Journal of Psychosocial Nursing and Mental Health Services

Psychopharmacology 

From Immediate Release to Long Acting Drug Delivery Systems: What Do They Mean and Why Do They Matter?

Laura G. Leahy, DrNP, APRN, PMH-CNS/FNP, BC

Abstract

Understanding the varied delivery systems of today's medications can not only simplify dosing schedules but also improve medication adherence, reduce adverse events and polypharmacy, and increase patients' overall quality of life. Whether a medication is noted as immediate, controlled, delayed, or extended release can influence patient adherence as well as tolerability of the drug. New and novel delivery systems, such as long-acting weekly formulations or biweekly and monthly injectable agents, can offer steady blood levels of the drug, avoiding the daily fluctuations that may lead to side effects. Other delivery systems, such as transdermal patches and extended-release orally disintegrating tablets, may offer convenience for those with gastrointestinal concerns or the inability to swallow tablets or capsules. The current article serves as a primer on drug delivery systems and why they are important to consider when introducing medications to a patient's treatment regimen. [Journal of Psychosocial Nursing and Mental Health Services, 55(5), 19–23.]

Abstract

Understanding the varied delivery systems of today's medications can not only simplify dosing schedules but also improve medication adherence, reduce adverse events and polypharmacy, and increase patients' overall quality of life. Whether a medication is noted as immediate, controlled, delayed, or extended release can influence patient adherence as well as tolerability of the drug. New and novel delivery systems, such as long-acting weekly formulations or biweekly and monthly injectable agents, can offer steady blood levels of the drug, avoiding the daily fluctuations that may lead to side effects. Other delivery systems, such as transdermal patches and extended-release orally disintegrating tablets, may offer convenience for those with gastrointestinal concerns or the inability to swallow tablets or capsules. The current article serves as a primer on drug delivery systems and why they are important to consider when introducing medications to a patient's treatment regimen. [Journal of Psychosocial Nursing and Mental Health Services, 55(5), 19–23.]

Exploring psychotherapeutic issues and agents in clinical practice

Various letters after drug names often appear on prescription bottles, but what do those letters really mean? The ER, XR, XL (extended release), LA (long acting), SR (sustained release), ODT (orally disintegrating tablet), and IM (intramuscular), among other acronyms, typically define the release of medication in the body or route of medication delivery (Table 1). It is important for nurses to be aware of and understand the meaning behind these acronyms because they affect how the body metabolizes the drug and, therefore, they affect the potential for adverse events and side effects. Understanding these drug delivery systems can also guide the prescriber to choose the most appropriate form of a medication given a patient's unique needs.


Medication Delivery System Acronyms

Table 1:

Medication Delivery System Acronyms

Psychotropic Medication Adherence

One rationale for considering a drug's delivery system is patient adherence. Globally, nonadherence to psychiatric medications is a major challenge confronting practitioners. In a 2014 Cochrane review (Nieuwlaat et al., 2014), overall adherence to all classes of medications was estimated to be approximately 50%; thus, patients are only receiving one half of the recommended pharmacotherapy, whereas adherence to psychotropic medications was reported to be potentially as low as 24%. Some of the most pertinent factors, which influence adherence, include: the severity and perception of illness, complexity of the treatment regimen, medication costs, patient education, and social supports (Nieuwlaat et al., 2014). For patients with psychiatric disorders, adherence is an even greater challenge. Many patients abandon their treatments once they begin to feel better; others may believe they simply do not need the medication, and still others may experience such severe psychiatric symptoms that they are unable to follow the directions or muster the energy to engage in their appointments and adhere to their medication regimens.

Prescriber considerations to improve adherence include: minimizing side effects of medications, convenient dosing schedules, offering time estimates as to when a medication might take effect and how long the individual may be expected to take the medications, and acknowledging that drug costs may be a significant factor. After all, convenience = compliance, and in the words of Former U.S. Surgeon General, C. Everett Koop, “Drugs don't work in patients who don't take them” (Osterberg & Blaschke, 2005). These considerations evoke the importance of a drug's delivery system.

Considering Drug Delivery Systems to Improve Adherence

Drug delivery systems can offer practitioners information on how long the drug will remain active in the patient's body. Many drugs labeled ER, XL, LA, or CR (controlled release) (Table 1) are considered extended release or long acting and offer the patient the benefit of less frequent dosing than drugs that are immediately released. ER medications are often dosed just one time per day and rarely more than twice per day, allowing patients to take their medication one time per day, typically in the morning or before bed, and then go about their daily routine. Table 2 presents some psychotropic medications with unique delivery systems.


Psychotropic Medications with Unique Delivery Systems
Psychotropic Medications with Unique Delivery Systems

Table 2:

Psychotropic Medications with Unique Delivery Systems

One outlier among psychotropic agents is the antidepressant fluoxetine (Prozac®). Due in part to its long half-life, Prozac Weekly delayed-release capsules, a once-per-week formulation, delivers approximately 13 mg per day of bioavailable fluoxetine (Wagstaff & Goa, 2001). This unique delivery system allows patients to take this drug only one time per week. Prozac Weekly is the longest acting oral medication available in psychiatry. Using a medication with such a long delivery system may prove beneficial for those patients who forget or are resistant to taking their medications. The delayed release allows for the beneficial effects of the drug to remain in the body over an extended period of time. Unfortunately, if there are side effects, those may remain for an extended period of time as well.

Long-acting injectable (LAI) anti-psychotic agents have aided those with chronic and persistent psychiatric illnesses, such as schizophrenia, to achieve stable blood levels of the drug, reduce relapse risk, lower treatment costs, improve patient confidentiality, reduce inpatient hospitalization stays, and improve adherence (Brissos, Veguilla, Taylor, & Balanzá-Martinez, 2014; Siegel, 2005; Waddell & Taylor, 2009). Although the biweekly to monthly dosing schedule of LAIs may provide all of the benefits listed above, there are potential disadvantages to prescribing/administering medication via this form of delivery system. Pain at the injection site is an obvious disadvantage, though more troublesome may be delayed emergence of side effects, reduced flexibility in dosage adjustments, and longer time required to achieve steady state. LAIs may require an overlap with oral medication and patients may experience the perception of stigma compared to IR or ER oral medications (Agid, Foussias, & Remington, 2010; Brissos et al., 2014; Guzman, 2017).

Another factor, which may influence the type of delivery system chosen for patients with psychiatric illness, is that many have comorbid substance use disorders and/or medical conditions that also require medication therapy. The cumulative nature of polypharmacy may lead to nonadherence with not only psychotropic medications but also those for treatment of patients' nonpsychiatric conditions. Dodler, Furtek, Lacro, and Jeste (2005) suggested that adherence improves when treatment regimens are simplified. By using various delivery systems, the number of oral medications taken daily may be reduced. For example, if a patient being treated for hypertension and type II diabetes is diagnosed with major depressive and alcohol abuse disorders, the potential for nonadherence due to polypharmacy escalates. If the patient is agreeable and able to tolerate the long-acting formulations of fluoxetine (e.g., Prozac Weekly) and naltrexone (Vivitrol®), the patient's depression can be treated on a weekly basis with the delayed release capsule and his/her sobriety can be effectively maintained monthly with the LAI.

Arguably, one of the most beneficial classes of ER delivery systems has been with psychostimulant medications. Gone are the long lines for the school nurse during lunch period, in which children diagnosed with attention-deficit/hyperactivity disorder (ADHD) stood to receive their second dose of Ritalin® (methylphenidate) to aid them through their afternoon classes. When Concerta® (methylphenidate ER) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD in 2000, it became the first, true once-per-day medication for ADHD. The delivery system is based on OROS® technology, in which a hard polymer shell with a semi-permeable outer membrane allows the drug to be released through a controlled osmotic process avoiding interference from gastrointestinal influences, such as pH, food intake, and motility (Gupta, Thakur, Jain, Banweer, & Jain, 2010). Subsequently, Adderall® XR (mixed amphetamine salts ER), a capsule containing an equal ratio of IR and ER beads, was introduced to the pharmaceutical market in mid-2001 and offered an alternative to the ER methylphenidate-based psychostimulant agent, again in a long-acting formulation (Melmed, 2005). Numerous other brand name psychostimulant agents with varying ratios of IR versus delayed release delivery mechanisms of methylphenidate have been approved by the FDA: Metadate® CD, Ritalin® LA, Focalin® XR, and Methylin® ER.

In 2006, the FDA approved Daytrana®, the first ER transdermal patch indicated for the treatment of ADHD. This delivery system has advantages over its oral formulations in that it bypasses first-pass metabolism, which potentially decreases the risk of side effects; however, there can be a potential for delayed onset of effect of approximately 2 hours after application of the patch (Melmed, 2005). In 2015, the FDA approved yet another novel delivery system for ADHD medications: Adzenys XR-ODT™. Adzenys XR-ODT is based on IR and ER amphetamine salt-loaded micro-particles that are compressed into the ODT and released by dissolving in the mouth without water or fluids (NEOS Therapeutics, 2015). These new and novel delivery systems may aid patients who cannot swallow oral medications or have gastrointestinal issues, which may be exacerbated by oral medication delivery.

Conclusion

Although most psychotropic medications are dosed and delivered orally, numerous alternative delivery systems exist to assist practitioners in tailoring the length of time a drug is delivered and/or how a drug is delivered to the individual patient. ER, CR, and delayed release oral medications offer more convenience as they are typically dosed only once per day, whereas long-acting, biweekly, or monthly injectables or weekly delayed release oral capsules offer even longer effects of the drug between doses. Similarly, the choice of ODT, transdermal, intramuscular, or oral delivery can also impact the potential for adherence, bioavailability, and/or adverse effects of medications. The current article serves as a primer to offer nurses and prescribers information to make informed decisions regarding not only the type of medication that may more effectively treat a patient's symptoms but also the most appropriate delivery system to enhance adherence, reduce adverse effects, and improve the patient's overall quality of life.

References

  • Agid, O., Foussias, G. & Remington, G. (2010). Long-acting injectable antipsychotics in the treatment of schizophrenia: Their role in relapse prevention. Expert Opinion on Pharmacotherapy, 11, 2301–2317. doi:10.1517/14656566.2010.499125 [CrossRef]
  • Brissos, S., Veguilla, M.R., Taylor, D. & Balanzá-Martinez, V. (2014). The role of long-acting injectable antipsychotics in schizophrenia: A critical appraisal. Therapeutic Advances in Psychopharmacology, 4, 198–219. doi:10.1177/2045125314540297 [CrossRef]
  • Dodler, C.R., Furtek, K., Lacro, J.P. & Jeste, D.V. (2005). Antihypertensive medication adherence and blood pressure control in patients with psychotic disorders compared to persons without psychiatric illness. Psychosomatics, 46, 135–141. doi:10.1176/appi.psy.46.2.135 [CrossRef]
  • Gupta, B.P., Thakur, N., Jain, N.P., Banweer, J. & Jain, S. (2010). Osmotically controlled drug delivery system with associated drugs. Journal of Pharmacy & Pharmaceutical Sciences, 13, 571–588. doi:10.18433/J38W25 [CrossRef]
  • Guzman, F. (2017). Long-acting injectable antipsychotics: A practical guide for prescribers. Retrieved from http://psychopharmacologyinstitute.com/antipsychotics/long-acting-injectable-antipsychotics-a-practical-guide-for-prescribers
  • Melmed, R.D. (2005). Advances in drug delivery systems for attention deficit/hyperactivity disorder. Medscape Psychiatry, 10(2).
  • NEOS Therapeutics. (2015). Adzenys XR-ODT. Retrieved from http://adzenysxrodt.com/about-adzenys/about
  • Nieuwlaat, R., Wilczynski, N., Navarro, T., Hobson, N., Jeffery, R., Keepanasseril, A. & Haynes, R.B. (2014). Interventions for enhancing medication adherence. Cochrane Database of Systematic Reviews, 20, CD000011. doi:10.1002/14651858.CD000011.pub4 [CrossRef]
  • Osterberg, L. & Blaschke, T. (2005). Adherence to medication. New England Journal of Medicine, 353, 487–497. doi:10.1056/NEJMra050100 [CrossRef]
  • Siegel, S.J. (2005). Extended release drug delivery strategies in psychiatry: Theory to practice. Psychiatry, 2(6), 22–31.
  • Waddell, L. & Taylor, M. (2009). Attitudes of patients and mental health staff to antipsychotic long-acting injections: Systematic review. British Journal of Psychiatry Supplement, 195, S43–S50. doi:10.1192/bjp.195.52.s43 [CrossRef]
  • Wagstaff, A.J. & Goa, K.L. (2001). Once-weekly fluoxetine. Drugs, 61, 2221–2228. doi:10.2165/00003495-200161150-00006 [CrossRef]

Medication Delivery System Acronyms

Mechanism of Drug Release
  Extended release (XR, XL, or ER)
  Sustained release (SR)
  Controlled release (CR)
  Controlled delivery (CD)
  Long acting (LA)
Routes of Drug Delivery
  Orally disintegrating tablet (ODT)
  Transdermal (TD)
  Sublingual (SL)
  Intramuscular (IM)

Psychotropic Medications with Unique Delivery Systems

GenericBrandDelivery FormIndication
Atypical Antipsychotic Medications
Aripiprazole Aripiprazole lauroxilAbilify®Abilify Maintena®Aristada®Tablet, ODT, solution ER IM injection ER IM injectionBipolar disorder, depression, autism spectrum agitation Schizophrenia Schizophrenia
AasenapineSaphris®Sublingual tabletsBipolar disorder, schizophrenia
OlanzapineZyprexa®Zyprexa Relprevv®Tablet, Zydis ODT ER IM injectionBipolar disorder, schizophrenia, treatment-resistant depression Schizophrenia
QuetiapineSeroquel®Seroquel XR®Tablet ER tabletBipolar disorder, schizophrenia, treatment-resistant depression, autism spectrum agitation
RisperidoneRisperdal®Risperdal Consta®Tablet, solution, M-tab SR IM injectionBipolar disorder, schizophrenia, autism spectrum agitation
ZiprasidoneGeodon®Capsules Acute IM injectionBipolar disorder, schizophrenia, autism spectrum agitation Agitation with schizophrenia
Selective Serotonin Reuptake Inhibitor Antidepressant Medications
FluoxetineProzac®Prozac® WeeklyCapsule, tablet, solution Delayed release capsuleDepression, anxiety, obsessive compulsive disorder (OCD), premenstrual dysphoric disorder (PDD)
ParoxetinePaxil®Paxil CR®Tablet, suspension CR tabletDepression, anxiety, panic disorder, OCD, PDD
Serotonin Norepinephrine Reuptake Inhibitor Antidepressant Medication
VenlafaxineEffexor®Effexor XR®Tablet ER capsuleDepression, anxiety
Monoamine Oxidase Inhibitor Antidepressant Medication
SelegilineEmsam®Transdermal patchDepression
Other Antidepressant Medications
Bupropion HCl Bupropion HBrWellbutrin®Wellbutrin SR®Wellbutrin XL®Forfivo XL®Aplenzin®Tablet SR tablet XL tablet XL tablet ER tabletDepression Depression, smoking cessation (Zyban®) Depression, seasonal affective disorder Depression Depression, seasonal affective disorder
MirtazapineRemeron®Remeron Soltab®Tablet ODTDepression
Mood Stabilizers
LithiumLithium®Lithium ER®Lithobid®Tablet, solution ER tablet Slow release tabletBipolar disorder
Divalproex sodiumDepakote®Depakote ER®Delayed release tablet ER tabletBipolar disorder, seizures, migraine prophylaxis
LamotrigineLamictal®Lamictal XR®Tablet, chewable tablet, ODT XR tabletBipolar disorder, seizures
Psychostimulant Medications
MethylphenidateRitalin®Ritalin LA®Concerta®Metadate CD®Metadate ER®Methylin®Daytrana®Quillivant XR®Quillichew ER®Tablet Biphasic release capsule OROS extended release Biphasic release capsule ER tablet Chewable tablet, solution Transdermal patch XR suspension Biphasic chewable tabletADHD, narcolepsy ADHD ADHD ADHD ADHD, narcolepsy ADHD, narcolepsy ADHD ADHD ADHD
Mixed amphetamine AmphetamineAdderall®Adderall XR®Adzenys XR-ODT™ Dyanavel XR®Tablet XR tablet XR ODT XR solutionADHD, narcolepsy ADHD, narcolepsy ADHD ADHD
Other ADHD Medications
ClonidineCatapres®Kapvay®Tablet ER tabletADHD, hypertension, off-label opioid withdrawal ADHD
GuanfacineTenex®Intuniv®Tablet ER tabletADHD, hypertension ADHD
Authors

Dr. Leahy is Family Psychiatric Advanced Practice Nurse and Master Clinician in Psychopharmacology, APNSolutions, LLC, Sewell, New Jersey.

The author has disclosed no potential conflicts of interest, financial or otherwise.

Address correspondence to Laura G. Leahy, DrNP, APRN, PMH-CNS/FNP, BC, Family Psychiatric Advanced Practice Nurse and Master Clinician in Psychopharmacology, APNSolutions, LLC, 123 Egg Harbor Road, Suite 703, Sewell, NJ 08080; e-mail: lgleahy@apnsolutions.com.

10.3928/02793695-20170420-02

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