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Year : 2018  |  Volume : 5  |  Issue : 2  |  Page : 165-166

A case report of preferential effectiveness of clonazepam over lorazepam in the management of a case of alprazolam withdrawal

Department of Psychiatry, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India

Date of Web Publication27-Dec-2018

Correspondence Address:
Dr. Arghya Pal
Department of Psychiatry, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jgmh.jgmh_25_18

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Benzodiazepines (BZDs) remain the mainstay in the management of withdrawal arising out of BZD use disorders. The choice of detoxifying agent is determined by the duration of action and also by the metabolic properties of the drug. Very rarely, we consider the chemical properties of the drug that we choose, though occasionally that may have profound clinical impact on the outcome. In this case report, we present the case of alprazolam withdrawal that was ineffectively managed by lorazepam and finally salvaged by the use of clonazepam. The chemical properties of the molecules involved and their clinical importance in the decision-making process have been subsequently reviewed.

Keywords: Alprazolam, clonazepam, lorazepam, withdrawal

How to cite this article:
Saxena V, Victor R, Pal A. A case report of preferential effectiveness of clonazepam over lorazepam in the management of a case of alprazolam withdrawal. J Geriatr Ment Health 2018;5:165-6

How to cite this URL:
Saxena V, Victor R, Pal A. A case report of preferential effectiveness of clonazepam over lorazepam in the management of a case of alprazolam withdrawal. J Geriatr Ment Health [serial online] 2018 [cited 2023 Mar 31];5:165-6. Available from:

  Introduction Top

Alprazolam is arguably the most common psychotropic medication and certainly the most common benzodiazepine (BZD) that is prescribed worldwide. It is also the most common BZD that is encountered in casualty patients presenting with medication misuse and also has the highest fatality rate among all the BZDs. Alprazolam specifically has received a lot of attention because it is known to have a high abuse liability and has potential to cause severe and complicated withdrawal symptoms. This potential stems from the fact that alprazolam has high potency, rapid absorption, short half-life, and low lipophilicity.[1] BZD use in the geriatric population requires special supervision because of higher propensity to develop dependence and also risk of inadvertent complications such as reversible cognitive deficits, motor incoordination, and risk of falls.[2] BZDs can further paradoxically worsen symptoms such as low mood, anxiety, and insomnia, often leading the patients to enter a vicious cycle, finally leading to BZD dependence. In this light, we hereby present the case of a critical patient who presented with alprazolam dependence in withdrawal, which showed us the importance of appropriate choice of BZD for the purpose of detoxification.

  Case Report Top

A 59-year-old male was admitted in the intensive care unit with delirium for 3–4 days following sudden cessation of alprazolam 6 mg/day that he was using for 6 years. The patient was also diagnosed with dilated cardiomyopathy 5 years back being treated conservatively. Further evaluation revealed that the patient consumed alcohol for 12 years in a dependent pattern till 6 years before admission when the patient required admission due to alcohol withdrawal-related complications. Any history suggestive of major neurocognitive disorder was ruled out from history. On being admitted for alcohol use disorder, patient underwent a treatment for the same. However, soon after being discharged, the patient now started using alprazolam and within few weeks attained dependent pattern in alprazolam use.

On admission, the patient presented with disorientation to time, place, and person, with associated excessive perspiration, poor sleep, and short-lasting psychotic symptoms, including auditory hallucinations, delusion of persecution, and reference. The Clinical Institute Withdrawal Assessment Scale-BZDs (CIWA-BZD) rating on admission was 16. The patient was started on 12 mg of lorazepam for control of the withdrawal symptoms, which was increased to 16 mg following inadequate control. After 3 days, following some improvement (CIWA-BZD-11), lorazepam was decreased from 16 to 14 mg, which led to increase in confusion and disorientation, decrease in his sleep, and increase in agitation. On the 6th day, the patient suffered from a seizure, probably due to withdrawal (CIWA-BZD-15). To rule out other possibilities, a noncontrast computed tomography scan of the brain and serum electrolyte levels done were found to be normal. To control his seizure, the dose of lorazepam was increased. Thereafter, it was decided to substitute his lorazepam with clonazepam. The patient was shifted to 6 mg clonazepam, following which his withdrawal symptoms gradually subsided. From the 7th day onward, it was noted that the patient's psychomotor activity decreased and his sleep improved (CIWA-BZD on day 12 was 4). His dose of clonazepam was gradually decreased, and he was discharged on 4.5 mg of clonazepam [Figure 1].
Figure 1: Graphical representation of the dosage of lorazepam and clonazepam (in mg/day) and the scores on Clinical Institute Withdrawal Assessment Scale-Benzodiazepines

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  Discussion Top

Alprazolam is a triazolobenzodiazepine. The exact significance of the triazole moiety is not clear. However, it is known to have unique effects on the receptor binding potential of the molecule, which is postulated to contribute to the short half-life of the drug.[3] Due to this property, it is rapidly metabolized by alpha-hydroxylation of the methyl substituent on the triazole ring. The subsequent metabolite is rapidly inactivated by glucuronidation, resulting in its short half-life.[1] There are other aspects of the triazole ring that is still unclear. Questions still remain about its putative contribution to the higher potency of the molecule.

The proper use of other BZD in the management of alprazolam withdrawal is a matter of intrigue. Usually, we manage the withdrawal symptoms with a long-acting BZD such as chlordiazepoxide or diazepam.[4] In cases when we suspect, liver dysfunction agents such as lorazepam or oxazepam are also used. However, previous reports are there to suggest that chlordiazepoxide or diazepam may be ineffective in treating alprazolam withdrawals.[5] There is one other case report as well of lorazepam being unable to control alprazolam withdrawal.[6] It is suggested that owing to the triazole moiety, alprazolam has unique binding to the BZD receptors, which probably explains the inadequate response of the nontriazole BZD such as diazepam or lorazepam. Clonazepam has been shown to be efficacious in managing such patients, probably owing to the presence of the triazole moiety.[7]

Our report points to the fact that alprazolam use is highly prevalent. Owing to its propensity to cause complicated withdrawals, the chances of encountering patients with alprazolam withdrawal are extremely high. Most prevalent guidelines advocate the use of long-acting BZD in managing the cases of alprazolam withdrawal. However, owing to the presence of unique triazole ring, we have to be careful in choosing our detoxifying agent and clonazepam may be the drug of choice. In our routine practice, when we encounter mixed withdrawal states or withdrawals of lesser severity, we may escape using a nontriazole BZD. However, in critical patients with severe withdrawals like ours, we have to be very specific regarding our choice. Proper history-taking and rigorous clinical examination should be stressed in such critical cases.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Ait-Daoud N, Hamby AS, Sharma S, Blevins D. A review of alprazolam use, misuse, and withdrawal. J Addict Med 2018;12:4-10.  Back to cited text no. 1
Singh S, Sarkar S. Benzodiazepine abuse among the elderly. Geriatr Ment Health 2016;3:123. Available from: [Last accessed on 2018 Nov 04].  Back to cited text no. 2
Juergens S. Alprazolam and diazepam: Addiction potential. J Subst Abuse Treat 1991;8:43-51.  Back to cited text no. 3
Gautam S, Jain S, Batra L, Lodha P. Clinical practice guide lines for management of barbiturates and benzobiazipines Dependence. Indian J Psychiatry 2006;1:66-83.  Back to cited text no. 4
Risse SC, Whitters A, Burke J, Chen S, Scurfield RM, Raskind MA, et al. Severe withdrawal symptoms after discontinuation of alprazolam in eight patients with combat-induced posttraumatic stress disorder. J Clin Psychiatry 1990;51:206-9.  Back to cited text no. 5
Sachdev G, Gesin G, Christmas AB, Sing RF. Failure of lorazepam to treat alprazolam withdrawal in a critically ill patient. World J Crit Care Med 2014;3:42-4.  Back to cited text no. 6
Patterson JF. Withdrawal from alprazolam dependency using clonazepam: Clinical observations. J Clin Psychiatry 1990;51Suppl:47-9.  Back to cited text no. 7


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