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PubMed2005

Pharmacokinetics of aripiprazole and concomitant lithium and valproate.

The objective of this study was to assess the pharmacokinetics of the antipsychotic aripiprazole when coadministered with lithium or valproate. Two open-label, sequential treatment design studies were conducted in chronically institutionalized patients with schizophrenia or schizoaffective disorder requiring treatment with lithium (n = 12) or valproate (divalproex sodium) (n = 10). Patients received aripiprazole 30 mg/day on days 1 to 14 and aripiprazole with concomitant therapy on days 15 to 36. Lithium was titrated from 900 mg until serum concentrations reached 1.0 to 1.4 mEq/L for at least 5 days. Valproate was titrated to 50 to 125 mg/L. Coadministration with lithium increased mean Cmax and AUC values of aripiprazole by about 19% and 15%, respectively, whereas the apparent oral clearance decreased by 15%. There was no effect on the steady-state pharmacokinetics of the active metabolite of aripiprazole. Coadministration with valproate decreased the AUC and Cmax of aripiprazole by 24% and 26%, respectively, with minimal effects on the active metabolite. Therapeutic doses of lithium and divalproex had no clinically significant effects on the pharmacokinetics of aripiprazole in patients with schizophrenia or schizoaffective disorder.

Adult↗
PubMed2006

Intramuscular aripiprazole or haloperidol and transition to oral therapy in patients with agitation associated with schizophrenia: sub-analysis of a double-blind study.

OBJECTIVE: A sub-population analysis of 325 patients with agitation (Positive and Negative Syndrome Scale Excited Component [PEC] score > or = 15 and < or = 32; score of > or = 4 on > or = 2 items) associated with schizophrenia in a randomized, double-blind study investigating the efficacy and tolerability of intramuscular (IM) aripiprazole 9.75 mg, IM haloperidol 6.5 mg, or IM placebo and the transition to oral therapy. RESEARCH DESIGN AND METHODS: Over 24 h, patients could receive up to three IM injections; the second and third administered > or = 2 and > or = 4 h, respectively, after the first, if deemed clinically necessary. Following IM treatment, oral aripiprazole or haloperidol was administered for 4 days. The primary efficacy measure was the mean change in PEC score from baseline at 2 h. RESULTS: At 2 h, mean improvements in PEC scores with IM aripiprazole (-8.0) were significantly greater versus IM placebo (-5.7; p < or = 0.01), and similar versus IM haloperidol (-8.3). Secondary efficacy measures also significantly improved with active IM treatment versus IM placebo. Continuation with oral treatment provided continued efficacy with both active treatments. The safety profiles of IM and oral aripiprazole were similar. The incidence of extrapyramidal symptom-related adverse events was 0% with IM aripiprazole, 1.6% with IM placebo and 16.5% with IM haloperidol. CONCLUSION: Intramuscular aripiprazole is effective in patients with acute agitation associated with schizophrenia, comparable to IM haloperidol, and enables convenient transfer to oral aripiprazole therapy.

Administration, Oral↗
PubMed2006

Efficacy with high-dose aripiprazole after olanzapine-related metabolic disturbances.

OBJECTIVE: To report a case in which a patient tolerated and responded to high-dose aripiprazole and lost weight after having been on olanzapine for several years; a secondary objective is to discuss the use of aripiprazole dosages at higher than those recommended in the product's labeling. CASE SUMMARY: A 57-year-old man with a 30 year history of schizophrenia had been taking olanzapine for 4 years, with the dosage titrated to 20 mg/day, to control the psychosis. After he had gained significant weight with olanzapine (the highest was 102.7 kg), his treatment was switched to aripiprazole. The patient required a high dose of aripiprazole (60 mg/day) to achieve full control of the psychiatric symptoms, and during aripiprazole therapy, he lost the weight he had gained while on olanzapine, weighing 85.9 kg within 7 months after the therapy switch. DISCUSSION: Dosages of atypical antipsychotics higher than those recommended by the Food and Drug Administration are often used in clinical practice for refractory patients, despite the lack of evidence. The literature available on this subject is limited to small, double-blind trials; open-label trials; and case reports. Although certain patients may benefit from higher doses of atypical antipsychotics, the lack of evidence limits their use. CONCLUSIONS: High-dose aripiprazole (60 mg/day) was well tolerated and controlled this patient's symptoms effectively. In addition, he lost weight that was gained while being treated with olanzapine. High-dose aripiprazole may be beneficial and safe in refractory patients; however, large, double-blind, randomized clinical trials are needed.

Antipsychotic Agents↗
PubMed2004

Aripiprazole: in acute mania associated with bipolar I disorder.

Aripiprazole, an oral quinolinone (carbostyril), is a novel atypical antipsychotic that has partial agonist activity at dopamine D(2) and serotonin 5-HT(1A) receptors, and antagonist activity at 5-HT(2A) receptors. Aripiprazole had a rapid onset of action (as early as day 4) and was effective in the treatment of patients with bipolar I disorder experiencing an acute manic or mixed episode. Aripiprazole was generally significantly more effective than placebo in improving manic symptoms (as defined by a mean change in Young Mania Rating Scale Total Score) in 3-week placebo-controlled trials, and demonstrated superior effectiveness to haloperidol (response rate 50% vs 28.4% in patients remaining on treatment) in a 12-week comparative trial. The time to relapse of symptoms in stabilised patients with bipolar I disorder who previously experienced a manic episode was significantly longer with aripiprazole than with placebo in a 26-week relapse prevention study. Aripiprazole was generally well tolerated and was not associated with weight gain, serum prolactin elevation or clinically significant QTc interval prolongation. black triangle Changes from baseline in extrapyramidal symptom scale scores with aripiprazole were small (<0.5 units), but generally significantly greater than with placebo in one of the 3-week trials. In the 12-week trial, changes from baseline were significantly smaller with aripiprazole than with haloperidol.

Antipsychotic Agents↗
PubMed2005

Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms.

In this study we have functionally characterized aripiprazole (OPC-14597; 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy-3,4-dihydro-2-(1H)-quinolinone), the prototype of a new generation antipsychotic drug termed dopamine-serotonin-system stabilizer, in cells expressing 5-hydroxytryptamine2 (5-HT2) receptor subtypes in comparison with olanzapine. In Chinese hamster ovary (CHO) cells stably expressing 5-HT2 receptors, aripiprazole displayed a dual agonist/antagonist profile for 5-HT2C receptor (VNI isoform) mediated calcium signaling (EC50 1070 nM, IC50 281 nM). It exhibited no appreciable 5-HT2A or 5-HT2B agonism, whereas it antagonized 5-HT-stimulated calcium increase at either 5-HT2A or 5-HT2B receptor expressed in CHO cells (IC50s of 369 and 0.46 nM, respectively). In comparison, olanzapine was devoid of agonism but was an antagonist at all three subtypes, with a potency rank order of 5-HT2A (IC50, 2.5 nM)>5-HT2B (47 nM)>5-HT2C (69 nM). In human embryonic kidney (HEK) cells transiently expressing 5-HT2C receptor isoforms, aripiprazole exhibited full agonism at the unedited INI, but partial agonism at the partially edited VNI and fully edited VSV isoforms (EC50s of 571, 1086 and 2099 nM, respectively). A partial antagonism was also observed for aripiprazole at the two edited isoforms (IC50s of 1138 and 1000 nM, respectively). In contrast, while lacking agonist activity at the VNI and VSV, olanzapine showed inverse agonism at the INI isoform (IC50 594 nM), reaching a maximal attenuation of 20%. In addition, olanzapine was a full antagonist at all three isoforms, with a rank order of potency of VNI (IC50, 79 nM)>VSV (101 nM)>INI (3856 nM). The modest 5-HT2A antagonism and 5-HT2C partial agonism, along with reported D2 and 5-HT1A partial agonism, may allow aripiprazole to stabilize the disturbed dopamine-serotonin interplay in schizophrenia with a moderate yet adequate pharmacological intervention. 5-HT2C agonism may also underlie the minimal weight gain seen with aripiprazole.

Animals↗
PubMed2006

A low dose of aripiprazole attenuates the subject-rated effects of d-amphetamine.

Despite increased reports of amphetamine abuse and dependence, a putative pharmacotherapy has yet to be identified. In a previous study from our laboratory, 20 mg aripiprazole, an atypical antipsychotic that has partial agonist activity at D(2) receptors, attenuated many of the behavioral effects of d-amphetamine. Aripiprazole (20 mg) also impaired performance on a computerized version of the DSST when administered alone, indicating that the attenuation observed may have been functional as opposed to receptor mediated. The present experiment was conducted to determine whether a lower dose of aripiprazole (10 mg) could acutely attenuate the discriminative-stimulus, subject-rated, and physiological effects of d-amphetamine (2.5-15 mg) without impairing performance as measured with a computerized version of the DSST. The results of the present experiment indicate that 10 mg aripiprazole attenuated some abuse-related behavioral effects of d-amphetamine and was generally devoid of effects, including significant performance impairment, when administered alone. These findings suggest that 10 mg aripiprazole would be a reasonable starting dose for the treatment of stimulant abuse and dependence. Future research should examine the effects of chronic aripiprazole administration in combination with methamphetamine or cocaine.

Adult↗
PubMed2003

Diminished catalepsy and dopamine metabolism distinguish aripiprazole from haloperidol or risperidone.

Catalepsy and changes in striatal and limbic dopamine metabolism were investigated in mice after oral administration of aripiprazole, haloperidol, and risperidone. Catalepsy duration decreased with chronic (21 day) aripiprazole compared with acute (single dose) treatment across a wide dose range, whereas catalepsy duration persisted with chronic haloperidol treatment. At the time of maximal catalepsy, acute aripiprazole did not alter neostriatal dopamine metabolite/dopamine ratios or homovanillic acid (HVA) levels, and produced small increases in dihydroxyphenylacetic acid (DOPAC). Effects were similar in the olfactory tubercle. Dopamine metabolism was essentially unchanged in both regions after chronic aripiprazole. Acute treatments with haloperidol or risperidone elevated DOPAC, HVA, and metabolite/dopamine ratios in both brain areas and these remained elevated with chronic treatment. The subtle effects of aripiprazole on striatal and limbic dopamine metabolism, and the decrease in catalepsy with chronic administration, illustrate fundamental differences in dopamine neurochemical actions and behavioral sequelae of aripiprazole compared to haloperidol or risperidone.

Administration, Oral↗
PubMed2005

Aripiprazole in the treatment of pediatric bipolar disorder: a systematic chart review.

BACKGROUND: Pediatric bipolar disorder is a serious neuropsychiatric disorder associated with high levels of morbidity and disability. OBJECTIVE: This is a systematic chart review of all outpatient youth with the diagnosis of bipolar disorder and bipolar spectrum disorder treated with aripiprazole either alone or as add-on to ongoing treatments. METHOD: Medical records were reviewed to identify all subjects with bipolar and bipolar spectrum disorder prescribed aripiprazole in our clinic. During the chart review, the Clinical Global Impression scale was completed by the treating clinicians to determine usefulness. RESULTS: Forty-one youths (mean age+/-SD: 11.4+/-3.5 years) with bipolar spectrum disorder who had been treated with aripiprazole were identified. These children received a mean daily dose of aripiprazole 16.0+/-7.9 mg over an average of 4.6 months. Using a Clinical Global Impression-Improvement scale score of <2 (very much/much improved) to define robust improvement, 71% showed improvement in manic symptoms. Treatment with aripiprazole was well tolerated. CONCLUSION: This study suggests that aripiprazole may be a useful and well-tolerated treatment for youth with bipolar disorder and it supports the need for controlled clinical trials of this compound in juvenile mania.

Adolescent↗
PubMedDate not supplied

Adjunctive aripiprazole in treatment-resistant bipolar depression.

BACKGROUND: There are limited management options for treatment-resistant depression in bipolar disorder (BD) patients. METHOD: Open adjunctive aripiprazole was administered to outpatients with treatment-resistant depression assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and followed with the STEP-BD Clinical Monitoring Form. RESULTS: Thirty BD (11 type I, 15 type II, 4 NOS) patients (mean age 44.4 +/- 17.0 years, 70% female) on a mean of 3.2 +/- 1.6 other psychotropic and 2.3 +/- 1.6 nonpsychotropic prescription medications received aripiprazole for a mean duration of 84 +/- 69 days, with a mean final dose of 15.3 +/- 11.2 (range 2.5-40) mg/day. Fourteen patients (47%) discontinued aripiprazole; due to inefficacy in 5/30 (17%), patient choice in 3/30 (10%), and adverse effects in 6/30 (20%). Aripiprazole yielded improvement in Clinical Global Impression-Severity (CGI-S, 4.4 +/- 1.1 to 3.8 +/- 1.2, p < 0.01), with 8/30 (27%) patients responding (CGI-S improvement > or = 2), including 4/30 (13%) who remitted (final CGI-S < or = 2). Global Assessment of Function, and depressed mood and suicidal ideation ratings also improved. Aripiprazole was generally well tolerated, with no significant change in mean adverse effect ratings or mean weight. CONCLUSION: Aripiprazole appeared effective and generally well tolerated in treatment-resistant bipolar depression. Controlled trials are warranted to systematically explore these preliminary naturalistic observations.

Adult↗
PubMed2005

Diabetic ketoacidosis associated with aripiprazole.

BACKGROUND: Atypical antipsychotics have become the mainstay of management of schizophrenia and other psychotic disorders due to low risk of extrapyramidal symptoms. However, postmarketing data has reported atypical antipsychotic agents being associated with hyperglycaemia and diabetic ketoacidosis (DKA). We believe this to be the first published report of hyperglycaemia and DKA with the newest atypical antipsychotic agent, aripiprazole. CASE REPORT: A 34-year-old African-American female with schizophrenia presented to the emergency department with nausea, vomiting, and malaise for 3-4 days shortly after initiation of aripiprazole therapy. Initial laboratory results revealed significant hyperglycaemia with metabolic acidosis. The patient received treatment for DKA with an intravenous insulin infusion and fluid replacement. Isophane insulin suspension (NPH insulin) was begun immediately following the insulin drip and continued upon discharge from the hospital. Outpatient follow-up information was not available. CONCLUSION: To our knowledge, this is the first case report of aripiprazole associated with hyperglycaemia and DKA. This case is striking in that DKA occurred 4 days following initiation of aripiprazole and the patient had rapid resolution of symptoms and normalization of laboratory values upon discontinuation of aripiprazole. It is important that health-care providers monitor for hyperglycaemia when prescribing atypical antipsychotics including aripiprazole.

Adult↗
PubMed2006

Aripiprazole in the treatment of patients with borderline personality disorder: a double-blind, placebo-controlled study.

OBJECTIVE: Aripiprazole is a relatively new atypical antipsychotic agent that has been successfully employed in therapy for schizophrenia and schizoaffective disorders. A few neuroleptics have been used in therapy for patients with borderline personality disorder, which is associated with severe psychopathological symptoms. Aripiprazole, however, has not yet been tested for this disorder, and the goal of this study was to determine whether aripiprazole is effective in the treatment of several domains of symptoms of borderline personality disorder. METHOD: Subjects meeting criteria for the Structured Clinical Interview for DSM-III-R Personality Disorders for borderline personality disorder (43 women and 9 men) were randomly assigned in a 1:1 ratio to 15 mg/day of aripiprazole (N=26) or placebo (N=26) for 8 weeks. Primary outcome measures were changes in scores on the symptom checklist (SCL-90-R), the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), and the State-Trait Anger Expression Inventory and were assessed weekly. Side effects and self-injury were assessed with a nonvalidated questionnaire. RESULTS: According to the intent-to-treat principle, 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 after 8 weeks. Self-injury occurred in the groups. The reported side effects were headache, insomnia, nausea, numbness, constipation, and anxiety. CONCLUSIONS: Aripiprazole appears to be a safe and effective agent in the treatment of patients with borderline personality disorder.

Aggression↗
PubMed2005

Effectiveness of aripiprazole v. haloperidol in acute bipolar mania: double-blind, randomised, comparative 12-week trial.

BACKGROUND: Despite several treatmentoptions, adherenceto therapy is poor in patients with bipolar disorder. AIMS: A double-blind, controlled comparison of aripiprazole and haloperidol in patients with bipolar I disorder experiencing acute manic or mixed episodes. METHOD: Patients (n=347) were randomised to receive aripiprazole or haloperidol in this 12-week, multicentre study. The primary outcome measure was the number of patients in response (greater, similar 50% improvement from baseline in Young Mania Rating Scale score) and receiving therapy at week 12. RESULTS: At week 12, significantly more patients taking aripiprazole (49.7%) were in response and receiving therapy compared with those taking haloperidol (28.4%; P < 0.001). Continuation rates differed markedly between treatments (week 12: aripiprazole, 50.9%; haloperidol, 29.1%). Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole (62.7% v. 24.0%). CONCLUSIONS: Aripiprazole showed superior levels of response and tolerability to haloperidol in the treatment of an acute manic episode for up to 12 weeks.

Acute Disease↗
PubMed2003

Aripiprazole: a new atypical antipsychotic drug.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of aripiprazole for the treatment of schizophrenia. DATA SOURCES: Information was selected from MEDLINE (1995-August 2002). Abstracts, scientific posters, and presentations were also used. STUDY SELECTION/DATA EXTRACTION: All published information regarding the pharmacokinetic, pharmacodynamic, and clinical characteristics of aripiprazole was considered. Studies providing a comprehensive description of aripiprazole were selected. DATA SYNTHESIS: Aripiprazole is a dopamine partial agonist and a serotonin-2A antagonist; it is dosed 10-30 mg/d, with no initial titration necessary. Short-term clinical trials demonstrated efficacy in acute exacerbations, and long-term studies showed that aripiprazole can maintain remission of schizophrenia. Most adverse events were mild. The incidence of extrapyramidal symptoms was low, with akathisia being the most common. CONCLUSIONS: Aripiprazole currently demonstrates comparable efficacy and safety for use in schizophrenia.

Antipsychotic Agents↗
PubMed2005

Clozapine-induced hyperlipidemia resolved after switch to aripiprazole therapy.

OBJECTIVE: To report a case of severe clozapine-induced hypercholesterolemia and hypertriglyceridemia that resolved after therapy was switched to aripiprazole. CASE SUMMARY: A 42-year-old white man with schizoaffective disorder experienced new-onset hyperlipidemia with the addition of clozapine therapy. Despite treatment with various antihyperlipidemic agents, his total cholesterol level reached 477 mg/dL and his triglyceride level reached 4758 mg/dL. After a decrease in adherence with clozapine and subsequent deterioration, the patient was hospitalized and his antipsychotic therapy was switched to aripiprazole. The patient's lipid levels improved dramatically to the point that antihyperlipidemic treatment was discontinued. Due to lack of adequate symptomatic relief of psychiatric symptoms, the patient was ultimately switched back to clozapine therapy, at which time his lipid levels started to worsen again. DISCUSSION: There is a critical scarcity of data that relate to aripiprazole-induced lipid changes. Some studies have suggested that aripiprazole is not associated with the development of hyperlipidemia. Our case indicates that aripiprazole therapy may not have an adverse effect on lipid levels, even in patients who have a history of hyperlipidemia induced by another atypical antipsychotic. CONCLUSIONS: Should aripiprazole be found to have a definitive lipid-neutral effect, then clinicians would be wise to factor this finding into overall benefit-versus-risk considerations in the antipsychotic treatment selection process, especially in a society in which cardiovascular disease continues to be a principal cause of morbidity and mortality.

Adult↗
PubMed2006

Acute dystonia with low-dosage aripiprazole in Tourette's disorder.

OBJECTIVE: To report a case of an acute dystonic episode in a patient with Tourette's disorder (TD) treated with the partial dopamine agonist aripiprazole. CASE SUMMARY: An 18-year-old male with TD was prescribed aripiprazole 10 mg orally daily, which produced a significant improvement in his symptoms. However, after 3 days of treatment, he experienced an acute episode of dystonia with facial muscle spasm, oculogyric crisis, and torticolis. All symptoms resolved after a single intramuscular injection of biperidine 5 mg. The Naranjo probability scale indicated that the adverse events were probably caused by aripiprazole. DISCUSSION: To our knowledge, as of this writing, this is the first report concerning an aripiprazole-induced dystonic episode in an adult, and it is especially notable because it occurred at low dosage. Aripiprazole is a dopamine partial agonist and a serotonin(2A) antagonist with a favorable adverse effect profile. Short-term clinical trials reported a very low incidence of extrapyramidal symptoms, with akathisia being the most common, although there have been reports of severe extrapyramidal symptoms in a 3-year-old child and in an adolescent with a previous history of such symptoms. CONCLUSIONS: Acute dystonic phenomena may be caused by aripiprazole, although the drug's suggested mode of action largely precludes them.

Acute Disease↗
PubMed2007

Aripiprazole in the treatment of schizophrenia: a consensus report produced by schizophrenia experts in Italy.

Schizophrenia is generally a chronic and disabling mental illness. Pharmacological therapy, which is used for relief of acute psychotic episodes and prevention of subsequent relapse, is essential for the effective management of schizophrenia. In order to alleviate the positive symptoms of schizophrenia, all antipsychotic agents act on the dopaminergic system. However, strong, high-affinity dopamine D(2)-receptor blockade may also be responsible for debilitating extrapyramidal symptoms (EPS) and hyperprolactinaemia. Unlike conventional antipsychotic agents, atypical antipsychotics also exert activity at other receptors, and it is generally acknowledged that, compared with conventional antipsychotics, atypical agents are associated with a broader spectrum of clinical efficacy and are better tolerated. However, other adverse effects such as weight gain and metabolic changes are cause for concern with some atypical antipsychotics. The novel atypical antipsychotic agent aripiprazole is a partial agonist at D(2) receptors that has been shown in clinical trials to be effective in treating both the positive and the negative symptoms of schizophrenia, and to be well tolerated, with a low propensity for EPS and no clinically significant weight gain, hyperprolactinaemia or corrected QT-interval prolongation. Aripiprazole thus provides clinicians with another treatment option, and in October 2005, schizophrenia experts participated in an expert consensus meeting that aimed to agree on a set of guidelines for best-practice use of aripiprazole in the acute and long-term management of schizophrenia in Italy. This report describes the outcome of the meeting. Our recommendations for dosage and administration of aripiprazole are in agreement with the manufacturer's prescribing information. Ideally, optimal dosing should be evaluated on an individual basis, taking into account patients' characteristics such as the presence or absence of agitation. Overall, in our experience, aripiprazole is generally a well accepted, well tolerated, safe and broadly effective first-line antipsychotic agent. Switching to aripiprazole from maintenance therapy with another antipsychotic also works well, provided the change is made gradually, involving tapering of the original medication.

Antipsychotic Agents↗
PubMed2005

Aripiprazole augmentation of antidepressants for the treatment of partially responding and nonresponding patients with major depressive disorder.

OBJECTIVE: To determine the efficacy and tolerability of aripiprazole, a dopamine D2 and 5-HT1A receptor partial agonist, as augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder. METHOD: Fifteen patients with major depressive disorder (diagnosed with a site-generated form described in the text) and an incomplete response or no response to > or = 8 weeks of antidepressant (selective serotonin reuptake inhibitor, venlafaxine, or bupropion) monotherapy were treated with aripiprazole augmentation in an 8-week, open-label study. Data were gathered from July 2003 to March 2004. RESULTS: The mean duration of antidepressant monotherapy at baseline was 43.1 weeks. At baseline, mean Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale for Depression (HAM-D) scores were 4.3 and 18.9, respectively. After initiation of aripiprazole augmentation, 6 of 15 patients achieved remission (HAM-D score < or = 7) at week 1, and 9 of 15 patients remitted by week 2. All 8 completers achieved remission by study endpoint. Akathisia in 2 patients who withdrew prematurely prompted a reduction in the starting dose of aripiprazole from 10 mg/day to 2.5 mg/day, resulting in a 50% reduction in attrition due to akathisia (2/7 withdrew due to akathisia with the 10-mg starting dose, 1/8 withdrew due to akathisia with the 2.5-mg starting dose). Discontinuation rates after 4 weeks of treatment were lower for the 2.5-mg starting dose (1/8 patients) than for the 10-mg starting dose (3/7 patients). Overall discontinuation rates at endpoint were lower for the 2.5-mg dose (3/8 patients) than the 10-mg dose (4/7 patients). Response to aripiprazole augmentation did not appear to be related to the antidepressant used at study initiation. CONCLUSION: Aripiprazole is an effective augmentation strategy for improving therapeutic response in patients with treatment-resistant major depressive disorder when administered in combination with standard antidepressant therapy. Based on this clinical signal, a double-blind, placebo-controlled trial is warranted.

Adult↗
PubMed2006

An open-label, rater-blinded, augmentation study of aripiprazole in treatment-resistant depression.

BACKGROUND: About 30% to 46% of patients with major depressive disorder (MDD) fail to fully respond to initial antidepressants. While treatment-resistant depression commonly refers to nonresponse or partial response to at least 2 adequate trials with antidepressants from different classes, due to variability in terminology, a staging system based on prior treatment response has been suggested. Aripiprazole is a novel atypical antipsychotic with partial agonism at dopamine D(2) and serotonin 5-HT(1A) receptors and antagonism at the 5-HT(2) receptors. The present study evaluated whether augmentation with aripiprazole would be beneficial and tolerable in patients with treatment-resistant MDD who had failed 1 or more trials of antidepressants. METHOD: In an open-label, rater-blinded study conducted from March 2003 through December 2003, 10 patients with DSM-IV MDD without psychotic features who had failed to respond to an adequate trial of at least 1 antidepressant were prescribed aripiprazole (10-30 mg/day) for 6 weeks. The dose of preexisting antidepressants remained unchanged. Treatment response was defined as a 50% or greater reduction in score on the Hamilton Rating Scale for Depression (HAM-D) from baseline to end of treatment. Secondary efficacy measures included scores on the Clinical Global Impressions-Improvement (CGI-I) and -Severity (CGI-S) scales. RESULTS: Eight of 10 patients had failed 2 or more antidepressant trials. The mean daily dose of aripiprazole was 13.21 mg. Intent-to-treat analysis showed that mean ± SD HAM-D scores reduced significantly from baseline (23.0 ± 8.1) to end of treatment (8.1 ± 6.0) (p < .001). There was a significant reduction in CGI-I (p < .05) and a trend toward decrease in CGI-S (p = .06) score. Seventy percent of the subjects were responders and 30% achieved remission. Common adverse effects were akathisia (20%), nausea (20%), and restlessness (20%). CONCLUSIONS: The study indicates the potential utility of aripiprazole as an augmenting agent in treatment-resistant depression, particularly in those who had failed 2 or more antidepressant trials. Adequately powered, randomized controlled trials are necessary to evaluate the role of aripiprazole in treatment-resistant depression.

Journal Article↗