Lithium Toxicity and Neuroleptic Malignant Syndrome in a Patient with Bipolar Disorder

Case Report

Austin Crit Care Case Rep. 2021; 5(4): 1034.

Lithium Toxicity and Neuroleptic Malignant Syndrome in a Patient with Bipolar Disorder

Öcal S¹*, Simsek M² and Irem Yildiz M³

¹Faculty of Medicine, Department of Medical Intensive Care Unit, Hacettepe University, Ankara, Turkey

²Department of Medical Intensive Care Unit, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey

³Faculty of Medicine, Department of Psychiatry, Hacettepe University, Ankara, Turkey

*Corresponding author: Serpil Öcal, Faculty of Medicine, Department of Medical Intensive Care Unit, Hacettepe University, Ankara, Turkey

Received: September 28, 2021; Accepted: October 27, 2021; Published: November 03, 2021

Abstract

A combination of treatments are usually preferred by psychiatrists in managing acute manic exacerbations in patients with bipolar disorder. The most commonly used mix of psychotropic drugs to control mania consists of a known mood stabilizer - such as lithium or divalproex - plus an antipsychotic, though, these drugs can cause serious side effects. Neuroleptic Malignant Syndrome (NMS) occurs rarely in patients taking antipsychotic drugs and this infrequency makes diagnosis difficult in critically ill, Intensive Care Unit (ICU) patients. On the other hand, lithium toxicity can occur frequently in patients with bipolar disorder due to its narrow therapeutic index. Although rare, lithium toxicity and NMS may occur simultaneously in patients using antipsychotics and lithium together, resulting in severe morbidity or even mortality. The following research describes a patient on concomitant olanzapine and lithium treatment, who was diagnosed with NMS and lithium toxicity.

Keywords: Lithium; Olanzapine; Antipsychotic; Toxicity; Intensive care unit

Introduction

NMS is a life-threatening, neurological and psychiatric danger, which typically manifests as altered mental status, muscular rigidity, hyperthermia and autonomic system dysfunction [1]. It occurs in 0.02–3% of patients taking antipsychotic drugs, a rarity that makes diagnosis difficult in critically ill ICU patients [2]. The mortality of patients with NMS has declined in recent years, with relevant studies reporting a mortality rate of 10-20% in untreated patients [3,4]. On the other hand, lithium toxicity occurs in 75–90% of patients receiving long-term lithium therapy [5]. While lithium toxicity shows mild side effects such as hand tremors in most patients, moderate to severe side effects including Central Nervous System (CNS) and renal involvement have also been seen in a sub-group of patients [6]. The mortality rate of lithium toxicity has decreased from 25% to less than 1% over the years [2,7], however, both incidence and mortality of the concurrent existence of lithium toxicity and NMS are unknown with only case reports found in literature. Herein, we examine a patient with bipolar disorder on concomitant olanzapine and lithium treatment, who was diagnosed with NMS and lithium toxicity.

Case Presentation

A 59-year-old female with a history of bipolar disorder for over 38 years was referred to our emergency department with speech impairment, lethargy, tremors and an altered mental state. Her medical history showed a significant risk of hypothyroidism, plus she had been taking 100mcg levothyroxine per day for 10 years. Her bipolar disorder medication was a weekly flupentixol depot dose of 20 mg, daily amisulpride of 600mg, 600mg of lithium and 3mg biperiden, for 2 years. About two weeks prior, after taking her last dose of flupentixol depot, these prescriptions were modified. The patient complaints began on the 10th day of the new therapy regimen, which consisted of lithium carbonate, 600mg twice daily, and olanzapine, 10mg/day.

Upon admission to the emergency department, the patient–s body temperature was 38°C, pulse rate 90 beats/minute, respiratory rate was 18 breaths/minute and blood pressure was 157/95 mmHg. A neurological examination revealed slurred speech, rigidity and tremors, in addition to a time, place and person disorientation. Lithium and olanzapine were halted and an intravenous saline infusion was started at a rate of 75ml/hour. Firstly, serum creatinine was 2.99mg/dL (0.67-1.17 mg/dL) and lithium level was 2.16mmol/L (therapeutic level: 0.8-1.2 mmol/L), thus intermittent hemodialysis was performed. During the patient–s hospital stay, her sodium level of 152mEq/L (136-146 mEq/L) was observed due to Nephrogenic Diabetes Insipidus (NDI). After the 6th day of hospitalization, the patient was transferred to the ICU due to a worsening of her general condition along with a decreasing Glasgow Coma Score (GCS) (9/15) and fluctuations in vital signs.

On admission to the ICU, she had persistent hyperthermia of about 38.5°C, pulse rate was 110 beats/minute, respiratory rate was 22 breaths/minute and blood pressure was 110/70 mmHg. Serum creatinine was 2.2mg/dL, serum Creatine Kinase (CK) was 524 IU/L (0-145 IU/L), sodium level was 154mEq/L and lithium level was 0.64mmol/L. In addition, serum C-reactive protein was 0.7mg/dL (0-0.8 mg/dL) and her white blood cell count was 10,400/mL (4300- 103,00/mL). Infection was ruled out clinically and microbiologically. Cerebrospinal fluid analysis was normal with no signs of infection either. During her ICU stay, episodes of sinus tachycardia (120-130 beats per minute), unrelated to hyperthermia episodes, were observed. Electroencephalography revealed moderate to severe diffuse slow activity, diffuse triphasic sharp waves and focal epileptiform activities in both hemispheres, which are consistent with lithium toxicity, metabolic encephalopathy or non-convulsive status epilepticus. Magnetic resonance imaging of the brain revealed minimal cerebral atrophy.

In light of the clinical findings as shown in Table 1, NMS was diagnosed in addition to lithium toxicity. For treatment, dantrolene 400 mg/day for 18 days and bromocriptine 10 mg/day for 6 days were given during the ICU stay. Fluctuations in blood pressure, body temperature, heart rate and respiratory rate are shown in Figure 1. At the end of one month, as her renal functions and consciousness improved, she was discharged from the ICU. After one year of follow-up, lingering clinical signs of moderate cerebellar dysfunction (dysartria, bilateral dysmetria, dysdiadokynesia) and asymmetric parkinsonism secondary to lithium toxicity were observed.

Citation:Öcal S, Simsek M and Irem Yildiz M. Lithium Toxicity and Neuroleptic Malignant Syndrome in a Patient with Bipolar Disorder. Austin Crit Care Case Rep. 2021; 5(4): 1034.