a) PEDIATRIC: In short term placebo controlled trials in which pediatric patients 6 to 17 years of age with autistic disorder received either aripiprazole 2 mg/day to 15 mg/day orally or placebo, pyrexia was reported in 9% of patients receiving aripiprazole (n=212) compared with 1% of patients receiving placebo (n=101) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) ADULT: In a pooled analysis of trials in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, blurred vision was reported in 3% of patients receiving aripiprazole (n=1843) compared with 1% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) ADULT: In pooled data of 2 placebo-controlled trials of adult patients with major depressive disorder receiving oral aripiprazole 2 mg to 20 mg/day for up to 6 weeks in addition to continued antidepressant therapy (n=371) or antidepressant therapy alone (n=366), blurred vision occurred in 6% versus 1% of patients, respectively (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
c) PEDIATRIC: In a short-term, placebo-controlled trial in which pediatric patients aged 10 to 17 years with bipolar mania received either aripiprazole 10 mg or 30 mg/day orally or placebo, blurred vision was reported in 8% of the aripiprazole group (n=197) compared with 0% of the placebo group (n=97) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) Compared with placebo, aripiprazole therapy resulted in a higher incidence of orthostatic hypotension among adult patients receiving oral aripiprazole (1% vs 0.3%; n=2467), in pediatric patients 6 to 17 years of age receiving oral aripiprazole (0.5% vs 0%; n=611), and in patients receiving IV aripiprazole (0.6% vs 0%; n=501) during short-term trials (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) In a pooled analysis of trials in which adult patients with agitation associated with schizophrenia or bipolar mania received either aripiprazole intramuscularly 5.25 mg/day or greater or placebo, tachycardia was reported in 2% of patients receiving aripiprazole (n=501) compared with less than 1% of patients receiving placebo (n=220) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) CASE REPORT: Drowsiness and tachycardia (115 beats/min) were the only reported effects in an adult following an intentional ingestion of 22 aripiprazole 15-mg tablets (330 mg). Signs and symptoms resolved within 8 hours (Carstairs & Williams, 2005).
b) CASE SERIES: In a retrospective poison center study, tachycardia was reported in 5 of 114 patients (4.4%) with exposure to aripiprazole only (Forrester, 2006).
c) CASE REPORT/CHILD: A 2-year-old child presented to the emergency department with tachycardia (160 beats/min), lethargy, tremors, and irritability 36 hours after ingesting 2 aripiprazole 5-mg tablets (0.92 mg/kg). Signs and symptoms persisted for 3 days postadmission. The patient was discharged on hospital day 4; however, telephone follow-up with the patient's mother, the day after discharge, revealed that intermittent tremor and irritability still persisted (Melhem et al, 2009).
d) CASE SERIES: According to a retrospective review of aripiprazole only exposures reported to the California Poison Control System from 2002 to 2006, tachycardia (heart rate of 102 to 186 beats/min) was reported in 20% of the patients (n=158) (Young et al, 2009).

a) CASE REPORT: An adult developed hypotension (85/45 mmHg) following ingestion of an unknown amount of aripiprazole. The patient recovered with supportive care (Young et al, 2009).
b) CASE REPORT/DELAYED PRESENTATION: A 25-year-old woman presented to the emergency department approximately 30 minutes after intentionally ingesting 15 aripiprazole 15-mg tablets (4.5 mg/kg). Following a complete physical and neurologic exam and a 3-hour observation period, the patient remained asymptomatic and was sent to a psychiatric holding unit for evaluation; subsequently she was transferred to the psychiatric inpatient unit for treatment of her suicidal ideation. Two hours later (approximately 9 hours postingestion), the patient became somnolent, hypotensive (80/40 mmHg), and bradycardic (50 beats/min). With supportive care the patient recovered without sequelae (Lo & Pizon, 2008).

a) CASE REPORT/DELAYED PRESENTATION: A 25-year-old woman presented to the emergency department approximately 30 minutes after intentionally ingesting 15 aripiprazole 15-mg tablets (4.5 mg/kg). Following a complete physical and neurologic exam and a 3-hour observation period, the patient remained asymptomatic and was sent to a psychiatric holding unit for evaluation; subsequently she was transferred to the psychiatric inpatient unit for treatment of her suicidal ideation. Two hours later (approximately 9 hours postingestion), the patient became somnolent, hypotensive (80/40 mmHg), and bradycardic (50 beats/min). With supportive care the patient recovered without sequelae (Lo & Pizon, 2008).

a) In pooled data of 2 placebo-controlled trials of adult patients with major depressive disorder receiving aripiprazole 2 mg to 20 mg/day for up to 6 weeks in addition to continued antidepressant therapy (n=371), compared with antidepressant therapy only (n=366), upper respiratory tract infection occurred in 6% versus 4% of patients, respectively (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) In a single case report, the administration of aripiprazole appeared to induce hiccups in a 28-year-old man with organic bipolar affective disorder. The patient had a history of measles, accidental insecticide poisoning, episodic illness, and a closed head injury, which left him with peritraumatic amnesia (retrograde and anterograde), left-sided hemiparesis, and behavioral problems. On admission, testing revealed increased tone, grade 4 power, and exaggerated left upper and lower tendon jerks. Carbamazepine 800 mg daily and olanzapine 10 mg/day were initiated with resolution of symptoms within a month's time. Due to excessive sedation, olanzapine was discontinued and aripiprazole 10 mg/day was added to the patient's existing drug regimen. Within 3 to 4 hours of aripiprazole initiation, the patient developed continual hiccups. The patient skipped the next dose of aripiprazole as advised, and within 30 hours following the last dose, the hiccups subsided. Upon aripiprazole rechallenge, the patient began experiencing hiccups again within a few hours. Aripiprazole was replaced with gradual dose titration of quetiapine 200 mg/day and carbamazepine 1000 mg/day. No further symptoms had reoccurred at 1 month follow-up (Ray et al, 2009).

a) ADULT: In a pooled analysis of trials in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, somnolence was reported in 5% of patients receiving aripiprazole (n=1843) compared with 3% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) PEDIATRIC: In short-term placebo controlled trial in which pediatric patients aged 10 to 17 years with bipolar mania received either oral aripiprazole (doses 10 mg/day or 30 mg/day ) or placebo, somnolence was reported in 23% of patients receiving aripiprazole (n=197) compared with 3% of patients receiving placebo (n=97) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
c) CASE REPORT: Mild CNS depression was reported in a 6-year-old child who received 2 therapeutic doses of aripiprazole, given as 10 mg once daily (Lofton & Klein-Schwartz, 2005).

a) Drowsiness or lethargy are the most common effects reported after overdose.
b) CASE SERIES: In a retrospective poison center study of 114 patients with exposure to aripiprazole only, 32 (28.1%) developed drowsiness or lethargy (Forrester, 2006).
c) There are several reports of moderate CNS depression that is usually self-limited. No patient required intubation (Carstairs & Williams, 2005; LoVecchio et al, 2005). Mild CNS depression was reported in a 2-year-old child who ingested 40 mg of aripiprazole (Lofton & Klein-Schwartz, 2005).
d) CASE REPORT: Prolonged somnolence occurred in a 9-year-old girl following ingestion of a single 15-mg dose of aripiprazole. The somnolence began approximately 3.5 hours postingestion and progressively worsened over the next 24 hours. Upon presentation to the emergency department, the patient was responsive to questions but was still very somnolent. Her vital signs and ECG were within normal limits. Over the 24 hour hospitalization period, the somnolence resolved and the patient was discharged to home without sequelae (Davenport et al, 2004).
e) CASE REPORT: Drowsiness and tachycardia (115 beats/min) were the only reported effects in an adult following an intentional ingestion of 22 aripiprazole 15-mg tablets (330 mg). Signs and symptoms resolved within 8 hours (Carstairs & Williams, 2005).
f) CASE REPORT: A 3-year-old child presented with severe lethargy, flat affect, intention tremor, truncal ataxia, and a Parkinsonian gait 48 hours after ingesting approximately 7.5 mg of aripiprazole. The symptoms completely resolved 7 days postingestion (Schonberger et al, 2004).
g) CASE REPORT: A 2.5-year-old child ingested 13 aripiprazole 15-mg tablets (17.1 mg/kg) and, within 1 hour, developed vomiting and lethargy that progressed to loss of consciousness. The patient's vital signs were stable and she gradually regained consciousness over the next 24 hours. On hospital day 2 the patient developed ataxia, and on day 4 she had tremulousness with fine motor activity of the hands; these effects gradually resolved over the next 7 days (Seifert et al, 2005).
h) CASE REPORT/CHILD: A 2-year-old child presented to the emergency department with tachycardia (160 beats/min), lethargy, tremors, and irritability 36 hours after ingesting 2 aripiprazole 5-mg tablets (0.92 mg/kg). Signs and symptoms persisted for 3 days postadmission. The patient was discharged on hospital day 4; however, telephone follow-up with the patient's mother, the day after discharge, revealed that intermittent tremor and irritability still persisted (Melhem et al, 2009).
i) CASE SERIES: A retrospective review of aripiprazole only exposures reported to the California Poison Control System from 2002 to 2006 revealed that somnolence was the most commonly reported symptom, occurring in 56% of patients (n=158) (Young et al, 2009). Other reported effects included: tremors (6%), agitation (2%), dizziness (2%), paresthesia (1%), and headache (1%).
j) CASE REPORT/DELAYED PRESENTATION: A 25-year-old woman presented to the emergency department approximately 30 minutes after intentionally ingesting 15 aripiprazole 15-mg tablets (4.5 mg/kg). Following a complete physical and neurologic exam and a 3-hour observation period, the patient remained asymptomatic and was sent to a psychiatric holding unit for evaluation; subsequently she was transferred to the psychiatric inpatient unit for treatment of her suicidal ideation. Two hours later (approximately 9 hours postingestion), the patient became somnolent, hypotensive (80/40 mmHg), and bradycardic (50 beats/min). With supportive care the patient recovered without sequelae (Lo & Pizon, 2008).
k) CASE REPORT/CHILD: A 2-year-old child developed lethargy, ataxia, hypothermia, and an episode of vomiting after a suspected ingestion of 3 15-mg tablets of aripiprazole. Although there was no evidence of amphetamine ingestion, an initial urine drug screen revealed an amphetamine concentration of 1048 ng/mL, and repeat urine testing the following day was also positive for amphetamines; however, quantitative confirmatory laboratory testing of urine and blood samples by an outside laboratory was negative for amphetamines, suggesting that in-house screening yielded false-positive results. With supportive care, the patient recovered uneventfully and was discharged 2 days post-admission (Kaplan et al, 2015).

a) ADULT: In a pooled analysis of short-term trials in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, tremor was reported in 5% of patients receiving aripiprazole (n=1843) compared with 3% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) PEDIATRIC: In short term placebo controlled trials in which pediatric patients 6 to 17 years of age with autistic disorder received either aripiprazole 2 mg/day to 15 mg/day orally or placebo, tremor was reported in 10% of patients receiving aripiprazole (n=212) compared with 0% of patients receiving placebo (n=101) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) Extrapyramidal symptoms have been minimal during oral aripiprazole therapy of schizophrenia in unpublished studies (Inoue & Nakata, 2001; Kane et al, 2000; Saha et al, 1999; Petrie et al, 1998a). In a 4-week study (n=410), the overall incidence of extrapyramidal side effects with aripiprazole 15 or 30 mg daily was similar to that in the placebo group; at least 1 dose of benztropine was required in 11% to 17% of patients receiving these doses of aripiprazole, compared with 36% assigned to haloperidol 10 mg daily (Kane et al, 2000). The frequency of extrapyramidal symptoms was also lower with aripiprazole than haloperidol in a phase 2 study (Saha et al, 1999).
b) ADULT: In a pooled analysis of 3-week, placebo-controlled trials in which adult patients with bipolar mania received oral aripiprazole 15 or 30 mg/day or placebo, extrapyramidal disorder was reported in 5% of aripiprazole-treated patients (n=917) compared with 2% of placebo-treated patients (n=753) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
c) PEDIATRIC: In a short-term placebo controlled trial in which pediatric patients aged 10 to 17 years with bipolar mania received either oral aripiprazole (doses 10 mg/day or 30 mg/day ) or placebo, extrapyramidal symptoms were reported in 20% of patients receiving aripiprazole (n=197) compared with 3% of patients receiving placebo (n=97) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) CASE REPORT: A 3-year-old child presented with severe lethargy, flat affect, intention tremor, truncal ataxia, and a Parkinsonian gait 48 hours after ingesting approximately 7.5 mg of aripiprazole. The symptoms completely resolved 7 days postingestion (Schonberger et al, 2004).
b) CASE SERIES: According to a retrospective review of aripiprazole only exposures reported to the California Poison Control System from 2002 to 2006, dystonia was reported in 13% of the patients (n=158) (Young et al, 2009).

a) CASE REPORT: A 57-year-old woman was initiated on 10 mg/day of aripiprazole as single-agent therapy for schizophrenia. By day 4 of therapy, the patient had developed a resting tremor, shuffling gait, confusion, fever, elevated white blood cell count, and tachycardia. Motor function recovered within 10 days after discontinuing the aripiprazole, but symptoms of confusion and drooling persisted for several weeks (Evcimen et al, 2007).
b) CASE REPORT: Neuroleptic malignant syndrome (NMS) was reported in a 71-year-old woman with prehypertension and paranoid schizophrenia. She was admitted due to an abrupt change in her baseline mental status, skin flushing, and worsening tardive dyskinesia including grimacing, tongue protrusion, lip sucking, and upper extremity choreiform movements. In the previous 9 months, the patient was receiving aripiprazole 15 mg/day with only subtle elevations of abnormal buccal oral muscle movement and upper arm athetosis 4 weeks prior to admission. Despite aripiprazole dose reduction to 10 mg/day 8 days prior to hospitalization and a 1-week treatment of benztropine 1 mg/day for extrapyramidal reactions, her clinical conditions worsened. Physical examination revealed a rectal temperature of 106.5 degrees F, pulse of 137 beats/min, respiratory rate of 22 breaths/min, and fluctuating blood pressure ranging between 99/54 mmHg and 147/100 mmHg. The patient exhibited distress, marked muscle rigidity, choreoathetoid movements, and progressively worsening slurred speech that became muted. CPK rose from 78 units/L at admission to 103 units/L 8 hours later. Further assessment revealed no leukocytosis, unremarkable metabolic panel, urine analysis, and normal aged-consistent atrophic changes on brain CT. Consequently, she was diagnosed with NMS and aripiprazole was discontinued. She was given intravenous hydration, supportive cooling therapy, bromocriptine 2.5 mg every 8 hours, benztropine 1 mg/day, and lorazepam 1 to 2 mg as needed. Five days later, the patient stabilized aside from tardive dyskinesia and was then transferred to the care of her psychiatrist in a psychiatric hospital (Molina et al, 2007).
c) CASE REPORT: A 14-year-old girl with psychotic depression and mental retardation developed partial neuroleptic malignant syndrome following aripiprazole treatment. The patient had no prior experience with any extrapyramidal symptoms with her past medications of risperidone and olanzapine during previous hospitalizations. She did not experience any side effects from quetiapine 300 mg daily which was discontinued 2 weeks prior to receiving aripiprazole 5 mg daily. Within 48 hours of aripiprazole initiation, the patient presented with tremors, drooling, severe cogwheel rigidity, unsteady gait, incontinence, and agitation. The patient was disoriented and had slurred, incoherent speech with fluctuating consciousness with 31 respirations/ min and a pulse of 131 beats/min. The patient's serum creatine phosphokinase (CPK) increased to 23,340 international units without myoglobinuria. However, her temperature and blood pressure were within normal parameters. Her white blood cell count was also within normal limits (9300 mm(3) of blood) and urine toxicology screen was negative. Along with other supportive measures, the patient was treated with sodium bicarbonate to alkalinize the urine. After 2 days, the patient's CPK decreased to 6157 international units and continued to decline. Lorazepam 2 mg every 4 hours was administered to treat the tremors and agitation. The patient eventually recovered and returned to baseline (Hammerman et al, 2006).

a) In a pooled analysis in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, insomnia was reported in 18% of patients receiving aripiprazole (n=1843) compared with 13% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) ADULT: In a pooled analysis of trials in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, akathisia was reported in 10% of patients receiving aripiprazole (n=1843) compared with 4% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) PEDIATRIC: In a short-term placebo controlled trial in which pediatric patients aged 10 to 17 years with bipolar mania received either oral aripiprazole (doses 10 mg/day or 30 mg/day ) or placebo, akathisia was reported in 10% of patients receiving aripiprazole (n=197) compared with 2% of patients receiving placebo (n=97) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) In a pooled analysis of trials in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, headache was reported in 27% of patients receiving aripiprazole (n=1843) compared with 23% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) In a pooled analysis of trials in which adult patients with agitation associated with schizophrenia or bipolar mania received either aripiprazole 5.25 mg/day or greater IM or placebo, headache was reported in 12% of patients receiving aripiprazole (n=501) compared with 7% of patients receiving placebo (n=220) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) CASE REPORT: A 25-year-old woman with schizophrenia developed characteristics associated with tardive dystonia following aripiprazole treatment. The patient was diagnosed with schizoaffective disorder that included 2 previous psychotic episodes and 3 previous manic episodes. She had a past medication history of changing to various antipsychotic medications due to adverse events which included skin rashes with carbamazepine, weight gain with olanzapine, galactorrhea and severe extrapyramidal symptoms with risperidone , and tremors and drowsiness with valproate. Because the patient had a recurrence of mania with quetiapine, the patient switched to lithium. Lithium was reduced to 450 mg/day because of memory loss and vomiting. The patient remained on lithium for 8 months with additional adverse effects. Aripiprazole 10 mg/day was added to lithium therapy due to a manic episode. After 4 weeks of treatment, aripiprazole was increased to 15 mg/day. After 2 months of lithium and aripiprazole therapy, she presented with backward arching with muscle spasms over the latissimus dorsi, which worsened over time. The patient did not experience any other symptoms such as: perioral tongue movements, facial grimacing, or difficulty in breathing or chewing. However, the Extrapyramidal Symptom Rating Scale (ESRS) demonstrated that she was suffering from moderate to severe levels of extrapyramidal symptoms. The patient was started on trihexyphenidyl 6 mg daily and the aripiprazole was discontinued. After 2 weeks, her dystonia improved and she had a ESRS score of zero. After 4 weeks, clozapine was added to the lithium treatment, which was titrated to 150 mg/day to treat her mood and psychotic symptoms. She remained symptom free 1 year after stopping aripiprazole therapy (Oommen et al, 2006).
b) CASE REPORT: A 10-year-old boy with bipolar disorder developed dystonia following aripiprazole treatment. The child was admitted to a psychiatric care unit because of high energy and violent, impulsive behaviors with aggression toward his family and peers. His current medications included divalproex 20 mg/kg per day divided 3 times daily plus guanfacine 0.5 mg 3 times daily. Divalproex was discontinued and aripiprazole 5 mg twice daily for mood stabilization was initiated the following day. Three days after initial aripiprazole therapy, the patient developed neck pain and stiffness with abnormal jaw sensations. Upon examination, his symptoms were consistent with acute torticollis. His neck symptoms completely resolved within 30 minutes of benztropine 1 mg administration and aripiprazole discontinuation. The patient did not have any recurrence of dystonia after he was treated with quetiapine 150 mg 3 times daily with bupropion SR 200 mg daily for mood disorder (Singh et al, 2007).

a) ADULT: In a pooled analysis of trials in which adult patients with schizophrenia or bipolar mania received either oral aripiprazole 2 mg/day or greater or placebo, dizziness was reported in 10% of patients receiving aripiprazole (n=1843) compared with 7% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) PEDIATRIC: In a short-term, placebo-controlled trial in which pediatric patients aged 10 to 17 years with bipolar mania received either aripiprazole 10 mg or 30 mg orally or placebo, dizziness was reported in 5% of the aripiprazole group (n=197) compared with 1% of the placebo group (n=97) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) CASE REPORT: A 46-year-old woman experienced oromandibular tardive dyskinesia following administration of aripiprazole to manage her treatment-resistant depression. At time of presentation, the patient had been experiencing depression symptoms consistently for 2 years while taking duloxetine (up to 120 mg/day) with only partial response. A low-dose of ziprasidone (40 mg/day) was administered but discontinued 2 weeks later due to akathisia and adverse effects. Ziprasidone was then switched to aripiprazole (a gradual dose increase to 15 mg/day). Several weeks later, the patient had attained full resolution of her depression. After 15 months of continued remission with duloxetine and aripiprazole, the patient began to develop involuntary lateral jaw movements, primarily on her left side at the rate of 2 to 3 movements every few minutes. Notably, she had no dentition problems or prior history of nervous or motor tics. Following a series of tests, aripiprazole was tapered and discontinued. Subsequently, the patient's lateral movements completely resolved 8 weeks later. Based on the Naranjo Scale, the probability score of oromandibular tardive dyskinesia directly related to aripiprazole was 5 on a 12-point scale (Schwartz & Raza, 2008).
b) Two case reports (involving Taiwanese women, aged 41 and 52 years) suggest a relationship between use of aripiprazole and tardive dyskinesia. The first patient was maintained on amisulpiride 200 mg/day with no adverse effects. However, she was concerned over amenorrhea following amisulpiride treatment. A combination of amisulpiride 200 mg/day and aripiprazole 10 mg/day was initiated and the patient's mental stability and menstrual cycle remained stable. After 11 months of therapy, the patient presented with Parkinsonian symptoms including rabbit syndrome, mask face, and hand tremor, which persisted for 4 months. Amisulpiride was withdrawn and aripiprazole 15 mg/day was given. Dyskinetic symptoms developed 3 months after amisulpiride discontinuation. However, the patient was reluctant to change medication since her psychotic symptoms were under control. Some of her dyskinetic symptoms improved and sustained after 21 months of aripiprazole therapy. The second patient, who had discontinued all the psychotropic medications (sulpiride 50 to 200 mg/day for 6 years) was admitted due to reoccurring psychotic symptoms. Upon admission, aripiprazole 5 mg/day was initiated titrating up to 10 mg/day in 1 week. She was discharged on this dose. After 2 months of aripiprazole treatment, the patient developed buccal dyskinesia (involuntary chewing and crunching movements). Diphenhydramine 150 mg/day was added to her regimen and her symptoms improved and eventually disappeared within 3 to 4 months (Wang et al, 2009).

a) In pooled data of 2 placebo-controlled trials of adult patients with major depressive disorder receiving aripiprazole 2 mg to 20 mg/day for up to 6 weeks in addition to continued antidepressant therapy (n=371) or antidepressant therapy alone (n=366), restlessness occurred in 12% versus 2% of patients, respectively (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) In a pooled analysis of 3-week, placebo-controlled trials in which adult patients with bipolar mania received oral aripiprazole 15 or 30 mg/day or placebo, restlessness was reported in 6% of aripiprazole-treated patients (n=917) compared with 3% of placebo-treated patients (n=753) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) In a short-term study of aripiprazole as adjunctive therapy for bipolar disorder, anxiety was reported in 4% of patients receiving aripiprazole 15 mg/day or 30 mg/day orally (n=253) compared with 1% of patients receiving placebo (n=130). Patients received lithium or valproate therapy in addition to aripiprazole or placebo for up to 6 weeks (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) In a pooled analysis of short-term trials in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, anxiety was reported in 17% of patients receiving aripiprazole (n=1843) compared with 13% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) ADULTS: In a pooled analysis of trials in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, nausea and vomiting were reported in 15% and 11% of patients, respectively, receiving aripiprazole (n=1843) compared with 11% and 6% of patients receiving placebo (n=1166), respectively (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) PEDIATRIC: In a short-term, placebo-controlled trial in which pediatric patients age 10 to 17 years with bipolar mania received either aripiprazole 10 mg or 30 mg/day orally or placebo, nausea was reported in 11% of the aripiprazole group (n=197) compared with 4% of the placebo group (n=97) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
c) In a pooled analysis of trials in which pediatric patients aged 6 to 17 years with schizophrenia, bipolar mania, or autism received either oral aripiprazole (doses 2 mg/day or greater) or placebo, vomiting was reported in 9% of patients receiving aripiprazole (n=611) compared with 7% of patients receiving placebo (n=298) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) CASE REPORT: Vomiting occurred in a 2-year-old child following an unintentional ingestion of 40 mg of aripiprazole (Lofton & Klein-Schwartz, 2005).
b) CASE SERIES: In a retrospective, poison center study of 114 patients with exposure to aripiprazole only, 2 patients (1.8%) developed nausea and 3 (2.6%) vomited (Forrester, 2006).
c) CASE SERIES: According to a retrospective review of aripiprazole only exposures reported to the California Poison Control System from 2002 to 2006, nausea and vomiting were reported in 18% of the patients (n=158) (Young et al, 2009).

a) PEDIATRIC: In a pooled analysis of trials in which pediatric patients age 6 to 17 years with schizophrenia, bipolar mania, or autistic disorder received either aripiprazole (doses 2 mg/day or greater) or placebo, diarrhea was reported in 5% of patients receiving aripiprazole (n=611) compared with 3% of patients receiving placebo (n=298) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) ADULT: In pooled data of 2 placebo-controlled trials of adult patients with major depressive disorder receiving oral aripiprazole 2 mg to 20 mg/day for up to 6 weeks in addition to continued antidepressant therapy (n=371) or antidepressant therapy only (n=366), increased appetite occurred in 3% versus 2% of patients, respectively (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) PEDIATRIC: In a pooled analysis of trials in which pediatric patients age 6 to 17 years with schizophrenia, bipolar mania, or autistic disorder received either aripiprazole (doses 2 mg/day or greater) or placebo, increased appetite was reported in 7% of patients receiving aripiprazole (n=611) compared with 3% of patients receiving placebo (n=298) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) In pooled data of 2 placebo-controlled trials of adult patients with major depressive disorder receiving oral aripiprazole 2 mg to 20 mg/day for up to 6 weeks in addition to continued antidepressant therapy (n=371) or antidepressant therapy only (n=366), constipation occurred in 5% versus 2% of patients, respectively (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) In a pooled analysis of trials in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, constipation was reported in 11% of patients receiving aripiprazole (n=1843) compared with 7% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) PEDIATRIC: In a pooled analysis of trials in which pediatric patients aged 6 to 17 years with schizophrenia, bipolar mania, or autistic disorder received either aripiprazole (doses 2 mg/day or greater) or placebo, decreased appetite was reported in 4% of patients receiving aripiprazole (n=611) compared with 2% of patients receiving placebo (n=298) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) ADULT: In a short-term study of aripiprazole as adjunctive therapy for bipolar disorder, dry mouth was reported in 2% of patients receiving aripiprazole 15 mg/day or 30 mg/day orally (n=253) compared with 1% of patients receiving placebo (n=130). Patients received lithium or valproate therapy in addition to aripiprazole or placebo for up to 6 weeks (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) ADULT: In a pooled analysis of trials in which adult patients with schizophrenia or bipolar mania received either aripiprazole 2 mg/day or greater orally or placebo, dry mouth was reported in 5% of patients receiving aripiprazole (n=1843) compared with 4% of patients receiving placebo (n=1166) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) In a short-term study of aripiprazole as adjunctive therapy for bipolar disorder, salivary hypersecretion was reported in 4% of patients receiving aripiprazole 15 mg/day or 30 mg/day orally (n=253) compared with 2% of patients receiving placebo (n=130). Patients received lithium or valproate therapy in addition to aripiprazole or placebo for up to 6 weeks (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) CASE REPORT: A 27-year-old man with bipolar affective disorder and current-episode mania with mood-congruent psychotic symptoms treated with valproate sodium 1 g/day developed sialorrhea 3 months after the institution of aripiprazole 10 mg/day for persistent psychotic symptoms. The patient did not present with any associated sign suggestive of extrapyramidal syndrome. A significant reduction in sialorrhea was noted 1 week after receiving trihexyphenidyl 2 mg/day (Praharaj et al, 2009).

a) In a pooled analysis of trials in which pediatric patients aged 6 to 17 years with schizophrenia or bipolar mania received either oral aripiprazole (doses 2 mg/day or greater) or placebo, rash was reported in 2% of patients receiving aripiprazole (n=611) compared with 1% of patients receiving placebo (n=298) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) CASE REPORT: A 6-year-old boy experienced drooling with flaccid facial muscles after taking 1 dose of aripiprazole 10 mg. His symptoms resolved in the evening without treatment; however ingestion of a second 10-mg dose resulted in the recurrence of symptoms. The patient completely recovered following discontinuation of the aripiprazole and administration of diphenhydramine (Lofton & Klein-Schwartz, 2005).

a) ADULT: In pooled data of 2 placebo-controlled trials of adult patients with major depressive disorder receiving aripiprazole 2 mg to 20 mg/day for up to 6 weeks in addition to continued antidepressant therapy (n=371) or antidepressant therapy alone (n=366), arthralgia occurred in 4% versus 3% of patients, respectively (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) PEDIATRIC: In a pooled analysis of trials in which pediatric patients aged 6 to 17 years with schizophrenia, bipolar mania, or autistic disorder received either oral aripiprazole (doses 2 mg/day or greater) or placebo, arthralgia was reported in 1% of patients receiving aripiprazole (n=611) compared with 0% of patients receiving placebo (n=298) (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) In pooled data of 2 placebo-controlled trials of adult patients with major depressive disorder receiving aripiprazole 2 mg to 20 mg/day for up to 6 weeks in addition to continued antidepressant therapy (n=371) or antidepressant therapy only (n=366), myalgia occurred in 3% versus 1% of patients, respectively (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) Serum prolactin levels have been unaffected or increased only slightly by oral aripiprazole (2 to 30 mg daily) in schizophrenic patients (Anon, 2000; Kane et al, 2000; Petrie et al, 1998a). Increases in prolactin levels were greater with haloperidol 10 mg daily in comparative studies (Kane et al, 2000; Saha et al, 1999).

a) CASE REPORT: A 48-year-old man, with no history of diabetes, presented to the emergency department with lethargy, confusion, and a decreased level of consciousness. Vital signs showed tachycardia (130 beats/min) and fever (102.9 degrees F rectally). His current medications included aripiprazole (30 mg once a day), benztropine, valproic acid, clonazepam, and diphenhydramine. Laboratory analysis revealed a serum glucose concentration of 2845 mg/dL and a urinalysis indicated glucosuria greater than 1000 mg/dL. Over the course of his hospital stay, the patient received insulin therapy for a presumed diagnosis of new-onset diabetes mellitus while continuing to receive aripiprazole. Following hospital discharge, as an outpatient, the patient's aripiprazole was discontinued and his diabetes resolved, indicating a possible causal relationship between aripiprazole therapy and the development of severe hyperglycemia (Campanella et al, 2008).

a) Although well-controlled studies have not been conducted with aripiprazole lauroxil during pregnancy, maternal use of antipsychotic drugs during the third trimester of pregnancy has been associated with development of neonatal extrapyramidal and/or withdrawal symptoms. Advise pregnant women of the potential for fetal harm if used during pregnancy (Prod Info ARISTADA(TM) intramuscular extended-release injection, 2015).
b) PREGNANCY REGISTRY

a) Aripiprazole administration in rats resulted in slightly prolonged gestation and a slight delay in fetal development with oral doses up to 30 mg/kg/day (10 times the maximum recommended human dose (MRHD) on a mg/m(2) basis) and decreased fetal weight and delayed skeletal ossification with IV doses of 27 mg/kg/day. In rabbits, increased abortions, increased fetal mortality, decreased fetal weight, fused sternebrae, and minor skeletal variations were reported with oral aripiprazole doses up to 100 mg/kg/day (65 times the MRHD on a mg/m(2) basis) and maternal toxicity, decreased fetal weight, increased fetal abnormalities (mostly skeletal), and decreased fetal skeletal ossification were reported with IV doses up to 30 mg/kg/day (19 times the MRHD on a mg/m(2) basis). The no-effect dose was 10 mg/kg (6 times the MRHD on mg/m(2) basis) (Prod Info ABILIFY(R) oral tablets, solution, IM injection, 2014; Prod Info ABILIFY DISCMELT(R) oral disintegrating tablets, 2014).
b) Aripiprazole administration in rats with oral doses of 30 mg/kg/day (10 times the maximum recommended human dose (MRHD)) from gestation day 17 through postpartum day 21 resulted in slight maternal toxicity, slightly prolonged gestation, an increase in stillbirths, a decrease in pup weight that persisted into adulthood, and a decrease in survival. Aripiprazole administration in rats with IV doses of 8 mg/kg/day and 20 mg/kg/day from gestation day 6 though postpartum day 20 resulted in increased stillbirths, and doses of 20 mg/kg/day resulted in decreased early postnatal pup weights and survival (Prod Info ABILIFY(R) oral tablets, solution, IM injection, 2014; Prod Info ABILIFY DISCMELT(R) oral disintegrating tablets, 2014).

a) During animal studies, no adverse maternal or developmental effects were reported with IM aripiprazole lauroxil at doses up to 18 times the maximum recommended human dose (Prod Info ARISTADA(TM) intramuscular extended-release injection, 2015).

a) Aripiprazole is excreted in human breast milk. Either discontinue aripiprazole or discontinue nursing, considering the importance of the drug to the mother (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection, 2014; Prod Info ABILIFY DISCMELT(R) oral disintegrating tablets, 2014a).

a) While the effects of aripiprazole lauroxil on a breastfeeding infant are unknown, aripiprazole is known to be present in human breast milk. Use only if the potential benefit outweighs the potential risk (Prod Info ARISTADA(TM) intramuscular extended-release injection, 2015).

a) Studies in female rats given oral doses of aripiprazole 2, 6, and 20 mg/kg/day (0.6, 2, and 6 times the maximum recommended human dose, respectively, on a mg/m(2) basis) from 2 weeks prior to mating through day 7 of gestation found no impairment of fertility. However, estrus cycle irregularities and increased corpora lutea were seen at all doses and increased preimplantation loss was seen at 6 and 20 mg/kg, and decreased fetal weight was seen at 20 mg/kg (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection, 2014; Prod Info ABILIFY DISCMELT(R) oral disintegrating tablets, 2014a).
b) Male rats given doses of aripiprazole at 60 mg/kg from 9 weeks prior to mating through mating revealed disturbances in spermatogenesis, and prostate atrophy was seen at doses of 40 and 60 mg/kg (13 and 19 times the maximum recommended human dose on a mg/m(2) basis). However no impairment of fertility was seen at doses up to 60 mg/kg/day (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection, 2014; Prod Info ABILIFY DISCMELT(R) oral disintegrating tablets, 2014a).

a) In fertility studies, IM administration of aripiprazole lauroxil, at doses up to 4 times the maximum recommended human dose (MRHD), resulted in lower mating and fertility indices in male animals. In females administered aripiprazole lauroxil at doses up to 6 times the MRHD, persistent diestrus was observed. Slight increases in corpora lutea, pre-implantation loss, and declines in mating, fertility, and fecundity indices were also reported (Prod Info ARISTADA(TM) intramuscular extended-release injection, 2015).

a) Monitor vital signs and neurologic exam (for CNS depression, akathisia, or extrapyramidal effects).

a) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.

1) CASE REPORT: A 25-year-old woman ingested 15 aripiprazole 15 mg tablets. She presented asymptomatic and was not treated with activated charcoal. She developed somnolence, bradycardia (50 beats/min) and hypotension (80/40 mm Hg) 9 hours after ingestion, and recovered with supportive care (Lo & Pizon, 2008).

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) DANTROLENE LOADING DOSE: 2.5 milligrams/kilogram, to a maximum of 10 milligrams/kilogram intravenously (Barkin, 1992).
b) DANTROLENE MAINTENANCE DOSE: 2.5 milligrams/kilogram intravenously every 6 hours (Barkin, 1992); 1 milligram/kilogram orally every 12 hours, up to 50 milligrams/dose has also been successful (May et al, 1983).
c) BROMOCRIPTINE DOSE: 5 milligrams three times a day orally (Mueller et al, 1983).
d) NON-PHARMACOLOGIC METHODS: Rapid cooling, hydration, and serial assessment of respiratory, cardiovascular, renal and neurologic function, and fluid status are used in conjunction with drug therapy and discontinuation of the neuroleptic agent (Knight & Roberts, 1986).

a) The time to complete resolution was also shorter with these therapeutic interventions (Rosenberg & Green, 1989).

a) BENZTROPINE: 1 to 4 mg once or twice daily intravenously or intramuscularly; maximum dose: 6 mg/day; 1 to 2 mg of the injection will usually provide quick relief in emergency situations (Prod Info benztropine mesylate IV, IM injection, 2009).
b) DIPHENHYDRAMINE: 10 to 50 mg intravenously at a rate not exceeding 25 mg/minute or deep intramuscularly; maximum dose: 100 mg/dose; 400 mg/day (Prod Info diphenhydramine hcl injection, 2006).

a) DIPHENHYDRAMINE: 5 mg/kg/day or 150 mg/m(2)/day intravenously divided into 4 doses at a rate not to exceed 25 mg/min, or deep intramuscularly; maximum dose: 300 mg/day. Not recommended in premature infants and neonates (Prod Info diphenhydramine hcl injection, 2006).

a) ORAL: Initial, 10 to 15 mg orally once daily, with or without food (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).
b) ORAL: Maintenance, maximum daily dosage is 30 mg/day orally; increase dose only after 2 weeks at each dose strength; efficacy has not been significantly greater with doses higher than 10 to 15 mg/day (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012)
c) EXTENDED-RELEASE IM INJECTION: Establish tolerability with oral aripiprazole before initiating extended-release IM injection; initial and maintenance dose, 400 mg IM once monthly (at least 26 days after the previous injection); oral aripiprazole or another antipsychotic medication should be given concurrently with the initial injection and should be continued for 14 consecutive days (Prod Info ABILIFY MAINTENA intramuscular injection extended-release suspension, 2013)

a) INITIAL: 441 mg IM (deltoid or gluteal) once monthly OR 662 mg IM (gluteal only) once monthly OR 882 mg IM (gluteal only) once monthly or every 6 weeks. Individualize based on established tolerability to oral dosing (Prod Info ARISTADA(TM) intramuscular extended-release injection, 2015)
b) MAINTENANCE: May adjust dose as needed taking into account prolonged-release characteristics of IM injection (Prod Info ARISTADA(TM) intramuscular extended-release injection, 2015)

a) 13 TO 17 YEARS: initial dose 2 mg/day orally. MAX: 30 mg/day (Prod Info ABILIFY(R) oral tablets, oral solution, intramuscular injection solution, 2012).

a) Safety and efficacy have not been established in pediatric patients (Prod Info ARISTADA(TM) intramuscular extended-release injection, 2015).