Neuroleptic malignant syndrome in an elderly with quetiapine: A case report and review of literature

Devakshi Dua; Sandeep Grover

doi:10.4103/jgmh.jgmh_16_17

CASE REPORT

Year : 2017 | Volume : 4 | Issue : 1 | Page : 64-68

Neuroleptic malignant syndrome in an elderly with quetiapine: A case report and review of literature

Devakshi Dua, Sandeep Grover
Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication

20-Jun-2017

Correspondence Address:
Sandeep Grover
Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jgmh.jgmh_16_17

Abstract

Over the years, there is an increase in the prescription of antipsychotics among elderly patients, and these are used for various clinical indications such as psychotic disorders, affective disorders, behavioral and psychological symptoms of dementia and delirium. Quetiapine is one of the preferred antipsychotics among elderly because of its safety profile. However, quetiapine has been rarely been associated with the development of neuroleptic malignant syndrome (NMS) among elderly. In this report, we discuss a case of NMS in a 70-year-old female, who developed symptoms of NMS at the dose of 200 mg/day, while quetiapine was being used along with lithium. A review of literature suggests that there are 12 cases of NMS reported in subjects older than 55 years of age.

Keywords: Elderly, neuroleptic malignant syndrome, quetiapine, side effects

How to cite this article:
Dua D, Grover S. Neuroleptic malignant syndrome in an elderly with quetiapine: A case report and review of literature. J Geriatr Ment Health 2017;4:64-8

How to cite this URL:
Dua D, Grover S. Neuroleptic malignant syndrome in an elderly with quetiapine: A case report and review of literature. J Geriatr Ment Health [serial online] 2017 [cited 2023 Jun 7];4:64-8. Available from: https://www.jgmh.org/text.asp?2017/4/1/64/208602

Introduction

In recent times, there is increase in the prescription rates of antipsychotics among elderly.^[1],[2] Antipsychotics are used among elderly for the management of psychotic disorders, affective disorders, behavioral and psychological symptoms of dementia and delirium.^[1],[3],[4] In addition, antipsychotics are used for various off-label indications, including sleep disturbances, tics, and hiccoughs.^[5]

Antipsychotics are not only used by the psychiatrists but are also prescribed by other specialists, and many a times, these are prescribed in doses which are recommended for adult population, rather than the elderly patients.^[6] These at times can lead to use of relatively higher doses among elderly.^[7],[8] Neuroleptic malignant syndrome (NMS) is a serious adverse effect associated with use of antipsychotics, and this has been described across all age groups with all the possible antipsychotic medications.^{[9],[10],[11],[12]} However, literature on NMS among elderly is limited.

In this report, we present the case of a 70-year-old female suffering from bipolar disorder who developed NMS while receiving a combination of quetiapine and lithium.

Case Report

A 70-year-old female presented to the emergency services with a history of 1-week duration characterized by weakness, fever, and confusion. Detailed evaluation of the history revealed that she had been suffering from bipolar disorder as per the International Classification of Diseases-10 criteria for the last 3 years. About a month before presentation, she had relapse of affective symptoms and developed severe depressive episode with psychotic symptoms and was started on lithium 600 mg/day about 3 weeks before presentation. About 10 days prior to presentation, in view of lack of improvement with lithium, she was directly started on tablet quetiapine at a dose 200 mg/day. After 2 days of starting quetiapine, she began to complain of weakness and difficulty in walking. She also had trembling of hands and would remain in bed for most part of the day. Family members attributed this to the new medications and began to give these medications to her erratically with no fixed schedule. Over the next 1 week, her condition worsened further, she started to appear confused, drowsy, her food and fluid intake were reduced significantly and developed fever.

At the emergency, initially she was evaluated for encephalopathy. She was started on intravenous fluids and antibiotics empirically. A psychiatry referral was made as the patient was on psychotropic medications.

At the initial evaluation by the psychiatry consultation-liaison team, she was found to be febrile, had diaphoresis, had coarse tremors, was drowsy, with fluctuation in the pulse rate (100–120 beats/min) and blood pressure (systolic 100–160 and diastolic 60–100 mm of Hg). Physical examination including cardiovascular, respiratory, and per abdominal examination did not reveal any abnormality. In the central nervous system (CNS) examination, there was no rigidity and the deep tendon reflexes were elicited. Sensory system could not be tested. On the basis of available information, differential diagnoses of lithium toxicity, NMS, and encephalopathy were considered. All the psychotropic medications were stopped. On mental status examination, she was drowsy and difficult to arouse for most part of the day. There was no history of hematuria, dysuria, cough with expectoration, upper respiratory tract infection, abdominal discomfort, diarrhea, exposure to excessive heat, use of any other medications, and intake of any other substance of abuse.

Laboratory investigations revealed hemoglobin of 10.6 g/dL, total leukocyte count to be 16,400/uL with 76% neutrophils, 13% lymphocytes, 8% monocytes, and 3% eosinophils. X-ray chest, electrocardiogram, magnetic resonance imaging of brain, cerebrospinal fluid evaluation did not reveal any abnormality. Serum lithium levels were 0.4 mmol/L. During the initial 2 days, she maintained in the same state and additionally developed rigidity of all the four limbs. Creatinine phosphokinase levels were found to be 45 U/L (Normal range 25–130 U/L). Her blood culture, urine examination, sputum examination, serum electrolytes, peripheral smear for malarial parasite, dengue serology, and arterial blood gas analysis did not reveal any abnormality. Based on all the available information, a possible diagnosis of NMS was considered. She was managed with bromocriptine 2.5 mg 4 times a day along with supportive management. From the next day of starting bromocriptine, patient's condition started to improve and within 3 days she was asymptomatic and all her symptoms resolved. She did not develop any complications and was discharged after 4 days from the emergency. No psychotropics were started at the time of discharge and were advised to follow-up in psychiatry outpatient department.

Discussion

NMS is a rare but potentially life-threatening idiosyncratic reaction to antipsychotic agents.^[9] Signs and symptoms of NMS include muscle rigidity, fever, autonomic dysfunction, and altered consciousness.^[9],[10] Laboratory findings may reveal leukocytosis and elevated serum creatine phosphokinase levels.^[12] Most commonly reported symptoms are fever, tremors, lead-pipe rigidity, tachycardia, diaphoresis, labile blood pressure, akinesia, dystonia, sialorrhea, coma, stupor, and tachypnea.^[13] In most cases, the full syndrome develops within 48 h of the onset of the first symptoms.^[13] However, incomplete or partial forms have been reported which do not show all classical symptoms. Index case had all the signs and symptoms except raised creatine phosphokinase levels. Some of the previous reports have also described patients with NMS, without raised creatine phosphokinase levels.^[14] Other atypicality seen in the index case included evolution of symptoms over the period of 8–10 days.

Over the years, many risk factors or predisposing factors have been identified to be associated with the development of NMS. These include dehydration, malnutrition, exhaustion, intramuscular injection of neuroleptics, advanced age, neuropsychiatric disorders, traumatic head injuries, neuroleptic dose increases, organic brain disease (e.g., dementia), mood disorders, male gender, infections, ethanol intoxication, HIV infection, and concomitant use of lithium and anticholinergics.^[11],[12] Typical neuroleptic agents have a greater propensity to cause NMS.^[10] However, NMS has also been reported with atypical antipsychotics too.^{[9],[10],[11],[12]} A few significant risk factors for second generation antipsychotic-induced NMS include male gender, confusion, dehydration, delirium, and presence of extrapyramidal side effects.^[15] Non-white ethnicity, number of antipsychotics, and increasing/fluctuant dosing patterns has also been implicated.^[15] However, other medications including atypical antipsychotics as well as nonpsychotropic medications such as prokinetic and antiemetic drugs have been reported to be associated with NMS.^[10] With these medications, there may be an atypical or forme fruste presentation of the syndrome. As a result, a high index of suspicion may be warranted for timely diagnosis as there is a significant overlap in symptoms with other disorders.^[11] The index case had predisposing factors in the form of mood disorder, concomitant use of lithium, and starting of quetiapine directly at the dose of 200 mg/day.

Differential diagnosis of NMS includes serotonin syndrome, malignant hyperthermia, malignant catatonia, central anticholinergic syndrome, and lithium toxicity.^[10],[11] Symptoms such as altered level of consciousness and autonomic instability may also occur in a number of other disorders including CNS and systemic infections, seizures, heat stroke, thyrotoxicosis, and phaeochromocytoma.^[16] In the index case there was no history of use of medications other than lithium and quetiapine. Diagnosis of lithium toxicity was ruled out on the basis of serum levels of 0.4 mmol/L and there was a history of poor compliance with the medications prior to presentation. In the index case there was no evidence of any infection. Hence, a diagnosis of NMS was considered.

Although NMS has been reported in all age groups, compared to literature in adults, data are limited in elderly. Elderly are more likely to have certain vulnerability factors for the development of NMS, such as presence of comorbidity, organic brain syndrome, dehydration, and malnutrition.^[11] The patient may also be receiving other agents which can precipitate NMS such as metoclopramide, promethazine, and domperidone.^[16] Elderly patients often are prescribed multiple medications,^[17] including psychotropics and often present to treatment services later in the course of their illness.^[18] As a result, the presentation may be more severe and complex. Mortality in elderly is reported to be up to 10% and is often due to cardiac, renal, and respiratory complications. The risk of poor outcome and mortality is correlated with older age, preexisting organic brain disease, treatment with long-acting drugs, higher temperatures, and coma during the episode.^[10]

There are few reports of NMS with quetiapine and these have been reviewed from time to time.^[19],[20] A review of reports of NMS with quetiapine identified 20 reported cases in literature, 6 of which were reported in persons older than 55 years of age. In more than half of these cases, diagnosis of NMS was associated with the presence of medical comorbidity or use of concomitant medications. In people older than 55 years of age, the associated factors included infection (n = 1), parkinsonism (n = 1), and Parkinson's disease (n = 2). In addition, some of the patients older than 55 years of age, who developed NMS, were also receiving other medications such as fluvoxamine and selegiline (both of which can increase the risk of serotonin syndrome), levodopamine and cabergoline, which can cause destabilization on withdrawal. Overall, 4 out of the 6 cases reported in patients older than 55 years of age had medical conditions and/or were receiving medications which could contribute to development of clinical syndromes which can mimic NMS.^[19] There are few more reports of NMS, after publication of this review among the elderly patients.^{[21],[22],[23],[24],[25],[26]}

We could locate 12 cases of NMS with quetiapine reported in the literature among subjects aged 55 or above [Table 1].^{[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31]} As is evident from the [Table 1], two-third of the patients were male, the dose range at which these subject developed NMS ranged from 50 to 300 mg/day and the symptoms of NMS were seen as early as 24 h and as late as 1 year of starting of quetiapine, with 4 out of the 12 cases seen within 8 days of starting quetapine (for few of the cases, the data were not available in terms of time to development of symptoms of NMS). A significant proportion of patients who developed NMS were also receiving some other medications along with quetiapine at the time of onset of NMS. The index case was concomitantly receiving lithium.

Table 1: Review of cases of neuroleptic malignant syndrome reported among elderly

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Conclusion

The present case demonstrates that NMS can develop among elderly patients receiving quetiapine, especially when it is started at a higher dose. Accordingly, a cautious approach must be followed while using antipsychotics among elderly. While prescribing antipsychotics among elderly, clinicians should weigh the pros and cons of such prescription and should closely monitor the patients for evolution of symptoms of NMS, especially during the initial phase of treatment. While starting antipsychotics among elderly 'start low and go slow' approach need to be followed rather that starting antipsychotics at higher doses or in doses which are the usual starting doses among adult patients. Further, the current case also suggests that diagnosis of NMS should be considered even in the absence of raised creatinine phosphokinase levels.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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