Benzodiazepinones

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a case series, one man and two women aged 59−74 years were described, who developed drug withdrawal symptoms following discontinuation of alprazolam, clonazepam, diazepam or reduction of lorazepam dose [routes, duration of treatment to reaction onset not stated; not all outcomes stated].

Case 1: A 64-year-old man developed drug withdrawal symptoms following discontinuation of treatment with alprazolam and clonazepam. The man, who had generalised anxiety disorder, panic disorder and opioid use disorder, was receiving clonazepam 6mg, alprazolam 2mg and zolpidem 10mg every day over the past 30 years for generalised anxiety disorder and panic disorder. However, he developed acute withdrawal symptoms related to alprazolam and clonazepam (benzodiazepines) withdrawal after losing his provider and slow taper with clonazepam was commenced. However, he experienced episodic anxiety and feelings of loss, indicating drug withdrawal symptoms related to clonazepam tapering. Additionally, his COVID-19 quarantine conditions contributed to worsening of his anxiety and protracted drug withdrawal symptoms. Thus, he started receiving methadone that led to sustained remission. He also developed sedative hypnotic use disorder related to lprazolam, zolpidem and clonazepam.

Case 2: A 74-year-old woman developed drug withdrawal symptoms following discontinuation of treatment with diazepam and lorazepam. The woman, who had generalised anxiety disorder, was receiving diazepam 40mg, lorazepam 2mg and zolpidem for the past 5 years for generalised anxiety disorder. She was also taking dexamfetamine [dextroamphetamine] for fatigue. However, her provider closed the practice that led to discontinuation of diazepam and lorazepam (benzodiazepines). Subsequently, she developed drug withdrawal symptoms diazepam and lorazepam (benzodiazepines) withdrawal. Over a period of two years, her medications were tapered using clonazepam and dexamfetamine was stopped. However, she reported fearfulness, loneliness, insomnia and chronic pain while receiving clonazepam 0.5 mg/day, indicating drug withdrawal symptoms related to clonazepam tapering. Her COVID-19 quarantine conditions contributed to worsening of drug withdrawal symptoms. Therefore, she started receiving treatment with mirtazapine that resulted into improvement of the withdrawal symptoms.

Case 3: A 59-year-old woman developed drug withdrawal symptoms following reduction of lorazepam dose while. The woman, who had post-traumatic stress disorder, major depressive disorder, alcohol use disorder, cannabis use disorder and cocaine use disorder, was receiving lorazepam 2 mg/day for major depressive disorder. Subsequently, the dose of lorazepam decreased by 25% every 3−4 weeks. However, she developed insomnia and depression, indicating drug withdrawal symptoms following reduction of lorazepam dose and her provider unable to administer naltrexone long acting injectable. Thus, mirtazapine was started to manage symptoms of insomnia and depression.