| Generic Brand |
Aripiprazole Abilify |
Clozapine Clozaril |
Olanzapine Zyprexa |
Quetiapine Seroquel |
Risperidone Risperdal |
Ziprasidone Geodon |
| Manufacturer | Bristol-Myers Squibb | Novartis | Eli Lilly | AstraZeneca | Janssen | Pfizer |
| Class | quinolone derivative |
dibenzo-diazepine | thienbenzo-diazepine | dibenzo-thiazepine | benzisoxazole | benzothizolylpi-perazine |
| Aggressive Dosing Titration for healthy adults (18-55 y/o) *Not intended for treatment-naïve patient |
Initial: 30 mg qd, then adjust dose downward as needed1 Low dose benzodiazepine, i.e. clonazepam or lorazepam 1 mg bid is recommended for prevention of akathisia | Initial: 25 mg qhs Titration: increased by 25-50 mg every day as tolerated to 300-500 mg/d in bid dose within 2-4 weeks |
Initial: 10-20 mg qhs2 Titration: may increase by 10 mg/d every 3-4 days to 30-40 mg/d |
Initial: 50-100 mg bid Titration: Increase by 100-200 mg every day to target dose3, 4 |
Initial: 1-2 mg bid6,7 Titration: Increase by 1-2 mg every day to 6-8 mg/d8 Daily dosages > 10 mg does not appear to confer any additional benefit |
Initial: 100-120 mg/d9 with food
Titration: Increased to 160 mg/d by day 2 and up to 200 mg/d as tolerated10 |
| General Adult Dosing Recommend-ation (Elderly dosing) | Initial: 10-15 mg qd Titration: may be increased to a maximum of 30 mg/d (Elderly initial dosing: 5-7.5 mg/d) |
Initial: 25 mg qhs Titration: increased by 25–50 mg every 1-3 days as tolerated to 300-500 mg/d in bid dose Max dose: 900 mg/d (Elderly initial dosing: 12.5 mg qhs) |
Initial: 10 mg qhs Titration: Increase by 5-10 mg/day at 1-week intervals Max dose: 20 mg/d (Elderly initial dosing: 2.5-5mg qhs) |
Initial: 25mg bid Titration: increase by 25-50 mg bid every 1-2 days to target dose of 400-600 mg5 Max: 800 mg/d |
Initial: 1 mg qd-bid Titration: Increase by 0.5 – 1 mg/d every 1-3 days Target dose: 4 –5 mg/d; can be given once daily if patient tolerates orthostasis |
Initial: 40 mg bid with food Titration: Increase by 20 mg bid every 2-3 days to 60-80 mg bid with food |
| Tapering Off Recommend-ations | slowly to prevent rebound psychosis, worsening of pre-existing TD, intense cholinergic rebound& other somatic sx | |||||
| Pharmacology | 5-HT2, D1,D2, D3, D4, M1, H1, α1 and α2 antagonism |
5-HT2A, 5-HT2C, D1, D2, D3, D4, M1-5, H1, and α1- antagonism |
D1, D2, 5-HT2A, 5-HT1A, H1, α1 and α2 |
5-HT2, D2, H1, α1- and α2 antagonism |
D2, D3, 5-HT2A, 5-HT2C, 5-HT1D and α1 antagonism; moderate inhibition of 5-HT and NE reuptake; 5-HT1A agonism |
|
| Absorption | Not affected by food | Not affected by food | Not affected by food | Not affected by food | Not affected by food | Doubled with food |
| Peak levels | 3-5° | 2.5° | 6° | 1.5° | 1-2° | 6–8° |
| Bioavailability | 87% | 50% | 60% | 100% | 70% | 60% with food |
| Protein Binding | 99% | 97% | 93% | 83% | 90% | > 99% |
| Half-life (T½) | 75° | 12° | 30° | 6° | 3° for risperidone; 20°for parent plus metabolite | 6.6° |
| Metabolism | CYP 2D6, 3A4 | CYP450 1A2, 3A4 | CYP450 1A2, 2D6 | CYP450 2D6 | CYP450 3A4 |
|
| Therapeutic serum level | N/A | >350 ng/ml | N/A | N/A | N/A | N/A |
| Sedation | + | ++++ | ++ | ++ | + | ++ |
| Weight gain | ± | ++++ | ++++ | ++ | ++ | ± |
| Orthostatic hypotension | ± | ++++ | ++ | ++ | ++ | + |
| Mean ∆ in QTc interval from baseline (msec)2 | Similar to placebo | N/A | 1.2 | 5.9 | 0.2 | 1.3 |
| EPS | + | ± | ++ | ± | ++ | ++ |
| Parkinsonism | >2% | >2% | >2% | >2% | >10% | >2% |
| Akathisia | >10% | >10% | >10% | >2% | >10% | >2% |
| Dystonic Rxs | <2% | <2% | <2% | <2% | - | >2% |
| Hyper- prolactinemia | ± | ± | + | ± | ++++ | + |
| Metabolic Complications of Atypical Antipsychotics: Results from the CATIE 11 Study (clozapine12 and aripiprazole14 data from separate sources) | ||||||
| Ref value compared to baseline | Aripiprazole Abilify |
Clozapine Clozaril |
Olanzapine Zyprexa |
Quetiapine Seroquel |
Risperidone Risperdal |
Ziprasidone Geodon |
| Weight Change (lbs/month) | - | 0.5 | 2 | 0.5 | 0.4 | -0.3 |
| HbA1c (%) | - | 0.1 | 0.4 | 0.04 | 0.07 | 0.1 |
| Blood Glucose (mg/dl) | 0.90 | 13.2 | 13.7 | 7.5 | 6.6 | 2.9 |
| Total Cholesterol (mg/dl) | -0.7 | 7.3 | 9.4 | 6.6 | -1.3 | -8.2 |
| Triglycerides (mg/dl) | 0.6 | 52.6 | 40.5 | 21.2 | -2.4 | -16.5 |
| Other Side Effects | Newest agent: least data and experience; most common adverse effects in pre-clinical trials: headache, anxiety, insomnia, nausea, akathisia, dizziness | Agranulocytosis (see
monitoring guidelines);
seizure (1-2% <300mg, 3-4% 300-599mg, 5% 600-900mg); hypersalivation, severe constipation, tachycardia, rarely myocarditis or cardiomyopathy |
Cases of hyperglycemia, diabetic ketoacidosis reported, weight gain severe in some patients | Dose titration required in order to minimize orthostasis and sedation | Dose titration to minimize orthostasis, tachycardia, nasal congestion, EPS and hyperprolactinemia generally occur at doses >6 mg/d | Contraindicated in patients with a known history of QT prolongation, including congenital long QT syndrome, with recent acute myocardial infarction, or with uncompensated heart failure hypokalemia or hypomagnesemia; avoid/discontinue in patients with persistent QTc measurements > 500 msec |
| Increased antipsychotic levels | azole antifungals erythromycin fluoxetine nefazodone paroxetine protease inhibitors quinidine |
azole antifungals ciprofloxacin fluoxetine fluvoxamine citalopram |
ciprofloxacin fluoxetine fluvoxamine |
azole antifungals erythromycin cimetidine fluvoxamine nefazodone protease inhibitors |
azole antifungals fluoxetine paroxetine quinidine ritonavir |
azole antifungals |
| Decreased antipsychotic levels | carbamazepine | omeprazole ritonavir smoking |
omeprazole ritonavir smoking |
carbamazepine nevirapine St. John’s wort |
carbamazepine | carbamazepine |
| Other | other agents which suppress bone marrow function (carbamazepine, chemotherapeutic agents) | other drugs which increase QT: quinidine, dofetilide, sotalol, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, moxifloxacin, sparfloxacin, gatifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol, or tacrolimus | ||||
References
- Casey DE, Carson WH, Saha AR, Liebeskind A, Ali MW, Jody D, Ingenito GG; Aripiprazole Study Group. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology (Berl). 2003 Apr;166(4):391-9. Epub 2003 Feb 28.
- Baker RW, Kinon BJ, Maguire GA, Liu H, Hill AL. Effectiveness of rapid initial dose escalation of up to forty milligrams per day of oral olanzapine in acute agitation. J Clin Psychopharmacol. 2003 Aug;23(4):342-8.
- Smith MA, McCoy R, Hamer-Maansson J, Brecher M. Rapid dose escalation with quetiapine: a pilot study. Journal of clinical psychopharmacology 2005;25:331-5
- Pajonk FG, Schwertner AK, Seelig MA. Rapid dose titration of quetiapine for the treatment of acute schizophrenia and acute mania: a case series. Journal of psychopharmacology 2006;20:119-24
- Small JG, Hirsch SR, Arvanitis LA, Miller BG, Link CG. Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group. Archives of general psychiatry 1997;54:549-57
- Nyberg S, Eriksson B, Oxenstierna G, Halldin C, Farde L. Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients. The American journal of psychiatry 1999;156:869-75
- Feifel D, Moutier CY, Perry W. Safety and tolerability of a rapidly escalating dose-loading regimen for risperidone. The Journal of clinical psychiatry 2000;61:909-11
- Kim CY, Shin YW, Joo YH, Hong JP, Lee GH, Choi SK. Risperidone dosing pattern and clinical outcome in psychosis: an analysis of 1713 cases. The Journal of clinical psychiatry 2005;66:887-93
- Mullins CD, Shaya FT, Zito JM, Obeidat N, Naradzay J, Harrison DJ. Effect of initial ziprasidone dose on treatment persistence in schizophrenia. Schizophrenia research 2006;83:277-84
- Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, Kreyenbuhl J; American Psychiatric Association; Steering Committee on Practice Guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004 Feb;161(2 Suppl):1-56.
- Lieberman JA, et al. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005 Sep 22;353(12):1209-23. Epub 2005 Sep 19.
- Spurling RD, Lamberti JS, Olsen D, Tu X, Tang W. Changes in metabolic parameters with switching to aripiprazole from another second-generation antipsychotic: a retrospective chart review. J Clin Psychiatry. 2007 Mar;68(3):406-9.
- McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, Swartz MS, Perkins DO, Keefe RSE, Davis CE, Severe J, Hsiao JK, for the CATIE Investigators. Effectiveness of Clozapine Versus Olanzapine, Quetiapine, and Risperidone in Patients With Chronic Schizophrenia Who Did Not Respond to Prior Atypical Antipsychotic Treatment. Am J Psychiatry. 2006 Apr;163(4):600-10. (Data located in Table 4.)