Atypical Antipsychotic Medication Re-initiation in the Emergency Department

PillsThe acute episode of intoxication and agitation has subsided and your patient is calm. She has been medically cleared and is ready to be moved to a less acute, less monitored portion of the ED to await further assessment and treatment for her underlying psychiatric conditions. As a well-intentioned emergency medicine practitioner, you wish to give your patient the tools she needs to maintain this calm status by restarting her home atypical antipsychotic medication. What is the best way to go about doing this?

While the atypical antipsychotics have generally been considered safer than the first generation agents due to the decreased risk of extrapyramidal side effects at therapeutic doses, this class is not without adverse effects. All of the medications in this class are capable of causing sedation due to their antihistaminergic effects and some of these agents also have an alpha-blockade effect possibly leading to orthostatic hypotension [1].

Re-Initiation Strategy: Atypical Antipsychotic Medication

When faced with the prospect of re-initiation of atypical antipsychotics, it is necessary to determine how long the patient has been without medication if possible. While there is a lack of literature regarding this topic, select medications make reference to re-initiation in their package inserts [4,8,9].These recommendations range from “an interval off” to “more than one week”, possibly indicating that a few missed doses may not have an impact on the re-initiation dose. However, when it is determined that a patient has been without their atypical antipsychotic for a few days to a week or the period of nonadherence is unknown, caution with re-initiation is justified and some package inserts call for restarting the initial dosing titration.

Medication
Package insert: Day 1 dosing
Re-initiation recommendation
Aripiprazole (Abilify)Schizophrenia: 10-15 mg PO Q 24 hours
Bipolar mania: 15 mg PO Q 24 hours
Bipolar mania (adjunctive therapy): 10-15 mg PO Q 24 hours
No recommendations
Asenapine (Saphris)Schizophrenia: 5 mg PO Q 12 hours
Bipolar mania (monotherapy): 10 mg PO Q 12 hours
Bipolar mania (adjunctive therapy): 5 mg PO Q 12 hours
No recommendations
Iloperidone (Fanapt)Schizophrenia: 1 mg PO Q 12 hoursWhen off > 3 days, the initial dosing titration schedule should be followed
Lurasidone (Latuda)Schizophrenia: 40 mg PO Q 24 hours
Bipolar depression: 20 mg PO Q 24 hours
No recommendations
Olanzapine (Zyprexa)Schizophrenia: 5-10 mg PO Q 24 hours
Bipolar disorder: 10-15 mg PO Q 24 hours
No recommendations
Paliperidone (Invega)Schizophrenia: 6 mg PO Q 24 hours
Schizoaffective disorder: 6 mg PO Q 24 hours
No recommendations
Quetiapine (Seroquel)Schizophrenia: 25 mg PO Q 12 hours
Bipolar mania: 50 mg PO Q 12 hours
Bipolar depression: 50 mg PO Q HS
When off ≥ 1 week, the initial dosing titration schedule should be followed
Risperidone (Risperdal)Schizophrenia: 2 mg PO Q 24 hours
Bipolar mania: 2-3 mg PO Q 24 hours
When off for an interval, the initial titration schedule should be followed
Ziprasidone (Geodon)Schizophrenia: 20 mg PO Q 12 hours
Bipolar I disorder: 40 mg PO Q12 hours
No recommendations

*Dosing above is not adjusted for renal or hepatic dysfunction or concomitantly administered interacting medications

Clozapine

Due to the risk of agranulocytosis for which there is a black box warning, all patients prescribed clozapine must be enrolled in a registry which monitors the patient’s white blood cell count and absolute neutrophil count.  As a result, clozapine dosing must be made in collaboration with the patient’s clozapine registry. In addition, clozapine also carries a black box warning for cardiovascular and respiratory effects and states that for patients who have been without clozapine for 2 or more days, they are to start with 12.5 mg once or twice daily [11].

Other Agents

For other agents, the course of action is less clear. Dosing decisions should ideally be made in conjunction with a psychiatric care provider; however this is not always feasible in the ED setting. For patients on atypical antipsychotics without clear re-initiation instructions in the prescribing information and doses higher than initial dosing (see table), consider a dose reduction. Anecdotally, re-initiating the dose at 50-80% of the maintenance dose seems reasonable in hemodynamically stable patients; however, there are not identified data to support this strategy. Regardless of the strategy implored, vigilance is important when re-initiating atypical antipsychotics. This is especially noteworthy in patients who will be in a less monitored area of the department.

Take Home Points

  • Determine how long the patient has been without their atypical antipsychotic if possible.
  • Use caution when re-initiating home doses of atypical antipsychotic agents and consider dosing reductions in patients who have been without their medications for more than a few doses.
  • Clozapine must be ordered in conjunction with the patient’s clozapine registry and when off for 2 or more days usually requires restarting initial dosing.
  • When the maintenance dose is above the initial dosing and re-initiation instructions are not within the package insert, consider a dose reduction (such as restarting  50-80% of the patient’s stabilized dose, depending on the clinical picture) to avoid adverse events, especially in less monitored patients

Reviewer: Clayton English, PharmD, BCPP

Associate Editor: Bryan Hayes, PharmD, DABAT (@PharmERToxGuy)

 

References

  1. Minns AB, Clark RF. Toxicology and overdose of atypical antipsychotic. J Emerg Med. 2012;43:906-13.
  2. Abilify® [package insert]. Tokyo, Japan. Otsuka Pharmaceutical Co; 8/2013.
  3. Saphris® [package insert]. Whitehouse Station, NJ. Merk & Co; 2009. Rev. 3/2013.
  4. Fanapt® [package insert]. East Hanover, NH. Novartis Pharmaceutical Corporation; 1/2013.
  5. Latuda® [package insert]. Marlborough, MA. Sunovion Pharmaceuticals; 7/2013.
  6. Zyprexa® [package insert]. Indianapolis, IN. Eli Lilly & Company. 1997. Rev. 2013.
  7. Invega® [package insert]. Titusville, NJ. Janssen Pharmaceutical, Inc; 2007. Rev 1/2014.
  8. Seroquel® [package insert]. Wilmington, DE. AstraZenica; 2013.
  9. Risperdal® [package insert].  Titusville, NJ. Janssen Pharmaceutical, Inc; 2007. Rev 11/2013.
  10. Geodon® [package insert]. New York, NY. Pfizer; Rev. 1/2014.
  11. Clozapine [package insert]. Morgantown, WV. Mylan Pharmaceuticals Inc. 5/2013

Image

Author information

Jill Logan, PharmD BCPS
Jill Logan, PharmD BCPS
Clinical Pharmacist
Baltimore Washington Medical Center

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Self-Regulated Learning and Forgetting

Young man with a book We go through school without realizing if our learning strategies are inefficient even more so when some assessments support these practices as opposed to discourage it. Unfortunately, exams and graduation run the risk of giving us a sense that learning is over, that what we have learned does not change, or that there are not more effective ways of learning. There is no way of unlearning what we have learned in the past, so it’s always a sensible practice to reassess our knowledge on a constant basis. 

Zimmerman defines self-regulated learning when students actively participate in their own learning using feedback, behavior, motivation, and metacognitive skills for effectiveness [1]. The problem is that active participation is not enough, learners also need effective learning strategies to acquire and maintain information highly retrievable and long-term retention. In a recent meta-analysis Dunlosky and colleagues[2] identified a number of effective and non-effective learning strategies practiced by students. Although learning strategies are useful, their effectiveness might not reach their potential in a curriculum without frequent testing, interleaved practice, formative assessments, distributed practice.

Studying Technique
Effect on Learning
Practice Testing High
Distributed PracticeHigh
Interleaved Practice Moderate
Elaborative InterrogationModerate
Self-explanation Moderate
RE-reading Low
Highlighting Low
Keyword mnemonic Low

Table adapted from BigThink

In a recent lecture at Harvard University Dr. Robert Bjork, an educational researcher from UCLA, talked about learning strategies and their implications in self-regulated learning. The title of the talk is quite intriguing and appropriate: Forgetting as a friend of learning: Implications for teaching and self-regulated learning.

These are a few of the concepts he addressed:

  1. Active retrieval is a learning process and a skill unto itself; so it requires practice.
  2. New theory of disuse: storage strength vs retrieval strength
  3. Performance is measurable and observable, learning is not.
  4. Conditions that reduce retrieval strength can, therefore, enhance learning.
  5. Practice retrieval, rather than looking things up, as often as possible.
  6. Mass practice shows rapid learning, but no benefit for long-term retention.
  7. Spaced practice shows forgetting, but helps long-term retention.
  8. Desirable learning difficulties: conditions of instruction that appear to create difficulties for the learner, slowing the rate of apparent learning, often optimize long-term retention and transfer.
  9. Induction: the ability to generalize concepts and categories through exposure to multiple exemplars. Block/Mass allows the learner to notice characteristics that unify category. Interleaving makes it difficult.
  10. The image below depicts active research and where learners can go wrong when managing and assessing their learning [3].

Self regulated learning graphic

This is a great panel discussion with Dr. John Dunlosky, Dr. Robert A. Bjork, Dr. Pooja K. Agarwal, Dr. Dan Robinson, Dr. Elizabeth Marsh, and Dr. Geoff Norman held at McMaster University last year.

These are a few of the points discussed:

  1. Effective and not effective learning strategies (mass learning, retrieval practice, etc)
  2. Myths in education (e.g. learning styles, MBTI personality types)
  3. Evidence-based education
  4. Desirable difficulties
  5. Cummulative exams
  6. Bloom’s Taxonomy
  7. Identification and emphasis of core knowledge
  8.  Technology might be helpful in learning (also consider cost)

 

References

  1. Zimmerman BJ. Self-regulated learning and academic achievement: An overview. Educational Psychologist. 1990;25, 3-17.
  2. Dunlosky J et al. Improving Students’ Learning With Effective Learning Techniques: Promising Directions From Cognitive and Educational Psychology. Psychological Science in the Public Interest. 2013;14 (1), 4-58 DOI:10.1177/1529100612453266
  3. Bjork RA, et al., (2013). Self-regulated learning: beliefs, techniques, and illusions., Annu Rev Psychol, 64:417-44 PMID: 23020639 

 

Further Reading

Retrieval Practice: 10 benefits of testing

Image credit

Author information

Javier Benitez, MD
Javier Benitez, MD
ALiEM Featured Contributor

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Trick of the Trade: Making your own homemade ultrasound gel

UltrasoundKenyaExpertPeerReviewStamp2x200You are spending a month in rural Kenya, doing an ultrasound teaching course. Your enthusiastic participants have been ultrasounding every chance they get. Unfortunately, this has caused your ultrasound gel supplies to dwindle. It will be a month before a new shipment of gel arrives from Nairobi. This gel will cost about $5 per bottle, which is a considerable expense for the local hospital’s budget.

Trick of the Trade: Homemade ultrasound gel

With a few simple and ubiquitous ingredients, you can make your own ultrasound gel to use. 

PIC1

Equipment Needed 

  • Corn starch
  • Water
  • Pot or pan
  • Heat source
  • Empty and clean bottle 

PIC2

Technique

  1. Combine 1 part corn starch to 10 parts water in a pan. Here, we use ¼ cup corn starch to 2 ½ cups water to make about 2 gel bottles full.
  2. Heat this mixture while stirring constantly at medium heat for 5-10 minutes.
  3. When the substance begins to boil, turn off the heat and allow the mixture to cool.
  4. Pour the mixture into a clean, preferably sterilized, container. Here, we use an old commercial ultrasound gel bottle which we placed in boiling water for 10 minutes first.
  5. Ultrasound away! Note that the gel should be used within 48-72 hours for best results. After that, it may begin to separate a bit.

PIC3

Word of Caution

This homemade gel does not have the same bacteriostatic ingredients that are in commercial ultrasound gel. Therefore we do no recommend its use for skin and soft tissue infections.

Expert Peer Review

April 11, 2014

For anyone who has spent time working abroad in a low resource area, you are likely familiar with the utility of ultrasound. It has a wide range of applications, it is easy to use, and there is an increasing number of portable machines available. There are very few ongoing costs associated with the use of ultrasound machines. The exception to this is ultrasound gel.

There is very little published about ultrasound gel alternatives. The 1995 WHO Manual of Diagnostic Ultrasound [1] contains a recipe for making your own ultrasound gel which requires many chemicals not available in most low resource settings. Olive oil has been studied as a feasible alternative [2] but is messy and provides less surface contact between the patient and the probe. Water baths have been looked at but are only applicable to extremity ultrasound [3].

In our recent pilot study [4], we found that a cornstarch-based alternative is at least comparable to commercial gel. Our study, which is a randomized blinded trial (abstract forthcoming at SAEM 2014) found no statistically significant difference between commercial gel and the cornstarch alternative in terms of image quality. The cornstarch-based alternative is an easily created, easily used, extremely inexpensive option that will hopefully make ultrasound more feasible and accessible in low resource settings.”

Reference

  1. Manual of diagnostic Ultrasound [PDF 3.6 MB], 2nd Edition. World Health Organization. 2011. Retrieved Aug 13, 2012 
  2. Luewan S, Srisupundit K, Tongsong T. A comparison of sonographic image quality between the examinations using gel and olive oil as sound media. J Med Assoc Thai. 2007 April; 90(4)624-7. Pubmed
  3. Blaivas M, Lyon M, Brannam L, et al. Water bath evaluation technique for emergency ultrasound of painful superficial structures. Am J Emerg Med. 2004 Nov;22(7):589-93. Pubmed
  4. Binkowski A, Riguzzi A, Fahimi J, Price D. Evaluation of a Cornstarch-Based Ultrasound Gel Alternative for Low-Resource Settings. J Emerg Med. 2013 Nov 12. pii: S0736-4679(13)01064-0. Pubmed
Allison Binkowski, MD, Emergency Physician, Ventura County Medical Center

 

Top image

 

Author information

Christine Riguzzi, MD
Christine Riguzzi, MD
Ultrasound Fellow
Department of Emergency Medicine
Highland General Hospital-Alameda Health System

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Understanding Phenytoin Equivalents

fosphenytoin image 1 (1)Sometimes, in an effort to make things simpler, we actually make them more confusing. Such is the case with phenytoin equivalents. 

Fosphenytoin is a water-soluble prodrug of phenytoin. After IV administration, much of the fosphenytoin is metabolized to phenytoin within 15 minutes. Advantages over phenytoin include the option for IM administration and less cardiotoxicity allowing for faster infusion rates. Even the potential for hyperphosphatemia from the release of phosphate is generally inconsequential. 

So, where is the confusion? 

If you want the patient to receive 500 mg of phenytoin, then you simply order fosphenytoin 500 mg PE (where PE stands for phenytoin sodium equivalents).

But… if you turn the vial around and look at the side, you’ll notice it says that each 10 mL vial contains fosphenytoin sodium 750 mg. Wait, so do we need to order fosphenytoin 750 mg to make sure the patient receives phenytoin 500 mg?

fosphenytoin image 2 (1)

Phenytoin Equivalent: Keeping it simple

Most, if not all, institutions have the process set up so that fosphenytoin is ordered as phenytoin equivalents. So, keep it simple.

  1. Choose your favorite phenytoin dosing calculator
  2. Calculate a dose
  3. Order that amount of fosphenytoin in PE units

I would have preferred to just learn a new weight-based dose for fosphenytoin, completely separate from phenytoin. But, this is what we have. Don’t over-think it. That’s where the confusion sets in.

Author information

Bryan Hayes, PharmD
Bryan Hayes, PharmD
ALiEM Associate Editor
Clinical Assistant Professor, University of Maryland (UM)
Clinical Pharmacy Specialist, EM and Toxicology

The post Understanding Phenytoin Equivalents appeared first on ALiEM.

Understanding Phenytoin Equivalents

fosphenytoin image 1 (1)Sometimes, in an effort to make things simpler, we actually make them more confusing. Such is the case with phenytoin equivalents. 

Fosphenytoin is a water-soluble prodrug of phenytoin. After IV administration, much of the fosphenytoin is metabolized to phenytoin within 15 minutes. Advantages over phenytoin include the option for IM administration and less cardiotoxicity allowing for faster infusion rates. Even the potential for hyperphosphatemia from the release of phosphate is generally inconsequential. 

So, where is the confusion? 

If you want the patient to receive 500 mg of phenytoin, then you simply order fosphenytoin 500 mg PE (where PE stands for phenytoin sodium equivalents).

But… if you turn the vial around and look at the side, you’ll notice it says that each 10 mL vial contains fosphenytoin sodium 750 mg. Wait, so do we need to order fosphenytoin 750 mg to make sure the patient receives phenytoin 500 mg?

fosphenytoin image 2 (1)

Phenytoin Equivalent: Keeping it simple

Most, if not all, institutions have the process set up so that fosphenytoin is ordered as phenytoin equivalents. So, keep it simple.

  1. Choose your favorite phenytoin dosing calculator
  2. Calculate a dose
  3. Order that amount of fosphenytoin in PE units

I would have preferred to just learn a new weight-based dose for fosphenytoin, completely separate from phenytoin. But, this is what we have. Don’t over-think it. That’s where the confusion sets in.

Author information

Bryan Hayes, PharmD
Bryan Hayes, PharmD
ALiEM Associate Editor
Clinical Assistant Professor, University of Maryland (UM)
Clinical Pharmacy Specialist, EM and Toxicology

The post Understanding Phenytoin Equivalents appeared first on ALiEM.

Neuraminidase Inhibitors for Influenza – The Truth, The Whole Truth, and Nothing But the Truth Finally

InfluenzaOver the last 5 years, the use of neuraminidase inhibitors for the treatment of influenza has skyrocketed. Emergency physicians have been pushed to prescribe these medications under the belief that they reduced symptoms, the risk of complications, hospitalizations, and transmission. However, the recommendation for the use of these drugs has never sat on firm evidence-based ground. So what did we know then, and what do we know now?

Background

A prior Cochrane review published in 2012 noted that much of the data was unavailable for them to review as it was not released by Roche pharmaceuticals [1]. The available data only supported a reduction in symptoms but marketing focused on reduction in complications and transmission. Many physicians have remained skeptical of the utility of these drugs. Why? Well, what we’ve always known is that the complete set of data and studies was never released.

What’s New?

Last week the BMJ published two systematic reviews on these drugs (via the Cochrane Acute Respiratory Infections Group) along with a number of editorials on the topic. With full access to the data, the blinders are off. We have a full picture of the data, and it doesn’t look good… at least not for oseltamivir (Tamiflu) and zanamivir (Relenza). Let’s take a look at each systematic review.

Article #1: Oseltamivir (Tamiflu)

Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014; 348: g2545. [2]

Design: Systematic review of RCTs on adults and children

Main outcome measure: Time to alleviation of symptoms, complications, hospital admissions and adverse events

Outcome measure
Finding
Alleviation of symptomsShortened by 16.8 hours with oseltamivir
Admission to hospitalNo difference
Reduction in confirmed pneumoniaNo difference
Other complicationsNo difference
Transmission in prophylaxis groupNo reduction
Side Effect
Results
NauseaIncreased (NNH 28)
VomitingIncreased (NNH 22)
Psychiatric eventsIncreased (NNH 94)
HeadacheIncreased (NNH 32)

* NNH = Number needed to harm  

Summary: Oseltamivir led to a minor decrease in time to symptom alleviation with no benefit for complications, hospitalization or transmission. Side effects were common.

Article #2: Zanamivir (Relenza)

Heneghan CJ, Onakpoya I, Thopson M, Spencer EA, Jones M, Jefferson T. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014; 348: g2547. [3]

Design: Systematic review of RCTs on adults and children

Main outcome measure: Time to alleviation of symptoms, complications, hospital admissions and adverse events 

Outcome Measure
Finding
Alleviation of symptomsShortened by 14.4 hours with zanamivir
Admission to hospitalNo data
Reduction in confirmed pneumoniaNo difference
Other complicationsNo difference
Prophylaxis1.98% reduction in symptomatic influenza (NNT 51)
 

Summary: Zanamivir led to a minor decrease in time to symptom alleviation with no benefit for complications or hospitalizations. There was a small decreased in transmission. Zanamivir was well tolerated without any major side effects seen in this data set.

Conclusions from these articles

Oseltamivir and zanamivir treatment showed modest decreases in time to symptom alleviation in comparison to placebo. However, there was no comparison made to standard supportive therapy for reduction of symptoms. A little acetaminophen or NSAID may be just as effective. Additionally, neither medication reduced the risk of complications or any other clinically important outcomes. Oseltamivir frequently led to side effects that may be worse than influenza itself. Lastly, prophylaxis was ineffective with oseltamivir and showed only modest benefits with zanamivir.

Editorial

In addition to the two Cochrane Acute Respiratory Infections Group publications, the BMJ published an accompanying editorial [4]. The authors discuss a number of issues but focus on the fact that despite this drug being approved for use for the last 15 years, we’ve never had access to the full data set. Roche pharmaceuticals left scores of data unpublished and, more insidiously, selectively published the studies that supported the use of the drug. The result is that billions have been spent on these drugs for treatment of influenza, prevention in close contacts of patients with influenza, and in creating stockpiles of medications in the event of an epidemic or pandemic. These issues have been picked up in the mainstream media (The Guardian editorial) as well.

We, as clinicians should demand more transparency. It would seem reasonable for regulatory organizations to require the disclosure of all data, not just published data, before approving a drug.

 

References 

  1. Jefferson T, Jones MA, Doshi P, Del Mar CB, Heneghan CJ, Hama R, Thompson MJ. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children (Review). Cochrane Database of Systematic Reviews 2012, Issue 1. Art. No.: CD008965. DOI: 10.1002/14651858.CD008965.pub3.
  2. Heneghan CJ, Onakpoya I, Thopson M, Spencer EA, Jones M, Jefferson T. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014; 348: g2547.
  3. Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014; 348: g2545
  4. Krumholz HM, Hines HH. Neuraminidase inhibitors for influenza: The whole truth and nothing but the truth. BMJ 2014; 348: g2548.

Image

Author information

Anand Swaminathan, MD MPH
Assistant Professor Emergency Medicine
Assistant Residency Director
Bellevue/NYU Emergency Department

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