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Quetiapine-induced hypokalemic periodic paralysis (QIHPP) is a rare condition. Herein, we present the case of a 31-year-old pregnant Malay woman diagnosed with bipolar II disorder and QIHPP. She presented to the casualty department with a 2-day history of bilateral lower limb weakness and numbness. Her renal function tests showed moderate hypokalemia (2.5 mmol/L), whereas other investigations were normal. Quetiapine was suspected to be the cause, prompting a psychiatric referral to manage her acute condition. Balancing the risks of untreated QIHPP against the potential relapse of bipolar symptoms from quetiapine discontinuation or dosage reduction poses a significant treatment challenge for pregnant women with QIHPP. Finally, we reduced the quetiapine dosage after careful consideration, leading to the normalization of potassium levels and symptom resolution. Therefore, clinicians should be aware of this side effect when initiating or continuing quetiapine treatment in women of childbearing age or pregnant women with psychiatric disorders. It is crucial to monitor serum electrolytes, especially potassium, following quetiapine administration and warn patients about its potential side effects.
Hypokalemic periodic paralysis (HPP) is a rare genetic condition characterized by episodic muscle weakness that occurs when serum potassium levels are below the normal range (<3.5 mmol/L) [1]. HPP may affect various muscles in the upper limbs, lower limbs, or trunk. Approximately 70% of cases are associated with mutations in the muscle calcium channel gene CACNA1S (1q31-32) and 20% are associated with mutations in the muscle sodium channel gene SCN4A (17q23-25) [2]. The CACNA1S gene encodes dihydropyridine-sensitive calcium channels. In individuals with mutations in this gene, triggers may cause abnormal potassium uptake by muscle cells, leading to an imbalance of potassium ions across cell membranes. This disrupts the membrane potential, causing the skeletal muscle to become unexcitable [3]. Triggers include stress, high carbohydrate intake, thyrotoxicosis, medications, and infection [1]. The prevalence of HPP is approximately 1 in 100,000 [1], and is more common in males aged 26–35 years than in females [4]. Common medications that can trigger hypokalemia include diuretics, insulin, beta-adrenergic agonists, verapamil, and steroids [5]. However, it is rarely triggered by antipsychotics. The standard treatment for HPP includes correction of serum potassium levels, prevention of debilitating complications, and management of the precipitating causes [5].
In principle, serum potassium levels are regulated by a balance between tubular reabsorption and secretion in the collecting tubule [6]. During pregnancy, renal potassium secretion is increased because of the elevated glomerular filtration rate and the renin-angiotensin-aldosterone system activation [7,8]. Increased aldosterone increases sodium reabsorption through epithelial sodium channels and promotes potassium and hydrogen ion secretion [9]. In addition, the physiological increase in plasma volume during pregnancy leads to hemodilution, and the increase in fetal demand for potassium reduces plasma potassium levels [10]. These factors may worsen hypokalemia in patients with other underlying conditions. Hypokalemia in pregnancy is considered high-risk, because it may lead to maternal arrhythmia and muscle paralysis, which, in severe cases, may require mechanical ventilation [11] and may cause fetal bradycardia [12].
Herein, we present a case of Quetiapine-induced hypokalemic periodic paralysis (QIHPP) in a pregnant woman to highlight the importance of early recognition of medication-induced HPP to prevent severe complications and the treatment challenges associated with psychiatric illness in pregnancy.
Case Report
A 31-year-old Malay primigravida at 16 weeks of gestation with a known case of bipolar II disorder presented to the emergency department with a sudden onset of bilateral lower limb weakness and numbness for 2 days, leading to difficulty in ambulation. She denied having fever, shortness of breath, leg pain, recent gastrointestinal loss, recent falls, or traumatic events involving her legs. During the first trimester, she experienced mild nausea and vomiting, which had completely resolved 2 weeks before the onset of her symptoms. Otherwise, she did not exhibit any signs or symptoms of labor. She had no family history of neuromuscular, thyroid, or autoimmune disorders. She had been treated for bipolar II disorder with oral quetiapine immediate-release (IR) 150 mg every night and oral lamotrigine 75 mg every night for 3 years and had remained in remission. She had never been hospitalized for medical or psychiatric reasons.
On examination, the patient was alert, conscious, and not tachypneic, with fair hydration status. Her blood pressure was 120/80 mm Hg, pulse 88 beats/min, respiratory rate 16/min, temperature 37.2 °C, capillary blood sugar 5.2 mmol/L, and oxygen saturation 100% under room air. No palpable thyroid swelling or lower limb deformities were observed upon inspection. Neurological examination revealed bilateral lower limb power of 2/5 with normal tone, reflex, and sensation. Systemic examinations were unremarkable.
Renal function test results revealed hypokalemia (2.5 mmol/L). Complete blood count, liver function, venous blood gas, and thyroid function tests were normal. Electrocardiography showed sinus rhythm without any hypokalemic changes. Therefore, common causes of hypokalemia, including gastrointestinal losses, hyperthyroidism, renal tubular acidosis, and chronic kidney disease, were ruled out.
Intravenous 1 g potassium chloride diluted in 100 mL l normal saline was infused over 1 hour, followed by an intravenous normal saline infusion (4 pints), with 1 g potassium chloride added to each pint, administered over 24 hours. Oral potassium chloride (1.2 g total dissolved solids [TDS]) and oral potassium chloride mist (15 mL TDS) were also added to the medication chart. Unfortunately, repeated renal function tests persistently showed hypokalemia (2.5 mmol/L) despite adequate potassium replacement therapy. Because no obvious causal factor was identified and the patient had no infective, thyroid, or gastrointestinal symptoms, quetiapine was suspected as the cause by the emergency team. The patient was then referred to the psychiatric team for further evaluation and management.
During our review, she was kempt, calm, cooperative, and had fair hygiene. She spoke relevantly and coherently. She described her mood as “okay.” Her affect was euthymic, broad-ranging, and nonlabile. She denied manic or depressive symptoms and claimed adherence to her medications. However, she was worried that she might lose her job because of her current immobilization. After a shared-decision discussion and considering her good psychiatric history, we reduced the dose of oral quetiapine IR to 100 mg every night because we suspected that the antipsychotic could have caused hypokalemia. Another intravenous potassium correction was administered, and her serum potassium level was planned to be re-evaluated.
On day 3, following the quetiapine dosage reduction, the patient’s potassium levels increased to 3.2 mmol/L and she was able to ambulate to the toilet without assistance. The muscle power in both lower limbs was 5/5 (Figure 1). She was discharged on day 3 of admission with oral quetiapine IR 100 mg every night, oral lamotrigine 75 mg every night, and a 3-day course of oral potassium supplements. A 1-week follow-up was scheduled to monitor her symptoms and serum potassium levels.
At the 1-week follow-up, her serum potassium level had normalized (Tables 1, 2). Given that her bipolar disorder was in remission, the oral quetiapine dose was maintained at 100 mg every night.
Written informed consent regarding the publication of clinical details related to this case report were obtained from the patient.
Discussion
Quetiapine is an atypical antipsychotic agent. It is a blocker of both serotonin 5HT2A and dopamine D2 receptors, which restores the balance of these hormones and manages mood and psychotic symptoms [13]. It also has a complex set of binding profiles with other neurotransmitter receptors, which explains why quetiapine may have effects beyond its original indications.
Common side effects include drowsiness, dizziness, headache, dry mouth, weight gain, urinary retention, parkinsonism, and constipation [13]. Electrolyte imbalances, such as hyponatremia and hypokalemia, are rare adverse drug reactions to quetiapine [14,15].
The mechanism by which antipsychotics, such as quetiapine, induce hypokalemia remains unclear. In general, three mechanisms may result in hypokalemia: excessive potassium loss, decreased potassium intake, and electrolyte influx into cells. One potential mechanism involves the drug’s effect on the sodium-potassium-adenosine triphosphatase (Na-K-ATPase) pump, leading to a transcellular shift of potassium ions into the cell, lowering potassium ion levels in the extracellular compartment [5]. Another possible mechanism involves potassium loss through the kidneys. Quetiapine is a dopamine receptor antagonist that enhances aldosterone release [16]. Aldosterone increases Na-K-ATPase in the basement membrane of the distal and collecting tubules of the glomerulus. This leads to increased sodium and water reabsorption from the urine and potassium excretion from the urine, resulting in hypokalemia (Figure 2).
In our case, quetiapine was suspected as the cause rather than lamotrigine, based on its pharmacokinetics. However, this patient was on the same dose of quetiapine for 3 years, and this is the first report of hypokalemia. She was 16 weeks pregnant and had hyperemesis, which resolved 2 weeks before the hypokalemia episode. Hyperemesis may cause volume depletion and metabolic alkalosis, which stimulate the renin-angiotensin-aldosterone system, leading to renal sodium retention and increased potassium excretion, contributing to hypokalemia [17]. This condition may worsen with poor food intake, which may trigger QIHPP.
To date, only a few cases of quetiapine-induced hypokalemia have been reported [15]. The hypokalemic episodes occurred early after initiating quetiapine, whereas in our case, QIHPP developed after 3 years of quetiapine initiation, probably triggered by pregnancy. In another case, hypokalemia occurred after the ingestion of a 750 mg quetiapine dose in a patient with schizophrenia who attempted to commit suicide. In contrast, in our case, hypokalemia developed after 3 years of using 150 mg of quetiapine [18].
Quetiapine is the first-line treatment for bipolar II disorder and is generally safe during pregnancy [13]. Nevertheless, managing QIHPP in a pregnant woman with bipolar II disorder was challenging. First, we had to balance the risk of relapse of bipolar symptoms against the benefits of antipsychotic dose adjustment. Second, as quetiapine is a dose-dependent drug, higher doses may be considered when an optimal response is not achieved at a lower dose [13]. A previous study suggested that the optimal dose of quetiapine during pregnancy is 500–700 mg twice a day [19]. As the patient’s mood was well controlled with quetiapine, we decided to reduce the dose from 150 to 100 mg every night rather than discontinuing it and switching to another type of antipsychotic, after mutual agreement. The patients’ mood and renal function were closely monitored during admission. To the best of our knowledge, this is the first reported case of QIHPP during pregnancy.
HPP is a rare neuromuscular disorder that occurs rarely in the general population, and even more rarely during pregnancy, with sporadic incidence [1]. One of the factors that trigger HPP is medication, which alters the physiological Na-K-ATPase pump and results in low serum potassium levels [5]. HPP is clinically diagnosed in the presence of non-infective acute flaccid paralysis, supported by biochemically low serum potassium levels [1]. It is a life-threatening condition that requires prompt evaluation and management. The mainstay of management is symptomatic therapy and treatment of the underlying cause [1,5]. In our case, despite the rapid correction of potassium levels and administration of oral potassium supplements, the condition did not improve, raising suspicion of QIHPP.
Following the reduction in quetiapine dosage, the serum potassium level gradually increased, and the patient regained her ability to walk and returned to work. This outcome supports our assessment of quetiapine as the cause. Finally, the serum potassium level normalized after 1 week of dose reduction during follow-up.
QIHPP is rare, particularly during pregnancy. This case emphasizes the importance of closely monitoring electrolyte levels, particularly potassium, in pregnant women receiving quetiapine to prevent the development of QIHPP. This case also contributes to our understanding of the potential adverse effects of quetiapine during pregnancy. It emphasizes the need for careful consideration and management of medication-related complications to ensure both maternal and fetal well-being.
Article Information
Conflict of interest
No potential conflict of interest relevant to this article was reported.
Funding
None.
Data availability
Not applicable.
Author contribution
Project administration: MHMP. Supervision: AAK, SID, ZMY. Writing–original draft: MHMP. Writing–review & editing: MHMP, AAK, SID, ZMY, WNWY. Final approval of the manuscript: all authors.
Figure. 1.
Timeline of the patient’s medications, symptoms, and intervention.
Figure. 2.
Mechanism of hypokalemia induced by quetiapine. ATPase, adenosine triphosphatase.
Table 1.
Blood test results on admission and follow-up
Reference interval
Day of presentation
Venous blood gas
pH
7.35–7.45
7.45
HCO3- (mmol/L)
20–29
26
Base (mmol/L)
–2.0 to 2.0
2.0
Lactate (mmol/L)
<2.0
0.8
Thyroid function test
Free T4 (pmol/L)
12–22
17.80
Thyroid-stimulating Hormone (mIU/L)
0.27–4.20
1.44
Table 2.
Potassium correction and management plan
Renal function test
Reference interval (mmol/L)
Day of presentation
Day 2 of admission
Day 3 of admission
Follow-up (1 wk after discharge)
Sodium
135–145
142
143
135
139
Potassium
3.5–5.1
2.5
2.5
3.2
3.8
Chloride
98–107
102
102
104
104
Urea
2.76–8.07
1.8
1.2
1.0
1.2
Creatinine
44–80
37
34
42
44
Magnesium
0.66–1.07
0.74
0.91
0.87
-
Phosphate
0.81–1.45
0.96
0.97
1.08
-
Calcium
2.15–2.5
-
-
2.24
-
Management
-
IV 1-g potassium chloride diluted in 100 mL normal saline run over 1 hour, 4 pints of IV normal saline with 1-g potassium chloride in each pint/24 hours, oral potassium chloride 1.2 g TDS, and oral mist potassium chloride 15 mL TDS.
The same treatment regime was continued and a referral to the psychiatry team was made. Quetiapine dose was reduced to 100 mg every night and lamotrigine was maintained at 75 mg every night.
Discharged with oral potassium chloride 1.2 g TDS, and oral mist potassium chloride 15 mL TDS for a 3-day duration.
-
IV, intravenous; TDS, total dissolved solids.
References
1. Phuyal P, Bhutta BS, Nagalli S. Hypokalemic periodic paralysis [Internet]. StatPearls Publishing; 2024 [cited 2024 Mar 18]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559178/
2. Nuzhnyi EP, Arestova AS, Rossokhin AV, Protopopova AO, Abramycheva NY, Suponeva NA, et al. Case report: a novel CACNA1S mutation associated with hypokalemic periodic paralysis. Front Neurol 2023;14:1267426.
8. Belzile M, Pouliot A, Cumyn A, Cote AM. Renal physiology and fluid and electrolyte disorders in pregnancy. Best Pract Res Clin Obstet Gynaecol 2019;57:1-14.
15. Yang Q, Guo X, Liu D. Hypokalemia caused by quetiapine and risperidone treatment in schizophrenia: a case report. Shanghai Arch Psychiatry 2018;30:204-6.
16. Romanova Z, Hlavacova N, Jezova D. Psychotropic drug effects on steroid stress hormone release and possible mechanisms involved. Int J Mol Sci 2022;23:908.
Quetiapine-induced hypokalemic periodic paralysis in a pregnant woman: a case report
Figure. 1. Timeline of the patient’s medications, symptoms, and intervention.
Figure. 2. Mechanism of hypokalemia induced by quetiapine. ATPase, adenosine triphosphatase.
Figure. 1.
Figure. 2.
Quetiapine-induced hypokalemic periodic paralysis in a pregnant woman: a case report
Reference interval
Day of presentation
Venous blood gas
pH
7.35–7.45
7.45
HCO3- (mmol/L)
20–29
26
Base (mmol/L)
–2.0 to 2.0
2.0
Lactate (mmol/L)
<2.0
0.8
Thyroid function test
Free T4 (pmol/L)
12–22
17.80
Thyroid-stimulating Hormone (mIU/L)
0.27–4.20
1.44
Renal function test
Reference interval (mmol/L)
Day of presentation
Day 2 of admission
Day 3 of admission
Follow-up (1 wk after discharge)
Sodium
135–145
142
143
135
139
Potassium
3.5–5.1
2.5
2.5
3.2
3.8
Chloride
98–107
102
102
104
104
Urea
2.76–8.07
1.8
1.2
1.0
1.2
Creatinine
44–80
37
34
42
44
Magnesium
0.66–1.07
0.74
0.91
0.87
-
Phosphate
0.81–1.45
0.96
0.97
1.08
-
Calcium
2.15–2.5
-
-
2.24
-
Management
-
IV 1-g potassium chloride diluted in 100 mL normal saline run over 1 hour, 4 pints of IV normal saline with 1-g potassium chloride in each pint/24 hours, oral potassium chloride 1.2 g TDS, and oral mist potassium chloride 15 mL TDS.
The same treatment regime was continued and a referral to the psychiatry team was made. Quetiapine dose was reduced to 100 mg every night and lamotrigine was maintained at 75 mg every night.
Discharged with oral potassium chloride 1.2 g TDS, and oral mist potassium chloride 15 mL TDS for a 3-day duration.
-
Table 1. Blood test results on admission and follow-up
, Azidah Abdul Kadir1*
