How to use melatonin in psychiatric disorders

1. Current evidences in
Psychiatric Disorders
DR ADARSH TRIPATHI, MD, MNAMS
ADDL PROFESSOR, DEPARTMENT OF PSYCHIATRY,
KING GEORGE’S MEDICAL UNIVERSITY, LUCKNOW

2. Limitations
 Studies – Few, Open level, Small sample
size, DB RCT?
 Heterogeneity
 Empirical
 Mix sample of children and adults

3. Outline
 Mapping the territory
 Indication
 Adverse effects
 Prescription guidelines

4. Endogenous Melatonin

5. Chronobiotic & Hypnotic

6. Pharmacological options for
treatment of sleep disorder
 BZDs
 Non-BZDs- Z drugs
 Antidepressants
 Antipsychotics
 Orexin Receptor Antagonist- Suvorexant
 Melatonin Receptor Agonists- Melatonin,
Ramelteon
 Miscellaneous- Pregabalin, Gabapentin,
Diphenhydramine, Cyclobenzaprine, Hydroxyzine

7. Exogenous melatonin (ExM)
 Clinical utility
 Sleep is a alternating pattern of neural activity,
controlled by homeostatic and circadian mechanism
 Homeostasis- length of prior wakefulness, controls
slow wave sleep
 Circadian mechanism- Timing of sleep onset and offset,
regulates distribution of REM phase Circadian phase
shifting effects (Chronobiological effect)
 Sleep promotion (Hypnotic effects)- Initiation,
maintenance and quality of sleep

8. ExM
 Limited bioavailability, pass BBB
 Highly variable pharmacokinetics due to
gastrointestinal CYP and first pass metabolism in
liver
 Substantial differences in bioavailability have
been reported (Upto 37 folds changes), females 2
times higher
 Pharmacological dose ranges 1-10mg/day

9. Indications
 Primary Insomnia
Especially in elderly, 3-5 mg/day
Utility is ? higher if endogenous melatonin level is low,
Melatonin Replacement Therapy

10.  Adult and children with primary insomnia , 2013
 Conclusion- Melatonin decreases sleep onset latency,
increases total sleep time and improves overall sleep.
The effects of melatonin on sleep are modest but do
not appear to dissipate with continued melatonin
use.
 Although the absolute benefit of melatonin compared
to placebo is smaller than other pharmacological
treatments for insomnia, melatonin may have a role
in the treatment of insomnia given its relatively
benign side-effect profile compared to these agents.

11. Indications
 REM Related parsomnia
 Melatonin can reduce rapid eye movement (REM) sleep
without atonia in REM sleep behavior disorder (RBD).
 Melatonin doses of 3–12 mg appear efficacious
 Minimal side effects may favor melatonin over clonazepam

12. Indications
 NREM related parasomnia
Melatonin and psychological therapies are promising treatment
options.

13. Indications
 Secondary insomnia in medically ill subjects
(Cerebrovascular Disease, Cardiovascular
Disease, DM, Asthma)
 Parkinsonism
 Alzheimer's disease- May be useful, dependent
on the severity of the symptoms and associated
problems
 Psychiatric Disorders in adults (Psychotic and
mood disorders)- +/-

14.  Although, some studies were positive, there were no
clear evidence of a therapeutic or prohylactic effect of
melatonin in depression or depressive symptoms

15. Indications
 Delirium
Treatment
Prevention ?
 Seasonal affective disorder
Treatment
Prevention?

16. Indications (cont.)
 Children with insomnia
 Severe learning difficulties
 ADHD
 Autism
 Intellectual disabilities
 Neurological disorders (tuberous sclerosis)
 ? Gadget use, life style related
 SOD, DSPD
 1-10 mg/day, 30-60 minutes before bedtime

17. Indications (cont.)
 Circadian rhythm sleep disorders
Delayed sleep-phase syndrome (often
misdiagnosed as sleep onset insomnia), 3
hours before bedtime
Jet lag- (Taken during the evening at the
local time of the new time zone)
Shift workers
Non-24 hours sleep/wake syndrome
(Blind individuals)

18. Anti-inflammatory, Oncostasis, endocrinal rhythm regulation, anti-
oxidant, Anti-aging, dermatology, wound healing, Bone repair etc.

19. Adverse effects
 Remarkably Well tolerated drug, even at very
high dosages, with various medical comorbidities
 Mild- less than 10% individuals
 Drowsiness, headache, confusion
 Nausea, vomiting, cramps
 Caution- Autoimmune disease
 Children- long term effects are not studies
extensively, (Sexual maturation, immune
functions)

20. Dose and route of
administration
 Oral- 1-10 mg/day (3-6 mg, 5-10 mg)
 Sublingual – 0.3 to 0.9 mg (2-3 puffs)
 30-60 minutes before bedtime
 ~3 hours before bedtime (DSPD)
 No interaction with medications, food,
psychoactive substances

21. Caution
 Patients using BZDs
 Sleep disorders with psychiatric
comorbidity
 Psychoactive Substance dependence
 Chronic pain
 Severe insomnia

22. Melatonin BZD/Zs
MOA Chronobiotic Sedative/Hynotics
Response Gradual and
accumulative
Rapid and more
predictable
Efficacy Modest Good
Dependence potential None High
Tolerance - +++
Withdrawal - +++
Next day drowsiness - ++
Dizziness, Gait
instability
+/- ++
Confusion +/- ++
Impaired cognition +/- ++
High dose
Amnesia, anesthesia
- ++
Long Term side effects Negligible ++

23. Sleeping is no mean art: for its sake one must
stay awake all day.
~Friedrich Nietzsche
Thank you