About Jill Logan, PharmD BCPS

Clinical Pharmacy Specialist, Emergency Medicine
University of Maryland Medical Center

Esmolol Use in Cardiac Arrest


There is an abundance of sympathetic stimulation in patients who present in ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) whether endogenously released as a stress response or exogenously administered in a resuscitation attempt.1 The hope is that sympathetic stimulation will increase the coronary and cerebral perfusion pressure of the patient and aid in resuscitation. However, there are numerous detrimental effects associated with epinephrine such as an increase in myocardial oxygen demand leading to increased ischemia.2

Contrary to traditional teaching, interesting evidence exists in both animal models as well as in limited reports in human subjects that show a potential benefit with beta blockade in cardiac arrest.


Valproic Acid-Induced Hyperammonemic Encephalopathy

Valproic AcidValproic acid is used for a variety of clinical indications including seizures, migraine prophylaxis and treatment, and bipolar disorder. A metabolite of valproic acid, thought to be propionic acid, has the ability to increase ammonia levels by inhibiting a step in the hepatic urea cycle, which may lead to valproic acid-induced hyperammonemic encephalopathy. As a result, patients treated with valproic acid presenting with signs and symptoms of acute mental status changes, increased seizure frequency, and/or gastrointestinal symptoms should be evaluated for elevated ammonia concentrations.


By |2016-11-16T09:41:30-08:00Oct 16, 2014|Tox & Medications|

Atypical Antipsychotic Medication Re-initiation in the ED

Pills antipsychotic medicationThe 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.2–4 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.

MedicationPackage insert: Day 1 dosingRe-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

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.5

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


  1. Minns A, Clark R. Toxicology and overdose of atypical antipsychotics. J Emerg Med. 2012;43(5):906-913. [PubMed]
  2. Risperdal® [package insert].  Titusville, NJ. Janssen Pharmaceutical, Inc; 2007. Rev 11/2013.
  3. Seroquel® [package insert]. Wilmington, DE. AstraZenica; 2013.
  4. Fanapt® [package insert]. East Hanover, NH. Novartis Pharmaceutical Corporation; 1/2013.
  5. Clozapine [package insert]. Morgantown, WV. Mylan Pharmaceuticals Inc. 5/2013.
By |2023-07-30T23:43:01-07:00Apr 22, 2014|Psychiatry, Tox & Medications|

Cyclobenzaprine vs TCA Toxicity

CyclobenzaprineShould we treat a cyclobenzaprine (Flexeril) overdose similar to a tricyclic antidepressant (TCA) overdose? With the only difference between the commonly prescribed muscle relaxant, cyclobenzaprine, and the TCA amitriptyline consisting of a single double bond, should the emergency provider be concerned for life threatening arrhythmias in cyclobenzaprine overdose?


By |2016-11-20T07:20:37-08:00Feb 13, 2014|Tox & Medications|

Tramadol: When to avoid it

TramadolTramadol is a popular agent for the treatment of pain and offers an alternative to opioid therapy. Tramadol exerts its analgesic effects through weak stimulation of the mu opioid receptor as well as inhibiting the reuptake of serotonin and norepinephrine similar to some antidepressant medications. While tramadol may be an effective option for mild to moderate pain in otherwise healthy individuals, the following patients may benefit from an alternative analgesic selection. 1–4


By |2016-11-11T19:18:03-08:00Jan 6, 2014|Tox & Medications|
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