Nick Longhi, PharmD Candidate

With pharmacy being an ever-growing and evolving profession, health care providers must take a step back and look ahead. In the past century alone, the pharmacy profession has grown drastically by pushing the boundaries. Pharmacists, pharmacy technicians, researchers, and other health care professionals must keep pushing these boundaries to continue advancing the field of medicine and providing effective patient care.

Drug pricing is a highly debated topic at every level of discussion. From patient and provider discussion to debates at the political level, drug prices will always be discussed. Drug pricing policies and acts must be highly considered to achieve a balance between patient access and funding for research/innovation while negating unintentional consequences and monopoly formation of the market.

The use of technology can be greatly beneficial to all, including both patients and providers. The use of smart devices (smartphones, watches, etc) can alert patients to refills, recalls, and information regarding medications in an extremely convenient and timely manner.

Smartwatches, in particular, use bioelectrical signals that can provide continuous health monitoring, which can notify the patient, emergency medical services, and health care providers immediately. Smartwatch devices have recently gained traction and attracted the attention of app developers in patients are affected by epilepsy.

Certain smartwatch devices use an integrated bioelectric scanner and accelerometer in the device to alert a care giver and record when a seizure is occurring. 

The FDA has also recently approved using technology to deliver treatment for children with attention-deficit hyperactivity disorder (ADHD) using a prescription-only video game (The EndeavorRx Device) alongside traditional ADHD treatment. This is a primary example of delivering digital therapeutics through the growing use of technology in medicine.

The World Health Organization also recognizes the potential of technology integration in patient services by stating that smart devices have a broad reach and acceptance by the public. The widespread availability of these smart devices is a call to app developers, IT personnel, and technology companies to traverse this uncharted territory to develop health care delivery systems that flawlessly integrate with the patient care process.

Technology and software systems can also integrate with the administrative side of pharmacy as well. Software that benefit pharmacies in ways such as automating tedious processes and streamlining the chain of distribution of medications, which both can greatly benefit the pharmacy and patients.

Personalized medicine is a unique field revolving around the world of pharmacy. It provides an opportunity for pharmacists to apply their knowledge of medicine to deliver treatment that is tailored to the specifics of each patient.

Advancements in pharmacogenomics can be applied to the patient care model, which can focus on specific individualizing treatment based on specific patient factors. Understanding the use of patient genetic testing and factors may provide health care providers with critical information that can deliver targeted and effective therapy for a specific disease state.

In a survey assessing community pharmacists knowledge and confidence regarding pharmacogenomics, a large percentage responded that they were not confident in their knowledge and recommendations regarding the human genome.

Since the conclusion of this survey, the Accreditation Council for Pharmacy Education (ACPE) has added a genomics element to pharmaceutics didactic programs so that new graduates will be practice ready.

With pharmacy and pharmacogenomics being a dynamic and ever-expanding field, perhaps in the future there will be a large call for pharmacists specializing in extensive knowledge of pharmacogenomics. Continuing education programs can also help introduce/reinforce findings in pharmacogenomics, advancements of pharmacogenomics, and places in practice to apply a pharmacist’s knowledge of pharmacogenomics to direct patient centered care.

s a PharmD Candidate at Marshall University’s School of Pharmacy, anticipated to graduate in spring 2021.

 is the founder and CEO of STACK, a pharmacy compliance management software, and serves as preceptor for a virtual Advanced Pharmacy Practice Experiential Rotation for specialty pharmacy, during which this article was composed.

1. Rampogal, S., Thome-Souza, S., Jackson, M., et al. Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy. Epilepsy & Behavior. Volume 37. August 2014. (2014). Ppg 291-307

2. The Food and Drug Administration. (2020, June 15). 

FDA Permits Marketing of First Game-Based Digital Therapeutic to Improve Attention Function in Children with ADHD. 

https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-first-game-based-digital-therapeutic-improve-attention-function-children-adhd

3.  Sansgiry SS, Kulkarni AS. The Human Genome Project: Assessing confidence in knowledge and training requirements for community pharmacists. Am J Pharm Educ. 2003;67(2):39.

4. Accreditation Standards and Key Elements for the Professional Program in Pharmacy Leading to the Doctor of Pharmacy Degree Accreditation Council for Pharmacy Education. Standards. 2016. [Accessed March 29, 2018]. Available from: 

https://www.acpe-accredit.org/pdf/Standards2016FINAL.pdf

Articles

Pharmacists, researchers, and other health care professionals must keep pushing these boundaries to continue advancing the field of medicine and providing effective patient care.

A Glimpse into the Future of Pharmacy

Esketamine (Spravato) is a CIII nasal spray that is indicated for treatment-resistant depression in adults in conjunction with oral antidepressant therapy. Esketamine, an S-enantiomer of racemic ketamine, is a non-selective and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, an inotropic glutamate receptor. The precise mechanism of action of esketamine in depression is currently unknown.

Esketamine shows promise for adults suffering from treatment-resistant depression. A recent study showed that approximately 30% of patients meet the criteria for treatment-resistant depression (TRD), having no positive therapeutic response even after trying 2 or more antidepressant medications.

Esketamine also has recently received attention as an effective and fast acting treatment for depression and suicidal ideation. Traditionally, oral anti-depressant therapy may take weeks for an individual to observe full therapeutic effects.

In contrast, esketamine nasal spray has been reported to rapid onset of full anti-depressant effects within 2 to 24 hours of administration of nasal esketamine spray.

 When compared with Midazolam in the treatment of patients with depression and suicidal ideations, ketamine was observed to produce a greater reduction in suicidal ideations within 24 hours.

Esketamine is a CIII nasal spray indicated for the treatment of treatment resistant depression in adults in combination with oral anti-depressant therapy. Esketamine is currently not approved as an anesthetic agent. The safety and efficacy of esketamine as an anesthetic agent has not been established.

Esketamine, the S-enantiomer of racemic ketamine. It is a non-selective, non-competitive antagonist of the NMDA receptor, an ionotropic glutamate receptor. The mechanism by which esketamine exerts its antidepressant effect is unknown. The major circulating metabolite of esketamine (noresketamine) demonstrated activity at the same receptor with less affinity.

Esketamine is administered via single use nasal spray devices and to be used in combination with oral anti-depressant therapy. Each single-use device delivers 28 mg of esketamine. The dosing schedule of esketamine is broken up into 2 phases: the induction phase (weeks 1-4), and the maintenance phase (weeks 4 to 8, then weeks 9-plus).

In the induction phase (weeks 1 to 4), on day 1, the initiation dose is 56 mg (2 devices). Subsequent doses in the induction phase may be 56 mg or 84 mg twice weekly based on efficacy and tolerability. In weeks 5 to 8 of the maintenance phase, either 56 mg or 84 mg may be administered once weekly. In the ninth week and thereafter, either 56 mg or 84 mg may be administered once weekly or once every 2 weeks. The frequency in weeks 9-plus is determined by the patient response and clinical judgment of the remission/response to treatment.

Esketamine is to be administered under supervision of a healthcare provider. After esketamine is administered, the patient must retain in a post-administration observation period of at least 2 hours at each treatment session due to sedative and dissociative adverse effects. 

Prior to each treatment of esketamine, a baseline blood pressure assessment must be obtained. After the administration of the medication, blood pressure must be re-evaluated after 40 minutes and when clinically indicated. Providers must consider short-term increases in blood pressure when administering esketamine. If an increase in blood pressure poses a serious risk treatment should be delayed.

Rapid reduction of depression symptoms at risk for imminent suicide

In a double blind, multi-proof of concept study, patients were administered esketamine 84 mg twice weekly for 4 weeks in addition to comprehensive care and compared with a placebo. The primary endpoint was to measure the change from baseline to 4 hours using the Montgomery-Åsberg Depression Rating Scale (MADRS).

Clinician global judgment of suicide risk (from the Suicide Ideation and Behavior Assessment Tool) was also assessed. The trial concluded that in in addition to comprehensive standard-of-care treatment, esketamine may result in significant rapid improvement of depressive symptoms and suicidal ideations in patients at risk for suicide.

In a randomized, double-blind clinical trial of 67 adults with treatment-resistant depression, patients were assessed at baseline using the MADRS scale and 1 week after administration of intranasal esketamine 24 mg to 84 mg twice weekly in adjunct with oral antidepressant therapy. The results of the study concluded that there were measurable improvements of depressive symptoms and scores using the MADRS scale persisted despite esketamine cessation and reduced dose frequency.

Esketamine is contraindicated in patient populations who have aneurysmal vascular disease, arteriovenous malformation, history of intracerebral hemorrhage or hypersensitivity to esketamine, ketamine, or any excipients in the medication.

Administration of esketamine alongside monoamine oxidase inhibitors may result in increased blood pressure.

Administration of esketamine alongside psychostimulants (eg, methylphenidate, amphetamines etc) may result in increased blood pressure.

: CNS depressants (alcohol, benzodiazepines, etc) may result in increased sedation if administered with esketamine. 

Esketamine is not recommended in pregnancy due to insufficient data supporting its usage.

Esketamine is present in human breast milk. Breast feeding is not recommended during treatment of this medication.

 Increased peak plasma concentrations and area under the curve (AUC) have been observed in the elderly when compared with younger adult patients.

Mild/moderate hepatic impairment (Child-Pugh class A & B): the AUC and t

 values were higher in comparison to patients with normal liver function.

Severe hepatic impairment (Child-Pugh class C)

: Usage of esketamine in severe hepatic impairment has not been studied at this time and its usage is recommended against.

Under the Federal Controlled Substances Act, esketamine is registered as a CIII. Patients with a history of substance abuse may be at an increased risk to abuse and become dependent on the use of esketamine.

Prolonged use of ketamine has been found to warrant physiological dependence on the drug along with tolerance to treatment. Health care providers must evaluate signs and symptoms of dependence upon discontinuing therapy.

Sedation and dissociation are largely the most common and notable AEs. Other AEs that have been reported are hypertension, cognitive impairment, inability to operate machinery/drive, ulcerative/intestinal cystitis, and embryo-fetal toxicity.

As esketamine is a Schedule III controlled substance, it must be stored in accordance to state and federal regulations regarding controlled substances. It can be stored in room temperature in accordance to USP standards. Esketamine must be disposed of in accordance to local, state, and federal regulations.

 is a PharmD candidate at Marshall University School of Pharmacy, anticipated to graduate in Spring 2021.

, is the founder and CEO of STACK, a pharmacy compliance management software, and serves as preceptor for a virtual Advanced Pharmacy Practice Experiential Rotation for specialty pharmacy, during which this article was composed.

1.  SPRAVATO® [Package Insert] Titusville, NJ. Janssen Pharmaceuticals Inc; 2020.

https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf

2. Nierenberg AA, Husain MM, Trivedi MH, et al. Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report [published online May 22, 2009] Psychological Medicine. 2010;40(1):41—50. doi: 10.1017/S0033291709006011

3. Daly EJ, Singh JB, FedgchinM, et al: Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatmentresistant depression: a randomized clinical trial. JAMA 2018; 75: 139—148

4. Grunebaum MF, Galfalvy HC, Choo TH, et al: Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolamcontrolled randomized clinical trial. Am J Psychiatry (Epub ahead of print, Dec 5, 2017)

5. Canuso C, et al. "Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Subjects Assessed to be at Imminent Risk for Suicide." Society of Biological Psychiatry 71st Annual Scientific Meeting. May 12-14, 2016.

6. Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. 

. 2018;75(2):139‐148. doi:10.1001/jamapsychiatry.2017.3739

Esketamine shows promise for adults suffering from treatment-resistant depression.