This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Letter to the Editor

Alprazolam Withdrawal Delirium and Brief Reversible Psychosis: A Case Report

Ralph R. McKenzie Jr, OMS-III, MS; Praveen Madadi, MD; and Taral R. Sharma, MD, MBA

Published: October 15, 2014

Alprazolam Withdrawal Delirium and Brief Reversible Psychosis: A Case Report

To the Editor: Documented cases of sedative, hypnotic, or anxiolytic withdrawal delirium are highlighted by autonomic instability, as well as particular physical examination findings that characterize the suspected diagnosis. We present a patient with alprazolam withdrawal delirium, who lacks measurable signs of withdrawal, including but not limited to, significant examination findings of tremor, psychomotor agitation, or grand mal seizures.


Case report: Mr A, a 33-year-old Middle Eastern man, was brought to the emergency department in 2014 for the investigation of altered mental status following alprazolam withdrawal 2 days prior. Previously, he had been prescribed alprazolam 4 mg daily. Subsequent to completion of his prescription, Mr A exhibited expansive behavior and hypervigilance, with periods of collapsing to appear dead. He also had recurrent delusions involving harm to both family and self. Mr A reportedly admitted to abusing alprazolam, consuming 6-7 pills (total 14 mg) daily. Based on the recommendation of Mr A’s primary care physician, the family administered an extra dose of risperidone 2 mg, trazodone 100 mg, and buspirone 15 mg to help calm him, which was unsuccessful. He received alprazolam 2 mg in route to the hospital. After presenting to the emergency department, Mr A displayed altered consciousness; disorientation to person, time, and purpose; flight of ideas; poor judgment and insight; and bizarre, agitated, and delusional behavior but no suicidal ideation. He received regularly scheduled doses of medications in the emergency department.

Mr A’s vital signs were within normal limits; his physical examination was unremarkable. Results of extensive laboratory work, including electrolytes, renal and liver function tests, and complete blood counts, were within normal limits. The urine toxicology screen was negative for amphetamines, cannabis, hallucinogens, benzodiazepines, cocaine, opiates, and 3,4-methylenedioxymethamphetamine. His blood alcohol result was < 0.01%. Workup for sudden onset of altered mental status revealed no abnormal results. Initial psychiatric evaluation obtained in the emergency department revealed disorientation to person, time, and purpose; poor judgment and insight; poor concentration; poor recent and remote memory; and no suicidal or homicidal ideation. Mr A was placed on involuntary commitment and transferred to a psychiatric hospital for further management. A diagnosis of alprazolam withdrawal delirium and brief reversible psychosis (DSM-5 criteria for sedative, hypnotic, or anxiolytic withdrawal) was made.

Mr A denied any psychiatric history and was physically healthy. Family expressed that he had a history of suicidal ideation, homicidal ideation, and violence toward others. Other pertinent details relayed by family included a history of anxiety, depression, and previous inpatient psychiatric admissions. Prior to admission to the emergency department, Mr A’s father, the primary caregiver, stated that he noticed the alprazolam pill counts were inaccurate. Soon after, his son’s behavior became bizarre; specifically, Mr A demonstrated prolonged periods of wakefulness and verbalized threats to harm himself and his family.


Diagnostic features of sedative, hypnotic, or anxiolytic withdrawal are highlighted by 2 or more symptoms including "autonomic hyperactivity (eg, increases in heart rate, respiratory rate, blood pressure, or body temperature, along with sweating); a tremor of the hands; insomnia; nausea, sometimes accompanied by vomiting; anxiety; and psychomotor agitation. 1(p558) We present a case of reversible brief delirium and psychotic episode following withdrawal of alprazolam in an otherwise healthy young man. Our case shows that sedative, hypnotic, or anxiolytic withdrawal delirium can occur in the absence of cardinal withdrawal symptoms. Alprazolam withdrawal delirium and brief psychosis is reversible and can be treated with use of long-acting benzodiazepines. In our case, we used clonazepam to control symptoms of alprazolam withdrawal delirium and psychosis. According to PubMed, there are 3 published cases of alprazolam withdrawal delirium4-6; all 3 patients experienced autonomic instability in the presence of delirium and brief reversible psychosis.

In conclusion, physicians should be aware of the possibility of alprazolam withdrawal delirium and brief reversible psychosis in the absence of cardinal withdrawal symptoms as outlined in the DSM-5. Alprazolam withdrawal should be included in the differential diagnosis of conditions with sudden onset of delirium and brief psychotic symptoms in younger individuals experimenting with illicit substances despite a negative toxicology screen. An increased incidence of reversible brief psychotic episodes might be induced by the short-acting benzodiazepine alprazolam, which is undetected in routine urine or blood drug screen after only 24 hours of discontinuation.


1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth edition. Arlington, VA: American Psychiatric Publishing; 2013.

2. Licata SC, Rowlett JK. Abuse and dependence liability of benzodiazepine-type drugs: GABA(A) receptor modulation and beyond. Pharmacol Biochem Behav. 2008;90(1):74-89. doi:10.1016/j.pbb.2008.01.001 PubMed

3. O’ brien CP. Benzodiazepine use, abuse, and dependence. J Clin Psychiatry. 2005;66(suppl 2):28-33. PubMed

4. Zipursky RB, Baker RW, Zimmer B. Alprazolam withdrawal delirium unresponsive to diazepam: case report. J Clin Psychiatry. 1985;46(8):344-345. PubMed

5. Zalsman G, Hermesh H, Munitz H. Alprazolam withdrawal delirium: a case report. Clin Neuropharmacol. 1998;21(3):201-202. PubMed

6. Freiberger JJ, Marsicano TH. Alprazolam withdrawal presenting as delirium after cardiac surgery. J Cardiothorac Vasc Anesth. 1991;5(2):150-152. doi:10.1016/1053-0770(91)90329-R PubMed

Ralph R. McKenzie Jr, OMS-III, MS

Praveen Madadi, MD

Taral R. Sharma, MD, MBA

Author affiliations: Edward Via College of Osteopathic Medicine, Carolinas Campus, Spartanburg (Dr Sharma and Mr McKenzie); Patrick B. Harris Psychiatric Hospital, Anderson (Drs Madadi and Sharma); and University of South Carolina School of Medicine Greenville, Greenville (Dr Sharma), South Carolina.

Potential conflicts of interest: None reported.

Funding/support: None reported.

Published online: October 30, 2014.

Related Articles

Volume: 16

Quick Links:


Buy this Article as a PDF