Aripiprazole Medication Study Guide

Aripiprazole Medication Study Guide

Aripiprazole Description

Aripiprazole is an FDA-approved antipsychotic medication for schizophrenia and bipolar disorder in patients above 13 years (Gettu & Saadabad, 2021). It is sold under the names Abilify (most common) and Aristada. The medication effectiveness varies among individuals and populations; thus, it can be used as monotherapy or adjunctive therapy in FDA-approved and off-label uses.

Aripiprazole Medication Study Guide

It helps relieve symptoms such as manic symptoms in bipolar 1, irritability, purposeless actions, major depression, and Tourette syndrome (Gettu & Saadabadi, 2021). In addition, it is used in children above six years for autistic disorder and Tourette syndrome.

It is an off-label treatment for patients with comorbid psychotic and substance use disorders (Gettu & Saadabadi, 2021). Other off-label uses include psychosis and agitation symptoms in dementia and delirium in parkinsonism, but cerebrovascular side effects limit its use.

Classification

Aripiprazole is a second-generation/atypical antipsychotic, which is slowly replacing typical antipsychotics due to the decreased side-effects profile.

Aripiprazole Pharmacokinetics

After oral administration, the drug has an 87% bioavailability and reaches maximum plasma concentration between 3-4 hours, depending on the dose (Soria-Chacartegui et al., 2021).

Soria-Chacartegui et al. (2021) also note that the drug has a linear pharmacokinetic, meaning that its effects depend on the plasma concentration.

In the liver, it is metabolized by CYP2D6 and CYP3A4 to the only active metabolite- dehydro-aripiprazole, which accounts for about 40% of the drug’s plasma concentration.

Drugs (such as codeine, quinidine, and paroxetine) or medical conditions (autoimmune hepatitis) that interfere with CYP2D6 can increase its half-life to 140 hours hence consideration (Soria-Chacartegui et al., 2021). Aripiprazole is mainly excreted in stools and a small amount in urine. Dose adjustments may be necessary when patients develop problems with difficulty urinating.

Aripiprazole Pharmacodynamics

The pharmacodynamics of aripiprazole includes the mechanism of action of a drug, drug interactions, and side effects, discussed shortly.

Mechanism of Action

Aripiprazole is a partial agonist of dopamine (D2) and serotonin (5HT-1a) and antagonizes 5HT-2a receptors, which primarily help it exert its effects. The medication helps achieve a dopamine and serotonin balance in vital brain centres (frontal cortex, nucleus accumbent, ventral tegmental area) and thus helps control negative, positive, and cognitive schizophrenic symptoms.

A 90% occupancy rate at the D2 receptors produces clinically significant results and less extrapyramidal effects (Soria-Chacartegui et al., 2021). Aripiprazole has antagonistic functions in the mesolimbic pathways due to the high dopamine concentration. It is inactive in areas with normal dopamine levels hence its preference over other drugs, such as olanzapine and haloperidol, with similar mechanisms of action.

Appropriate Dosing, Administration Route, and Dosing Alterations Considerations

Aripiprazole is available in tablets, oral solutions, disintegrating tablets, and IM injections. The oral daily dose is between 5-30mg daily given in titrated doses depending on the effectiveness and side effects. The IM long-acting injection is given every 4-6weeks with a three-week-oral dose overlap.

In bipolar 1, the recommended dose is 15mg daily, increased to 30mg PO daily as the need arises. The maximum dose targeted when the drug is used as an adjunct therapy is 15mg daily. Drug dose reductions are necessary for concurrent CYP3A4 and CYP2D6 inhibitors administration. The medication is gradually titrated when weaning the patient to prevent withdrawal symptoms.

Aripiprazole in Special Populations

Aripiprazole is FDA-approved for schizophrenia and bipolar disorder in patients above 13 years. It is only used for Tourette syndrome and agitation in autistic disorders. The medication is safe for pregnant women, but the baby is observed for withdrawal symptoms.

It is used with caution in elderly patients with dementia-induced psychosis. The medication is stopped when patients develop mood changes and suicidal ideations and are contraindicated in patients with suicidal behaviors and tendencies.

Half-life

Half-life is the time it takes the drug’s plasma concentration to reduce by half. The half-life of medications helps care providers determine the appropriate dosing, frequency, and duration of a drug while maintaining therapeutic effectiveness and avoiding side effects. It also helps care providers avoid issues such as toxicity.

The drug achieves a similar plasma concentration after oral or IM drug administration. It has a half-life of 75 hours and achieves a steady concentration after fourteen days.

Drug Side Effects

The drug’s common side effects include visual changes, drooling, muscle stiffness, and akathisia. The drug has various side effects, but the extrapyramidal and metabolic effects are few compared to those in other antipsychotics due to the specificity of dopamine and serotonin receptors (Gettu & Saadabadi, 2021).

The drug carries an FDA-black box warning of cerebrovascular events and death in seniors and suicidal thoughts and ideations, and children, adolescents, and younger adults (Coustals et al., 2021).

Overdose Considerations

Drug doses above 30mg/day are considered an overdose and lead to drug toxicity. Drug overdose can be deliberate or result from using it with other drugs. It does not have an antidote, and management is supportive. However, activated charcoal may bind the drug and prevent absorption.

Complications

Although rare, complications such as neuroleptic malignant syndrome, liver pathologies, jaundice, agranulocytosis, and epilepsy may result from aripiprazole use.

Contraindications

Contraindicated in patients with hypersensitivity to the drug

Dementia-related psychosis in elderly patients (Lertxundi et al., 2021)

Individuals with suicidal thoughts and behaviors

The dose is adjusted in adjunct therapies with other antipsychotics due to the exacerbation of positive psychotic symptoms (Gettu & Saadabadi, 2021)

Diagnostics and Lab Monitoring (BULLBO)

Baseline measurements such as weight, height, and vital signs

Urea and UECs

Liver function tests

Libido- sexual drive changes

Blood sugar measurements (FBS, RBS, and HbA1c)

Ocular exams (for visual changes, a common side effect)

Legal and Ethical Considerations in Aripiprazole Use

The drug should be prescribed by a nurse practitioner, psychiatrist, or a primary care provider

Before administration, a care provider should obtain baseline measurements, including EKG, blood pressure, CMP, CBC, liver transaminase levels, BUN, and creatinine due to its side effects (Gettu & Saadabadi, 2021)

Switching from one aripiprazole to another medication should be gradual, and vice versa and documentation should be promptly done.

Medication should be used for the indicated symptom, no sharing of drugs, and they should be kept out of reach of children.

The medication should be reconsidered for patients with high-risk jobs, such as truck drivers to the side effects (Predo & Shapiro et al., 2020).

Pertinent Patient Education

It is vital to educate the patient on the drug, dosage, and side effects (such as suicidal ideations and mood ideas should be promptly reported).

When a patient misses the dose, they should take the dose immediately after they remember but should skip the dose if the time for the next dose is near- taking two diseases can be toxic

Overdose symptoms include drowsiness, nausea and vomiting, irritability, confusion, tremors, tachycardia, bradycardia, and syncope. An individual should report to the healthcare facility immediately.

Only use the medication for the purpose indicated, keep it away from children, and do not share the drugs.

Conclusion

Aripiprazole is a second-generation antipsychotic medication used in schizophrenia and bipolar 1 disorder.

The medication is safe for patients aged 13 and above

It is also used in children above age six for Tourette syndrome and autistic disorder

It should be used with caution in elderly patients and pregnant mothers

Withdrawal of the drug should be gradual, and so should be dose increment

The drug is associated will less metabolic and extrapyramidal side effects

References

  • Coustals, N., Ménard, M. L., & Cohen, D. (2021). Aripiprazole in children and adolescents. Journal of Child and Adolescent Psychopharmacology31(1), 4-32. https://doi.org/10.1089/cap.2020.0014
  • Gettu, N., & Saadabadi, A. (2021). Aripiprazole. In StatPearls [Internet]. StatPearls Publishing.
  • Lertxundi, U., Hernández, R., & Medrano, J. (2021). Aripiprazole: features and use in the aged. In Assessments, Treatments, and Modeling in Aging and Neurological Disease (pp. 355-365). Academic Press. https://doi.org/10.1016/B978-0-12-818000-6.00032-9
  • Preda, A., & Shapiro, B. B. (2020). A safety evaluation of aripiprazole in the treatment of schizophreniaExpert Opinion on Drug Safety19(12), 1529-1538. https://doi.org/10.1080/14740338.2020.1832990
  • Soria-Chacartegui, P., Villapalos-García, G., Zubiaur, P., Abad-Santos, F., & Koller, D. (2021). Genetic polymorphisms associated with the pharmacokinetics, pharmacodynamics and adverse effects of olanzapine, aripiprazole and risperidone. Frontiers in Pharmacology, 12, 711940. https://doi.org/10.3389/fphar.2021.711940

Assignment: Study Guide for Medication Treatment Schizophrenia Spectrum and Other Psychosis Disorders Instructions

Psychosis and schizophrenia greatly impact the brain’s normal processes, which interfere with the ability to think clearly. When symptoms of these disorders are uncontrolled, patients may struggle to function in daily life. However, patients often thrive when properly diagnosed and treated under the close supervision of a psychiatric mental health practitioner.

For this Assignment, you will develop a study guide for an assigned psychotropic agent for treating patients with Schizophrenia Spectrum and Other Psychotic Disorders. You will share your study guide with your colleagues. In sum, these study guides will be a powerful tool in preparing for your course and PMHNP certification exam.

To prepare for this Assignment:

Review this week’s Learning Resources, including the Medication Resources indicated for this week.
Reflect on the psychopharmacologic treatments you might recommend for treatment of patients with Schizophrenia Spectrum and Other Psychotic Disorders.

Research your assigned psychotropic medication agent using the Walden Library. Then, develop an organizational scheme for the important information about the medication.
Review Learning Resource: Utah State University. (n.d.). Creating study guides. https://www.usu.edu/academic-support/test/creating_study_guides

The Assignment

Create a study guide for your assigned psychotropic medication agents. Your study guide should be in the form of an outline with references, and you should incorporate visual elements such as concept maps, charts, diagrams, images, color coding, mnemonics, and/or flashcards. Be creative! It should not be in the format of an APA paper. Your guide should be informed by the FDA-approved and Evidenced-Based, Clinical Practice Guidelines Research but also supported by at least three other scholarly resources.

Areas of importance you should address, but are not limited to, are:

Title page
Description of the Psychopharmacological medication agent including brand and generic names and appropriate FDA indication uses
Any supporting, valid and reliable research for non-FDA uses
Drug classification
The medication mechanism of action
The medication pharmacokinetics
The medication pharmacodynamics
Mechanism of Action
Appropriate dosing, administration route, and any considerations for dosing alterations
Considerations of use and dosing in specific specialty populations to consider children, adolescents, elderly, pregnancy, suicidal behaviors, etc.
Definition of Half-life, why half-life is important, and the half-life for your assigned medication
Side effects/adverse reaction potentials
Contraindications for use including significant drug to drug interactions
Overdose Considerations
Diagnostics and labs monitoring
Comorbidities considerations
Legal and ethical considerations
Pertinent patient education considerations
Reference Page
Note: Support your rationale with a minimum of five academic resources. While you may use the course text to support your rationale, it will not count toward the resource requirement. You should be utilizing the primary and secondary literature.

Rubric

Excellent

Point range: 90–100 Good

Point range: 80–89 Fair

Point range: 70–79 Poor

Point range: 0–69
Create a study guide, in outline form with references, for your assigned medication. Incorporate visual elements such as concept maps, charts, diagrams, images, color coding, mnemonics, and/or flashcards.
27 (27%) – 30 (30%)
The response is in a well-organized and detailed outline form. Informative and well-designed visual elements are incorporated.

Followed directions correctly by uploading assignment to Gradebook and submitted to the discussion forum area.
24 (24%) – 26 (26%)
The response is in an organized and detailed outline form. Appropriate visual elements are incorporated.

Partially followed directions by uploading assignment to Gradebook but did not submit to the discussion forum area.
21 (21%) – 23 (23%)
The response is in outline form, with some inaccuracies or details missing. Visual elements are somewhat vague or inaccurate.

Partially followed directions by submitting to the discussion forum area but did not upload assignment to Gradebook.
0 (0%) – 20 (20%)
The response is unorganized, not in outline form, or is missing. Visual elements are inaccurate or missing.

Did not follow directions as did not submit to discussion forum area and did not upload assignment to gradebook per late policy.
Study guide completion elements addressed in Week 7 assignment area
45 (45%) – 50 (50%)
The response thoroughly addresses all required content areas.
40 (40%) – 44 (44%)
The response adequately addresses all required content areas. Minor details may be missing.
35 (35%) – 39 (39%)
The response addresses all required content areas, with some inaccuracies or vagueness.
0 (0%) – 34 (34%)
The response vaguely or inaccurately addresses the required content areas. Or, three or more content areas are missing.
Support your guide with references and research providing at least five evidence-based, peer-reviewed journal articles or evidenced-based guidelines. Be sure they are current (no more than 5 years old).
9 (9%) – 10 (10%)
The response is supported by the 5 current, evidence-based resources from the literature.
8 (8%) – 8 (8%)
The response provides at least 4 current, evidence-based resources from the literature that appropriately support the study guide information.
7 (7%) – 7 (7%)
3 evidence-based resources are provided to support the study guide, but they may only provide vague or weak justification.
0 (0%) – 6 (6%)
2 or fewer resources are provided to support assessment and diagnosis decisions. The resources may not be current or evidence-based.
Written Expression and Formatting – English writing standards:
Correct grammar, mechanics, and proper punctuation
5 (5%) – 5 (5%)
Uses correct grammar, spelling, and punctuation with no errors.
4 (4%) – 4 (4%)
Contains a few (1 or 2) grammar, spelling, and punctuation errors.
3.5 (3.5%) – 3.5 (3.5%)
Contains several (3 or 4) grammar, spelling, and punctuation errors.
0 (0%) – 3 (3%)
Contains many (≥ 5) grammar, spelling, and punctuation errors that interfere with the reader’s understanding.
Written Expression and Formatting – The paper follows correct APA format for title page, headings, font, spacing, margins, indentations, page numbers, parenthetical/in-text citations, and reference list.
5 (5%) – 5 (5%)
Uses correct APA format with no errors.
4 (4%) – 4 (4%)
Contains a few (1 or 2) APA format errors.
3.5 (3.5%) – 3.5 (3.5%)
Contains several (3 or 4) APA format errors.
0 (0%) – 3 (3%)
Contains many (≥ 5) APA format errors.

Clozapine Study Guide Example

Description

Clozapine Study Guide

Clozapine is an FDA-approved second-generation antipsychotic medication used to treat psychotic symptoms in the mentally ill, especially schizophrenic patients, as a second-line medication (U.S. Food & Drug Administration). Clozapine is used to manage recurrent suicidal behavior in schizophrenia and schizoaffective disorders. It is marketed as Clozaril, Fazaclo ODT, Versacloz, CloZAPine Synthon, Denzapine, and Zaponex. The REMSprogram regulates these manufacturers to provide a central prescribing and monitoring center (Haidary & Pathy, 2021). Clozapine is an effective medication used for refractory bipolar disorder as an off-label medication.

Classification

Clozapine is a second-generation antipsychotic- an atypical antipsychotic in the class.

Mechanism of Action

Clozapine binds to the serotonin and dopamine receptors. It has a high affinity for D4 receptors but also binds to D1, D2, D3, and D5 receptors (Haidary & Padhy, 2021). The drug is more active in the limbic than striatal regions; hence, less extrapyramidal effects are experienced in other medications. The drug is a partial serotonin receptor agonist, thus its ability to improve anxiety, depression, and negative symptoms. The drug also acts on adrenergic, cholinergic, and histamine receptors hence its side effects.

Side effects

The mnemonic CLOZIE can be used to indicate its side effects

C- cytopenia (agranulocytosis) (Mijovic & MacCabe, 2020)

L- bradycardia and reflex tachycardia

O- obesity- weight gain, constipation,

Z- Zap-sedation, drowsiness, dizziness, constipation, and excessive salivation

I- Incontinence- urinary incontinence

E- epilepsy in non-epileptic patients due to the lowered threshold and worsening seizures in epileptic patients (U.S. Food & Drug Administration)

Comorbidities associated with clozapine

The most severe side effect of the drug is neutropenia leading to severe bone infections, hence the need to monitor absolute neutrophil count for patients on clozapine. Haidary and Padhy (2021) note that clozapine is also associated with increased risk and incidences of myocarditis. In addition, other comorbidities include neutropenia, hypotension, bradycardia, and syncope. In addition, patients can experience seizures, myocarditis, and an increased risk of death.

Pharmacokinetics

Clozapine is well-absorbed, with 6-70% bioavailability after oral consumption due to first-pass metabolism (U.S. Food & Drug Administration). The major metabolite, norclozapine, is metabolically active, but the other metabolites are for excretion in urine and feces. The cytochrome P450 isoenzyme 1A2 is the major enzyme in clozapine metabolism. Thus, agents that induce or inhibit the enzyme can affect its metabolisms and subsequent bioavailability. For example, cigarette smoke indices the CYP450 system, and thus the non-smokers require almost a double dose to achieve the same drug plasma level as non-smokers (U.S. Food & Drug Administration). The peak plasma concentration time is 21/2 hours, and food does not affect its absorption. Thus, it can be taken with food, before or after food.

Half-life

Figure 3 Clozapine half-life

Half-life is the amount of time taken for the plasma volume of a drug to reduce by half. The half-life of clozapine is 14 hours, but that depends on the dose and frequency. Thus, studying the plasma levels can help predict drug compliance, metabolic status, possible interference, dose-effect relationship, and toxicity monitoring.

Appropriate dosing, administration route, and any considerations for dosing alterations

The ideal dosage for clozapine is 12.5mg orally once daily. The dose is then titrated to 20 -50mg daily, given in divided doses. Subsequent increments after two weeks can entail 100mg weekly, and the maximum dose is 900mg per day, above which toxicity sets in (Medicine.com, n.d.).

Clozapine treatment is commenced at a low dose due to the severe drug side effects. The doses also vary, with younger patients requiring smaller doses and older adults much lower doses. Maintenance therapy is usually best done at night before bedtime to promote quality sleep because the drug induces drowsiness, affecting work quality.

Dosage alteration to reduce the dose is necessary for renal and liver disorders because the drug is metabolized in the liver and excreted in bile and urine. The drug should be withdrawn in cases of neutropenia. Reduce dose when using a concurrently CYP450 1A2 inhibitor, such as an increased dose when using a CYP450 1A2 inducer such as carbamazepine. Routine dose-effect monitoring for weak inducers and inhibitors of the CYP450 1A2 is recommended.

Lab monitoring

WBC count and WBC differentials

Urea ad electrolytes due to risk for QT elongation (Funk et al., 2018)

EKG/ECG to monitor cardiac function

Weight, lipid profile, and blood sugar measurements (HbA1c)

Suicidal tendencies and behaviors assessment

Contraindications

Clozapine is contraindicated in patients with uncontrolled epilepsy, myeloproliferative disease, and agranulocytosis secondary to prior clozapine treatment (Funk et al., 2018).

It is contraindicated in pregnant and breastfeeding mothers.

De Leon et al. (2020) notes that the clozapine medication dose is altered for patients on fluvoxamine and requires magnitude dose adjustment if the two drugs are used concurrently because it inhibits clozapine metabolism.

Combining the drug with aripiprazole may worsen cardiovascular symptoms

Alcohol increases the central nervous system suppression hence worsening drowsiness, dizziness, and poor attention

Legal and Ethical Considerations

Clonazepam is used in patients who have been resistant to other medications. It is important to consider the potential for morbidities in immunocompromised patients, issues such as drug adherence, and the importance of a treatment assistant. These patients should have a treatment companion who monitors their medication adherence and other symptoms. Convincing schizophrenic patients to involve their family members in their management is challenging but vital (Stern et al., 2016). Most importantly, care providers should weigh the drug’s benefits against the risks for individual patients before initiating therapy.

Patient Education Pertinent to the drug

Patient education often entails patient and family education. It should entail information on side effects and risk for agranulocytosis and participation in the REMS program for monitoring (De Leon et al., 2020). Information on risk for bradycardia, syncope, and effects on thinking, judgment, and motor skills.

After missing the drugs for two days, the patient should also visit the healthcare provider. In addition, contact the healthcare professional if pregnant, breastfeeding, or planning to be pregnant.

References

De Leon, J., Ruan, C. J., Schoretsanitis, G., & De las Cuevas, C. (2020). A rational use of clozapine based on adverse drug reactions, pharmacokinetics, and clinical pharmacopsychology. Psychotherapy and Psychosomatics89(4), 200-214. https://doi.org/10.1159/000507638

Funk, M. C., Beach, S. R., Bostwick, J. R., Celano, C. M., Hasnain, M., Pandurangi, A., Khandai, A., Taylor, A., Levenson, J. L., Riba, M., & Kovacs, R. J. (2018). Resource document on QTc prolongation and psychotropic medications. American Psychiatric Association. https://www.psychiatry.org/File%20Library/Psychiatrists/Directories/Library-and-Archive/resource_documents/Resource-Document-2018-QTc-Prolongation-and-Psychotropic-Med.pdf

Haidary, H. A., & Padhy, R. K. (2021). Clozapine. In StatPearls [Internet]. StatPearls Publishing.

Medicine.com (n.d.). Clozapine. https://www.medicine.com/drug/clozapine/hcp

Mijovic, A., & MacCabe, J. H. (2020). Clozapine-induced agranulocytosis. Annals of hematology99(11), 2477-2482. https://doi.org/10.1007/s00277-020-04215-y

Stern, T. A., Favo, M., Wilens, T. E., & Rosenbaum, J. F. (2016). Massachusetts General Hospital psychopharmacology and neurotherapeutics. Elsevier.

U.S. Food & Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm