|
|
                  |
Aripiprazole (Abilify): This is a very good anti-psychotic with no average weight gain. Whether it is as good as other anti-psychotics is uncertain since the amount of available research is very limited. It almost certainly has less tardive dyskinesia risk than traditional anti-psychotics. It appears as good at treating psychosis as haloperidol or risperidone. It is unfortunately quite expensive: $3200 per year for the typical 15 mg a day maintenance dose. Fluoxetine can double its blood level. Aripiprazole is very long-acting; its half-life is 75 hours! A very simple cost saving strategy would be to take a 30 mg tablet every other day instead of a 15 mg tablet daily. This would save $1000 per year since the 30 mg capsules are a better bargain. For patients needing an anti-depressant as well as an anti-psychotic and who can tolerate an SSRI, another cost-saving strategy might be to take fluoxetine 20 mg and aripiprazole 30 mg every third or fourth day. The fluoxetine would raise the aripiprazole half-life still further and the blood level would be at least as high despite taking less medicine. This would save an additional $735-$1100 per year. Good Profile: Strong 5-HT(2a) receptor antagonism and is similar to ziprasidone in also having agonistic activity at the 5-HT(1a) receptor. Among the atypical antipsychotics, aripiprazole displays the lowest affinity for alpha(1)adrenergic, histamine (H1) and muscarinic (M1) receptors. This combination of effects may be responsible for its efficacy in positive and negative symptoms of schizophrenia and in bipolar disorder. Similarly, this profile may be the reason for the low rates of reported side effects observed. This includes general adverse events, a low incidence of reported weight gain and a low liability for inducing movement disorders. Other early data suggest that aripiprazole may induce reductions in plasma prolactin, as well as in plasma glucose and lipid profiles. Finally, results also support the proposition that aripiprazole may lead to reductions in corrected QT interval. Aripiprazole: profile on efficacy and safety. Goodnick PJ, Jerry JM. Expert Opin Pharmacother 2002 Dec;3(12):1773-81; Partial agonist at dopamine D2 receptors, thereby reducing excessive suppression supposedly. Review: One published DB PC and several unpublished of 4-6 week duration with >1500 inpatients. Benefit similar to haloperidol or risperidone. Also, reportedly helped manic episodes. Starting dose 10-15mg/d. Metabolized by both CYP2D6 and CYP3A4 so dose halved with agents that inhibit these (fluoxetine, paroxetine, itraconazole) and doubled with carbamazepine or other CYP3A4 inducers. No QT-prolongation, hyperglycemia, hyperlipidemia, hyperprolactinemia. EPS similar to placebo. Side-effects: anxiety, headache, nausea, vomiting, constipation, insomnia, lightheadedness, and somnolence. Med Let ’03;45:15-6 Studies: Unpublished 52-week aripiprazole 30 mg QD = haloperidol 10 mg QD in 1294 with acute relapse of chronic schizophrenia. No difference in decrease in PANSS. 26D inhibitors fluoxetine and paroxetine and 3A4 inhibitor erythromycin double blood level. 3A4 inducer carbamazepine cuts blood level in half. Aripiprazole = Haldol in Large DBs: Two DB PC studies involving 1294 schizophrenic patients for 1 year by the University of Vienna found aripiprazole 30 mg/d as good as haloperidol 10 mg/d. More patients stopped haldol overall, but more patients stopped aripiprazole due to inadequate benefit. More EPS was noted with haldol. Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Kasper S, Lerman MN, McQuade RD, Saha A, Carson WH, Ali M, Archibald D, Ingenito G, Marcus R, Pigott T. Int J Neuropsychopharmacol. 2003 Dec;6(4):325-37 Aripiprazole 15 mg/d Better than Placebo but not Great: A 26-week DB PC study of 310 patients found aripiprazole 15 daily better than placebo with 57% vs. 34% without relapse (not very impressive). U Florida. Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia: a placebo-controlled 26-week study. Pigott TA, Carson WH, Saha AR, Torbeyns AF, Stock EG, Ingenito GG; Aripiprazole Study Group. J Clin Psychiatry. 2003 Sep;64(9):1048-56. Borderline: Better than Placebo But Not Impressive: In an 8-week, DB PC study of 50 borderline personality patients, significant changes in scores on most scales of the SCL-90-R, the HAM-D, the HAM-A, and all scales of the State-Trait Anger Expression Inventory were observed in the subjects treated with aripiprazole. Self-injury occurred in both groups. The reported side effects were headache, insomnia, nausea, numbness, constipation, and anxiety. Aripiprazole in the treatment of patients with borderline personality disorder: a double-blind, placebo-controlled study. Nickel MK, et al. Inntalklinik, Simbach am Inn, Germany. . Am J Psychiatry 2006 May;163(5):833-8. Ed: Use of anti-psychotics has become very common in the U.S. thanks to the promotions for the drug industry, but the results of studies have not been impressive. Inexpensive anti-depressants and lithium are usually better first interventions to try. Mania: Aripiprazole Better than Haldol in Industry Study: In a 12-week DB PC industry-funded study of 347 patients with bipolar I disorder experiencing acute manic or mixed episodesmore patients taking aripiprazole, 49.7% vs. 28.4%, were in response and receiving therapy compared with those taking haloperidol (28.4%; P < 0.001). Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole (62.7% v. 24.0%). Effectiveness of aripiprazole v. haloperidol in acute bipolar mania: double-blind, randomised, comparative 12-week trial. Vieta E, et al. University of Barcelona, Spain. Br J Psychiatry 2005 Sep;187:235-42. Ed: The high rate of EPS side-effects with haloperidol suggests that the industry-funded psychiatrists did not allow patients on haloperidol to take preventive medicine against EPS. I suspect the poor showing of haloperidol is due to this more than any inferiority of anti-manic effect. Mania: Aripiprazole Better than Placebo: 2 week response 30mg/d 41% vs. 19% for placebo. Paul Keck, U Cincinnati, AJP 9/03. 262 manic or mixed bipolars in DB PC. Side-effect drop-outs no higher than placebo. A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Keck PE Jr, Marcus R, Tourkodimitris S, Ali M, Liebeskind A, Saha A, Ingenito G; The Aripiprazole Study Group Am J Psychiatry 2003;160:1651-1658 Mania Relapse Prevention Better than Placebo: In an 26-week DB PC study of 161 bipolar I patients recently hospitalized for a manic or mixed episode first stabilized on aripiprazole 15 or 30 mg/day for 6-18 weeks, aripiprazole was superior to placebo in delaying the time to relapse (p = .02) with fewer relapses 25% vs. 43%; p = .013. No significant differences were observed in time to depressive relapse (p = .68). Weight gain (> or = 7% increase) occurred in 13% aripiprazole vs. 0% placebo-treated patients. Adverse events (> or = 5% incidence and twice that of placebo) reported by aripiprazole-treated patients were akathisia, pain in the extremities, tremor, and vaginitis. A randomized, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder. Keck PE Jr, et al. University of Cincinnati. . J Clin Psychiatry 2006 Apr;67(4):626-37. Ed: This industry-funded study was carefully designed to make Abilify look good. The result, while positive, is not impressive. The weight gain surprised me. Abilify is significantly more expensive in the U.S. than Geodon, another anti-psychotic with no weight gain, and much more expensive than the gold-standard for main, i.e., lithium. Perphenazine and Abilify Equally Effective for Treatment Resistant Schizophrenia: In a 6-week DB PC study of 300 schizophrenia patients who had failed to adequately improve after 4 to 6 weeks of open-label treatment with olanzapine or risperidone, aripiprazole (15-30 mg/day) did no better than perphenazine (8-64 mg/day) with 27% and 25% showing a >or = to 30% decrease in PANSS total score or a Clinical Global Impressions-Improvement score of 1 or 2. Perphenazine-treated patients had a higher incidence of extrapyramidal symptoms and a higher rate of elevated prolactin levels than aripiprazole (57.7% vs. 4.4%, p < .001). Improvements in quality of life considered to be clinically relevant (>or= 20% improvement in Quality of Life Scale score) occurred in 36% of the aripiprazole-treated patients and in 21% of those treated with perphenazine (p = .052). Aripiprazole for treatment-resistant schizophrenia: results of a multicenter, randomized, double-blind, comparison study versus perphenazine. Kane JM, et al. Albert Einstein College of Medicine. [email protected]. J Clin Psychiatry 2007 Feb;68(2):213-23. Ed: It appears that EPS side-effects may have been inadequately treated, making perphenazine appear at a disadvantage. Also, an elevated prolactin level is often a benign and asymptomatic finding. Abilify costs $392-553/month at doses used in this study vs. $92-260 for perphenazine at Walgreen prices. Perphenazine can be obtained for as little as $4 per month at Wal-Mart. Also, this study put perphenazine at a disadvantage since 8 mg is only one-quarter of the standard dose while Abilify 15 mg is a full standard dose. Aripiprazole > Placebo, Risperidone Also Compared: 4 week DB PC 404 schizophrenic patients 20mg/d or 30mg/d aripiprazole, 6mg/6 risperidone or placebo. All better than placebo by PANSS and CGI. Decrease prolactin with aripiprazole and increase considerably with risperidone. No EPS with aripiprazole. Aripiprazole, an Antipsychotic With a Novel Mechanism of Action, and Risperidone vs. Placebo in Patients With Schizophrenia and Schizoaffective Disorder. UC Irvine. Potkin SG, Saha AR, Kujawa MJ, Carson WH, Ali M, Stock E, Stringfellow J, Ingenito G, Marder SR Arch Gen Psychiatry. 2003 Jul;60(7):681-90 Aripiprazole > Placebo, Haldol Also Compared: 4 week DB PC 15 or 30mg/d aripiprazole or 10 mg/d haloperidol. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. Kane JM, Carson WH, Saha AR, McQuade RD, Ingenito GG, Zimbroff DL, Ali MW. J Clin Psychiatry. 2002 Sep;63(9):763-71 Switching Easy: Open trial of switching patients to aripiprazole found can do so immediately at 30mg/d, or gradually phase one and gradually start aripiprazole, or start aripiprazole and gradually phase out the other over two weeks. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Casey DE, Carson WH, Saha AR, Liebeskind A, Ali MW, Jody D, Ingenito GG; Aripiprazole Study Group. Psychopharmacology (Berl). 2003 Apr;166(4):391-9. Aripiprazole Weight Loss vs. Olanzapine Weight Gain: In a DB study done by the makers of Abilify of 317 patients for 26 weeks, at the end of the study, patients on aripiprazole had lost 3 pounds vs. those on olanzapine had gained 9 pounds. The total cholesterol, high-density lipoprotein cholesterol, and triglycerides worsened with olanzapine. Psychiatric improvement was similar between the two. A comparison of weight change during treatment with olanzapine or aripiprazole: results from a randomized, double-blind study. McQuade RD, Stock E, et al. Otsuka America Pharmaceutical. J Clin Psychiatry. 2004;65 Suppl 18:47-56. Elevated lipase and diabetic ketoacidosis associated with aripiprazole: Reddymasu S, et al. Aripiprazole Called Safe Up to 75 mg/day: The Physician's Desk Reference (PDR) was established to provide for the practicing of a complete listing of all medications with the FDA-approved labelling, including dosage recommendations. Perhaps in order to maximise individual usage of medications, pharmaceutical companies have frequently targeted lowest possible doses for FDA approval. However, many patients with a variety of illnesses due to resistance and/or multiple illnesses, may need higher than these dose ranges. Only risperidone initially obtained approval for a dose for psychosis (16 mg) higher than that suggested currently (maximum of 8 mg). The dose that was approved for mania was lower: a maximum of 6 mg. The others: respectfully, olanzapine (schizophrenia: 15 mg, mania: 20 mg), quetiapine (schizophrenia: 750 mg; mania: 800 mg), ziprasidone (schizophrenia and mania: 160 mg) and aripiprazole (schizophrenia and mania: 30 mg) obtained approvals for psychosis that may limit adverse events but, at the same time, limit benefits. Other data from various sources (double-blind trials, open-label trials, reviews and case reports) have found safety and/or efficacy for the following maximum doses: olanzapine (40 mg), quetiapine (1600 mg), ziprasidone (320 mg) and aripiprazole (75 mg). In many situations, feared increase in adverse events were not magnified by use of higher doses. Higher than Physician's Desk Reference (US) doses on atypical antipsychotics. Goodnick PJ. UMDNJ Robert Wood Johnson School of Medicine. . Expert Opin Drug Saf 2005 Jul;4(4):653-68. |