1. Commonly Prescribed for
    • Schizophrenia (ages 13 and older)
    • Maintaining stability in schizophrenia
    • Acute mania/mixed mania (ages 10 and older; monotherapy and adjunct)
    • Bipolar maintenance (monotherapy and adjunct)
    • Depression (adjunct)
    • Autism-related irritability in children ages 6 to 17
    • Acute agitation associated with schizophrenia or bipolar disorder (IM)
    • Bipolar depression
    • Other psychotic disorders
    • Behavioral disturbances in dementias
    • Behavioral disturbances in children and adolescents
    • Disorders associated with problems with impulse control
  2. Class
    Dopamine partial agonist (dopamine stabilizer, atypical antipsychotic, third generation antipsychotic; sometimes included as a second generation antipsychotic; also a mood stabilizer)
  3. How the Drug Works
    • Partial agonism at dopamine 2 receptors
    • Theoretically reduces dopamine output when dopamine concentrations are high, thus improving positive symptoms and mediating antipsychotic actions
    • Theoretically increases dopamine output when dopamine concentrations are low, thus improving cognitive, negative, and mood symptoms
    • Actions at dopamine 3 receptors could theoretically contribute to aripiprazole’s efficacy
    • Partial agonism at 5HT1A receptors may be relevant at clinical doses
    • Blockade of serotonin type 2A receptors may contribute at clinical doses to cause enhancement of dopamine release in certain brain regions, thus reducing motor side effects and possibly improving cognitive and affective symptoms
    • Blockade of serotonin type 2C and 7 receptors as well as partial agonist actions at 5HT1A receptors may contribute to antidepressant actions
  4. How Long Until Abilify Works
    • Psychotic and manic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition and affective stabilization
    • Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients require up to 16–20 weeks to show a good response, especially on cognitive symptoms
  5. If Abilify Works
    • Most often reduces positive symptoms in schizophrenia but does not eliminate them
    • Can improve negative symptoms, as well as aggressive, cognitive, and affective symptoms in schizophrenia
    • Most schizophrenic patients do not have a total remission of symptoms but rather a reduction of symptoms by about a third
    • Perhaps 5–15% of schizophrenic patients can experience an overall improvement of greater than 50–60%, especially when receiving stable treatment for more than a year
    • Such patients are considered super-responders or “awakeners” since they may be well enough to be employed, live independently, and sustain long-term relationships
    • Many bipolar patients may experience a reduction of symptoms by half or more
    • Continue treatment until reaching a plateau of improvement
    • After reaching a satisfactory plateau, continue treatment for at least a year after first episode of psychosis
    • For second and subsequent episodes of psychosis, treatment may need to be indefinite
    • Even for first episodes of psychosis, it may be preferable to continue treatment indefinitely to avoid subsequent episodes
    • Treatment may not only reduce mania but also prevent recurrences of mania in bipolar disorder
  6. If Abilify Doesn’t Work
    • Try one of the other atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, paliperidone, amisulpride, asenapine, iloperidone, lurasidone)
    • If two or more antipsychotic monotherapies do not work, consider clozapine
    • Some patients may require treatment with a conventional antipsychotic
    • If no first-line atypical antipsychotic is effective, consider higher doses or augmentation with valproate or lamotrigine
    • Consider noncompliance and switch to another antipsychotic with fewer side effects or to an antipsychotic that can be given by depot injection
    • Consider initiating rehabilitation and psychotherapy such as cognitive remediation
    • Consider presence of concomitant drug abuse
  7. Best Augmenting Combos for Partial Response or Treatment Resistance for Abilify
    • Valproic acid (valproate, divalproex, divalproex ER)
    • Other mood-stabilizing anticonvulsants (carbamazepine, oxcarbazepine, lamotrigine)
    • Lithium
    • Benzodiazepines
  8. Monitoring before starting an atypical antipsychotic
    • Weigh all patients and track BMI during treatment
    • Get baseline personal and family history of diabetes, obesity, dyslipidemia, hypertension, and cardiovascular disease
    • Get waist circumference (at umbilicus), blood pressure, fasting plasma glucose, and fasting lipid profile
    • Determine if the patient is overweight (BMI 25.0–29.9)obese (BMI >30)has pre-diabetes (fasting plasma glucose 100–125 mg/dL)has diabetes (fasting plasma glucose >126 mg/dL)has hypertension (BP >140/90 mm Hg)has dyslipidemia (increased total cholesterol, LDL cholesterol, and triglycerides; decreased HDL cholesterol)
    • Treat or refer such patients for treatment, including nutrition and weight management, physical activity counseling, smoking cessation, and medical management
  9. Monitoring after starting an atypical antipsychotic
    • BMI monthly for 3 months, then quarterly
    • Consider monitoring fasting triglycerides monthly for several months in patients at high risk for metabolic complications and when initiating or switching antipsychotics
    • Blood pressure, fasting plasma glucose, fasting lipids within 3 months and then annually, but earlier and more frequently for patients with diabetes or who have gained >5% of initial weight
    • Treat or refer for treatment and consider switching to another atypical antipsychotic for patients who become overweight, obese, pre-diabetic, diabetic, hypertensive, or dyslipidemic while receiving an atypical antipsychotic
    • Even in patients without known diabetes, be vigilant for the rare but life-threatening onset of diabetic ketoacidosis, which always requires immediate treatment, by monitoring for the rapid onset of polyuria, polydipsia, weight loss, nausea, vomiting, dehydration, rapid respiration, weakness and clouding of sensorium, even coma
    • Patients with low white blood cell count (WBC) or history of drug-induced leucopenia/neutropenia should have complete blood count (CBC) monitored frequently during the first few months and aripiprazole should be discontinued at the first sign of decline of WBC in the absence of other causative factors
  10. How Abilify Causes Side Effects
    • By blocking alpha 1 adrenergic receptors, it can cause dizziness, sedation, and hypotension
    • Partial agonist actions at dopamine 2 receptors in the striatum can cause motor side effects, such as akathisia
    • Partial agonist actions at dopamine 2 receptors can also cause nausea, occasional vomiting, and activating side effects
    • Mechanism of any possible weight gain is unknown; weight gain is not common with aripiprazole and may thus have a different mechanism from atypical antipsychotics for which weight gain is common or problematic
    • Mechanism of any possible increased incidence of diabetes or dyslipidemia is unknown; early experience suggests these complications are not clearly associated with aripiprazole and if present may therefore have a different mechanism from that of atypical antipsychotics associated with an increased incidence of diabetes and dyslipidemia
  11. Notable Side Effects of abilify
    • Dizziness, insomnia, akathisia, activation
    • Nausea, vomiting
    • Orthostatic hypotension, occasionally during initial dosing
    • Constipation
    • Headache, asthenia, sedation
    • Theoretical risk of tardive dyskinesia
  12. Life-Threatening or Dangerous Side Effects of Abilify
    • Rare neuroleptic malignant syndrome (much reduced risk compared to conventional antipsychotics)
    • Rare seizures
    • Increased risk of death and cerebrovascular events in elderly patients with dementia-related psychosis
  13. Weight Gain with Abilify
    • Reported in a few patients, especially those with low BMIs, but not expected
    • Less frequent and less severe than for most other antipsychotics
    • May be more risk of weight gain in children than in adults
  14. Sedation with Abilify
    • Reported in a few patients but not expected
    • May be less than for some other antipsychotics, but never say never
    • Can be activating
  15. What to Do About Side Effects of Abilify
    • Wait
    • Wait
    • Wait
    • Reduce the dose
    • Anticholinergics or a low dose benzodiazepine or a beta blocker may reduce akathisia when present
    • Weight loss, exercise programs, and medical management for high BMIs, diabetes, dyslipidemia
    • Switch to another atypical antipsychotic
  16. Best Augmenting Agents for Side Effects of Abilify
    • Benztropine or trihexyphenidyl for motor side effects and akathisia
    • Many side effects cannot be improved with an augmenting agent
  17. Usual Dosage Range for Abilify
    • 15–30 mg/day for schizophrenia and mania
    • 2–10 mg/day for augmenting SSRIs/SNRIs in depression
    • 300–400 mg/4 weeks (depot)
  18. Dosage Forms of Abilify
    • Tablet 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg
    • Orally disintegrating tablet 10 mg, 15 mg
    • Oral solution 1 mg/mL
    • Injection 9.75 mg/1.3 mL
    • Depot 300 mg, 400 mg
  19. How to Dose Abilify
    • Schizophrenia, mania: initial approved recommendation is 10–15 mg/day; maximum approved dose 30 mg/day
    • Depression, autism: 5–10 mg/day; maximum 15 mg/day
    • Agitation: 9.75 mg/1.3 ml; maximum 30 mg/day
    • Depot: must initiate oral aripiprazole first; after tolerability is established can administer initial injection along with an overlapping 14-day dosing of oral aripiprazole; initial and maintenance dose of injection is 400 mg/month; can decrease to 300 mg/month if needed
    • Oral solution: solution doses can be substituted for tablet doses on a mg-per-mg basis up to 25 mg; patients receiving 30-mg tablet should receive 25-mg solution
  20. Dosing Tips for Abilify – Oral
    • For some, less may be more: frequently, patients not acutely psychotic may need to be dosed lower (e.g., 2.5–10 mg/day) in order to avoid akathisia and activation and for maximum tolerability
    • For others, more may be more: rarely, patients may need to be dosed higher than 30 mg/day for optimum efficacy
    • Consider administering 1–5 mg as the oral solution for children and adolescents, as well as for adults very sensitive to side effectsAlthough studies suggest patients switching to aripiprazole from another antipsychotic can do well with rapid switch or with cross-titration, clinical experience suggests many patients may do best by adding either an intermediate or full dose of aripiprazole to the maintenance dose of the first antipsychotic for at least several days and possibly as long as 3 or 4 weeks prior to slow down-titration of the first antipsychotic.
    • Rather than raise the dose above these levels in acutely agitated patients requiring acute antipsychotic actions, consider augmentation with a benzodiazepine or conventional antipsychotic, either orally or intramuscularly
    • Rather than raise the dose above these levels in partial responders, consider augmentation with a mood stabilizing anticonvulsant, such as valproate or lamotrigine
    • Children and elderly should generally be dosed at the lower end of the dosage spectrumDue to its very long half-life, aripiprazole will take longer to reach steady state when initiating dosing, and longer to wash out when stopping dosing, than other atypical antipsychotics
    • Treatment should be suspended if absolute neutrophil count falls below 1,000/mm3
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