Aripiprazole in the Treatment of Schizophrenia

Giovan B. Cassano; Andrea Fagiolini; Lorenzo Lattanzi; Palmiero Monteleone; Cinzia Niolu; Emilio Sacchetti; Alberto Siracusano; Antonio Vita

Disclosures

Clin Drug Invest. 2007;27(1):1-13.

Conclusion

Our recommendations for dosage and administration of aripiprazole in patients experiencing schizophrenia are in agreement with the manufacturer's prescribing information. However, the optimal dose has to be evaluated individually for each case, depending on the characteristics of the patient. Use of aripiprazole in maintenance therapy usually requires a switch from a previous antipsychotic. In our experience, this works well, provided the change is made gradually by slowly decreasing the previous antipsychotic while increasing aripiprazole. If agitation is present in the acute episode, use of sedative drugs in combination with aripiprazole is highly recommended because aripiprazole does not have sedative effects at therapeutic doses.

Ultimately, the utility of an antipsychotic agent is determined by how the agent performs in everyday clinical practice, and how a patient feels and functions during treatment with that agent. Risk-benefit assessment is important when deciding on an anti-psychotic agent for the treatment of schizophrenia. There are many conventional and atypical anti-psychotic drugs currently available for the treatment of schizophrenia, and choosing the appropriate antipsychotic for the acute episode and long-term maintenance treatment can be a matter of trial and error until an acceptable balance is achieved between maximisation of efficacy and minimisation of adverse effects. Based on clinical data and our own clinical experience, aripiprazole is generally a well accepted, tolerated and safe first-line antipsychotic agent that is broadly effective against the positive and negative symptoms of schizophrenia.

Aripiprazole also represents a particularly useful alternative in patients in whom issues such as weight gain and hyperprolactinaemia and/or metabolic factors are currently or potentially problematic. In our experience, the majority of patients who have made the switch to aripiprazole have considered the effort to be worthwhile. The most frequent adverse events reported by patients treated with aripiprazole are generally transient and easily manageable. It must, however, be stated that aripiprazole is a relatively newly introduced antipsychotic agent, and further clinical experience and research data could help to fully understand its risk-benefit profile in the long-term management of schizophrenia.

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Acknowledgments

The editorial assistance of Joanne Dalton, Wolters Kluwer Health Medical Communications, is gratefully acknowledged.

Funding information

This publication was supported by an educational grant from Bristol Myers Squibb.

Reprint Address

Dr Giovan B. Cassano, Università di Pisa, Casa di Cura S. Rossore Viale delle Cascine, Pisa, 152 56122, Italy. E-mail: gcassano@psico.med.unipi.it

Cite this: Aripiprazole in the Treatment of Schizophrenia - Medscape - Jan 01, 2007.

Receptor Binding Profile of Aripiprazole and Reference Antipsychotics ^a
Receptor	Aripiprazole	Olanzapine	Risperidone	Quetiapine	Ziprasidone	Clozapine	Haloperidol
D₁	265^b	31	430	455	525	85	210
D₂	0.34^b	11	4	160	5	126	0.7
D₃	0.8^b	49	10	340	7	473	2
D₄	44^b	27	9	1600	32	35	3
5-HT_1A	1.7^b	>10,000	210	2800	3	875	1100
5-HT_2A	3.4^b	4	0.5	295	0.4	16	45
5-HT_2C	15^b	23	25	1500	1	16	>10,000
a₁	57	19	0.7	7	11	7	6
H₁	61^b	7	15	11	50	6	440
M₁	>10,000	1.9	>10,000	120	>1000	1.9	>1500

^aData are expressed as K_i (nmol/L).
^bData refer to cloned human receptors.

Suggestions for the Management of Concomitant Symptoms and Adverse Effects in Patients With Schizophrenia Treated With Aripiprazole
Symptom	Management
Agitation	Benzodiazepines (lorazepam) or Anticholinergic drugs^a or Antihistaminic drugs^a (e.g. diphenhydramine) or Valproic acid or Gabapentin
Nausea	Administer aripiprazole with a meal or Reduce aripiprazole dose or Add an antiemetic (only if above measures fail)
Insomnia	Add an hypnotic agent during the first days of treatment Administer aripiprazole in the morning Divide dose of aripiprazole into two daily half doses (am and pm)
Akathisia	Reduce dose or Benzodiazepines or β-Adrenoceptor antagonist (propranolol) or Gabapentin or Anticholinergic agent

^aConsider previous antipsychotic withdrawal after switching antipsychotic agents and use antihistaminic or anticholinergic drug as appropriate.

Guide to Aripiprazole Dosage and Administration in the Management of the Acute Episode of Schizophrenia in Different Patient Groups ^a
Treatment Setting	Dosage	Dosage Review
Acute Episode in Treatment-naive (First Psychotic Episode) or Drug-free (Previous Treatment) Patients - Agitated^b
Inpatient	Starting dose 15 mg/day	From day 2: dose may be increased up to 30 mg/day if necessary The dose may be reduced to 10 mg/day if tolerability problems arise (also see table II for management of adverse effects)
Outpatient	Starting dose 10-15 mg/day	After 2 weeks: dose may be increased up to 30 mg/day if necessary Dose may be reduced to 10 mg/day if tolerability problems arise (also see table II for management of adverse effects)
Acute Episode in Treatment-naive (First Psychotic Episode) or Drug-free (Previous Treatment) Patients -- Non-agitated
Hospital/Outpatient	Starting dose 10-15 mg/day	Dose may be reduced to 10 mg/day if tolerability problems arise (also see table II for management of adverse effects)
Outpatient (Drug Sensitive)	Patients may need to start with 5 mg/day for 1-2 weeks	After 2 weeks: dose may be increased to 10-15 mg/day according to clinical judgement
Low/non-compliance with Previous Medication - Agitated^a
Hospital	Starting dose 15 mg/day	From day 2: dose may be increased up to 30 mg/day (maximum) if necessary
Outpatient	Starting dose 15 mg/day	After 2 weeks: dose may be increased up to 30 mg/day (maximum) if necessary Dose may be reduced to 10 mg/day if tolerability problems arise (also see table II for management of adverse effects)
Low/non-compliance with Previous Medication - Non-agitated
Hospital/Outpatient	Starting dose 10 mg/day	After 2 weeks: dose may be increased to 15 mg/day if necessary; if therapeutic response is insufficient consider increasing to 30 mg/day after a further 2 weeks Dose may be reduced to 10 mg/day if tolerability problems arise (also see table II for management of adverse effects)

^aTreatment-naive (first psychotic episode) or drug-free (previous treatment) patients may respond to lower doses and be more sensitive to side effects. In these patients, as well as in outpatients with a history of high sensitivity to side effects and/or low complicance, a starting dose of 10mg (or sometimes even 5mg) is usually preferred. Adjunctive agents such as benzodiazepines or antihistaminic agents may be added in the first period of treatment to help control anxiety, agitation, insomnia and hostility.
^bBenzodiazepine or antihistaminic or anticholinergic drug may be added to control anxiety, agitation and hostility.

Strategies for Switching From Another Antipsychotic Agent to Aripiprazole in the Outpatient Setting ^a
Time	Aripiprazole Dose	Previous Medication Dose	Aripiprazole Dosage Variation
Starting Dose	10-15 mg/day	Maintain dose
End Week 2	10-15 mg/day	Reduce by about 50%	Dose may be reduced to 10 mg/day if tolerability problems arise (also see table II for management of adverse effects)
End Week 4	10-30 mg/day	Reduce by about 50%	15 mg/day is the maintenance dose; very few patients may need to increase to 30 mg/day; dose may be reduced to 10 mg/day if tolerability problems arise (also see Table 2 for management of adverse effects)

^aBenzodiazepine or antihistaminic or anticholinergic drugs may be added to aripiprazole in order to control rebound effects due to the discontinuation of medications with high antihistaminic or anticholinergic properties.

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Aripiprazole in the Treatment of Schizophrenia

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