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Sleep Medicine in Egypt :
Current & Future Perspectives
Dr.Tarek Asaad
Prof. of Psychiatry, Ain Shams University
Director of Psychophysiology & Sleep Unit
Chief Editor : Current Psychiatry ME Journal
Director of Cross Cultural Psychiatry Center
HISTORY OF SLEEP MEDICINE
• Berger (1929).
• Loomis & Harvey (1937).
• Kleitman & Aserinsky (1953).
• Dement & Kleitman (1957).
• Stanford Narcolepsy center (1964).
• Manual for scoring of sleep (1968).
• PSG (1975).
• ASDA (1977).
• ICSD -1 (1991).
• ICSD -2 (2005).
• ICSD-3 (Updated 2014).
UPDATES IN ASSESSMENT OF SLEEP
• PSG.
• MSLT, MWT,…
• Microstructure sleep analysis, CAP, A/D,..
• Actigraphy.
• Genetic studies: Narcolepsy?
• Brain imaging.
• Psychometric tools.
• Others.
Classification of sleep disorders :
• DSM-IV : phenomenological ?
• ICD-10 : phenomenological/ aetiological
• ICSD-1
• ICSD-1-Revised
• ICSD-II
• ICSD-II-Revised
• ICSD-3
-phenomenological / aetiological /
research / statistical ……
ICSD – II ( 2005 )
• INSOMNIA.
• SRBD.
• HYPERSOMNIAS OF CENTRAL ORIGIN.
• CR SLEEP DISORDERS.
• PARASOMNIAS ( NREM,REM,Others ).
• SR MOVEMENT DISORDERS.
• ISOLATED,N.VARIANTS,UNRESOLVED…
• OTHERS
• APPENDIX : Associated / Psychiatric….
ICSD-3 (Updated,2014)
• SIX CATEGORIES OF SLEEP DISORDERS :
1-Insomnia.
2-Sleep related Breathing Disorders.
3-Central Disorder Hypersomnolence.
4-CR Sleep Wake Disorders.
5-Parasomnia.
6-Sleep related Movement Disorders.
WHAT IS POLYSOMNOGRAPHY?
• HYPNOGRAM (E.E.G.,E.O.G.,chin EMG).
• RESPIRATORY EVENTS: airflow,chest ………
and abdominal effort, O2 saturation.
• LEG MOVEMENTS.
• OTHERS : E.C.G., body position,snoring
………..detector,tumescence detector,
………..capnograph…etc.
Portable PSG
• Easy
• More acclimatization
• Allow subjects to move
• Recorded on a memory card
• Sleep atmosphere = “natural”
EEG waves
A
P.S.G. VOCABULARY
• SLEEP CONTINUITY: TST , SL, SE,
………………arousal index, awakenings…
• SLEEP ARCHITECTURE :stage I,II,III and IV, SWS
%.
• REM PARAMETERS:
……………....REM%,REML,REMD,
…………...1st.REM duration and density.
• RESPIRATION: apnea index,RDI,O2
……………….desaturation.…
• PLMS Index.
• OTHERS.
PSG in different conditions
• Different stages of sleep
• Sleep apnea : Obstructive / Central
• Periodic limb movements
Management of INSOMNIA :
PHARMACOTHERAPY
A) SELF-MEDICATION (OTC DRUGS):
e.g. Anti-histaminics, Melatonin, Herbal
(Valerian, Kava, Natra dose, Passiflora)
B) NEWER BENZODIAZEPINES:
selective, short-acting, e.g.Estazolam..
C) BZ AGONISTS:
--- Zolpidem (Stilnox, Ambien) (MR)
--- Zaleplon (Sonata, Siesta) ( ext. release II)
--- Zopiclone (Ximovan )
--- Es-Zopiclone (Lunesta)
Management of INSOMNIA
D) Newer Ads:
--- SARIs: Nefazodone, Trazodone..
--- NASSA: Mirtazapine..
E) DRUGS recently present or in DEVELOPMENT :
--- Neuro-active steroids e.g.Ganaxolone
--- H3 Agonists
--- Orexin antagonists
(Belsomra (Suvorexant )recently approved in 8/2014).
--- Selective MT1/MT2-receptor agonists (Ramelteon
(Rozerem) TAK-375 , Agomelatine
( with 5HTantagonist ) …
F) Others:
--- Selective GABA-A agonist (Gaboxadol) (III)
--- GABA potentiator (Indiplone) IR-MR
--- SGRI (Tiagabine)
Management of INSOMNIA
• Early clinical trials :
- Other GABA A compounds eg neurosteroids
-Intra-nasal & subligual forms eg Zolpidem (I)
, Trizolam (II)…
-5HT2 a/c antagonists :
Eplivanserine / Emirtazapine (II)…
-Other MT agonists eg Enol 3 IPA
-Other psychotropics : Quetiapine, Olz…
Management of INSOMNIA
-H3-agonist , H1-antagonist
-CRF-antagonist (I)
-Adenosine enhancers ?
-Others : CB1,
…………. CCK ,
…………. Cytokines e.g. IL6 ,
…………. Neuropeptide S…….
Management of INSOMNIA
• PIPELINE INSOMNIA DRUGS-2018 :
1-GABA-A >>>> Zaleplon CR / EVT-201 (phaseII)
2-Orexin >>>> Filorexant / Leborexant (phase-III)
(Eisai) / ACT541468 (phase-II)…
3-H1 >>>> LY2624803
4-5HT2A >>>> ITI-007 / Lumateperone (phaseII)
5-Melatonin/5HT1A >>> Piromelatin
6-Prolonged release melatonin
7-Testimelteon ( Pediatric sleep & CR disruption?)
What is an “ideal” hypnotic ?
• Suitable for all types of insomnia
• Suitable for short & long term use
• NO : dependence / hangover / cognitive
dysfunction….
• Sleep promoting i.e. improves quality not
only quantity of sleep / improves SWS
• Minimal drug interaction & adverse effects
SuitabilityDaytime
sleepiness
Dependence
potential
PSG profileLong term useMechanismDrug
Short term use ,
especially if
associated with
anxiety
Yes
( depending on
T1/2)
YesREM & SWS
suppressant
Not
recommended
GABA-A
receptor / non-
selective
( alpha 1,2,3 &5)
BZs
1st line
treatment for
1ry insomnia
Less likily
( depending on
T1/2)
Less likelyLess REM
suppressant
Approved for
some
e.g.eszopiclone
GABA-A PAMs
( alpha 1
subunit)
Z-hypnotics
Under testingLessLessAs Z-hypnotics?Alpha 1
selective GABA-
APAM
Indiplon (IR
& CR)
Under testingLessLess??Selective delta-
GABA-A
receptor PAM
( modulate
extrasynaptic
GABA)
Gaboxadol
(Neuro-
steroids )
Especially for
sleep onset &
CR
LessNoNormalizing ?can be usedMT1 / MT2
agonist
Ramelteon
Chronic & 2ry
insomnia
+ / -NoSWS promotingCan be used5HT2 A & C
antagonists
AD
( Trazadone ,
nefazadone
Mirtazepine
)
SUITABILITYSLEEP
PROMOTING
EFFECT ( SWS)
DAYTIME
SEDATION
DEPENDENCE
Short term /
anxiety
-ve++++++GABA-ergic
Initial
insomnia, CR
disrupton…
++ / --veMelatonergic
Chronic /
secondary /
elderly..
++++ / --veSerotonergic
Secondary ,
situational , with
caution in elderly
+ / -+++-veHistaminergic
Management of INSOMNIA :
NON-PHARMACOLOGICAL
(A)-Behavioral & Cognitive Techniques
( SCT,SRT,relaxation, CBT…)
(B)-Light Therapy.
(C)-Transcranial – electro stimulation.
(D)- GOOD SLEEP HYGEINE :
( food,beverage,exercise,bed behaviour &
sleep atmosphere,sleep/wake habits…)
D.D.OF HYPERSOMNOLENCE
• SUBJECTIVE –LONG SLEEPERS.
• CIRCADIAN RHYTHM DISRUPTION.
• INSOMNIA ??
• PHYSICAL/ SUBSTANCE INDUCED.
• PRIMARY SLEEP DISORDER :
---Narcolepsy ---Sleep apnea
---PLMS ---Idiopathic.
• PSYCHIATRIC AETIOLOGY.
Management of OSAS
1) CPAP / BiPAP
2) Modafinil and Armodafinil.
3) Surgery ( UPPP operation & others )
4) New techniques in surgery.
5) Wt loss
6) Dental appliances
Updates in Management of OSAS
• The most recently FDA- approved treatment
for OSAS :
1-BiPAP.
2-Adaptive Servo-Ventilator (ASV).
3-Inspire Implant Device (Pulse generator).
4-Armodafinil.
Recent FDA-Approvals for Sleep Apnea
• In Spire ( Hypoglossal Nerve Stimulator /
UAW stimulator) ( FDA-2014)
• Expiratory Positive Airway Pressure (EPAP)
• First Implant Device for “Central Sleep
Apnea” –Phrenic nerve stimulator (FDA,
6/10/2017)
• Meridian PM oral appliance ( 21/3/2018)
• CURVE Positive Airway Pressure delivery
system (FRESCA Medical) (26/6/2018)
Treatments in Development for Sleep Apnea
• Dronabinol ( Cannabis-like) : centrally acting,
first curative, rather than symptomatic drug?
(Science Daily News, 30/11/2017)
• Provent Therapy = Nasal application to deliver
positive airway pressure
• Z Quiet >>> for snoring
• Other pillows, devices, implants….
UPDATES IN PHARMACOTHERAPY OF RLS
• 1) DOPAMINERGIC AGENTS:
-- L-Dopa/ Pramipexole/ Pergolide
-- Ropinirole/ Cabergoline (D2
agonist).
• 2) OPIOIDS: Propoxyphene
• 3) BZs: Clonazepam,Triazolam
• 4) ANTI-CONVULSANTS:
-- Gabapentin,Cz,Lamotrigen,..
• 5) IRON.
• 6) OTHERS (e.g. Botulinum toxins??)
Sleep Medicine in Egypt : Current Status
• Services :
• 1st Sleep Lab was in Early 1990s in Chest
Department, Ain Shams University, then in 1992,
Institute of Psychiatry, Ain Shams University
• Nowadays, nearly in most University Hospitals
(Cairo, Ain Shams, Alexandria, Tanta, Mansoura,
Menufia, Assiut..), Military Hospitals, some
Governmental Hospitals (Abbassia, Khanka..)
However, Sleep labs are NOT working properly
in most of them!
Sleep Medicine in Egypt : Current Status
• Private Sleep Study Centers are now
expanding, but , honestly speaking, with few
exceptions, most of them are just running
commercial sleep studies, without proper
service as sleep centers!
• Few years ago, Egyptian Sleep Association
was established, but still, its active role is far
beyond expectations!
Sleep Medicine in Egypt : Current Status
• Training & Certification :
-Training is very limited, only dependent on
irregular courses in some university
hospitals!
-No Certification is available till now!
-No standard system for training or certification
of poly-somnographic technologists !
-Number of qualified or professional sleep
specialists is VERY limited!
Sleep Medicine in Egypt : Current Status
• Researches:
-Despite lack of proper service & training, more
than 50 articles have been published in National
& International Journals, including chapters in
well-cited Books !
-Available psychometric tools, in Arabic !
• International Representation :
-Representatives for North Africa & Middle East in
WASM, had been selected from Egypt for the
last 8 years, with fair representation in WASM
meetings !
Sleep Medicine in Egypt : Current Status
• Available Treatments :
-Deficiency in drugs for most sleep disorders !
-CPAP machines are fairly available
-Deficiency in other non-pharmacological
treatment approaches, due to lack of
qualified sleep psychologists
Sleep Medicine in Egypt : Future Hopes
• Services & Training
• Certification
• Available Treatments
• Research & publications
THANK YOU

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Sleep Medicine in Egypt

  • 1. Sleep Medicine in Egypt : Current & Future Perspectives Dr.Tarek Asaad Prof. of Psychiatry, Ain Shams University Director of Psychophysiology & Sleep Unit Chief Editor : Current Psychiatry ME Journal Director of Cross Cultural Psychiatry Center
  • 2. HISTORY OF SLEEP MEDICINE • Berger (1929). • Loomis & Harvey (1937). • Kleitman & Aserinsky (1953). • Dement & Kleitman (1957). • Stanford Narcolepsy center (1964). • Manual for scoring of sleep (1968). • PSG (1975). • ASDA (1977). • ICSD -1 (1991). • ICSD -2 (2005). • ICSD-3 (Updated 2014).
  • 3. UPDATES IN ASSESSMENT OF SLEEP • PSG. • MSLT, MWT,… • Microstructure sleep analysis, CAP, A/D,.. • Actigraphy. • Genetic studies: Narcolepsy? • Brain imaging. • Psychometric tools. • Others.
  • 4. Classification of sleep disorders : • DSM-IV : phenomenological ? • ICD-10 : phenomenological/ aetiological • ICSD-1 • ICSD-1-Revised • ICSD-II • ICSD-II-Revised • ICSD-3 -phenomenological / aetiological / research / statistical ……
  • 5. ICSD – II ( 2005 ) • INSOMNIA. • SRBD. • HYPERSOMNIAS OF CENTRAL ORIGIN. • CR SLEEP DISORDERS. • PARASOMNIAS ( NREM,REM,Others ). • SR MOVEMENT DISORDERS. • ISOLATED,N.VARIANTS,UNRESOLVED… • OTHERS • APPENDIX : Associated / Psychiatric….
  • 6. ICSD-3 (Updated,2014) • SIX CATEGORIES OF SLEEP DISORDERS : 1-Insomnia. 2-Sleep related Breathing Disorders. 3-Central Disorder Hypersomnolence. 4-CR Sleep Wake Disorders. 5-Parasomnia. 6-Sleep related Movement Disorders.
  • 7. WHAT IS POLYSOMNOGRAPHY? • HYPNOGRAM (E.E.G.,E.O.G.,chin EMG). • RESPIRATORY EVENTS: airflow,chest ……… and abdominal effort, O2 saturation. • LEG MOVEMENTS. • OTHERS : E.C.G., body position,snoring ………..detector,tumescence detector, ………..capnograph…etc.
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  • 9. Portable PSG • Easy • More acclimatization • Allow subjects to move • Recorded on a memory card • Sleep atmosphere = “natural”
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  • 16. P.S.G. VOCABULARY • SLEEP CONTINUITY: TST , SL, SE, ………………arousal index, awakenings… • SLEEP ARCHITECTURE :stage I,II,III and IV, SWS %. • REM PARAMETERS: ……………....REM%,REML,REMD, …………...1st.REM duration and density. • RESPIRATION: apnea index,RDI,O2 ……………….desaturation.… • PLMS Index. • OTHERS.
  • 17. PSG in different conditions • Different stages of sleep • Sleep apnea : Obstructive / Central • Periodic limb movements
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  • 30. Management of INSOMNIA : PHARMACOTHERAPY A) SELF-MEDICATION (OTC DRUGS): e.g. Anti-histaminics, Melatonin, Herbal (Valerian, Kava, Natra dose, Passiflora) B) NEWER BENZODIAZEPINES: selective, short-acting, e.g.Estazolam.. C) BZ AGONISTS: --- Zolpidem (Stilnox, Ambien) (MR) --- Zaleplon (Sonata, Siesta) ( ext. release II) --- Zopiclone (Ximovan ) --- Es-Zopiclone (Lunesta)
  • 31. Management of INSOMNIA D) Newer Ads: --- SARIs: Nefazodone, Trazodone.. --- NASSA: Mirtazapine.. E) DRUGS recently present or in DEVELOPMENT : --- Neuro-active steroids e.g.Ganaxolone --- H3 Agonists --- Orexin antagonists (Belsomra (Suvorexant )recently approved in 8/2014). --- Selective MT1/MT2-receptor agonists (Ramelteon (Rozerem) TAK-375 , Agomelatine ( with 5HTantagonist ) … F) Others: --- Selective GABA-A agonist (Gaboxadol) (III) --- GABA potentiator (Indiplone) IR-MR --- SGRI (Tiagabine)
  • 32. Management of INSOMNIA • Early clinical trials : - Other GABA A compounds eg neurosteroids -Intra-nasal & subligual forms eg Zolpidem (I) , Trizolam (II)… -5HT2 a/c antagonists : Eplivanserine / Emirtazapine (II)… -Other MT agonists eg Enol 3 IPA -Other psychotropics : Quetiapine, Olz…
  • 33. Management of INSOMNIA -H3-agonist , H1-antagonist -CRF-antagonist (I) -Adenosine enhancers ? -Others : CB1, …………. CCK , …………. Cytokines e.g. IL6 , …………. Neuropeptide S…….
  • 34. Management of INSOMNIA • PIPELINE INSOMNIA DRUGS-2018 : 1-GABA-A >>>> Zaleplon CR / EVT-201 (phaseII) 2-Orexin >>>> Filorexant / Leborexant (phase-III) (Eisai) / ACT541468 (phase-II)… 3-H1 >>>> LY2624803 4-5HT2A >>>> ITI-007 / Lumateperone (phaseII) 5-Melatonin/5HT1A >>> Piromelatin 6-Prolonged release melatonin 7-Testimelteon ( Pediatric sleep & CR disruption?)
  • 35. What is an “ideal” hypnotic ? • Suitable for all types of insomnia • Suitable for short & long term use • NO : dependence / hangover / cognitive dysfunction…. • Sleep promoting i.e. improves quality not only quantity of sleep / improves SWS • Minimal drug interaction & adverse effects
  • 36. SuitabilityDaytime sleepiness Dependence potential PSG profileLong term useMechanismDrug Short term use , especially if associated with anxiety Yes ( depending on T1/2) YesREM & SWS suppressant Not recommended GABA-A receptor / non- selective ( alpha 1,2,3 &5) BZs 1st line treatment for 1ry insomnia Less likily ( depending on T1/2) Less likelyLess REM suppressant Approved for some e.g.eszopiclone GABA-A PAMs ( alpha 1 subunit) Z-hypnotics Under testingLessLessAs Z-hypnotics?Alpha 1 selective GABA- APAM Indiplon (IR & CR) Under testingLessLess??Selective delta- GABA-A receptor PAM ( modulate extrasynaptic GABA) Gaboxadol (Neuro- steroids ) Especially for sleep onset & CR LessNoNormalizing ?can be usedMT1 / MT2 agonist Ramelteon Chronic & 2ry insomnia + / -NoSWS promotingCan be used5HT2 A & C antagonists AD ( Trazadone , nefazadone Mirtazepine )
  • 37. SUITABILITYSLEEP PROMOTING EFFECT ( SWS) DAYTIME SEDATION DEPENDENCE Short term / anxiety -ve++++++GABA-ergic Initial insomnia, CR disrupton… ++ / --veMelatonergic Chronic / secondary / elderly.. ++++ / --veSerotonergic Secondary , situational , with caution in elderly + / -+++-veHistaminergic
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  • 40. Management of INSOMNIA : NON-PHARMACOLOGICAL (A)-Behavioral & Cognitive Techniques ( SCT,SRT,relaxation, CBT…) (B)-Light Therapy. (C)-Transcranial – electro stimulation. (D)- GOOD SLEEP HYGEINE : ( food,beverage,exercise,bed behaviour & sleep atmosphere,sleep/wake habits…)
  • 41. D.D.OF HYPERSOMNOLENCE • SUBJECTIVE –LONG SLEEPERS. • CIRCADIAN RHYTHM DISRUPTION. • INSOMNIA ?? • PHYSICAL/ SUBSTANCE INDUCED. • PRIMARY SLEEP DISORDER : ---Narcolepsy ---Sleep apnea ---PLMS ---Idiopathic. • PSYCHIATRIC AETIOLOGY.
  • 42. Management of OSAS 1) CPAP / BiPAP 2) Modafinil and Armodafinil. 3) Surgery ( UPPP operation & others ) 4) New techniques in surgery. 5) Wt loss 6) Dental appliances
  • 43. Updates in Management of OSAS • The most recently FDA- approved treatment for OSAS : 1-BiPAP. 2-Adaptive Servo-Ventilator (ASV). 3-Inspire Implant Device (Pulse generator). 4-Armodafinil.
  • 44. Recent FDA-Approvals for Sleep Apnea • In Spire ( Hypoglossal Nerve Stimulator / UAW stimulator) ( FDA-2014) • Expiratory Positive Airway Pressure (EPAP) • First Implant Device for “Central Sleep Apnea” –Phrenic nerve stimulator (FDA, 6/10/2017) • Meridian PM oral appliance ( 21/3/2018) • CURVE Positive Airway Pressure delivery system (FRESCA Medical) (26/6/2018)
  • 45. Treatments in Development for Sleep Apnea • Dronabinol ( Cannabis-like) : centrally acting, first curative, rather than symptomatic drug? (Science Daily News, 30/11/2017) • Provent Therapy = Nasal application to deliver positive airway pressure • Z Quiet >>> for snoring • Other pillows, devices, implants….
  • 46. UPDATES IN PHARMACOTHERAPY OF RLS • 1) DOPAMINERGIC AGENTS: -- L-Dopa/ Pramipexole/ Pergolide -- Ropinirole/ Cabergoline (D2 agonist). • 2) OPIOIDS: Propoxyphene • 3) BZs: Clonazepam,Triazolam • 4) ANTI-CONVULSANTS: -- Gabapentin,Cz,Lamotrigen,.. • 5) IRON. • 6) OTHERS (e.g. Botulinum toxins??)
  • 47. Sleep Medicine in Egypt : Current Status • Services : • 1st Sleep Lab was in Early 1990s in Chest Department, Ain Shams University, then in 1992, Institute of Psychiatry, Ain Shams University • Nowadays, nearly in most University Hospitals (Cairo, Ain Shams, Alexandria, Tanta, Mansoura, Menufia, Assiut..), Military Hospitals, some Governmental Hospitals (Abbassia, Khanka..) However, Sleep labs are NOT working properly in most of them!
  • 48. Sleep Medicine in Egypt : Current Status • Private Sleep Study Centers are now expanding, but , honestly speaking, with few exceptions, most of them are just running commercial sleep studies, without proper service as sleep centers! • Few years ago, Egyptian Sleep Association was established, but still, its active role is far beyond expectations!
  • 49. Sleep Medicine in Egypt : Current Status • Training & Certification : -Training is very limited, only dependent on irregular courses in some university hospitals! -No Certification is available till now! -No standard system for training or certification of poly-somnographic technologists ! -Number of qualified or professional sleep specialists is VERY limited!
  • 50. Sleep Medicine in Egypt : Current Status • Researches: -Despite lack of proper service & training, more than 50 articles have been published in National & International Journals, including chapters in well-cited Books ! -Available psychometric tools, in Arabic ! • International Representation : -Representatives for North Africa & Middle East in WASM, had been selected from Egypt for the last 8 years, with fair representation in WASM meetings !
  • 51. Sleep Medicine in Egypt : Current Status • Available Treatments : -Deficiency in drugs for most sleep disorders ! -CPAP machines are fairly available -Deficiency in other non-pharmacological treatment approaches, due to lack of qualified sleep psychologists
  • 52. Sleep Medicine in Egypt : Future Hopes • Services & Training • Certification • Available Treatments • Research & publications