Tables for:
Consensus on Drug Treatment, Definition and Diagnosis for Insomnia

[Clin Drug Invest 23(6):351-385, 2003. © 2003 Adis Data Information BV]

Table I. Pharmacokinetics of benzodiazepines and non-benzodiazepine hypnotics

Generic nameOnset of actionHalf-life (h)Active metabolites
Benzodiazepine anxiolytics
AlprazolamFast to intermediate12 15No
ChlordiazepoxideIntermediate8 28Yes
ClonazepamSlow18 50No
Dipotassium clorazepateFast48Yes
DiazepamFast20 50Yes
EstazolamFast10 24No
LorazepamIntermediate10 20No
OxazepamIntermediate to slow5 20No
TemazepamIntermediate to slow9.5 12No
Benzodiazepine hypnotics
TriazolamFast1.7 5No
MidazolamFast1 4No
LoprazolamFast5 8Yes
LormetazepamFast12 20No
FlunitrazepamFast19 22Yes
FlurazepamFast40 114Yes
QuazepamFast25 41Yes
Non-benzodiazepine hypnotics
ZolpidemFast1.5 4.5No
ZopicloneFast3 6Yes

Table II. Effects of hypnotics on sleep architecture (! = decrease, ! = increase, !! = no significant effects)

DrugHalf-lifePSG in healthy individualsACP effectsaRebound and residual effectsbLatencyTotal sleep timeDelta sleepREMSleep qualityComments
Benzodiazepine hypnotics
TriazolamShortc<pathol. ACP rateRebound insomnia!!!!!! stage 2
MidazolamShortccRebound insomnia!!!!!!stage 2
BrotizolamShortccRebound insomnia!!!!!! stage 2
LoprazolamIntermediateccRebound insomnia!!!!!! stage 2
LormetazepamIntermediateccRebound insomnia!!!!!!stage 2
FlunitrazepamIntermediate! slow wavesc< latencies in MSLT. No rebound!!!!!!stage 2
FlurazepamLong! slow wavesc< latencies in MSLT. No rebound!!!!!! stage 2
NitrazepamLongcc< latencies in MSLT. No rebound!!!!!!stage 2
QuazepamLongcc< latencies in MSLT. No rebound!!!!!! stage 2
Non-benzodiazepine hypnotics
ZolpidemShortNo or few changes<pathol. ACP rateNo rebound or residual effects!!!!!!!! waking
ZopicloneShortNo or few changes<pathol. ACP rateNo rebound!!!!!!!! waking
ZaleplonShortNo changescNo rebound or adverse effects!!!!cc

aAlternating cyclic pattern: pseudo-periodic activation phenomenon of slow sleep characterised in the EEG by limited duration waves that can appear spontaneously or after waking stimuli. <ACP means that these compounds decrease the ACP index.
bConfirmed by the multiple sleep latency test ( MSLT). < = decreases.
cNo conclusive data.

Table III. Undesired effects and complications of treatment with hypnotics at therapeutic dosesa

Drug/chemical class (half-life)Hangover effectRebound insomniaToleranceDependence/ abuseComment
Benzodiazepine hypnotics
Triazolam/Benzodiazepine (short: <6h)0++++++++Triazolam may have fewer respiratory depressive effects than other benzodiazepines. No more than 0.25mg should be administered to avoid increasing adverse CNS effects
Loprazolam/Benzodiazepine (medium: 6 24h)+/++++/+++++/+++++More marked hangover effect at higher doses
Flurazepam/Benzodiazepine (long: >24h)+++0b+++Avoid in elderly, since increased risk of falls and fractures
Non-benzodiazepine hypnotics
Zolpidem/Imidazopyridine (short)0+00Hangover effect and tolerance can occur with supratherapeutic doses and/or very long-term treatment
Zopiclone/Cyclopyrrolone (short)+++++++Doses >7.5mg increase adverse effects without improving efficacy
Zaleplon/Pyrazolopyrimidine (short)c0after 5 wkscNo sedation seen on following day, 5 6.5h after 10mg taken at midnight, with no significant psychomotor changes

aRefer also to tableIV and section 4.6.
bWith long half-life benzodiazepines, rebound insomnia is uncommon and appears late.
cNo conclusive data are available in the consulted literature.
0 = no effect; + = mild effect; = no tolerance observed until that time; ++ = moderate effect; +++ = severe effect.

Table IV. Effects of hypnotics on memory and psychomotor performance

DrugMemoryPsychomotor performance
Night of administrationFollowing day
Short-acting benzodiazepine hypnotics[76]!!!!
Intermediate-acting benzodiazepine hypnotics[76]!! or !!!
Long-acting benzodiazepine hypnotics[76]!!!
Zolpidem[51]!! or !!!!!
Zopiclone[50,51,66]!!!!! or !

! = worsening; !! = no significant effects.

Table V. Effects of hypnotics on respiratory and cardiac function

DrugCOPD and compensated restrictive pulmonary diseasesTreated OSASCardiac function
Short-acting benzodiazepine hypnoticsa!!?
Intermediate-acting benzodiazepine hypnotics!!?
Long-acting benzodiazepine hypnotics!!?

aIn mild to moderate stable diseases, triazolam does not impair oxygen saturation
COPD = chronic obstructive pulmonary disease; OSAS = obstructive sleep apnoea syndrome; ! = Worsening; ? = inconclusive or missing data; !! = no changes.

Table VI. Hypnotic efficacy, untoward effects and tolerability of hypnotics in elderly patients

DrugEfficacyUntoward effects or complicationsTolerability
Benzodiazepine hypnoticsGood!Good
ZopicloneGood!! or !Good

! = increased; !! = no significant effects.

Table VII. Types of insomnia according to different classifications: International Classification of Sleep Disorders (ICSD), International Classification of Diseases, 9th and 10th editions (ICD-9 and ICD-10, respectively), and Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)

1a. Adjustment sleep disorder307.41-0Transient disorder of initiating or maintaining sleep307.41Non-organic insomniaF51.0  
1b. Psychophysiological insomnia307.42-0Persistent disorder of initiating or maintaining sleep307.42Non-organic insomniaF51.0Primary insomnia307.4
Other insomnia780.52Disorder of initiating or maintaining sleepG47.0  
5b. Central sleep apnoea syndrome780.51-0Insomnia with sleep apnoea780.53Sleep apnoeaG47.3Breathing-related sleep disorder780.5
5c. Central alveolar hypoventilation syndrome780.51-1      
5f. Altitude insomnia289Altitude insomnia289Other altitude effectsT20.2  
7a. Short sleeper307.49.0      
8e. Fatal familial insomnia337.9Fatal familial insomnia337.9Other degenerative diseasesG31Insomnia due to ...indicate medical pathology780.X
11. Idiopathic insomnia780.52.7Other insomnia780.52Disorder of initiating or maintaining sleepG47.0Primary insomnia307.4