ABIMBOLA FARINDE, PhD, PharmD
Abimbola Farinde, PhD., PharmD is a healthcare professional and professor who has gained experience in the field and practice of mental health, geriatrics, and pharmacy. She has worked with active duty soldiers with dual diagnoses of a traumatic brain injury and a psychiatric disorder providing medication therapy management and disease state management. Dr. Farinde has also worked with mentally impaired and developmentally disabled individuals at a state supported living center. Her different practice experiences have allowed her to develop and enhance her clinical and medical writing skills over the years. Dr. Farinde always strives to maintain a commitment towards achieving professional growth as she transitions from one phase of her career to the next.
Topic Overview Aripiprazole is an atypical, second-generation antipsychotic that is mainly indicated in the treatment of depression, anxiety, bipolar I disorder and schizophrenia. It is also used for agitation in autism and for the treatment of Tourette disorder. Adult and pediatric use of aripiprazole is discussed in the literature and the American Pediatric Association has developed guidelines for the use of aripiprazole for the treatment of conduct disorder with aggression, irritability in children with autism and other personality disorders in youth. The potential of neuroprotective effects with aripiprazole use has been studied. Studies also show a lower risk of adverse effects with aripiprazole as compared with other antipsychotic drugs.
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Credits: 1 hour of continuing education credit
Type of Activity: Continuing education
Media: Internet Fee Information: $9
Estimated time to complete activity: 1 hour, including Course Test and course evaluation
Published: May 10, 2021 Expires: May 9, 2024
Target Audience: This continuing education activity is intended for licensed pharmacists and associates to update knowledge on influenza vaccination and on safe prescribing guidelines.
How to Earn Credit: From May 10, 2021, through May 9, 2024, participants must:
1) Read the “learning objectives” and “author and planning team disclosures;” 2) Study the section entitled “educational activity;” and 3) Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)
Educational Objectives: Upon completion of this educational activity, participants should be able to:
1. Describe the basic pharmacological profile, use and clinical outcomes of aripiprazole treatment
2 RXCE.com 2. Identify the dosing and uses for oral and long-acting injectable forms of aripiprazole, as well as the recommendations when switching between antipsychotics 3. Compare the benefits and risks of aripiprazole use for chronic mentally illness patients compared to other antipsychotics 4. Identify the contraindications and potential side effects of aripiprazole
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3 RXCE.com Introduction
Aripiprazole is a second-generation, atypical antipsychotic that is best known under the brand name Abilify®. It was originally approved for the treatment of schizophrenia and bipolar I disorder but it has also been used for other psychiatric conditions in children and adults. Studies suggest that aripiprazole is superior to placebo and many first- and second-generation antipsychotics, and it is typically well tolerated. Aripiprazole is available in oral and long-acting injectable forms, which have unique pharmacokinetic profiles that must be considered when formulating a treatment plan. Treatment plans should account for the adverse effects antipsychotic medications may cause but aripiprazole has a favorable side-effect profile when compared to other antipsychotics. There are also recommendations clinicians should follow when switching to aripiprazole from another antipsychotic.
Pharmacological Profile of Aripiprazole
Aripiprazole is a second-generation, atypical antipsychotic that can be neuroprotective.1,2 Aripiprazole is a dopamine partial agonist due to its agonist pharmacology at certain receptor targets, most notably D2 autoreceptors. This distinguishes it from the first-generation dopamine antagonist or blockers.3 While still referred to as a second-generation antipsychotic, aripiprazole is also referred to as a “prototypical third-generation antipsychotic” because of its unique characteristics.3 Moreover, it is also likely an H1 antagonist.3
Uses and Dosing for Aripiprazole
Aripiprazole has a labeled use to treat schizophrenia, bipolar I disorder, Tourette’s syndrome, and as an adjunctive therapy for major depressive disorder.1 Aripiprazole also has approved use as a treatment for autistic disorder with symptoms of irritability;4 and, it is used for other psychiatric conditions involving symptoms of depression and anxiety. Individuals reporting symptoms of agitation and/or psychosis associated with dementia have been treated successfully with aripiprazole as an off-label use.5
4 RXCE.com Clinical trials have established the efficacy and tolerability of oral aripiprazole at dosing ranges between 10 to 15 mg once daily, which can be increased in 5 mg increments approximately every week to a maximum dose of 30 mg/day.1,2 Aripiprazole is also available in a long-acting, monthly injectable form.6
Long-acting Injectable Form
Long-acting injectable antipsychotics have a unique pharmacokinetic profile, which make them particularly beneficial in the treatment of psychiatric conditions such as schizophrenia.6 Studies show that these drugs reduce psychopathology, hospitalizations, and mortality risks in patients. This is partly due to the development and use of new delivery mechanisms that enable long-acting injectables to help improve patient adherence to a treatment plan. This in turn reduces the likelihood that a patient may relapse.6
It is important for clinicians to understand the pharmacokinetic and other differences between the oral and long-acting forms of aripiprazole: a misunderstanding of these differences may lead to poorer outcomes for patients.6 For example, a long-acting injectable form of aripiprazole will “exhibit flip-flop kinetics” that impact the time it takes for the drug to reach steady state because of its slower rate of absorption.6 Long-acting injectables “have more restrictive dose limitations than oral treatments.”6 This may not be important since high-dose long-acting injectable treatment may not provide a better treatment outcome compared to doses within the normal therapeutic range.6 Correll, et al. (2021) discuss the importance of individualizing a treatment plan, utilizing an oral antipsychotic before switching to a long-acting form, knowing when it is best to make dose adjustments, understanding the different dosing schedules for the distinctive forms of aripiprazole, e.g., aripiprazole lauroxil versus aripiprazole monohydrate, etc., and understanding that if adverse effects do present with aripiprazole, the use of a long-acting drug may prolong their duration.6
5 RXCE.com Switching Antipsychotic Drugs
Careful monitoring of a patient is recommended when the patient switches from one antipsychotic to another.7,8 For example, a patient’s provider may recommend that the patient change from seroquel or risperdal to aripiprazole. The patient should be evaluated for metabolic responses after the change in drugs.7,8 Metabolic responses may include weight gain but this is typically not clinically significant with aripiprazole.2 A clinician may prescribe metformin or a statin to control this effect.7
Side Effects of Aripiprazole
Aripiprazole has a favorable side-effect profile when compared to first- generation antipsychotics and when compared to other atypical antipsychotics.2,9 Aripiprazole has a low incidence of extrapyramidal side- effects, weight gain, cardiovascular issues, hyperprolactinemia, hypercholesterolemia, and metabolic syndrome.2 Aripiprazole does not appear to have a higher incidence of extrapyramidal side-effects when compared to placebo at any dose; however, when aripiprazole is combined with haloperidol, there may be a slightly higher increase in extrapyramidal side-effects.2
Children and adolescents have been reported to have an increase in extrapyramidal side-effects when they are treated with aripiprazole. There is also one reported case of acute dystonia from a single dose of aripiprazole in a patient suffering from a cocaine dependence.2
At doses of 20 and 30 mg/day, aripiprazole was associated with a minimal increase in body weight but this was not “clinically significant” since the incidence of weight gain differed about 7% when compared to patients who received a placebo.2 The long-acting injectable form of aripiprazole perform similarly when it comes to side-effects.2
6 RXCE.com Aripiprazole Treatment
Bipolar I Disorder
The initial clinical trials of aripiprazole as an acute treatment for onset of manic episodes in patients who had bipolar I disorder established its effectiveness for this purpose.10-12 Subsequent research, published literature, authoritative reviews, and meta-analyses have confirmed this, and have reported significant efficacy in reducing the severity of manic episodes in patients who have bipolar disorder.13-17 In addition, aripiprazole in combination with lithium or valproic acid has been shown to be effective as a maintenance treatment for treating patients who have bipolar I disorder.17,18
Recommended monotherapy or adjunctive dosing of aripiprazole for the treatment of manic or mixed mood states associated with bipolar I disorder include 10 to 15 mg once daily, which may increase 5 to 10 mg/day over a one-week period to a maximum dose of 30 mg/day depending on a patient’s response and tolerability.1
Long-acting injectable aripiprazole was approved in July 2017 by the FDA as a maintenance monotherapy treatment for adults who have bipolar I disorder.18 The approval was based on the results of a double-blind, placebo- controlled, 52-week randomized withdrawal study.18 This study found that a once a month 400 mg IM dose of injectable aripiprazole significantly decreased the time to recurrence of mood episodes and the rate of mood episodes.18
Major Depressive Disorder
The atypical antipsychotics are recommended as an adjunctive treatment for the treatment of major depressive disorder, and aripiprazole has a comparatively favorable benefit and risk profile. It was approved by the FDA for this purpose in 2007, and the initial clinical trials and later research established that aripiprazole is effective and that the clinical benefits are long- lasting.19-22
7 RXCE.com Schizophrenia
Aripiprazole has been proven to be an effective treatment for schizophrenia.23-28 There is currently no convincing evidence that one antipsychotic is better than any other in terms of efficacy for treating schizophrenia, and comparative studies of the atypical antipsychotics have been described as having low to very low quality of evidence and are difficult to use clinically. However, there are definite and important differences between antipsychotics in their adverse effect profiles and their suitability for a specific patient.23-28 Many clinicians consider the adverse effect profile of aripiprazole (risk of metabolic changes, risk for anticholinergic effects, orthostatic hypotension, and QT prolongation) to be equal to many of the other atypical antipsychotics, which are believed to be superior to first- generation antipsychotics.23-28
Long-acting antipsychotics, including aripiprazole, have been effective at reducing the symptoms of schizophrenia.23-28 Long-acting injectable antipsychotics seem to have better adherence rates for schizophrenic patients when compared to oral forms. Reports of schizophrenic patients using oral antipsychotics have shown adherence below 60%.27 The long-acting injectable antipsychotics have inherent advantages like a need for less frequent dosing that would intuitively seem to help increase patient adherence. However, the evidence that the long-acting injectable formulations of the antipsychotics increase adherence is inconclusive.27,28
Autistic Disorder
Aripiprazole has FDA approval (2009) for treating irritability in children who have autism spectrum disorder and has been recommended for this purpose.29,30 Multiple clinical trials found that aripiprazole significantly improved the Aberrant Behavior Checklist (ABC) and Clinical Global Impressions – Improvement (CGI-I) scale of children and adolescents.30,31
One 52-week, open-label study of aripiprazole flexible-dosing of 2– 15 mg/day focused on the treatment of irritability associated with autistic
8 RXCE.com disorder in children and adolescents.32 An estimated 38.2% of the study subjects were given concomitant antidepressants (13.4%), psychostimulants (11.5%), and antiepileptics (5.9%).32 At week 52, the authors reported, “mean change from baseline in Aberrant Behavior Checklist Irritability subscale scores was −8.0 in de novo subjects and −6.1 in prior placebo subjects; prior aripiprazole subjects maintained symptom improvement that was achieved with treatment in the prior study.”32 A majority of study subjects reportedly had a Clinical Global Impressions–Improvement score of 2 (much improved) or 1 (very much improved).32
The evidence suggests that aripiprazole may be an effective maintenance treatment for symptoms of irritability in children with autistic disorder. Clinicians should be informed that aripiprazole use has been associated with significant side effects including aggression, extrapyramidal symptoms, increased appetite, sedation, and weight gain.29-31
Tourette’s Syndrome
Until 2014, the typical antipsychotics haloperidol and pimozide had been the only medication with an FDA-approved, labeled use for treating Tourette syndrome but aripiprazole was approved for this use in that year.33 Case reports had found that aripiprazole was effective for treating Tourette’s syndrome, and clinical studies that measured its effectiveness with the Yale Global Tic Severity Scale YGTSS) and the Clinical Global Impression – Tourette Syndrome (CGI-TS) confirmed the data from the earlier research.33,34 A subsequent study suggested that aripiprazole could be a treatment option for children and adolescents with tic disorders.35 Children and adolescents appear to tolerate this drug fairly well. Adverse events common to this age group in this study were “somnolence, headache, sedation, and nausea and vomiting.”35
9 RXCE.com Suicidal Ideation
The FDA requires a U.S. Boxed Warning about antidepressants and suicide. Aripiprazole is not categorized as an antidepressant; however, the atypical antipsychotics are often prescribed for patients who have unipolar major depression.11,12 Although the FDA data analysis that was used as the basis for the U.S. Boxed Warning about antidepressants and suicide did not include information about the atypical antipsychotics, the prescribing information for aripiprazole and the other atypical antipsychotics is required to include the U.S. Boxed Warning about suicide.11,12
There is some evidence that atypical antipsychotics may reduce the risk for suicide. To this end, certain atypical antipsychotics have a labeled use for reducing the risk of suicidal behavior in patients with schizophrenia or schizoaffective disorder.36 The strength of this effect and whether it truly occurs is unclear, and this is also true of aripiprazole. There is encouraging evidence that aripiprazole decreases the risk for suicide but the evidence is not conclusive.36 Ringbäck, et al. (2014) reported that patients who were prescribed aripiprazole, along with patients presecribed clozapine or olanzapine, had a reduced risk of suicide compared to patients administered other antipsychotics.36 Weisler, et al. (2011) reported on study subjects prescribed aripiprazole 2 mg, 10 mg, or a placebo for six weeks, and suicidal ideation was noticed more in subjects who had taken the placebo.37
Some prior studies suggested that aripiprazole use could correspond with worsening decompensation in psychotic patients previously treated with antipsychotic drugs. This involved either switching to or adding aripiprazole in patients thought to be treatment resistant and/or susceptible to dopamine supersensitivity psychosis (DSP), which is thought to be the basis of rebound psychosis, drug tolerance, and tardive dyskinesia.38 Many of these were difficult cases that involved prior antipsychotic dosing that prescribed higher than recommended dosing. While some studies reported increased psychiatric treatment failure with aripiprazole use as compared to other antipsychotic drug use, other reviews of clinical trials involving severe mental illness showed no association between aripiprazole use and worsening psychosis when
10 RXCE.com compared to other antipsychotic drug use.39 More research is needed on the potential risk of psychiatric treatment failure in patients with more severe psychiatric diseases and who were highly exposed to antipsychotic drugs before switching to aripiprazole.
Dementia-Related Psychosis
The prescribing information for many of the atypical antipsychotics has a U.S. Boxed Warning that advises clinicians that the use of these drugs in elderly patients who have dementia increases the risk of death.1,12,40 This Boxed Warning was added to the prescribing information because an analysis by the FDA of 17 placebo-controlled trials found that the risk of death in the treated patients was 1.6 – 1.7 times that of the patients who received a placebo.40 The rate of death in the patients receiving an antipsychotic was 4.5%, and for the placebo group it was 2.6%; most of the deaths appeared to be from cardiovascular causes or infection.12,40 In 2008 this warning was extended.40 The FDA had determined that the typical antipsychotics were associated with this risk as well, and their assessment was confirmed by a randomized, placebo-controlled trial and a separate meta-analysis.40
Rubino, et al. (2020) stated that “several studies reported a decreased prevalence of antipsychotic medication use by elderly patients with dementia after the 2005 warning. However, the warning’s long-term association with health outcomes in elderly patients remains unknown.”40 The authors attempted to compare the use of atypical antipsychotics with other psychiatric medications, and opioids, by looking at health events, cardiovascular and cerebrovascular events, falls and/or fractures, and mortality. They suggested that the boxed warning on the use of antipsychotics may have been associated with unanticipated outcomes and potential harm.40 According to Furey and Wilkins (2016), no FDA-approved treatment options are available for prescribers to reference in the treatment of dementia-related behavioral disorders, such as agitation and psychosis, but there are randomized controlled trials supporting atypical antipsychotic use in cautious amounts to help control symptoms.41 Expert consensus and professional guidelines reference second-generation antipsychotics for certain cases involving elderly
11 RXCE.com patients where other treatment has failed.41 The off-label atypical antipsychotic use for elderly patients, including those diagnosed with dementia has reportedly increased over the recent years.41
Case Study: Aripiprazole
The following case study focuses on the treatment of psychosis in older patients with dementia.42 The authors of this case study reported on a 74- year-old female who was diagnosed with Alzheimer's disease (AD) exhibiting hypersexual tendencies to other females, including caregivers and family members.42 The patient eventually required placement at a nursing home where she continued to behave hypersexual toward female peers and staff.42
A social history was obtained that revealed the patient had been married once and had three adult children. Following the death of her husband, the patient’s family noticed that she showed odd behavior, and then developed increased forgetfulness, repetitive behavior, and social withdrawal following hip surgery. A neurologist was consulted and diagnosed her with Alzheimer’s disease (AD) and started donepezil 10 mg daily.42
The patient reportedly became more anxious, restless and showed hallucinatory behavior. Citalopram was titrated up to 40 mg daily, which alleviated symptoms of anxiety but hallucinations (visual and auditory) were increased and corresponded with paranoid delusions. The patient thought someone was chasing her, and isolated indoors with windows closed. She was also noticed to wear bright colorful clothes. Cognitive deficits included “severe memory deficits and visual and auditory hallucinations during the night time.”42
A neuropsychological assessment that used several evaluation scoring tools showed severe “memory impairment, moderate deficit in executive functions, visuospatial ability, attention, and concentration.”42 Memantine (titrated to) 20 mg and quetiapine 25 mg at bedtime were recommended. Symptoms of hallucinations and delusions were reduced on this treatment, although she continued to show a cognitive deficit.42
12 RXCE.com Two of the patient’s three siblings had been diagnosed with Alzheimer’s dementia. Recommended genetic testing had been declined by the patient’s family. Laboratory testing was performed; however, including a complete blood count, electrolytes, renal and liver function tests and vitamin B12 and folate levels, which were within normal limits. An electroencephalogram (EEG) showed “diffuse background slowing without epileptiform activity.”42 A magnetic resonance imaging (MRI) scan was unremarkable.42
Quetiapine 25 mg had been the patient’s mainstay for medication treatment until it was replaced with aripiprazole 2.5 mg, which gradually increased to 10 mg daily. The patient’s hypersexual behaviors toward female staff began to reduce shortly after starting Abilify®, and no hypersexual behaviors were reported while taking aripiprazole treatment. She was able to interact appropriately with other residents and staff of both genders.42
The authors of this case study referenced published reports focused on hypersexuality among patients with dementia and other conditions such as traumatic brain injuries and other neurological disorders. They stated that dementia, specifically, commonly results in hypersexuality and disordered sexual conduct. Despite this fact, there remains a paucity of research to help guide clinicians in the pharmacological and nonpharmacological treatment of individuals with dementia and sexualized behavioral issues.37 Patients, families, nursing staff, amongst other members of the health team need to be educated on the treatment of people diagnosed with dementia who display sexual behavior.42
Summary
Aripiprazole is a second-generation, atypical antipsychotic that is best known under the brand name Abilify®. It was originally approved for the treatment of schizophrenia and bipolar I disorder but it has also been used for other psychiatric conditions in children and adults.
Aripiprazole is available in oral and long-acting injectable forms, which have unique pharmacokinetic profiles that must be considered when
13 RXCE.com formulating a treatment plan. It is important for clinicians to understand the pharmacokinetic and other differences between the oral and long-acting forms of aripiprazole: a misunderstanding of these differences may lead to poorer outcomes for patients: a long-acting injectable form of aripiprazole will impact the time it takes for the drug to reach steady state because of its slower rate of absorption. Long-acting injectables have specific dose limitations compared to oral treatments.
Treatment plans should account for the adverse effects antipsychotic medications may cause but aripiprazole has a favorable side-effect profile when compared to other antipsychotics. Children and adolescents have been reported to have an increase in extrapyramidal side-effects when they are treated with aripiprazole. There are also recommendations clinicians should follow when switching to aripiprazole from another antipsychotic.
Aripiprazole in combination with lithium or valproic acid has been shown to be effective as a maintenance treatment for treating patients who have bipolar I disorder. The atypical antipsychotics are recommended as an adjunctive treatment for the treatment of major depressive disorder. Aripiprazole has been proven to be an effective treatment for schizophrenia. Aripiprazole also has use for the treatment of Tourette’s syndrome and tic disorders.
14 RXCE.com Course Test
1. Aripiprazole is categorized as a second-generation
a. anticonvulsant. b. atypical antipsychotic. c. mood stabilizer. d. typical antipsychotic.
2. Careful monitoring of a patient is recommended when the patient switches to aripiprazole from another antipsychotic because
a. weight gain is a potentially significant adverse effect with aripiprazole. b. patients should be evaluated for metabolic responses after a change in drugs. c. aripiprazole is a first-generation antipsychotic. d. patients usually experience withdrawal syndrome.
3. Aripiprazole is a dopamine
a. antagonist. b. blocker. c. full antagonist. d. partial agonist.
4. Aripiprazole is used as an adjunctive therapy to treat
a. major depressive disorder. b. schizophrenia. c. bipolar I disorder. d. elderly patients with dementia-related psychosis.
5. True or False: Aripiprazole was FDA approved for the treatment of Tourette’s syndrome.
a. True b. False
15 RXCE.com 6. The long-acting injectable form of aripiprazole exhibits ______that impact(s) the time it takes for the drug to reach steady state.
a. rapid absorption b. D2 antagonism c. flip-flop kinetics d. rapid concentration
7. Clinical trials have established the efficacy and tolerability of oral aripiprazole dosing
a. between 15 to 30 mg once daily with incremental increases up to 50 mg/day. b. at a maximum of 50 mg/day. c. starting at 30 mg/day. d. between 10 to 15 mg once daily with incremental increases up to 30 mg/day.
8. Which of the following statements best explains the role of aripiprazole in reducing the risk of suicidal ideation?
a. The evidence proves that aripiprazole reduces this risk. b. There is encouraging evidence that aripiprazole decreases the risk for suicide but the evidence is not conclusive. c. Suicidal ideation is always the same whether a patient receives aripiprazole or a placebo. d. Aripiprazole increases the risk for suicide and suicidal ideation.
9. The reported incidences of extrapyramidal side-effects from the use of aripiprazole
a. are high compared to other antipsychotics. b. are similar to first-generation antipsychotics. c. may be higher when aripiprazole is combined with haloperidol. d. All of the above
10. ______is reportedly higher in children and adolescents who are treated with aripiprazole.
a. extrapyramidal side-effects b. weight loss c. autism spectrum disorder d. tic syndrome
16 RXCE.com References
1. Lexicomp. Aripiprazole (oral and long-acting injectable [Abilify Maintena]): Drug information. UpToDate. 2021. Retrieved from https://www.uptodate.com/contents/aripiprazole-short-acting-oral- and-injectable-and-long-acting-injectable-abilify-maintena-drug- information?search=aripiprazole&source=search_result&selectedTitle= 1~81&usage_type=default&display_rank=1#F136777 2. Tuplin EW, Holahan MR. Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity. Curr Neuropharmacol. 2017;15(8):1192-1207. doi:10.2174/1570159X15666170413115754 3. Casey AB, Canal CE. Classics in Chemical Neuroscience: Aripiprazole. ACS Chem Neurosci. 2017;8(6):1135-1146. doi:10.1021/acschemneuro.7b00087 4. Finding, R, et al. PRACTICE PARAMETER FOR THE USE OF ATYPICAL ANTIPSYCHOTIC MEDICATIONS IN CHILDREN AND ADOLESCENTS. American Academy of Child and Adolescent Psychiatry. 2011. Retrieved from https://www.aacap.org/App_Themes/AACAP/docs/practice_parameter s/Atypical_Antipsychotic_Medications_Web.pdf 5. Kohen I, Lester PE, Lam S. Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole. Neuropsychiatr Dis Treat. 2010;6:47-58. Published 2010 Mar 24. doi:10.2147/ndt.s6411 6. Correll CU, Kim E, Sliwa JK, et al. Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview. CNS Drugs. 2021;35(1):39-59. doi:10.1007/s40263-020-00779-5 7. Stroup TS, McEvoy JP, Ring KD, et al. A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: comparison of antipsychotics for metabolic problems (CAMP). Am J Psychiatry. 2011;168(9):947-956. doi:10.1176/appi.ajp.2011.10111609 8. Liao X, Ye H, Si T. A Review of Switching Strategies for Patients with Schizophrenia Comorbid with Metabolic Syndrome or Metabolic Abnormalities. Neuropsychiatr Dis Treat. 2021;17:453-469. Published 2021 Feb 11. doi:10.2147/NDT.S294521 9. Stroup TS, Gray N. Management of common adverse effects of antipsychotic medications. World Psychiatry. 2018;17(3):341-356. doi:10.1002/wps.20567 10. Center for Drug Evaluation and Research. Abilify. 2016. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/021436Or ig1s041.pdf 11. Aristada. Package Insert. Waltham, MA: Alkermes, Inc. 2018. Retrieved from https://www.aristada.com/downloadables/ARISTADA- PI.pdf.
17 RXCE.com 12. Jibson M. Second-generation antipsychotic medications: Pharmacology, administration, and side effects. UpToDate. 2020. Retrieved from https://www.uptodate.com/contents/second- generation-antipsychotic-medications-pharmacology-administration- and-side- effects?search=abilify%20drug%20interactions&source=search_result &selectedTitle=2~74&usage_type=default&display_rank=1 13. Li DJ, Tseng PT, Stubbs B, et al. Efficacy, safety and tolerability of aripiprazole in bipolar disorder: An updated systematic review and meta-analysis of randomized controlled trials. Prog Neuropsychopharmacol Biol Psychiatry. 2017; 79(Pt B): 89-301. 14. Brown R, Taylor MJ, Geddes J. Aripiprazole alone or in combination for acute mania. Cochrane Database Syst Rev. 2017; (12):CD005000. 15. Stovall J. Bipolar disorder in adults: Choosing pharmacotherapy for acute mania and hypomania. UpToDate. 2018. Retrieved from https://www.uptodate.com/contents/bipolar-disorder-in-adults- choosing-pharmacotherapy-for-acute-mania-and- hypomania?search=bipolar%20disorder%20adult%20treatment&sourc e=search_result&selectedTitle=2~150&usage_type=default&display_r ank=2#H186702750. 16. Lindström L, Lindström E, Nilsson M, Höistad M. Maintenance therapy with second generation antipsychotics for bipolar disorder - A systematic review and meta-analysis. J Affect Disord. 2017; 213:138- 150. 17. Torres-Llenza V, Lakshmin P, Lieberman DZ. Spotlight on once- monthly long-acting injectable aripiprazole and its potential as maintenance treatment for bipolar I disorder in adult patients. Neuropsychiatr Dis Treat. 2018; 14:285-292. 18. Calabrese JR, Jin N, Johnson B. Aripiprazole once-monthly as maintenance treatment for bipolar I disorder: a 52-week, multicenter, open-label study. Int J Bipolar Disord. 2018; 6(1):14. 19. Thase M, Connolly KR. Unipolar depression in adults: Treatment of resistant depression. UpToDate. 2020. Retrieved from https://www.uptodate.com/contents/unipolar-depression-in-adults- choosing-treatment-for-resistant- depression?search=Unipolar%20depression%20in%20adults:%20Trea tment%20of%20resistant%20depression&source=search_result&selec tedTitle=1~150&usage_type=default&display_rank=1 20. Kamijima K, Yasuda M, Yamamura K, Fukuta Y. Real-world effectiveness and safety of aripiprazole augmentation therapy in patients with major depressive disorder. Curr Med Res Opin. 2018; 12:1-8. 21. Lenze EJ, Mulsant BH, Blumberger DM, et al. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for
18 RXCE.com treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet. 2015; 386(1001):2404-2412. 22. Thase M, Connolly KR. Unipolar depression in adults: Management of highly resistant (refractory) depression. UpToDate. 2020. Retrieved from https://www.uptodate.com/contents/unipolar-depression-in- adults-management-of-highly-resistant-refractory- depression?search=Unipolar%20depression%20in%20adults:%20Man agement%20of%20highly%20resistant%20(refractory)%20depression &source=search_result&selectedTitle=1~150&usage_type=default&dis play_rank=1 23. Stroup TS, Marder S. Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. 2020. Retrieved from https://www.uptodate.com/contents/pharmacotherapy-for- schizophrenia-acute-and-maintenance-phase- treatment?search=Pharmacotherapy%20for%20schizophrenia:%20Ac ute%20and%20maintenance%20phase%20treatment&source=search _result&selectedTitle=1~150&usage_type=default&display_rank=1 24. Khanna P, Suo T, Komossa K, et al. Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2014; (1):CD006569. 25. Correll CU, Kohegyi E, Zhao C, et al. Oral aripiprazole as maintenance treatment in adolescent schizophrenia: results from a 52-week, randomized, placebo-controlled withdrawal study. J Am Acad Child Adolesc Psychiatry. 2018; 56(9):784-792. 26. Wang C, Shi W, Huang C, Zhu J, Huang W, Chen G. The efficacy, acceptability, and safety of five atypical antipsychotics in patients with first-episode drug-naïve schizophrenia: a randomized comparative trial. Ann Gen Psychiatry. 2017; 16:47. 27. Lauriello J, Campbell AR. Pharmacotherapy for schizophrenia: Long- acting injectable antipsychotic drugs. UpToDate. 2020; Retrieved from https://www.uptodate.com/contents/pharmacotherapy-for- schizophrenia-long-acting-injectable-antipsychotic- drugs?search=Pharmacotherapy%20for%20schizophrenia:%20Long- acting%20injectable%20antipsychotic%20drugs&source=search_result &selectedTitle=1~150&usage_type=default&display_rank=1 28. Marcus SC, Zummo J, Pettit AR, Stoddard J, Doshi JA. Antipsychotic adherence and rehospitalization in schizophrenia patients receiving oral versus long-acting injectable antipsychotics following hospital discharge. J Manag Care Spec Pharm. 2015; 21(9):754-768. 29. Hirsch LE, Pringsheim T. Aripiprazole for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2016; (6):CD009043. Published 2016 Jun 26. doi:10.1002/14651858.CD009043.pub3 30. Weissman L. Autism spectrum disorder in children and adolescents: Pharmacologic interventions. UpToDate. 2020. Retrieved from
19 RXCE.com https://www.uptodate.com/contents/autism-spectrum-disorder-in- children-and-adolescents-pharmacologic- interventions?search=Autism%20spectrum%20disorder%20in%20chil dren%20and%20adolescents:%20Pharmacologic%20interventions&so urce=search_result&selectedTitle=1~150&usage_type=default&displa y_rank=1 31. Lamy M, Erickson CA. Pharmacological management of behavioral disturbances in children and adolescents with autism spectrum disorders. Curr Probl Pediatr Adolesc Health Care. 2018; 48(10):250- 264. 32. Marcus RN, Owen R, Manos G, et al. Aripiprazole in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder: results from a 52-week, open-label study. J Child Adolesc Psychopharmacol. 2011; 21(3):229-236. 33. Quezada J, Coffman KA. Current Approaches and New Developments in the Pharmacological Management of Tourette Syndrome. CNS Drugs. 2018; 32(1):33-45. doi:10.1007/s40263-017-0486-0 34. Sallee F, Kohegyi E, Zhao J, et al. Randomized, double-blind, placebo- controlled trial demonstrates the efficacy and safety of oral aripiprazole for the treatment of Tourette's disorder in children and adolescents. J Child Adolesc Psychopharmacol. 2017; 27(9):771-781. 35. Yang C, Yi Q, Zhang L, Cui H, Mao J. Safety of aripiprazole for tics in children and adolescents: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98(22):e15816. doi:10.1097/MD.0000000000015816 36. Ringbäck Weitoft G, Berglund M, Lindström EA, Nilsson M, Salmi P, Rosén M. Mortality, attempted suicide, re-hospitalisation and prescription refill for clozapine and other antipsychotics in Sweden-a register-based study. Pharmacoepidemiol Drug Saf. 2014; 23(3): 290- 298. 37. Weisler RH, Khan A, Trivedi MH, et al. Analysis of suicidality in pooled data from 2 double-blind, placebo-controlled aripiprazole adjunctive therapy trials in major depressive disorder. J Clin. Psychiatry. 2011; 72:548–555. 38. Yin J, Barr AM, Ramos-Miguel A, Procyshyn RM. Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review. Curr Neuropharmacol. 2017;15(1):174-183. doi:10.2174/1570159x14666160606093602 39. Montastruc F, Nie R, Loo S, et al. Association of Aripiprazole With the Risk for Psychiatric Hospitalization, Self-harm, or Suicide. JAMA Psychiatry. 2019;76(4):409–417. doi:10.1001/jamapsychiatry.2018.4149 40. Rubino A, Sanon M, Ganz ML, et al. Association of the US Food and Drug Administration Antipsychotic Drug Boxed Warning With
20 RXCE.com Medication Use and Health Outcomes in Elderly Patients With Dementia. JAMA Netw Open. 2020;3(4):e203630. doi:10.1001/jamanetworkopen.2020.3630 41. Furey, K and Wilkins K. Prescribing “Off-Label”: What Should a Physician Disclose? AMA J Ethics. 2016;18(6):587-593. doi: 10.1001/journalofethics.2016.18.6.ecas3-1606. 42. Sarikaya S, Sarikaya B. Aripiprazole for the Treatment of Inappropriate Sexual Behavior: Case Report of an Alzheimer's Disease Patient Known as Heterosexual with Recently Shifted Sexual Orientation to Same Gender. Journal of Alzheimer's Disease Reports. 2018 Jun; 2(1):117- 121. DOI: 10.3233/adr-170041.
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