Catatonia due to alprazolam withdrawal

Abstract

A 50-year-old man with multiple psychiatric comorbidities including major depressive disorder and general anxiety disorder presented to the emergency room (ER) with altered mental status, immobility and mutism. The patient was unresponsive to commands and unable to provide any history. In the ER he was given a provisional diagnosis of cerebrovascular accident (CVA). Vital signs on admission were stable. On physical examination, he exhibited grimacing, muscle rigidity and areflexia. Workup for CVA and infectious aetiology was unremarkable and the patient’s urine toxicology screen was negative. History from the patient’s family revealed that 4 days prior to presentation, the patient had discontinued his prescribed dose of alprazolam 1 mg four times per day. The patient was diagnosed with catatonia due to benzodiazepine withdrawal and had gradual return to baseline with administration of lorazepam 1 mg intravenous three times per day.

Background

Benzodiazepine withdrawal is known to cause a variety of symptoms, most commonly including anxiety, insomnia, irritability, nausea, palpitations and headache.¹ On rare occasion severe complications such as seizures or psychotic reactions have been reported.¹ Few cases of catatonia induced by discontinuation of benzodiazepines have been documented.^2–11 Here we present a patient with multiple psychiatric conditions including major depressive disorder and generalised anxiety disorder who presented to the emergency room (ER) with altered mental status, immobility and mutism. Eventually after extensive workup for cerebrovascular accident (CVA) and infectious aetiology, his signs were recognised to be part of a clinical syndrome suggesting catatonia and he was subsequently diagnosed with catatonia due to benzodiazepine withdrawal.

Catatonia constitutes a syndrome that occurs due to many differing aetiologies; benzodiazepine withdrawal remains a rare cause of catatonia that is not easily differentiated from other causes of catatonia.² Recognition of the signs of catatonia is important to guide clinicians toward the proper management of this condition and to save providers from extensive workup for other conditions. Since benzodiazepines are such widely prescribed medications, it is important for general practitioners to be aware of this entity.¹² Catatonia induced by benzodiazepine withdrawal remains a clinical diagnosis with pertinent history and responds well to benzodiazepines, which is the treatment of choice for this condition as well as other causes of catatonia.^{6 13} Electroconvulsive therapy (ECT) remains a good second-line option for treatment.^{2 13 14}

Case presentation

The patient was a 50-year-old obese man with hypertension, hyperlipidaemia, type 2 diabetes mellitus, major depressive disorder and general anxiety disorder who presented to the ER with altered mental status, immobility and mutism. The patient was unresponsive to verbal commands and unable to provide any history and was given a presumptive diagnosis of CVA. Vital signs on admission included the following: temperature of 97.8 degrees Fahrenheit, blood pressure of 154/88 mm Hg, pulse of 84 beats per minute, respiratory rate of 16 breaths per minute and an oxygen saturation of 99% on room air. On initial examination, the patient was found to be tremulous, somnolent and displayed extreme negativism. He exhibited bilateral facial droop and bilateral ptosis as well as grimacing and staring. Neurological examination showed diffuse hypertonicity and rigidity of all extremities as well as an upgoing Babinski reflex on his left side. He withdrew all extremities in response to pain and had normal strength in all extremities. Psychiatric examination showed an anxious appearing man with poor eye contact who was awake and obtunded. His orientation was unable to be assessed. His medical history was unattainable at initial presentation because the patient was mute and no family members were present at the bedside. Our workup for CVA and infectious aetiology was unremarkable and the result of patient’s urine toxicology screen was negative. History gathered from his family the day after admission indicated that 3 months prior to admission his psychiatrist prescribed him quetiapine 100 mg per day, escitalopram 20 mg per day and increased his dose of alprazolam from 0.25 mg four times per day to 1 mg four times per day. Further history from his family indicated that he was self-administering additional alprazolam tablets purchased without a prescription. Additional medications included losartan 25 mg per day, rosuvastatin 20 mg per day, metformin 500 mg two times per day and sitagliptin 100 mg per day. Per his family, he stopped taking all of his medications 4 days prior to admission, after which his condition started to deteriorate. He became increasingly withdrawn until he was found unresponsive and incontinent the morning of his admission.

Investigations

Laboratory investigations were largely unremarkable but showed the following as seen in table 1: hypokalaemia, elevated blood urea nitrogen: creatinine, hyperglycaemia, leucocytosis and thrombocytosis.

Table 1.

Workup performed by internal medicine team

Laboratory/diagnostic test	Result
Sodium	139 meq/L
Potassium	3.4 meq/L
Chloride	104 meq/L
CO2	21 meq/L
BUN	35 mg/dL
Creatinine	1.6 mg/dL
Glucose	341 mg/dL
Haemoglobin	14.9 mg/dL
Haematocrit	45.8%
White cell count	16.2×109/L
Platelets	459×109/L
CT brain	Negative
CTA head/neck	Negative
MRI brain	Negative
Echocardiogram	Negative
Electroencephalogram	Negative
Lumbar puncture	Negative
Urine toxicology screen	Negative
Blood cultures	Negative
HIV test	Negative
Rapid plasma reagin test	Negative

Differential diagnosis

Differential diagnoses include neuroleptic malignant syndrome, serotonin syndrome, CVA, major depressive disorder with psychotic features, selective serotonin reuptake inhibitor (SSRI) withdrawal and antipsychotic withdrawal.

Treatment

Due to the presumptive diagnosis of CVA, the patient was initially allowed to have permissive hypertension. His glucose level was controlled with sliding scale insulin. The patient was placed nil per os (NPO) due to his inability to swallow. Intravenous fluids with normal saline were started. Psychiatry was consulted on the fourth day post-admission. The patient met criteria for catatonia based on DSM-5 criteria, as the patient exhibited stupor, catalepsy, waxy flexibility, mutism, negativism, posturing and grimacing.¹⁵ The patient also met 10/14 screening criteria for catatonia based on the Bush-Francis Catatonia Rating Scale (no excitement, echopraxia/echolalia, stereotypy or mannerisms), with a severity score of 39/69.¹⁶ After establishing the diagnosis of benzodiazepine withdrawal-induced catatonia, the patient was started on lorazepam 1 mg intravenous three times per day, after which his mentation and motor function significantly improved. He was able to ambulate, swallow and had return of normal speech. He was continued on this treatment for 5 days in the hospital before being discharged on lorazepam 1 mg two times per day for 1 week and he was recommended to follow up with his psychiatrist.

Outcome and follow-up

The patient had rapid reversal of his condition after being treated with lorazepam for 1 day. He continued to improve clinically during the next 4 days of lorazepam treatment and was discharged on lorazepam 1 mg two times per day for 1 week. He was able to recall some of the events that occurred while he was in the catatonic state but did not have a good sense as to how long he had been in the hospital. The patient did not want to pursue inpatient psychiatric treatment and was recommended to follow-up with his outpatient psychiatrist for management and tapering of his benzodiazepine dose. He was seen 2 months later in outpatient clinic by a member of our team and was found to be doing well with no residual symptoms.

Discussion

The patient’s catatonia occurred secondary to rapid discontinuation of high-dose alprazolam. It was reasonable that this patient was initially worked up for CVA given his presentation of altered mental status, motor weakness and speech deficit. It is possible that some of the workup may have been avoided had we been able to obtain adequate history from family members at bedside, but they were not present the day he was admitted.

At least one dozen case reports of benzodiazepine withdrawal-induced catatonia have been recorded in the literature. Past case reports of benzodiazepine withdrawal-induced catatonia typically involve the rapid discontinuation of high-dose benzodiazepines that the patient has been taking for an extended period of time.² This was the case with our patient, who had been prescribed alprazolam for the past 15 years. Signs of catatonia usually arise within the first week after discontinuation.² Based on previous case reports, it seems that the middle aged and elderly are more prone to developing this side effect, although it has been documented in the paediatric population as well.^{3 4} As benzodiazepines are widely prescribed among both younger and older age groups, all providers should be aware of the effects of abruptly discontinuing high-dose benzodiazepines.¹² This is especially true with regards to the elderly population, who have a greater rate of chronic benzodiazepine use.¹²

The mechanism underlying benzodiazepine withdrawal-induced catatonia remains undetermined, but based on its response to benzodiazepine treatment, it is hypothesised to involve a decrease in gamma-Aminobutyric acid (GABA) activity in the central nervous system.^{2 6} Some commonly encountered signs of catatonia include immobility, rigidity, mutism, posturing, staring and negativism, among many others.^{14 17} A combination of these signs should prompt clinicians to consider a diagnosis of catatonia. Although the patient discontinued his other medications at the same time, including quetiapine and escitalopram, it is less likely that he was suffering a withdrawal episode from these drugs due to the response seen with benzodiazepine administration. Additionally, neuroleptic malignant syndrome and serotonin syndrome remained unlikely due to the lack of autonomic features that characterise these disorders as well as the patient’s stable vital signs.

Finally, providers should keep in mind that the treatment approach to catatonia secondary to benzodiazepine withdrawal is no different than treating other causes of catatonia and involves timely administration of benzodiazepines, with lorazepam being used most commonly.^{6 13} ECT has been shown to be of benefit if the patient does not respond to benzodiazepine administration or has features of malignant catatonia.^{2 13 14} Further evaluation by a psychiatrist may be recommended to determine the course of tapering of the benzodiazepine dose or to determine if the patient may need to be continued on a low dose of a benzodiazepine due to unsuccessful attempts to taper.

Learning points.

• Regardless of aetiology, catatonia should be suspected in a patient with any combination of immobility, rigidity, mutism, posturing, staring and negativism, among other signs.

• Although rare, providers should be aware of benzodiazepine withdrawal as a potential cause of catatonia and can be alerted to this by clues in the patient’s history.

• Catatonia secondary to benzodiazepine withdrawal is treated with benzodiazepine administration and shows good prognosis with appropriate identification and treatment.