1. Insomnia pharmacotherapy: Off-label antipsychotics
Flavio Guzmán, MD

2. Outline Quetiapine, Olanzapine Summary Receptor profile
Efficacy trials
Summary

3. Quetiapine

4. Quetiapine - Receptor affinity profile
Antipsychotic effects:
5-HT2A/D2 antagonism
Effects on other receptors
5-HT1A: partial agonism
H1: antagonist
Alpha 1: antagonist
Cheer, S. M., & Wagstaff, A. J. (2004). Quetiapine. CNS drugs, 18(3),

5. Quetiapine – Hypnotic dose
mg/day
Morin, A (2014) Off-label use of atypical antipsychotic agents for treatment of insomnia. Mental Health Clinician: March 2014-Trends in sedative-hypnotic therapy, Vol. 4, No. 2, pp

6. Quetiapine – Efficacy as hypnotic
Dx: Primary insomnia
Quetiapine 25 mg vs placebo for 2 weeks
Outcomes measured:
TST
Daytime alertness
Sleep satisfaction
Results:
Lack of statistical significance
Authors point out a trend to improvement in TST
Tassniyom, K.et al(2010). Quetiapine for primary insomnia: a double blind, randomized controlled trial. J Med Assoc Thai, 93(6),

7. Quetiapine- Efficacy Open pilot study N=18
Quetiapine 25 to 75 mg/day for 6 weeks
Improvement in several subjective and objective sleep parameters
Efficacy as hypnotic
Wiegand MH, Quetiapine in primary insomnia: a pilot study. Psychopharmacology(Berl). 2008;196:337–338.

8. Olanzapine

9. Olanzapine – Receptor affinity profile
Antipsychotic effect:
5-HT2A/D2 antagonism
Effects on other receptors:
H1: antagonist
M1: antagonist
Alpha 1: antagonist
5-HT2C: antagonist
Stahl, S M. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4thd ed. New York: Cambrigde University Press; 2013

10. Olanzapine – Hypnotic dose
mg/day
Morin, A (2014) Off-label use of atypical antipsychotic agents for treatment of insomnia. Mental Health Clinician: March 2014-Trends in sedative-hypnotic therapy, Vol. 4, No. 2, pp

11. Olanzapine – Clinical efficacy
RCTs in healthy volunteers
Significant increases in TST, SE and SWS
SSRI-resistant depressed patients
N= 12
Significant improvement in SE and increase in SWS
Morin, A (2014) Off-label use of atypical antipsychotic agents for treatment of insomnia. Mental Health Clinician: March 2014-Trends in sedative-hypnotic therapy, Vol. 4, No. 2, pp
Sharpley, A. L., et al (2005). Olanzapine increases slow wave sleep and sleep continuity in SSRI-resistant depressed patients. The Journal of clinical psychiatry, 66(4),

12. Consider antipsychotic side effects
Metabolic effects
Weight gain
Dyslipidemia
Orthostatic hypotension
Extrapyramidal symptoms

13. Conclusions Role of APs in primary insomnia: Unknown
Use as first-line agents should be discouraged
Available clinical evidence
May provide improvements noted in overall sleep quality, sleep efficiency and TST
Small and uncontrolled studies
Few report side effects

14. Conclusions Who may benefit:
Patients who already need antipsychotic treatment (schizophrenia, bipolar disorder)
Use of sedating antipsychotics can reduce polypharmacy