A case of etizolam dependence.

Etizolam is a thienodiazepine anxiolytic which is said to have lower dependence potential than other benzodiazepines. We report a case of etizolam dependence in a young male with social anxiety disorder and moderate depression. This case report highlights the fact that the same caution be exercised while prescribing etizolam with respect to its potential to cause dependence as with any other benzodiazepine.

Introduction

The dependence and abuse potential of benzodiazepines is well recognized.[1] This has resulted in the search for novel anxiolytics devoid of such potential.[1] Etizolam is a thienodiazepine anxiolytic and is said to have low tolerance and dependence liability than benzodiazepines.[2] We report a case of etizolam dependence in a young male with Social Anxiety disorder to highlight the abuse and dependence potential of etizolam.

Case Report

We present a case of 23-year-old male who presented to the outpatient department with 3 years history of feeling anxious in social situations, feeling scrutinized and focus of attention in social situations and marked avoidance behavior. For past few months the patient also had pervasive sadness of mood, lack of interest, ideas of hopelessness and worthlessness. The patient was diagnosed as Social Anxiety disorder with Moderate Depressive episode. The patient was earlier on treatment with paroxetine up to 12.5 mg, escitalopram 10 mg and sertraline up to 50 mg/day before coming in our contact. The patient was also taking etizolam up to 2.5 mg/day.

There was a history of progressive increase in dose of etizolam taken by the patient. Initially, he was prescribed etizolam at dose of 0.25 mg/day. Initially, he would take on S.O.S. basis when he would face any social situation. Gradually, he started taking etizolam regularly, and his intake increased to 2.5 mg/day over a period of 1 month. The patient would have palpitations, tremulousness, impaired sleep, would feel agitated on taking lower dose of etizolam resembling the characteristic benzodiazepine withdrawal symptoms. He would also have craving for etizolam. He continued to self-medicate himself with etizolam even after the physician had stopped prescribing the same. Hence, the patient was found to have tolerance and compulsion to take the substance and experienced withdrawal symptoms for etizolam and thus fulfilled the criteria for dependence syndrome as given by the International Classification of Diseases-10 (ICD-10) Classification of Mental and Behavioral Disorders.[3] The patient was prescribed paroxetine up to 25 mg/day with clonazepam 3 mg/day. The patient showed marked improvement in depression and social anxiety but continued to take etizolam. He continued his etizolam intake despite being aware that etizolam might be harmful to him and is not to be taken on long term basis. Impression diagnosis of etizolam dependence was thus made.

Discussion

Although a thienodiazepine, etizolam is clinically regarded as a benzodiazepine because of its mode of action via benzodiazepine receptor.[4] The potency and efficacy of etizolam for allosteric potentiation of γ-Aminobutyric acid evoked Cl− current mediated by recombinant α1 β2 γ2S receptors is lower than those of classical benzodiazepines which has been proposed as a reason for a reduced liability of etizolam for the development of tolerance and dependence.[2] The claim of low dependence potential of etizolam has led to it being prescribed liberally in the markets where it is available for a long time, like Japan.[4] This myth is being realized now after it has become the most frequently prescribed benzodiazepine there.[5] Perhaps, this is the reason for its nonavailability in developed markets of United States of America and Europe.[6] It was approved for use in India on October 29, 2007 and perhaps because of late entry, remains one of the least used benzodiazepine in India.[67]

Etizolam has been occasionally associated with skin lesions and blepharospasm.[89] However, the literature about its abuse and dependence potential is sparse. The rapid relief of anxiety by ultra-short-action and feeling of anxiety after the action wears off may lead to dependence by both positive and negative behavioral reinforcement.

The case described in this article developed dependence on etizolam after experiencing relief in his anxiety symptoms with its therapeutic use. Five (a, b, c, d, and f) out of six criteria for establishing dependence syndrome (F13.2) as per ICD-10, against a diagnostic threshold of three were present in this case in context of etizolam use. Hence, a case of etizolam dependence is established beyond doubt. Paroxetine has proven efficacy for social anxiety disorder, depressive episode and for tapering benzodiazepine use[10] and successfully resulted in remission of former two conditions in this patient. However, the patient was finding it difficult to taper etizolam use and dropped out of follow-up.

This case report highlights the fact that the same caution be applied while prescribing etizolam with respect to dependence potential as for any other benzodiazepine. In the case of development of dependence, treatment of the primary disorder, substitution with longer-acting benzodiazepines, Selective Serotonin Reuptake Inhibitors and psychotherapy are various options that can be exercised.