Document name:
Focus on Aripiprazole
(Abilify™)
Portfolio
Document type:
Medicines Management
Staff group to whom it
applies:
All prescribers, pharmacy and clinical
staff within the Trust
Distribution:
The whole of the Trust
How to access:
Intranet
Issue date:
Date of issue
August 2008
Version 2, April 2011
Communication
Update TA213
Reviewed July 2011
Reviewed May 2013
Next review:
May 2016
Approved by:
Drug and Therapeutics Sub Committee
Developed by:
Kate Dewhirst and updated by Paul
Hardy
Director leads:
Medical Director
Contact for advice:
Med.information@swyt.nhs.uk
Drug and Therapeutics Committee Communication
Focus on Aripiprazole (Abilify™)
in the treatment of schizophrenia in adults and adolescents and the treatment and
prevention of manic episodes in adults with Bipolar 1 disorder
Introduction
Aripiprazole should be used in accordance with the BNF1 and recommendations in the NICE
clinical guideline for the treatment of schizophrenia2, as well as the appropriate Trust
guidelines for management of schizophrenia and bipolar disorder. For the use of aripiprazole
injection in acute psychiatric emergency please refer to the Trust guideline on rapid
tranquillisation.
This communication should be read in conjunction with detailed prescribing information
available in the Summary of product characteristics (SmPC) for aripiprazole from
http://emc.medicines.org.uk
In common with its guidance for other antipsychotics, the Trust recommends that
aripiprazole be used as monotherapy. Theoretically, as a partial agonist with a high D2
receptor affinity, it may be more problematic in combination with potent D2 antagonists (such
as conventional antipsychotics, risperidone and amisulpride). This is partly borne out by the
literature3,4, although some evidence is contradictory5. Aripiprazole is also recommended6 as
an adjunct a) to clozapine7 for augmentation, and b) to manage antipsychotic-induced
hyperprolactinaemia8. In hyperprolactinaemia management however two double-blind
placebo-controlled trials gave opposing results9,10, so it should only be considered where
therapeutic substitution or dose reduction have been unsuccessful or are unsuitable.
For any combination of aripiprazole with another antipsychotic, consider discussing with your
locality pharmacist to see if a Clinical Query submission is warranted.
Aripiprazole is licensed in the UK for the treatment of
 Schizophrenia in adults and adolescents aged 15 years and over.
 Moderate to severe manic episodes and the prevention of new manic episodes in
Bipolar I disorder in adults (it is not effective in preventing depressive episodes).
 Aripiprazole is not licensed for use in dementia-related psychosis
Aripiprazole should be used with caution in:
 severe hepatic impairment
 cardiovascular disease
 patients with history of epilepsy
 elderly patients
.
Dosage and Administration of Oral Aripiprazole
Schizophrenia: initial dose 10 or 15mg once daily. Maintenance dose 15mg daily. Doses up
to 30mg are available, but enhanced efficacy above 15mg has not been demonstrated.
Manic episodes in Bipolar 1 disorder: initially 15mg once daily. As above, doses of 30mg
have not shown enhanced efficacy.
For prevention of further manic episodes in patients who responded to aripiprazole in an
acute episode, continue with the same dose as the acute episode.
Lower starting doses are recommended for patients over 65 years of age.
All patients prescribed doses over 15mg should have a medication review, the outcome of
which should be clearly documented on RiO.
Aripiprazole is an option for treatment of schizophrenia in people aged 15 to 17 years of age
when risperidone is contraindicated, has not been tolerated, or has not adequately controlled
their symptoms.
Side effects
Restlessness, insomnia, anxiety and akathisia and somnolence are common (> 1/100 <
1/10), and prescribers may consider short-term benzodiazepine anxiolytic treatment when
aripiprazole is initiated. Extrapyramidal side effects can occur, but are less common than
other antipsychotics.
In adolescents the pattern of side effects is similar to that seen in the adult population,
except that somnolence and extrapyramidal side effects are more common.
Major drug-drug interactions11
Drug
Other antipsychotics
CYP3A4 inducers e.g.
Carbamazepine
Phenytoin
St John’s Wort
CYP 450 inhibitors e.g.
Fluoxetine
Paroxetine
Ketoconazole
Itraconazole
Action
Avoid except during switching, and as discussed above
Increase the dose of aripiprazole
(dose may need to be doubled)
Decrease the dose of aripiprazole
(dose may need to be halved)
Switching between aripiprazole and other antipsychotics
Aripiprazole, when introduced as a cross-taper from another antipsychotic, can displace the
previous antipsychotic causing poor tolerability on changeover. The SmPC makes no
specific recommendations and advises a starting dose of 10mg, but one source has
suggested a starting dose of 5mg and a gradual cross-taper12. Switching strategies are of
course dictated by tolerance, side effects and clinical progress; in the absence of definitive
guidance, please feel free to discuss the conversion with your locality pharmacist.
Therapeutic drug level monitoring
Aripiprazole plasma levels can now be obtained by special request, but there is little value in
this for routine treatment. Circumstances in which a plasma level could be considered useful
are;



Intention to increase the dose above 15mg daily
Inadequate treatment response
Intolerable side effects
A putative therapeutic range of 150-210 microgram/litre has been has been suggested13,14.
For patients showing either poor response or intolerable extrapyramidal side effects this
range could be considered as a target. A dose increase above 15mg for patients with a
plasma level already within this range would not be expected to improve clinical response.
References
1.
Joint Formulary Committee. British National Formulary. 65th ed. London: BMJ Group and
Pharmaceutical Press; 2013.
2.
NICE. Schizophrenia: Core Interventions in the Treatment and Managements of Schizophrenia
in Primary and Secondary Care (update). National Institute for Health and Clinical Excellence.
National Institute for Health and Clinical Excellence; 2009.
3.
Letmaier M, Painold A, Holl AK, Grohmann R, Vergin H. Severe psychotic exacerbation during
combined treatment with aripiprazole/haloperidol after prior treatment with risperidone.
International journal of psychiatry in clinical practice. Informa Healthcare Stockholm; 2012 Jun
8;16(2):153–6.
4.
Adan-Manes J, Garcia-Parajua P. Aripiprazole in combination with other antipsychotic drugs
may worsen psychosis. Journal of clinical pharmacy and therapeutics. 2009 Apr;34(2):245–6.
5.
Kuo J, Hwu H-G. Aripiprazole and haloperidol: beneficial combination antipsychotic therapy for
a schizophrenic patient. Clinical Neuropharmacology. 2008. p. 173–5.
6.
Taylor D, Paton C, Kapur S. The Maudsley Prescribing Guidelines in Psychiatry. John Wiley &
Sons; 2012.
7.
Karunakaran K, Tungaraza TE, Harborne GC. Is clozapine-aripiprazole combination a useful
regime in the management of treatment-resistant schizophrenia? Journal of
psychopharmacology (Oxford, England). 2007 Jun 1;21(4):453–6.
8.
Lu M-L, Shen WW, Chen C-H. Time course of the changes in antipsychotic-induced
hyperprolactinemia following the switch to aripiprazole. Progress in neuropsychopharmacology
biological psychiatry. Elsevier Inc.; 2008 p. 1978–81.
9.
Kane JM, Correll CU, Goff DC, Kirkpatrick B, Marder SR, Vester-Blokland E, et al. A
multicenter, randomized, double-blind, placebo-controlled, 16-week study of adjunctive
aripiprazole for schizophrenia or schizoaffective disorder inadequately treated with quetiapine
or risperidone monotherapy. The Journal of clinical psychiatry. 2009;70(10):1348–57.
10.
Shim J-C, Shin J-GK, Kelly DL, Jung D-U, Seo Y-S, Liu K-H, et al. Adjunctive treatment with a
dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a
placebo-controlled trial. The American Journal of Psychiatry. 2007;164(9):1404–10.
11.
Baxter K. Stockley’s Drug Interactions: A Source Book of Interactions, Their Mechanisms,
Clinical Importance and Management. London: Pharmaceutical Press; 2007.
12.
Bazire S. Psychotropic Drug Directory 2012: The Professionals’ Pocket Handbook and Aide
Memoire. Dorsington, Warwickshire: Lloyd-Reinhold Communications; 2012.
13.
Kirschbaum KM, Müller MJ, Malevani J, Mobascher A, Burchardt C, Piel M, et al. Serum levels
of aripiprazole and dehydroaripiprazole, clinical response and side effects. The world journal of
biological psychiatry the official journal of the World Federation of Societies of Biological
Psychiatry. 2008;9(3):212–8.
14.
Sparshatt A, Taylor D, Patel MX, Kapur S. A systematic review of aripiprazole--dose, plasma
concentration, receptor occupancy, and response: implications for therapeutic drug monitoring.
The Journal of clinical psychiatry. 2010;71(11):1447–56.