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American Family Physician Dec 2016Autism spectrum disorder is characterized by difficulty with social communication and restricted, repetitive patterns of behavior, interest, or activities. The... (Review)
Review
Autism spectrum disorder is characterized by difficulty with social communication and restricted, repetitive patterns of behavior, interest, or activities. The Diagnostic and Statistical Manual of Mental Disorders, 5th ed., created an umbrella diagnosis that includes several previously separate conditions: autistic disorder, Asperger syndrome, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified. There is insufficient evidence to recommend screening for autism spectrum disorder in children 18 to 30 months of age in whom the disorder is not suspected; however, there is a growing body of evidence that early intensive behavioral intervention based on applied behavior analysis improves cognitive ability, language, and adaptive skills. Therefore, early identification of autism spectrum disorder is important, and experts recommend the use of a validated screening tool at 18- and 24-month well-child visits. Medications can be used as adjunctive treatment for maladaptive behaviors and comorbid psychiatric conditions, but there is no single medical therapy that is effective for all symptoms of autism spectrum disorder. Prognosis is heavily affected by the severity of diagnosis and the presence of intellectual disability. Children with optimal outcomes receive earlier, more intensive behavioral interventions and less pharmacologic treatment.
Topics: Antipsychotic Agents; Aripiprazole; Asperger Syndrome; Autism Spectrum Disorder; Autistic Disorder; Behavior Therapy; Child Development Disorders, Pervasive; Child, Preschool; Early Diagnosis; Early Medical Intervention; Humans; Infant; Primary Health Care; Referral and Consultation; Risperidone
PubMed: 28075089
DOI: No ID Found -
The New England Journal of Medicine Mar 2023The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied.
METHODS
We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression.
RESULTS
In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups.
CONCLUSIONS
In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).
Topics: Aged; Humans; Antidepressive Agents; Aripiprazole; Bupropion; Depression; Drug Therapy, Combination; Nortriptyline; Treatment Switching; Lithium Compounds
PubMed: 36867173
DOI: 10.1056/NEJMoa2204462 -
International Journal of Molecular... Sep 2022Schizophrenia and depression are heterogeneous disorders. The complex pathomechanism of the diseases imply that medication responses vary across patients. Many... (Review)
Review
Schizophrenia and depression are heterogeneous disorders. The complex pathomechanism of the diseases imply that medication responses vary across patients. Many psychotropic drugs are available but achieving optimal therapeutic effect can be challenging. The evidence correlates well with clinical observations, suggesting that new atypical antipsychotic drugs are effective against negative and cognitive symptoms of schizophrenia, as well as against affective symptoms observed in depression. The purpose of this review presents the background and evidence for the use of the new second/third-generation antipsychotics (aripiprazole, cariprazine, lurasidone, asenapine, brexpiprazole, lumateperone, pimavanserin) in treatment of schizophrenia and depression. We have first provided a brief overview of the major neurobiological underpinnings of schizophrenia and depression. We then shortly discuss efficacy, safety and limitations of ongoing pharmacotherapy used in depression and schizophrenia. Mainly, we have focused this review on the therapeutic potential of new atypical antipsychotic drugs-currently existing-to be effective in psychotic, as well as in affective disorders.
Topics: Antipsychotic Agents; Aripiprazole; Depression; Humans; Lurasidone Hydrochloride; Psychotropic Drugs; Schizophrenia
PubMed: 36142523
DOI: 10.3390/ijms231810624 -
Acta Psychiatrica Scandinavica Oct 2022Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and meta-analysis aimed to synthesise the evidence of efficacy, acceptability and tolerability of treatments for individuals with rapid cycling bipolar disorder (RCBD).
METHOD
A systematic search was conducted to identify randomised controlled trials assigning participants with RCBD to pharmacological and/or non-pharmacological interventions. Study inclusion and data extraction were undertaken by two reviewers independently. The primary outcome was continuous within-subject RCBD illness severity before and after treatment. Pre-post random effects meta-analyses were conducted for each outcome/intervention arm studied, generating a standardised effect size (hedge's g) and 95% confidence interval (CI).
RESULTS
A total of 34 articles describing 30 studies were included. A total of 16 separate pharmacological treatments were examined in contrast to 1 psychological therapy study. Only quetiapine and lamotrigine were assessed in >5 studies. By assessing 95% CI overlap of within-subject efficacy effects compared to placebo, the only interventions suggesting significant depression benefits (placebo g = 0.60) were olanzapine (with/without fluoxetine; g = 1.01), citalopram (g = 1.10) and venlafaxine (g = 2.48). For mania, benefits were indicated for quetiapine (g = 1.01), olanzapine (g = 1.19) and aripiprazole (g = 1.09), versus placebo (g = 0.33). Most of these effect sizes were from only one trial per treatment. Heterogeneity between studies was variable, and 20% were rated to have a high risk of bias.
CONCLUSIONS
While many interventions appeared efficacious, there was a lack of robust evidence for most treatments. Given the limited and heterogeneous evidence base, the optimal treatment strategies for people with RCBD are yet to be established.
Topics: Aripiprazole; Bipolar Disorder; Citalopram; Fluoxetine; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Venlafaxine Hydrochloride
PubMed: 35778967
DOI: 10.1111/acps.13471 -
JAMA Psychiatry May 2019The effectiveness of antipsychotic polypharmacy in schizophrenia relapse prevention is controversial, and use of multiple agents is generally believed to impair physical... (Comparative Study)
Comparative Study
IMPORTANCE
The effectiveness of antipsychotic polypharmacy in schizophrenia relapse prevention is controversial, and use of multiple agents is generally believed to impair physical well-being.
OBJECTIVE
To study the association of specific antipsychotic combinations with psychiatric rehospitalization.
DESIGN, SETTING, AND PARTICIPANTS
In this nationwide cohort study, the risk of psychiatric rehospitalization was used as a marker for relapse among 62 250 patients with schizophrenia during the use of 29 different antipsychotic monotherapy and polypharmacy types between January 1, 1996, and December 31, 2015, in a comprehensive, nationwide cohort in Finland. We conducted analysis of the data from April 24 to June 15, 2018. Rehospitalization risks were investigated by using within-individual analyses to minimize selection bias.
MAIN OUTCOMES AND MEASURES
Hazard ratio (HR) for psychiatric rehospitalization during use of polypharmacy vs during monotherapy within the same individual.
RESULTS
In the total cohort, including 62 250 patients, 31 257 individuals (50.2%) were men, and the median age was 45.6 (interquartile range, 34.6-57.9) years. The clozapine plus aripiprazole combination was associated with the lowest risk of psychiatric rehospitalization in the total cohort, being superior to clozapine, the monotherapy associated with the best outcomes, with a difference of 14% (HR, 0.86; 95% CI, 0.79-0.94) in the analysis including all polypharmacy periods, and 18% in the conservatively defined polypharmacy analysis excluding periods shorter than 90 days (HR, 0.82; 95% CI, 0.75-0.89; P < .001). Among patients with their first episode of schizophrenia, these differences between clozapine plus aripiprazole vs clozapine monotherapy were greater (difference, 22%; HR, 0.78; 95% CI, 0.63-0.96 in the analysis including all polypharmacy periods, and difference, 23%; HR, 0.77; 95% CI, 0.63-0.95 in the conservatively defined polypharmacy analysis). At the aggregate level, any antipsychotic polypharmacy was associated with a 7% to 13% lower risk of psychiatric rehospitalization compared with any monotherapy (ranging from HR, 0.87; 95% CI, 0.85-0.88, to HR, 0.93; 95% CI, 0.91-0.95; P < .001). Clozapine was the only monotherapy among the 10 best treatments. Results on all-cause and somatic hospitalization, mortality, and other sensitivity analyses were in line with the primary outcomes.
CONCLUSIONS AND RELEVANCE
Combining aripiprazole with clozapine was associated with the lowest risk of rehospitalization, indicating that certain types of polypharmacy may be feasible in the treatment of schizophrenia. Because add-on treatments are started when monotherapy is no longer sufficient to control for worsening of symptoms, it is likely that the effect sizes for polypharmacy are underestimates. Although the results do not indicate that all types of polypharmacy are beneficial, the current treatment guidelines should modify their categorical recommendations discouraging all antipsychotic polypharmacy in the maintenance treatment of schizophrenia.
Topics: Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Patient Readmission; Polypharmacy; Schizophrenia; Treatment Outcome
PubMed: 30785608
DOI: 10.1001/jamapsychiatry.2018.4320 -
The International Journal of... Apr 2020Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term... (Comparative Study)
Comparative Study Randomized Controlled Trial
Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone.
BACKGROUND
Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up.
METHOD
From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy.
RESULTS
The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea.
CONCLUSIONS
Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.
Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Female; Follow-Up Studies; Haloperidol; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Young Adult
PubMed: 31974576
DOI: 10.1093/ijnp/pyaa004 -
Pharmacotherapy Jun 2019The objective of this trial, Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART), was to provide support and guidance for an evidence-based approach... (Randomized Controlled Trial)
Randomized Controlled Trial
The objective of this trial, Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART), was to provide support and guidance for an evidence-based approach for the selection and monitoring of initial pharmacotherapy in patients with autism by assessing predictors of efficacy, tolerability, and safety. This randomized double-blind parallel-group study was conducted in three academic medical centers and a single private pediatric practice. Eighty children or adolescents (aged 6-17 yrs) with autistic disorder were enrolled, and 61 patients were randomized to the study drug. Of those patients, 51 completed the 10-week trial, and 31 completed an optional 12-week blinded extension phase. All patients were treated with 2 weeks of placebo before random assignment to receive aripiprazole (31 patients) or risperidone (30 patients) for 10 weeks. Sixteen placebo responders (20%) were excluded from further analysis. Drug dosing followed U.S. Food and Drug Administration (FDA) labeling, and weekly dosage adjustments were allowed until week 4; patients were then maintained on a fixed dose for 6 additional weeks. Safety, physical, and psychological assessments were recorded weekly or every 2 weeks. No significant differences in severity of illness between the aripiprazole and risperidone groups were noted at baseline. All patients significantly improved on the Aberrant Behavior Checklist-Irritability subscale after 1 week and continued for the remaining 9 weeks and the extension phase. Improvement was greatest in the risperidone group at every assessment period and was statistically significantly better than that in the aripiprazole group at weeks 3 and 6 (p<0.05). No dose-limiting adverse events occurred during the dose-titration period. Mean weight gain in the aripiprazole group was significantly less than that in the risperidone group at week 4 (0.62 vs 1.38 kg, p=0.033) and week 10 (1.61 vs 3.31 kg, p<0.001), but the difference became nonsignificant for the 31 patients completing the 3-month extension phase (4.36 vs 5.55 kg, p=0.26). Pharmacotherapy of patients with autism spectrum disorder resulted in behavioral improvement within 1 week and lasted at least 22 weeks. Weight gain occurred to a greater degree with risperidone than aripiprazole initially, but the differences became nonsignificant by the end of the trial. Our trial supports previous results of drug efficacy and safety in patients with autism spectrum disorder from other trials and extends the evidence-based support for choosing an FDA-approved drug for initial pharmacotherapy for autism spectrum disorder.
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Autism Spectrum Disorder; Child; Double-Blind Method; Female; Humans; Male; Risperidone; Treatment Outcome; Weight Gain
PubMed: 31063671
DOI: 10.1002/phar.2271 -
Palliative & Supportive Care Aug 2015The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone,... (Comparative Study)
Comparative Study
OBJECTIVE
The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone, olanzapine, and aripiprazole in the management of delirium.
METHOD
The Memorial Delirium Assessment Scale (MDAS), the Karnofsky Performance Status (KPS) scale, and a side-effect rating were recorded at baseline (T1), after 2-3 days (T2), and after 4-7 days (T3). Some 21 cases were case-matched by age, preexisting dementia, and baseline MDAS scores, and subsequently analyzed.
RESULTS
The baseline characteristics of the medication groups were not different: The mean age of the patients ranged from 64.0 to 69.6 years, dementia was present in between 23.8 and 28.6%, and baseline MDAS scores were 19.9 (haloperidol), 18.6 (risperidone), 19.4 (olanzapine), and 18.0 (aripiprazole). The doses of medication at T3 were 5.5 mg haloperidol, 1.3 mg risperidone, 7.1 mg olanzapine, and 18.3 mg aripiprazole. Over one week, the decline in MDAS scores between medications was equal, and no differences between individual MDAS scores existed at T2 or T3. After one week, the MDAS scores were 6.8 (haloperidol), 7.1 (risperidone), 11.7 (olanzapine), and 8.3 (aripiprazole). At T2, delirium resolution occurred in 42.9-52.4% of cases and at T3 in 61.9-85.7%; no differences in assessments between medications existed. Recorded side effects were extrapyramidal symptoms (EPSs) in haloperidol- and risperidone-managed patients (19 and 4.8%, respectively) and sedation with olanzapine (28.6%).
SIGNIFICANCE OF RESULTS
Haloperidol, risperidone, aripiprazole, and olanzapine were equally effective in the management of delirium; however, they differed in terms of their side-effect profile. Extrapyramidal symptoms were most frequently recorded with haloperidol, and sedation occurred most frequently with olanzapine.
Topics: Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Delirium; Dementia; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Risperidone
PubMed: 25191793
DOI: 10.1017/S1478951514001059 -
American Journal of Health-system... May 2021This article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability,...
PURPOSE
This article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability, drug interactions, contraindications, and dosing regimens.
SUMMARY
Hyperprolactinemia is a common adverse effect of antipsychotics. First-line management includes reducing the dose of the offending antipsychotic, discontinuing the antipsychotic, or switching to another antipsychotic associated with a lower risk of hyperprolactinemia. However, these options are not always practical and are associated with a risk of relapse of the psychiatric illness. Other management options include adjunctive aripiprazole, dopamine agonists (cabergoline and bromocriptine), metformin, and herbal supplements. A search of Embase, PubMed, and Google Scholar using key terms such as hyperprolactinemia, prolactin, antipsychotic, treatment guidelines, aripiprazole, dopamine agonist, cabergoline, bromocriptine, metformin, herbals, supplements, and medications was conducted for literature retrieval. Upon evaluation of the available literature we found the following: (1) aripiprazole is safe and effective in lowering prolactin levels within normal limits; (2) adjunctive cabergoline and bromocriptine decrease elevated prolactin levels, while cabergoline may be more effective in reducing prolactin but can also be associated with a more serious adverse effect of cardiac valvular abnormalities; (3) metformin causes a mild reduction of prolactin levels; and (4) there are limited data to support use of herbal medications (chamomile, Peony-Glycyrrhiza decoction, and shakuyaku-kanzo-to) in antipsychotic-induced hyperprolactinemia.
CONCLUSION
There are treatments available for antipsychotic-induced hyperprolactinemia in patients who are unable to alter their current antipsychotic regimen. However, there remains a need for additional short- and long-term studies to determine the efficacy and safety of these treatment strategies, given that patients taking antipsychotics typically require chronic, life-long treatment for their illnesses.
Topics: Antipsychotic Agents; Aripiprazole; Humans; Hyperprolactinemia; Mental Disorders; Prolactin
PubMed: 33954421
DOI: 10.1093/ajhp/zxab065 -
Pharmacopsychiatry Sep 2022Early-onset schizophrenia (EOS) - onset before age 18 - is linked with great disease burden and disability. Decision-making for EOS pharmacological treatment may be... (Review)
Review
Early-onset schizophrenia (EOS) - onset before age 18 - is linked with great disease burden and disability. Decision-making for EOS pharmacological treatment may be challenging due to conflicting information from evidence and guidelines and unidentified care needs may remain unmet.We searched for systematic reviews, meta-analyses and umbrella reviews of EOS pharmacological treatment published in PubMed over the past 10 years and selected five clinical guidelines from Europe, North-America and Australia. Based on predefined outcomes, we critically compared the evidence supporting EOS-approved drugs in Europe and/or North-America with guidelines recommendations. We also evaluated the coverage of these outcomes to identify unmet needs.One systematic review, nine meta-analyses and two umbrella reviews (k=203 trials, N=81,289 participants, including duplicated samples across selected articles) were retrieved. Evidence supported the efficacy of aripiprazole, clozapine, haloperidol, lurasidone, molindone, olanzapine, quetiapine, risperidone and paliperidone in EOS, all of which obtained approval for EOS either in Europe and/or in North-America. Cognition, functioning and quality of life, suicidal behaviour and mortality and services utilisation and cost-effectiveness were poorly covered/uncovered.Among the antipsychotics approved for EOS, aripiprazole, lurasidone, molindone, risperidone, paliperidone and quetiapine emerged as efficacious and comparably safe options. Olanzapine is known for a high risk of weight gain and haloperidol for extrapyramidal side-effects. Treatment-resistant patients should be offered clozapine. Future long-term trials looking at cognition, functioning, quality of life, suicidal behaviour, mortality, services utilisation and cost-effectiveness are warranted. Closer multi-agency collaboration may bridge the gap between evidence, guidelines and approved drugs.
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Haloperidol; Humans; Lurasidone Hydrochloride; Molindone; Olanzapine; Paliperidone Palmitate; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Systematic Reviews as Topic
PubMed: 35777418
DOI: 10.1055/a-1854-0185