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Journal of Psychopharmacology (Oxford,... Mar 2023Major depressive disorder (MDD) is a highly burdensome health condition, for which there are numerous accepted pharmacological and psychological interventions.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorder (MDD) is a highly burdensome health condition, for which there are numerous accepted pharmacological and psychological interventions. Adjunctive treatment (augmentation/combination) is recommended for the ~50% of MDD patients who do not adequately respond to first-line treatment. We aimed to evaluate the current evidence for concomitant approaches for people with early-stage treatment-resistant depression (TRD; defined below).
METHODS
We systematically searched Medline and Institute for Scientific Information Web of Science to identify randomised controlled trials of adjunctive treatment of ⩾10 adults with MDD who had not responded to ⩾1 adequate antidepressant. The cochrane risk of bias (RoB) tool was used to assess study quality. Pre-post treatment meta-analyses were performed, allowing for comparison across heterogeneous study designs independent of comparator interventions.
RESULTS
In total, 115 trials investigating 48 treatments were synthesised. The mean intervention duration was 9 weeks (range 5 days to 18 months) with most studies assessed to have low ( = 57) or moderate ( = 51) RoB. The highest effect sizes (ESs) were from cognitive behavioural therapy (ES = 1.58, 95% confidence interval (CI): 1.09-2.07), (es)ketamine (ES = 1.48, 95% CI: 1.23-1.73) and risperidone (ES = 1.42, 95% CI: 1.29-1.61). Only aripiprazole and lithium were examined in ⩾10 studies. Pill placebo (ES = 0.89, 95% CI: 0.81-0.98) had a not inconsiderable ES, and only six treatments' 95% CIs did not overlap with pill placebo's (aripiprazole, (es)ketamine, mirtazapine, olanzapine, quetiapine and risperidone). We report marked heterogeneity between studies for almost all analyses.
CONCLUSIONS
Our findings support cautious optimism for several augmentation strategies; although considering the high prevalence of TRD, evidence remains inadequate for each treatment option.
Topics: Adult; Humans; Aripiprazole; Risperidone; Depression; Depressive Disorder, Major; Ketamine
PubMed: 35861202
DOI: 10.1177/02698811221104058 -
Pediatrics Feb 2016Autism spectrum disorder (ASD) is increasingly recognized as a public health issue. Irritability and aggression (IA) often negatively affect the lives of people with ASD... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autism spectrum disorder (ASD) is increasingly recognized as a public health issue. Irritability and aggression (IA) often negatively affect the lives of people with ASD and their families. Although many medications have been tested for IA in ASDs in randomized controlled trials (RCTs), critical quantitative analyses of these trials are lacking in the literature.
OBJECTIVES
To systematically review and quantitatively analyze the efficacy and safety of pharmacologic treatments for IA in youth with ASD.
DATA SOURCES
Studies were identified from Medline, PsycINFO, Embase, and review articles.
METHODS
Original articles on placebo-controlled RCTs of pharmacologic treatments of IA in youth age 2 to 17 years with ASD were included. Data items included study design, study goals, details of study participants, details of intervention, study results, statistical methods, side effects, and risks of bias. The primary study outcome measure was the effect size of reduction in the Aberrant Behavioral Checklist-Irritability (ABC-I) scores in the medication group, as compared with placebo, in RCTs using parallel groups design.
RESULTS
Forty-six RCTs were identified. Compared with placebo, 3 compounds resulted in significant improvement in ABC-I at the end of treatment. Risperidone and aripiprazole were found to be the most effective, with the largest effect sizes. Sedation, extrapyramidal sides effects, and weight gain were assessed quantitatively.
CONCLUSIONS
Although risperidone and aripiprazole have the strongest evidence in reducing ABC-I in youth with ASD, a few other compounds also showed significant efficacy with fewer potential side effects and adverse reactions in single studies.
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Autism Spectrum Disorder; Child; Child Development Disorders, Pervasive; Child, Preschool; Humans; Irritable Mood; Problem Behavior; Risperidone; Self-Injurious Behavior
PubMed: 26908468
DOI: 10.1542/peds.2015-2851K -
European Neuropsychopharmacology : the... Jan 2022Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic... (Meta-Analysis)
Meta-Analysis Review
Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1-12 weeks and followed-up for 24-104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34-0.51, p<0.00001). Significantly lower risk of new BD episodes was observed with the following individual drugs: aripiprazole, asenapine, lithium, olanzapine, quetiapine, and risperidone long-acting (ORs varied 0.19-0.46). Adding aripiprazole, divalproex, quetiapine, or olanzapine/risperidone to lithium or an MSA was more effective compared with lithium or MSA monotherapy (OR=0.37; 95%CI 0.25-0.55, p<0.00001). Active treatment favored prevention of mania over depression. The key limitations were "responder-enriched" design in most trials and high outcomes heterogeneity. PROSPERO registration number is CRD42020162663.
Topics: Adult; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Lithium; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone
PubMed: 34489127
DOI: 10.1016/j.euroneuro.2021.08.264 -
Journal of Affective Disorders Nov 2019Depression and anxiety are prevalent psychiatric disorders that carry significant morbidity. Pharmacological and psychosocial interventions are used to manage these...
BACKGROUND
Depression and anxiety are prevalent psychiatric disorders that carry significant morbidity. Pharmacological and psychosocial interventions are used to manage these conditions, but their efficacy is limited. Recent interest into the use of psychedelic-assisted therapy using ayahuasca, psilocybin or lysergic acid diethylamide (LSD) may be a promising alternative for patients unresponsive to traditional treatments. This review aims to determine the efficacy and tolerability of psychedelics in the management of resistant depression.
METHODS
Clinical trials investigating psychedelics in patients with depression and/or anxiety were searched via MEDLINE, EMBASE and PsychINFO. Efficacy was assessed by measuring symptom improvement from baseline, and tolerability was evaluated by noting the incidence and type of adverse effects reported. Risk of bias was assessed.
RESULTS
Seven studies, with 130 patients, were analysed in this review. Three were conducted in patients with depression, two in patients with anxiety and two in patients with both. In a supportive setting, ayahuasca, psilocybin, and LSD consistently produced immediate and significant anti-depressant and anxiolytic effects that were endured for several months. Psychedelics were well-tolerated. The most common adverse effects were transient anxiety, short-lived headaches, nausea and mild increases in heart rate and blood pressure.
LIMITATIONS
At present, the number of studies on this subject is very limited; and the number of participating patients within these is also limited as the treatment under investigations is a relatively novel concept.
CONCLUSIONS
Though further evidence is required, psychedelics appear to be effective in significantly reducing symptoms of depression and anxiety and are well-tolerated.
Topics: Adult; Anxiety Disorders; Depressive Disorder; Female; Hallucinogens; Humans; Lysergic Acid Diethylamide; Psilocybin
PubMed: 31382100
DOI: 10.1016/j.jad.2019.07.076 -
Journal of the American Academy of... Feb 2023Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-analysis: Efficacy of Pharmacological Interventions for Irritability and Emotional Dysregulation in Autism Spectrum Disorder and Predictors of Response.
OBJECTIVE
Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a broad range of pharmacological interventions for emotional dysregulation and irritability in ASD and predictors of response.
METHOD
Following a preregistered protocol (PROSPERO: CRD42021235779), we systematically searched multiple databases until January 1, 2021. We included placebo-controlled randomized controlled trials (RCTs) and evaluated the efficacy of pharmacological interventions and predictors of response for emotional dysregulation and irritability. We assessed heterogeneity using Q statistics and publication bias. We conducted subanalyses and meta-regressions to identify predictors of response. The primary effect size was the standardized mean difference. Quality of studies was assessed using the Cochrane Risk of Bias Tool (RoB2).
RESULTS
A total of 2,856 individuals with ASD in 45 studies were included, among which 26.7% of RCTs had a high risk of bias. Compared to placebo, antipsychotics (standardized mean difference = 1.028, 95% CI = 0.824-1.232) and medications used to treat attention-deficit/hyperactivity disorder (ADHD) (0.471, 0.061-0.881) were significantly better than placebo in improving emotional dysregulation and irritability, whereas evidence of efficacy was not found for other drug classes (p > .05). Within individual medications, evidence of efficacy was found for aripiprazole (1.179, 0.838-1.520) and risperidone (1.074, 0.818-1.331). Increased rates of comorbid epilepsy (β = -0.049, p = .026) were associated with a lower efficacy.
CONCLUSION
Some pharmacological interventions (particularly risperidone and aripiprazole) have proved efficacy for short-term treatment of emotional dysregulation and irritability in ASD and should be considered within a multimodal treatment plan, taking into account also the tolerability profile and families' preferences.
Topics: Humans; Risperidone; Aripiprazole; Antipsychotic Agents; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity
PubMed: 35470032
DOI: 10.1016/j.jaac.2022.03.033 -
PloS One 2022Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of... (Review)
Review
AIM
Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of schizophrenia. This study aims to provide a comprehensive review on the efficacy of first-generation and second-generation LAI antipsychotics in recent-onset, first-episode, and early psychosis patients.
METHODS
MEDLINE, EMBASE, PsycINFO, and Web of Science Core databases were used to search for studies that used LAIs in early psychosis patients. Studies published up to 06 Jun 2019 were included with no language restrictions applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years.
RESULTS
33 studies were included: 8 RCTs, 4 post-hoc analyses, 2 case reports, and 19 naturalistic studies. The majority of studies evaluated risperidone LAIs (N = 14) and paliperidone palmitate (N = 10), while the remainder investigated fluphenazine decanoate (N = 3), flupentixol decanoate (N = 2), and aripiprazole (N = 1). Two studies did not specify the LAI formulation used, and one cohort study compared the efficacy of multiple different LAI formulations.
CONCLUSIONS
While the majority of data is based on naturalistic studies investigating risperidone LAIs or paliperidone palmitate, LAIs may be an effective treatment for early psychosis patients in terms of adherence, relapse reduction, and symptom improvements. There is still a need to conduct more high quality RCTs that investigate the efficacy of different LAI formulations in early psychosis patients.
Topics: Antipsychotic Agents; Cohort Studies; Delayed-Action Preparations; Humans; Paliperidone Palmitate; Psychotic Disorders; Risperidone
PubMed: 35486616
DOI: 10.1371/journal.pone.0267808 -
Journal of Affective Disorders Aug 2022Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the... (Review)
Review
OBJECTIVES
Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling.
METHODS
A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected.
RESULTS
Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found.
LIMITATIONS
Small sample sizes, different index episodes and variety of outcome measures.
CONCLUSION
Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted.
Topics: Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Valproic Acid
PubMed: 35545157
DOI: 10.1016/j.jad.2022.05.017 -
Neuromolecular Medicine Mar 2014Double-blinded, randomized, placebo-control trials of selective serotonin 3 receptor antagonists (5-HT3R-ANTs) for schizophrenia have differed in outcome. This... (Meta-Analysis)
Meta-Analysis Review
Double-blinded, randomized, placebo-control trials of selective serotonin 3 receptor antagonists (5-HT3R-ANTs) for schizophrenia have differed in outcome. This meta-analysis tests the hypothesis that 5-HT3R-ANTs are effective for the treatment for schizophrenia. We searched PubMed, the Cochrane Library database, and PsycINFO up to June 15, 2013. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing 5-HT3R-ANTs add-on therapy with placebo. The risk ratio (RR), 95 % confidence intervals (CI), and standardized mean difference (SMD) were calculated. A random-effects model was used. Six studies (total n = 311) were identified. These included one granisetron plus risperidone study, one ondansetron plus risperidone study, one ondansetron plus haloperidol, and three tropisetron plus risperidone studies. The statistically significant effects of 5-HT3R-ANTs add-on therapy on Positive and Negative Syndrome Scale (PANSS) total scores were SMD = -1.03, CI = -1.70 to -0.36, p = 0.003 (I (2) = 82 %, 5 studies, n = 261); on negative scores were SMD = -1.10, CI = -1.82 to -0.39, p = 0.002 (I (2) = 84 %, 5 studies, n = 261); and on PANSS general scores were SMD = -0.70, CI = -1.23 to -0.17, p = 0.01 (I (2) = 73 %, 5 studies, n = 261). However, 5-HT3R-ANTs add-on therapy was not superior to placebo in PANSS positive scores (SMD = -0.12, p = 0.33). Dropout due to all cause (RR = 0.80, p = 0.50), inefficacy (RR = 0.76, p = 0.65), or adverse events (RR = 0.84, p = 0.75) was similar in both groups. Constipation occurred significantly more often with 5-HT3R-ANTs than placebo (RR = 2.05, CI = 1.07-3.91, p = 0.03, NNH = 11, p = 0.02). 5-HT3R-ANTs add-on therapy is more beneficial on the psychopathology (especially negative symptoms) than controls in patients with schizophrenia, and 5-HT3R-ANTs seem to be well-tolerated treatments.
Topics: Antipsychotic Agents; Constipation; Double-Blind Method; Drug Therapy, Combination; Granisetron; Haloperidol; Humans; Indoles; Nausea; Ondansetron; Randomized Controlled Trials as Topic; Receptors, Serotonin, 5-HT3; Risperidone; Schizophrenia; Serotonin 5-HT3 Receptor Antagonists; Severity of Illness Index; Symptom Assessment; Treatment Outcome; Tropisetron; Vomiting
PubMed: 23896722
DOI: 10.1007/s12017-013-8251-0 -
Psychiatry Research Jan 2021Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present... (Meta-Analysis)
Meta-Analysis
Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present an update of our previously published algorithms for the use of psychopharmacologic agents in these patients taking into account more recent studies and findings in meta-analyses, reviews, and other published algorithms. We propose three algorithms: BPSD in an emergent, urgent, and non-urgent setting. In the emergent setting when intramuscular (IM) administration is necessary, the first-line recommendation is for olanzapine (since IM aripiprazole, previously favored, is no longer available) and haloperidol injection is the second choice, followed by possible consideration of an IM benzodiazepine. In the urgent setting, the first line would be oral second-generation antipsychotics (SGAs) aripiprazole and risperidone. Perhaps next could be then prazosin, and lastly electroconvulsive therapy is a consideration. There are risks associated with these agents, and adverse effects can be severe. Dosing strategies, discontinuation considerations, and side effects are discussed. In the non-emergent setting, medications are proposed for use in the following order: trazodone, donepezil and memantine, antidepressants such as escitalopram and sertraline, SGAs, prazosin, and carbamazepine. Other options with less support but potential future promise are discussed.
Topics: Academic Medical Centers; Aged; Algorithms; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Citalopram; Dementia; Electroconvulsive Therapy; Haloperidol; Humans; Olanzapine; Psychopharmacology; Risperidone
PubMed: 33340800
DOI: 10.1016/j.psychres.2020.113641 -
European Journal of Psychotraumatology 2021: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all... (Meta-Analysis)
Meta-Analysis
: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. : A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. : Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.28, 95% CI -0.39 to -0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. : Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies.
Topics: Adrenergic alpha-1 Receptor Antagonists; Antipsychotic Agents; Drug Synergism; Drug Therapy, Combination; Humans; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic
PubMed: 34992738
DOI: 10.1080/20008198.2020.1802920