Although improvements to drug formulations and alternative administration routes, like extended or controlled release oral products, orally disintegrating tablets (ODTs), and long-acting injectables can help to improve patient adherence, they are not beneficial to all patient populations or suitable for some medications. While few studies have evaluated alternative administration routes for these drugs, the review authors did locate the following:
Inhalation: Inhalation is an ideal administration route due to the large surface area of the lungs, the permeability of vasculature, and rapid absorption. Loxapine is the only psychotropic medication approved for oral inhalation and must be administered in a healthcare facility enrolled in the Risk Evaluation and Mitigation Strategy program.
Intranasal: Although this route can have rapid absorption, there is also a potential for irritation. One small study found that haloperidol was promising for intranasal administration.
Buccal: Because buccal tissue is less readily permeable and results in slower absorption, medications with a long half-life and wide therapeutic range are targets for this administration. A case report of amitriptyline tablets crushed and dissolved in a patient's mouth to promote buccal absorption was found in the review, along with a study on selegiline ODT administration for buccal absorption in which MAO-A inhibition was similar to a transdermal delivery system.
Sublingual: Sublingual mucosa is relatively permeable and can result in rapidly absorbed but less sustained drug delivery. Asenapine is the only FDA-approved sublingual dosage form for any antipsychotic or antidepressant medication. Case studies have reported on administration of sublingual olanzapine, haloperidol, alprazolam, and fluoxetine in terminally ill patients and patients with gastrointestinal complications.
Transdermal: Benefits of transdermal administration include avoidance of first-pass metabolism, controlled drug delivery over time, and modification of sites of drug delivery. Selegiline is the only FDA-approved antidepressant with transdermal delivery formulation. Case reports of transdermal delivery of fluoxetine, amitriptyline, and doxepin have been published, although transdermal administration of haloperidol and chlorpromazine have been less successful in small studies.
Rectal: This method can have less predictable absorption but reduced first-pass metabolism. There are no commercially available rectal preparations for antidepressants or antipsychotics but case reports have described rectal administration of trazodone, amitriptyline via supposititories, doxepin, and fluoxetine.
The authors conclude that development of alternative formulations could assist clinicians in treating patients with psychiatric disorders who cannot tolerate oral or injectable forms of medication and prevent discontinuation of drug therapy due to administration barriers.