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Year : 2016  |  Volume : 36  |  Issue : 5  |  Page : 194-196

Using benzodiazepine detoxification and cognitive behavioral psychotherapy in the treatment of a patient with generalized anxiety disorder comorbid with high-dose zolpidem dependence

1 Department of Psychiatry, Armed Forces Tao-Yuan General Hospital, Taoyuan, Taiwan, China
2 Department of Psychiatry, National Defense Medical Center, School of Medicine, Tri-Service General Hospital, Taipei, Taiwan, China
3 Department of Psychiatry, Armed Forces Tao-Yuan General Hospital, Taoyuan; Department of Psychiatry, National Defense Medical Center, School of Medicine, Tri-Service General Hospital, Taipei, Taiwan, China

Date of Submission05-Feb-2016
Date of Decision13-Jun-2016
Date of Acceptance24-Jun-2016
Date of Web Publication24-Oct-2016

Correspondence Address:
Han-Wei Chou
No. 168, Zhongxing Rd., Longtan District, Taoyuan City 325, Taiwan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1011-4564.192831

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In recent years, literature has shown that zolpidem dependence is not uncommon in the clinical practice, but there is no standard guideline for treatment of zolpidem dependence. Benzodiazepine detoxification has been widely used for alcohol detoxification, which is also an inhibitory substance. We would like to share the experience of benzodiazepine detoxification and cognitive behavioral psychotherapy in a patient with high-dose zolpidem dependence comorbid with generalized anxiety disorder.

Keywords: Benzodiazepine detoxification, cognitive behavioral therapy, zolpidem dependence

How to cite this article:
Lu SH, Tzeng NS, Chou HW. Using benzodiazepine detoxification and cognitive behavioral psychotherapy in the treatment of a patient with generalized anxiety disorder comorbid with high-dose zolpidem dependence. J Med Sci 2016;36:194-6

How to cite this URL:
Lu SH, Tzeng NS, Chou HW. Using benzodiazepine detoxification and cognitive behavioral psychotherapy in the treatment of a patient with generalized anxiety disorder comorbid with high-dose zolpidem dependence. J Med Sci [serial online] 2016 [cited 2021 Feb 27];36:194-6. Available from: https://www.jmedscindmc.com/text.asp?2016/36/5/194/192831

  Introduction Top

Zolpidem, known as a nonbenzodiazepine hypnotic agent, is useful for treating insomnia. [1] It can bind to the α1-containing g-aminobutyric acid (GABA) A receptors with high affinity but low or no affinity to those α2, α3, or α5 GABA A receptors. [2] Due to its selectivity in binding, as we known, it has strong hypnotic effect with weak muscle relaxant, anxiolytic, and anticonvulsant effect. [3] The previous review studies revealed that zolpidem has low or minimal dependence risk epidemiologically. [4],[5] Nevertheless, growing evidence showed that zolpidem has the potential for abuse and dependence. [6]

A few studies mentioned the psychotherapy effect to treat zolpidem dependence, [7] and there was no standard guideline for treatment of zolpidem dependence. However, we have a lot of clinical experiences in the management of alcohol dependence, which is also an inhibitory substance dependence disorder. We would like to share the experience of treating a high-dose zolpidem dependence patient successfully with benzodiazepine detoxification and cognitive behavioral therapy (CBT), which is frequently used in the alcohol dependence.

  Case Report Top

Mr. H was a 23-year-old man who just graduated from a college. He had circadian phase shift during the college life and slept less and less since the 3 rd year in the college. He could only sleep 4-6 h since then and felt fatigue easily at day time. He went to one local clinic and the general practitioner prescribed zolpidem 10 mg before bedtime for him, but the hypnotic effects decreased several months later. He turned out to buy the zolpidem in illegal pharmacy dispensers because the previous general practitioner refused to prescribe higher dosage. Four months later, he had to use 60-100 mg zolpidem every night; moreover, he took it at daytime for relaxing. Soon, he found that he could not afford it because he had to take 60-100 tablets (10 mg per tablet) of zolpidem every single day. He came to our psychiatric department, and we prescribed lorazepam 2 mg and clonazepam 2 mg every night for replacing zolpidem. After 1 month therapy, Mr. H still used 40-60 tablets of zolpidem every day and was suggested admission.

After he was admitted under the diagnosis of zolpidem dependence without other substance abuse or dependence, zolpidem was stopped at once and we replaced it by lorazepam 2 mg q.i.d and clonazepam 4 mg every night. No withdrawal symptoms (tremor, palpitation, sweating, or seizure) emerged during hospitalization. We decreased 25% of the medication dosage every week, and the detoxification therapy was done smoothly 4 weeks later. Mr. H was discharged after completing the detoxification.

During the hospitalization, we found that he had been having difficulty in facing his father's authority with consequent anxiety and also met the diagnoses of generalized anxiety disorder and cluster B personality traits. After discussing with him and his family, we performed CBT instead of antidepressant for him. CBT was conducted 1 h weekly by the psychologist for him with a 10-week program to decrease his difficulty of facing authority, including his father in the outpatient department. Mr. H stopped any hypnotic after 2-year follow-up and could make effective communications with his father.

  Discussion Top

According to previous literature, there were different reasons causing zolpidem dependence. Some patients feel anxiolytic effect and others get strong sedation effect and euphoria. [8],[9] Some people might even misuse zolpidem to extremely high dose (400-1000 mg per day) which could cause death or seizure if withdrawal syndrome happened suddenly. [10] Obviously, there must be discreet reasons making some addictive people use hundreds of times of usual dosage of zolpidem.

It was reported that we could treat high-dose zolpidem dependence patients with long-acting benzodiazepines, such as diazepam. [11],[12] However, there was no standard guideline for treatment of zolpidem dependence. We used the alcohol abstinence experiences to treat zolpidem dependence, which is also a central nervous system depressant. During detoxification, benzodiazepines are used as substitution of cross-tolerant drugs to prevent progression from minor alcohol withdrawal symptoms to major ones. [13],[14] Lorazepam is one of the most frequently used benzodiazepines. The possible biomechanism is that zolpidem might lose its selectivity on GABA A receptor and exert the same pharmacological effects as classical benzodiazepines or alcohol. [15]

A few studies mentioned the psychotherapy effect to treat zolpidem dependence. [7] Darker et al. performed two meta-analyses showing that CBT plus taper is effective only in the short-term (3-month period) in reducing benzodiazepine use and insufficient evidence to support the use of motivational interviewing to reduce benzodiazepine use. [16]

We suggest that all the high-dose zolpidem dependence patients have to be admitted during abstinence due to safety issue. Besides the zolpidem dependence, it is necessary to find out whether the patient has psychiatric comorbidity, such as mood disorder, anxiety disorder, or other substance dependence. Combining medication and psychological therapy for an addictive patient is effective, and motivation interviewing can reduce the extent of substance abuse. [17],[18] In this case, we found some dynamic factors and forced Mr. H to face the anxiety and weakened his dependent behavior. We share this case with abstinence from zolpidem successfully under alcohol abstinence model, that is, combination of benzodiazepine detoxification and cognitive behavioral psychotherapy. We hope it is helpful for other similar patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Dang A, Garg A, Rataboli PV. Role of zolpidem in the management of insomnia. CNS Neurosci Ther 2011;17:387-97.  Back to cited text no. 1
Pritchett DB, Seeburg PH. Gamma-aminobutyric acidA receptor alpha 5-subunit creates novel type II benzodiazepine receptor pharmacology. J Neurochem 1990;54:1802-4.  Back to cited text no. 2
Holm KJ, Goa KL. Zolpidem: An update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Drugs 2000;59:865-89.  Back to cited text no. 3
Darcourt G, Pringuey D, Sallière D, Lavoisy J. The safety and tolerability of zolpidem - An update. J Psychopharmacol 1999;13:81-93.  Back to cited text no. 4
Hajak G, Müller WE, Wittchen HU, Pittrow D, Kirch W. Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: A review of case reports and epidemiological data. Addiction 2003;98:1371-8.  Back to cited text no. 5
Victorri-Vigneau C, Dailly E, Veyrac G, Jolliet P. Evidence of zolpidem abuse and dependence: Results of the French centre for evaluation and information on pharmacodependence (CEIP) network survey. Br J Clin Pharmacol 2007;64:198-209.  Back to cited text no. 6
Keuroghlian AS, Barry AS, Weiss RD. Circadian dysregulation, zolpidem dependence, and withdrawal seizure in a resident physician performing shift work. Am J Addict 2012;21:576-7.  Back to cited text no. 7
Bailey JE, Papadopoulos A, Seddon K, Nutt DJ. A comparison of the effects of a subtype selective and non-selective benzodiazepine receptor agonist in two CO (2) models of experimental human anxiety. J Psychopharmacol 2009;23:117-22.  Back to cited text no. 8
Heydari M, Isfeedvajani MS. Zolpidem dependence, abuse and withdrawal: A case report. J Res Med Sci 2013;18:1006-7.  Back to cited text no. 9
Gilbert DL, Staats PS. Seizure after withdrawal from supratherapeutic doses of zolpidem tartrate, a selective omega I benzodiazepine receptor agonist. J Pain Symptom Manage 1997;14:118-20.  Back to cited text no. 10
Rappa LR, Larose-Pierre M, Payne DR, Eraikhuemen NE, Lanes DM, Kearson ML. Detoxification from high-dose zolpidem using diazepam. Ann Pharmacother 2004;38:590-4.  Back to cited text no. 11
Chen SC, Chen HC, Liao SC, Tseng MC, Lee MB. Detoxification of high-dose zolpidem using cross-titration with an adequate equivalent dose of diazepam. Gen Hosp Psychiatry 2012;34:210.e5-7.  Back to cited text no. 12
Hoffman RS, Weinhouse G, Traub SJ, Grayzel J. Management of moderate and severe alcohol withdrawal syndromes. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. [Last accessed on 2015 Nov 15].  Back to cited text no. 13
Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA 1997;278:144-51.  Back to cited text no. 14
Huang MC, Lin HY, Chen CH. Dependence on zolpidem. Psychiatry Clin Neurosci 2007;61:207-8.  Back to cited text no. 15
Darker CD, Sweeney BP, Barry JM, Farrell MF, Donnelly-Swift E. Psychosocial interventions for benzodiazepine harmful use, abuse or dependence. Cochrane Database Syst Rev 2015;5:CD009652.  Back to cited text no. 16
Kelly TM, Daley DC, Douaihy AB. Treatment of substance abusing patients with comorbid psychiatric disorders. Addict Behav 2012;37:11-24.  Back to cited text no. 17
Smedslund G, Berg RC, Hammerstrøm KT, Steiro A, Leiknes KA, Dahl HM, et al. Motivational interviewing for substance abuse. The Cochrane Library 2011;(5):CD008063.  Back to cited text no. 18

This article has been cited by
1 Zolpidem abuse
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