, SciELO, Cochrane Library, and BIREME databases. The following search queries were used: “lupus AND electroconvulsive therapy” and “SLE AND electroconvulsive therapy.” Articles and abstracts in Portuguese, Spanish, or English from 1967 to 2014 were included in the literature review. Clinical response to ECT was assessed by the Bush-Francis Catatonia Rating Scale, which is one of the most widely used systems for catatonia classification. Catatonia was identified according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria (three or more of the following symptoms are required: catalepsy, waxy flexibility, stupor, agitation, mutism, negativism, posturing, mannerisms, stereotypies, grimacing, echolalia, and echopraxia).

Case reports

Patient 1

A 25-year-old female patient with a 13-year history of SLE, who had thrombocytopenia, non-erosive arthritis, positive antinuclear antibodies (ANA), positive anti-ribosomal P protein antibody, and neuropsychiatric lupus, was treated with glucocorticoids and cyclophosphamide, followed by azathioprine as maintenance therapy. Six years later, she presented with a new episode of neuropsychosis and was treated with methylprednisolone and cyclophosphamide pulse therapy for six months, at which time a new relapse was detected. This relapse did not respond to pulse therapy with methylprednisolone, cyclophosphamide, rituximab, or intravenous immunoglobulin. Brain magnetic resonance imaging (MRI) was normal, cerebrospinal fluid (CSF) analysis was nonspecific for infections, and tests for antiphospholipid, anti-double-stranded DNA (anti-dsDNA) and anti-Sm antibodies were negative. The patient developed catatonia (agitation, stereotypies, and grimacing)and depression with suicidal ideation. Despite treatment with immunosuppressive drugs, antipsychotics, antidepressants, and anxiolytics, no response was obtained. As psychiatric symptoms persisted despite intensive medical therapy, the patient received ECT, applied with bilateral electrodes and using a brief-pulse square wave ECT device (Mecta Spectrum 4000 M). After the fourth ECT session, the patient exhibited significant improvement in psychiatric symptoms, with restoration of the sleep-wake cycle. Recovery of function was assessed using the Bush-Francis Catatonia Rating Scale, which yielded scores of 20 before ECT and 8 after the last ECT session, denoting significant clinical improvement.

Patient 2

A 26-year-old woman with SLE was admitted for management of neuropsychiatric lupus. The patient had been diagnosed with SLE at age 18 years, presenting with the following diagnostic criteria: positive ANA, non-erosive arthritis, malar rash, and photosensitivity. Hydroxychloroquine and intermittent topical and/or oral glucocorticoids had been used to control cutaneous and articular disease activity. Three months before admission, the patient’s cutaneous manifestations worsened gradually, with psoriasiform lesions consistent with subacute cutaneous lupus progressing to diffuse erythroderma with small, painless oral ulcers on the palate and tongue. Subsequently, she developed mental confusion, disorientation, and psychosis, associated with visual and auditory hallucinations, cognitive disturbance, loss of critical judgment, and catatonic episodes (stupor, mutism, and grimacing). The patient had no history of convulsions and no family history of psychotic diseases. Laboratory tests revealed autoimmune hemolytic anemia and low complement levels (C3 and C4). Tests for antiphospholipid, anti-dsDNA, and anti-Sm antibodies were negative. Brain MRI and electroencephalography were normal and CSF analysis was noncontributory. Positron emission tomography (PET) images were consistent with cerebral perfusion defects in the frontoparietal and thalamic regions. After ruling out infection, immunosuppressive therapy with cyclophosphamide and pulse therapy with methylprednisolone were administered in combination with antipsychotics, antidepressants, and anxiolytics, but failed to produce any clinical response. As psychiatric symptoms remained unchanged despite two months of pharmacotherapy, the patient received 12 consecutive sessions of ECT, which were applied with bilateral electrodes and using a brief-pulse square wave ECT device (Mecta Spectrum 4000 M). Progressive improvement was observed after the third session. After the end of ECT, she was able to return to daily activities, with restoration of critical judgment and cognitive improvement. The patient’s Bush-Francis Catatonia Rating Scale score decreased from 45 immediately before ECT to 1 after ECT.

Patient 3

A 35-year-old woman with a six-year history of SLE (with malar rash, photosensitivity, non-erosive arthritis, hemolytic anemia, alopecia, positive ANA and negative antiphospholipid and anti-dsDNA antibodies at the time of diagnosis) was admitted to our hospital with psychotic symptoms, agitation, and disorientation. Brain MRI and CSF analysis showed no abnormalities. The patient received methylprednisolone and cyclophosphamide pulse therapy. After three weeks, psychiatric symptoms progressed to a catatonic state (agitation, mutism, and stereotypies), despite institution of quetiapine and lorazepam therapy. A trial of ECT was started on the 30th hospital day. ECT was performed with unilateral electrodes and using a brief-pulse square wave ECT device (Mecta Spectrum 4000 M) three times a week. The patient exhibited a dramatic response after the third session, with recovery of ability to speak and obey commands. ECT was discontinued after the 10th session. The patient displayed continuous improvement of cognitive function, without recurrence of psychotic symptoms after 12 months of follow-up on maintenance treatment with mycophenolate mofetil, hydroxychloroquine, and risperidone. The patient’s Bush-Francis Catatonia Rating Scale score decreased from 27 immediately before ECT to 3 after ECT.

Discussion

Psychosis is an uncommon and severe neuropsychiatric manifestation of SLE. In a longitudinal study that followed SLE patients for nine years, Appenzeller et al. reported symptoms of psychosis in 17% of patients; 66% of cases were attributable to disease activity, 31% were associated with glucocorticoid therapy, and 3% were a result of primary psychosis.^3,4 In another study of 11 SLE patients who presented with psychosis, the average time between diagnosis of SLE and onset of psychotic symptoms was 10 months, with 80% of cases occurring in the first year of the disease and 60% of patients presenting with psychotic manifestations at the time of SLE diagnosis.⁵ The average age at diagnosis of psychosis was 29 years (similar to that of the cases described in our series), with all patients developing psychosis as part of multisystem SLE activity and 90% presenting with simultaneous cutaneous lesions.⁵

There are few reported cases in which ECT was used in the treatment of neuropsychiatric lupus. In 1967, Guze described the potential benefits of ECT in the treatment of psychiatric disorders associated with SLE.⁵ In 1978, Allen and Pitts reported two cases in which ECT had been used to manage depression in patients with SLE, with excellent results.⁶ Douglasand Schwartz, in 1982, reported one case of severe depression associated with lupus cerebritis refractory to immunosuppressive treatment, high doses of glucocorticoid, and antipsychotics, which responded dramatically to ECT.⁷ In 1990, Fricchione et al.described a single case of neuropsychiatric lupus with catatonia that was managed successfully with cyclophosphamide and ECT.⁸ In 1992, Ditmore et al. reported an experience with ECT in a patient with severe psychosis, mania, and catatonia, also with excellent results.⁹ Subsequently, other cases of successful use of ECT as an adjunct therapy in severe neuropsychiatric lupus were published^10–12that included the use of ECT in juvenile SLE presenting with catatonia and severe depression.^2,13–15 Table 1 provides a detailed review of all cases reported in the literature.

Table 1

Clinical profile and results of ECT treatment of patients with refractory neuropsychiatric lupus

Authors/Reference	Age (years)	Disease duration (years)	Clinical and laboratorial features	Usual treatment	Number of ECT	Response
Leon et al.²	14	2	Alopecia, thrombocytopenia, anticardiolipin, anti-Ro, anti-La and anti-P ribosomal protein	Methylprednisolone, cyclophosphamide, rituximab and lorazepam	11	Improvement
Grover et al.¹⁴	18	<1	Malar rash, fever, mania and necrotizing vasculitis	Prednisolone, cyclophosphamide, trifluoperazine, haloperidol, benzodiazepine, olanzapine and venlafaxine	6	Improvement
Tan and Tan¹²	43	10	Alopecia, arthritis, mucocutaneous lesions, nephritis, hemolytic anemia, hypocomplementemia, ANA and anti-dsDNA	Methylprednisolone, cyclophosphamide, lorazepam, olanzapine and haloperidol	5	Improvement
	28	6	Malar rash, palmar vasculitis, photosensitivity, arthralgias, leukopenia, ANA and anti-dsDNA	Prednisolone, cyclophosphamide, fluoxetine, haloperidol, lorazepam and risperidone	3	Improvement
	38	13	Malar rash, mucocutaneous lesions, polyarthralgia, anemia, neuropsychiatric symptoms, ANA and anti-dsDNA	Methylprednisolone, cyclophosphamide, olanzapine, haloperidol and risperidone	4	Improvement
Mon et al.¹³	15	<1	Alopecia, arthritis, hypocomplementemia, hemolytic anemia, lymphopenia, thrombocytopenia, proteinuria, anticardiolipin, ANA, anti-Sm, anti-RNP and anti-Ro	Methylprednisolone, cyclophosphamide, plasmapheresis for seven days, intravenous immunoglobulin and rituximab Olanzapine, diazepam, lorazepam and amantadine	20	Improvement
Fam et al.¹¹	25	4	Catatonia, ANA and anti-dsDNA	Methylprednisolone, cyclophosphamide, lorazepam, haloperidol, olanzapine and quetiapine	6	Improvement
Malur et al.¹⁰	26	<1	Lupus cerebritis with communicating hydrocephalus and catatonia	Prednisolone and lorazepam	14	Improvement
Ditmore et al.⁹	27	<1	Alopecia, arthritis, malar rash, leukopenia, proteinuria, hypocomplementemia, ANA, anti-Sm, anti-RNP, severe psychosis and mania.	Methylprednisolone and cyclophosphamide	11	Improvement
Fricchione et al.⁸	25	3	Malar rash, photosensitivity, discoid skin lesions, leukopenia, pleuritis, oral ulcers, ANA, anti-RNP, anti-Sm and anti-dsDNA	Methylprednisolone, cyclophosphamide and plasmapheresis for three days Phenytoin, haloperidol, lorazepam and carbamazepine	17	Improvement
Douglas and Schwartz⁷	30	1	Arthralgias, alopecia, malar rash, cerebritis, glomerulonephritis and ANA	Methylprednisolone, imipramine and trifluoperazine	11	Improvement
Allen and Pitts⁶	28	14	ANA, depression and suicide attempt	Prednisone and amitriptyline	12	Improvement
	30	4	Depression and ANA	Prednisone, neuroleptics and tricyclics	6	Improvement
Bica et al. (present study)	25	13	Thrombocytopenia, arthritis, neuropsychiatric lupus, ANA and anti-P ribosomal protein	Methylprednisolone, cyclophosphamide, rituximab and intravenous immunoglobulin Antipsychotics, antidepressants and anxiolytics	4	Improvement
	26	8	Arthritis, malar rash, photosensitivity and ANA	Methylprednisolone, cyclophosphamide, antipsychotics, antidepressants and anxiolytics	12	Improvement
	35	6	Malar rash, photosensitivity, arthritis, hemolytic anemia, alopecia and ANA	Methylprednisolone, cyclophosphamide, lorazepam and quetiapine	10	Improvement

ECT: electroconvulsive therapy;ANA: antinuclear antibodies; anti-dsDNA: anti-double-stranded DNA.

In view of the current literature, neuropsychiatric SLE with catatonia appears to respond satisfactorily to ECT, but these data must be approached with caution because of the likelihood of publication bias (i.e. positive results tend to be published more often than studies with negative results). Despite promising results with the use of ECT, the European League Against Rheumatism (EULAR) recommendations published in 2010 do not include ECT as an alternative treatment for refractory neuropsychiatric lupus.¹⁶ Therefore, we believe that additional studies should be conducted to clarify the role of ECT in the treatment of neuropsychiatric lupus, especially when associated with catatonia.

Conclusion

Severe neuropsychiatric lupus is an unusual manifestation of SLE, but it can have a devastating effect on patient quality of life. In cases refractory to immunosuppressive therapy and antipsychotics, ECT may be considered a safe and promising treatment option.

Footnotes

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest statement

The authors have no conflicts of interest to declare.

References

Pego-Reigosa

Isenberg

. Psychosis due to systemic lupus erythematosus: Characteristics and long-term outcome of this rare manifestation of the disease. Rheumatology 2008; 47: 1498–1502.

Leon

Aguirre

Pesce

Sanhueza

Toro

. Electroconvulsive therapy for catatonia in juvenile neuropsychiatric lupus. Lupus 2014; 23: 1066–1068.

Appenzeller

Cendes

Castallat

. Acute psychosis in systemic lupus erythematosus. Rheumatol Int 2008; 28: 237–243.

Mak

RCM

Lau

. Clinical implications of neuropsychiatric systemic lupus erythematosus. Adv Psychiatr Treat 2009; 15: 451–458.

Guze

. The occurrence of psychiatric illness in systemic lupus erythematosus. Am J Psychiatry 1967; 123: 1562–1570.

Allen

Pitts

FN Jr

. ECT for depressed patients with lupus erythematosus. Am J Psychiatry 1978; 135: 367–368.

Douglas

Schwartz

. ECT for depression caused by lupus cerebritis: A case report. Am J Psychiatry 1982; 139: 1631–1632.

Fricchione

Kaufman

Gruber

Fink

. Electroconvulsive therapy and cyclophosphamide in combination for severe neuropsychiatric lupus with catatonia. Am J Med 1990; 88: 442–443.

Ditmore

Malek-Ahmadi

Millis

Weddige

. Manic psychosis and catatonia stemming from systemic lupus erythematosus: Response to ECT. Convuls Ther 1992; 8: 33–37.

10.

Malur

Pasol

Francis

. ECT for prolonged catatonia. JECT 2001; 17: 55–59.

11.

Fam

Lee

. Electroconvulsive therapy for catatonia in neuropsychiatric systemic lupus erythematosus. J ECT 2010; 26: 143–144.

12.

Tan

. Electroconvulsive therapy for severe neuropsychiatric lupus with psychosis. J ECT 2013; 29: 243–246.

13.

Mon

L’Ecuyer

Farber

. The use of electroconvulsive therapy in a patient with juvenile systemic lupus erythematosus and catatonia. Lupus 2012; 21: 1575–1581.

14.

Grover

Aarya

Sharma

. Use of electroconvulsive therapy in an adolescent with systemic lupus erythematosus for management of depression. J ECT 2013; 29: 50–51.

15.

Nazarian

Liebman

Kellner

. Electroconvulsive therapy (ECT) for catatonia: Delay may be risky. Lupus 2013; 22: 336–336.

16.

Bertsias

Ioannidis

JPA

Aringer

. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: Report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 2010; 69: 2074–2082.