Abrupt Discontinuation of Alprazolam and Cognitive Style in Patients With Panic Disorder

Abstract

The objective of this study was to ascertain the relationship of alprazolam plasma levels and an anxiety-prone cognitive style to the characteristics and severity of early withdrawal after abrupt discontinuation of alprazolam in 26 patients with panic disorder. After 8 and 9 weeks of fixed-dose treatment, patients were hospitalized for 24 hours. On 1 admission, ordered at random, treatment was maintained; on the other, placebo was substituted double blind. The Anxious Thoughts and Tendencies questionnaire was administered before treatment. Alprazolam plasma levels were measured 7 times on the day after each admission. Before each blood sampling, the Profile of Mood States and performance tasks were administered, and vital signs were recorded. On the day after abrupt discontinuation of alprazolam, Profile of Mood States anxiety, depression, fatigue, and confusion increased; vigor and elation decreased; speed on the digit symbol substitution task improved; and systolic blood pressure increased substantially over time. High Anxious Thoughts and Tendencies scores were related specifically to more anxiety. Our findings (1) confirm that dysphoric mood, fatigue, low energy, confusion, and elevated systolic blood pressure are part of the early syndrome of withdrawal from alprazolam in patients with panic disorder, notably as the drop in plasma levels approaches 50%; (2) indicate a psychomotor deficit persisting beyond dose stabilization; (3) suggest that an anxiety-prone cognitive style measurable before undertaking treatment may be a risk factor for more severe anxiety upon discontinuation; and (4) provide a rationale for applying cognitive behavior therapy during benzodiazepine taper.

A Fatal Case of Benzodiazepine Withdrawal

“…The early stage of benzodiazepine withdrawal can show increased irritability, rebound anxiety, apprehension, headache, anorexia, insomnia, perceptual disturbances, and autonomic dysregulation, whereas psychosis, delirium, myoclonus, and seizure appear later. [2][3][4][5][6][7][8][9][10][11] Symptoms of alprazolam withdrawal usually begin within 72 hours of the last dose; however, some symptoms have been described as early as 14 hours after discontinuation. 2 Others report symptoms beginning as late as 4 days after the last dose, 12 similar to the current case.…”

“…6 Seizures secondary to alprazolam withdrawal are well described despite being one of the less common symptoms of alprazolam withdrawal. 2,3,6,7,9,12,15 Patients usually suffer grand mal tonic-clonic seizures; however, 1 case of atypical-absence nonconvulsive seizure reported by Olnes et al 15 presented with a waxing and waning state of confusion and bizarre behavior. In a recent review of FDA phase II and III clinical trials by Alper et al, 16 alprazolam was associated with increased incidence of seizure when compared with placebo.…”

Cognitive style, alprazolam plasma levels, and treatment response in panic disorder

“…Therefore, an anxiety-prone cognitive style seemed a potential predictor of poor response to the treatment of panic disorder. During a study designed to assess the early effects of abrupt discontinuation of alprazolam in patients with panic disorder [Uhlenhuth et al, 2006a], we had the opportunity to explore an anxietyprone cognitive style as a potential predictor of poor response during the 8-week alprazolam treatment phase before discontinuation. We measured this cognitive style at baseline with the Anxious Thoughts and Tendencies (AT&T) questionnaire [Ganellen et al, 1986;Uhlenhuth et al, 2002a].…”