TABLE B-6 IOM Summary of Studies Investigating Possible Unique Anxiogenic Effects During Administration of Halcion, and Anxiogenic or Insomnia-Promoting Effects with Withdrawal

Source

Type

Population

Number of Subjects

Drug and Dose

Duration

Outcome/Comments

Greenblatt et al. (1989)

Placebo, active drug

Bedtime

16

12

13

11

Placebo

Flurazepam 15 mg

Temazepam 15 mg

Halcion 0.25 mg

Single dose

Halcion only hypnotic to initially slow thinking speed. Similar increase above baseline for all but flurazepam at 24 h. Increased thinking speed could be related

Pinnock et al. (1985)

Placebo, diazepam

Medical

28

30

29

Placebo

Diazepam 10 mg

Halcion 0.25 mg

Single dose presurgery

VAS anxiety diazepam, but not Halcion acutely anxiolytic; no difference 6 h postawakening.

Kales et al. (1986)

Placebo, quazepam; sleep laboratory

Insomnia

6

6

Placebo, Halcion 0.25 mg Placebo, Quazepam 15 mg

2 days then 14 days; 3-day withdrawal

Carryover sedation with quazepam. (SWS suppression) rebound insomnia with halcion. Rate of "excitatory" effects reported to be 0.5 for Halcion vs. 0.14 for quazepam. Withdrawal-related anxiety/panic for Halcion ("excitatory effects": anxiety, hyperarousal, inability to concentrate, paranoid ideation, nightmares). Not clear that quazepam group was followed long enough to adequately rule out rebound (loss of quazepam).

Hegelbach-Feller et al. (1988)

Placebo, midazepam; crossover

Insomnia

30

Placebo

Halcion 0.5 mg

Midazepam 15 mg

11 days

More rebound decline in sleep quantity and restlessness during night with Halcion.

Lee and Lader (1988)

Placebo, quazepam; crossover

Bedtime

12

Placebo

Quazepam 15 mg

14 days

Mild rebound anxiety more clear with quazepam. Withdrawal-related onset of metallic taste with Halcion.

Fleming et al. (1990)

Zopiclone

Insomniacs

24

24

Zopiclone 7.5 mg

Halcion 0.25 mg

21 days

In first week of withdrawal subjective agitation equivalent: 3 zopiclone, 2 Halcion.

Mouret et al. (1990)

Zopiclone

Elderly insomniacs

10

Halcion 0.25 mg

Zopiclone 7.5 mg

15 days.

Withdrawal insomnia during treatment with zopiclone but not Halcion; 3 days for Halcion vs. 2 days for zopiclone. Did not see "extremely marked" withdrawal as described by Kales et al. (1976, 1983).

Elie et al. (1990)

Zopiclone

Elderly insomniacs

44

Halcion 0.125 mg

Halcion 0.25 mg

Zopiclone 5 mg

Zopiclone 7.5 mg

3 weeks

After withdrawal from Halcion, increased sleep latency and decreased sleep soundness end quality for 3 days. No significant change with zopiclone.



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