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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 nonbenzodiazepine hypnotics


Generic name

Onset of action

Half-life (h)

Active metabolites

Fast to intermediate

12 15

No

Intermediate

8 28

Yes

Clonazepam

Slow

18 50

No

Dipotassium clorazepate

Fast

48

Yes

Diazepam

Fast

20 50

Yes

Estazolam

Fast

10 24

No

Lorazepam

Intermediate

10 20

No

Oxazepam

Intermediate to slow

5 20

No

Prazepam

Slow

70

Yes

Intermediate to slow

9.5 12

No

Triazolam

Fast

1.7 5

No

Midazolam

Fast

14

No

Brotizolam

Fast

Yes

Loprazolam

Fast

58

Yes

Lormetazepam

Fast

12 20

No

Flunitrazepam

Fast

19 22

Yes

Flurazepam

Fast

40 114

Yes

Nitrazepam

Fast

24

Yes

Quazepam

Fast

25 41

Yes

Fast

1.5 4.5

No

Benzodiazepine anxiolytics
Alprazolam
Chlordiazepoxide

Temazepam
Benzodiazepine hypnotics

Non-benzodiazepine hypnotics
Zolpidem

Zopiclone

Fast

36

Yes

Zaleplon

Fast

No

Table II. Effects of hypnotics on sleep architecture (! =


decrease, ! = increase, !! = no significant effects)

Drug

Rebou
nd
and
PSG in
residu
healthy ACP
al
individu effect effects Laten
b
Half-life
als
sa
cy

Tot
al
sle Delt
Slee
ep
a
p
tim sle RE quali Comme
e
ep M
ty
nts

Benzodiazepine hypnotics
Triazolam

Short

Midazolam

Short

Brotizolam

Short

Loprazola
m

Intermed
iate

<path Rebou
ol.
nd
ACP insomn
rate
ia

! stage 2

Rebou
nd
insomn
ia

!stage 2

Rebou
nd
insomn
ia

! stage 2

Rebou
nd
insomn
ia

! stage 2

Lormetaze Intermed
pam
iate

Rebou
nd
insomn
ia

!stage 2

Flunitrazep Intermed
am
iate

! slow
waves

<
latenci
es in
MSLT.
No

!stage 2

reboun
d
Flurazepa
m

Long

! slow
waves

<
latenci
es in
MSLT.
No
reboun
d

! stage 2

Nitrazepa
m

Long

<
latenci
es in
MSLT.
No
reboun
d

!stage 2

Quazepam

Long

<
latenci
es in
MSLT.
No
reboun
d

! stage 2

Non-benzodiazepine hypnotics
Zolpidem

Short

No or <path
No
few
ol. reboun
changes ACP
d or
rate residu
al
effects

!!

!!

! waking

Zopiclone

Short

No or <path
No
few
ol. reboun
changes ACP
d
rate

!!

!!

! waking

Zaleplon

Short

No
changes

No
reboun
d or
advers
e
effects

a Alternating 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.
b Confirmed by the multiple sleep latency test ( MSLT). < = decreases.
c No conclusive data.

Table III. Undesired effects and complications of treatment


with hypnotics at therapeutic dosesa

Drug/chemical class
(half-life)

Reboun
d
Hangov insomni Toleranc Dependenc
er effect
a
e
e/ abuse

Comment

Benzodiazepine hypnotics
Triazolam/Benzodiazepin
e (short: <6h)

+++

+++

++

Midazolam

+++

+++

++

Brotizolam

+++

+++

++

Loprazolam/Benzodiaze
pine (medium: 6 24h)

+/++

++/+++

++/+++

++

Lormetazepam

+/++

++/+++

++/+++

++

Flunitrazepam

+/++

++/+++

++/+++

++

Flurazepam/Benzodiaze
pine (long: >24h)

+++

0b

++

Triazolam may
have fewer
respiratory
depressive
effects than
other
benzodiazepin
es. No more
than 0.25mg
should be
administered to
avoid
increasing
adverse CNS
effects

More marked
hangover effect
at higher doses

Avoid in
elderly, since
increased risk
of falls and

fractures
Nitrazepam

+++

0b

++

Quazepam

+++

0b

++

Non-benzodiazepine hypnotics
Zolpidem/Imidazopyridin
e (short)

Hangover
effect and
tolerance can
occur with
supratherapeuti
c doses and/or
very long-term
treatment

Zopiclone/Cyclopyrrolon
e (short)

++

++

++

Doses >7.5mg
increase
adverse effects
without
improving
efficacy

No sedation
seen on
following day, 5
6.5h after
10mg taken at
midnight, with
no significant
psychomotor
changes

Zaleplon/Pyrazolopyrimid
ine (short)

after 5
wks

a Refer also to tableIV and section 4.6.


b With long half-life benzodiazepines, rebound insomnia is uncommon and appears
late.
c No 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
Drug

Memory

Psychomotor

Night of
administration

Following
day

performance

Short-acting benzodiazepine
hypnotics[76]

!!

Intermediate-acting
benzodiazepine hypnotics[76]

! or !!

Long-acting benzodiazepine
hypnotics[76]

!! or !

!!

!!

Zopiclone[50,51,66]

!!

!! or !

Zaleplon[40]

!!

!!

!!

Zolpidem[51]

! = worsening; !! = no significant effects.

Table V. Effects of hypnotics on respiratory and cardiac


function
COPD and compensated
restrictive pulmonary
diseases

Treated
OSAS

Cardiac
function

Short-acting
benzodiazepine hypnoticsa

Intermediate-acting
benzodiazepine hypnotics

Long-acting
benzodiazepine hypnotics

Zolpidem

!!

!!

!!

Zopliclone

!!

!!

Zaleplon

?!!

?!!

Drug

a In 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

Efficacy

Untoward effects or
complications

Tolerability

Benzodiazepine
hypnotics

Good

Good

Zolpidem

Good

!!

Good

Zopiclone

Good

!! or !

Good

Zaleplon

Good

!!

Good

Drug

! = 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 (DSMIV)
ICSD

ICD-9
name

1a. Adjustment
sleep disorder

code

name

ICD-10
code

name

DSM-IV
code

name

code

307.41- Transient 307.4 Non-organic F51.0


0
disorder of 1
insomnia
initiating or
maintainin
g sleep

1b.
307.42- Persistent 307.4 Non-organic F51.0 Primary 307.4
Psychophysiologic 0
disorder of 2
insomnia
insomnia
al insomnia
initiating or
maintainin
g sleep
Other
insomnia

780.5 Disorder of G47.


2
initiating or 0
maintaining
sleep

5b. Central sleep


apnoea syndrome

780.51- Insomnia 780.5 Sleep


0
with sleep 3
apnoea
apnoea

5c. Central
alveolar
hypoventilation
syndrome

780.511

5f. Altitude
insomnia

289

7a. Short sleeper

307.49.
0

8e. Fatal familial


insomnia

337.9

11. Idiopathic
insomnia

780.52. Other
7
insomnia

Other
altitude
effects

G47. Breathing 780.5


3
-related
sleep
disorder

Altitude
insomnia

289

T20.2

Fatal
familial
insomnia

337.9 Other
G31
degenerativ
e diseases

Insomnia 780.
due
X
to ..
.indicate
medical
patholog
y

780.5 Disorder of G47. Primary 307.4


2
initiating or 0
insomnia
maintaining
sleep