Intranasal Olanzapine: New Drug-Device Product for Acute Agitation?

Agitation is seen in various psychiatric disorders including bipolar disorder and schizophrenia. The use of intramuscular and intravenous medications is common in hospital settings for the management of agitation. These routes of administration are invasive and hence have limitations. 

Inhaled loxapine is the only available intranasal antipsychotic for treatment of acute agitation.

  • This medication carries the risk of inducing bronchospasm, so use is limited for patients with pulmonary diseases. 

In the pursuit of the next intranasal antipsychotic for the management of acute agitation, a new product (INP105) has been studied recently.


  • New drug-device combination product
  • Contains: powder formulation of olanzapine + Precision Olfactory Delivery (POD) technology.
  • POD delivers olanzapine to the vascular-rich upper nasal space.
  • Addition of POD technology is known to improve the bioavailability of olanzapine without giving intravenous or intramuscular injections.
Here is a picture of the research device that was used in the SNAP 101 study.

Picture Courtesy of Stephen Shrewsbury, MD, Chief Medical Officer, Impel NeuroPharma, Inc.

The efficacy of INP105 was examined in the following phase 1, active and double-blind placebo comparator–controlled, ascending-dose, 2-period, incomplete-block, 1-way crossover study:

  • Period 1: randomized to single doses of Olanzapine IM (5 or 10 mg) or Olanzapine ODT (10 mg).
  • Period 2: then randomized to 1 of 3 doses (5 mg, 10 mg, or 15 mg) of INP105 or placebo.

(A) Olanzapine Absorption:

  • fastest after INP105 administration.

Median Tmax:

  • INP105 (depending on dose): 9.5 to 15 minutes
  • Olanzapine IM 5 mg: 20 minutes
  • Olanzapine ODT 10 mg: 120 minutes.

==> reaching median peak plasma levels 5 minutes earlier than other formulations.

(B) Effects as measured with VAS (visual analog scale), ACES (Agitation/Calmness Evaluation Scale), and DSST (Digit Symbol Substitution Test): 

  • INP105 5 mg effects were comparable to those with Olanzapine IM 5 mg
  • earlier onset for INP105 10 mg and 15 mg
  • greater effects than placebo and Olanzapine ODT. 

(C) Treatment-Emergent Adverse Events:

  • NP105 5 mg: 80%
  • NP105 10 mg: 66.7%
  • NP105 15 mg: 75%
  • Olanzapine IM 5 mg: 90%
  • Olanzapine IM 10 mg: 100%
  • Olanzapine ODT 10mg: 83.3%


Most common adverse events:

  • Dizziness
  • Hypotension
  • Orthostatic symptoms


  • Shrewsbury SB, Hocevar-Trnka J, Satterly KH, Craig KL, Lickliter JD, Hoekman J. The SNAP 101 Double-Blind, Placebo/Active-Controlled, Safety, Pharmacokinetic, and Pharmacodynamic Study of INP105 (Nasal Olanzapine) in Healthy Adults. J Clin Psychiatry. 2020;81(4):19m13086. Published 2020 Jun 30. (pubmed)



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