Aripiprazole dosing

Concomitant use with potential CYP3A4 inhibitors - During coadministration of ketoconazole with aripiprazole, reduce the aripiprazole dose to one-half of the usual dose. 

When concomitant administration of ketoconazole with aripiprazole occurs, aripiprazole dose should be reduced to one-half of its normal dose. Other strong inhibitors of CYP3A4 (itraconazole) would be expected to have similar effects and need similar dose reductions weaker inhibitors (erythromycin, grapefruit juice ) have not been studied... 

Lile JA, Stoops WW, Hays LR, Rush CR. The safety, tolerability, and subject-rated effects of acute intranasal cocaine administration during aripiprazole maintenance II increased aripiprazole dose and maintenance period. Am J Drug Alcohol Abuse 2008 34(6) 721-9. 

Current or past anti-cholinergic side effects Risperidone, quetiapine, aripiprazole ziprasidone Olanzapine (low dose)... 

Olanzapine Zyprexa 20, 30 mg Tablets 2.5, 5, 7.5, 10, 5-20 mg/day in 1 or 2 doses combination with lithium or valproate for the acute treatment of mania or mixed states for bipolar I disorder. Olanzapine and aripiprazole are approved for relapse prevention as well as for acute therapy... 

Risperidone Aripiprazole 2D6 > 3A4 2D6, 3A4 Carbamazepine and phenytoin topiramate hypericum (St. John s Wort). Paroxetine, fluoxetine, sertraline (high dose) grapefruit juice 2D6 or 3A4 substrates acting as competitive inhibitors. 

Quetiapine (Seroquel). Another atypical antipsychotic, quetiapine has also been approved by the FDA for the treatment of acute mania. It is usually administered twice daily at doses of 150-750mg/day. Like its counterparts, quetiapine is a well-tolerated medication. Its common side effects are drowsiness, dizziness, and headache. It causes less weight gain than olanzapine or clozapine but more than ziprasidone or aripiprazole. Quetiapine also does not cause agranulocytosis nor does it increase the risk of seizures. It can occasionally cause mild changes in liver function tests, but these usually return to normal even if the patient continues taking quetiapine. 

Aripiprazole (Abilify). Aripiprazole is indicated for the treatment of acute mania and for maintenance therapy. It is dosed at 5-30mg/day. Aripiprazole is well tolerated with the most common side effects being headache, agitation, anxiety, insomnia, and nausea. 

Daily doses of aripiprazole range from 5 to 30 mg. Aripiprazole is very well tolerated. Common side effects include headache, insomnia, nausea, dizziness, and constipation. 

Atypical antipsychotics may be helpful in managing the delusions and agitated behavior that can accompany dementia. These medications, include risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), and olanzapine (Zyprexa). All antipsychotics, typical and atypical, appear to increase the risk of death in patients with dementia and psychosis. This appears as a warning in the package inserts of the newer drugs. A prudent approach is to discuss this risk with the caregiver, use the lowest effective dose, and monitor for effectiveness. 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

Antipsychotics in a few small studies have been shown to be helpful. To date this research is limited to typical antipsychotics. Nevertheless, the excellent track record of atypical antipsychotics in treating schizophrenia and the lower burden of side effects lead us to recommend atypical antipsychotics as a first-line treatment for STPD as well. Low doses of risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole are all reasonable options. If no therapeutic effect is observed, doses should be increased. 

This group includes risperidone, quetiapine, olanzapine, ziprasidone, and aripiprazole. But all these agents cause dose-related EPS and appear in general more likely to cause diabetes and other metabolic problems than some of the older drugs (see Duggan et ah, 2005). 

Aripiprazole has been approved for treatment of schizophrenia and acute manic or mixed episodes in bipolar disorder. This medication is also indicated for maintenance treatment in bipolar I disorder. The recommended starting and target dose for aripiprazole in patients with schizophrenia is 10 or 15 mg/day. This is a once-daily dose, and patients can take the medication with or without food. Although this medication has been shown to be effective in doses ranging from 10 to 30 mg/day, doses higher than 10-15 mg have not been shown to be more effective than 10- to 15-mg doses in patients with schizophrenia. The recommended starting dose for treatment of an acute manic or mixed episode is 30 mg the recommended dose for maintenance treatment in stable patients is 15 mg/day. The elimination half-life is 75 hours, and steady-state concentrations are reached within 2 weeks. Therefore, dose adjustments are recommended every 2 weeks, to allow time for clinical assessments of the medication s effects to be observed at steady-state concentration. Peak plasma concentrations occur within 3-5 hours. At equivalent doses, the plasma concentrations of aripiprazole from the solution were higher compared with plasma concentrations associated with the tablet form. 

The most common side effects associated with aripiprazole include headache, nausea, dyspepsia, agitation, anxiety, insomnia, somnolence, and akathisia. Dose-related adverse events include somnolence and akathisia. Early clinical experience indicates that akathisia may be avoided by starting the medication at doses lower than 10 mg and increasing the dose slowly. Aripiprazole is not associated with significant sedation, anticholinergic side effects, weight gain, or cardiovascular side effects (Petrie et al. 1997). 

Aripiprazole is hepatically metabolized, mainly by two cytochrome P450 enzymes CYP 2D6 and CYP 3A4. Therefore, dosage adjustments are necessary when this medication is given with other medications that either inhibit or induce these enzymes. For example, the dose of aripiprazole should be halved when this medication is given with ketoconazole, a CYP 3A4 inhibitor, or at least decreased when given with fluoxetine, a CYP 2D6 inhibitor. When aripiprazole is given with CYP 3A4 inducers such as carbamazepine, the dose should be doubled. 

Other drug effects that decrease DA activity also support this position. Thus, when DA synthesis is blocked by a-methyl- p-tyrosine (AMPT), the dose necessary for an antipsychotic effect is reduced (i.e., the dose-response curve is shifted to the left by the interaction between dopamine and AMPT). A drug such as reserpine that can deplete DA stores also has relatively mild antipsychotic properties. Also, aripiprazole, which has D 2 presynaptic agonist properties, decreases the production of DA, as well as blocking D2 postsynaptic receptors. 

Hyperprolactinemia in women results in the amenorrhea-galactorrhea syndrome and infertility in men, loss of libido, impotence, and infertility may result. Hyperprolactinemia may cause osteoporosis, particularly in women. If dose reduction is not indicated, or ineffective in controlling this pattern, switching to one of the atypicals that do not raise prolactin levels, eg, aripiprazole, may be indicated. 

Aripiprazole Blockade of 5HT2A receptors > blockade of D2 receptors Some a blockade (clozapine, risperidone, ziprasidone) and M-receptor blockade (clozapine, olanzapine) variable receptor blockade (all) Schizophrenia—improve both positive and negative symptoms bipolar disorder (olanzapine or risperidone adjunctive with lithium) agitation in Alzheimer s and Parkinson s (low doses) major depression (aripiprazole) Toxicity Agranulocytosis (clozapine), diabetes (clozapine, olanzapine), hypercholesterolemia (clozapine, olanzapine), hyperprolactinemia (risperidone), QT prolongation (ziprasidone), weight gain (clozapine, olanzapine)... 

Raja, M. (2007). Improvement or worsening of psychotic symptoms after treatment with low doses of aripiprazole. International Journal of Neuropsychopharmacology, 10, 107-110. 

In 142 adult patients who took aripiprazole (mean final daily dose 16 mg, 0.20 mg/kg) for psychotic, major affective, or other disorders, adverse effects occurred in 16, were three times more likely among women, and most often involved moderate behavioral activation or nausea, with no new episodes of mania (4). 

In a 4-week, double-blind, randomized placebo-con-trolled study in 36 US centers 414 patients with schizophrenia or schizoaffective disorder were randomized to aripiprazole (15-30 mg/day) or haloperidol (10 mg/day) (5). Haloperidol and both doses of aripiprazole produced statistically significant improvements from baseline compared with placebo. Unlike haloperidol, aripiprazole was... 

Aripiprazole causes mild somnolence in about 11% of patients and severe somnolence has also been reported in a 9-year-old girl 3.5 hours after a single dose of aripiprazole 15 mg (9). 

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