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Biomedicines Dec 2022Evidence about the use of pharmacologic agents in the treatment of Anorexia Nervosa (AN) is lacking, especially in childhood and adolescence. A systematic scoping review... (Review)
Review
Evidence about the use of pharmacologic agents in the treatment of Anorexia Nervosa (AN) is lacking, especially in childhood and adolescence. A systematic scoping review was conducted to outline current literature evidence about the use of antipsychotics in this population. A total of 499 studies were identified with the initial search, and 28 of these studies were selected regarding the use of olanzapine (n = 13), risperidone (n = 4), aripiprazole (n = 3), chlorpromazine (n = 3), pimozide (n = 1) clotiapine (n = 1) and multiple antipsychotics (n = 3) in these patients. Overall, major side effects were reported infrequently; improvements in psychopathology and weight measures have been suggested in the majority of the considered studies. Nonetheless, the lack of RCT or good-quality studies strongly limits the generalizability of results in clinical practice.
PubMed: 36551922
DOI: 10.3390/biomedicines10123167 -
Brain Sciences Nov 2022cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving... (Review)
Review
BACKGROUND
cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving efficacy of pharmacotherapies tested for cocaine use disorder, in the context of randomized-controlled clinical trials.
OBJECTIVES
we assessed the databases of the U.S. National Library of Medicine, Google Scholar, and PsycINFO, without date restrictions up to August 2022, to identify relevant studies.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
we included double-blinded randomized-controlled trials investigating pharmacotherapies for cocaine craving and/or cocaine use disorder whose outcomes included cocaine craving.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two authors screened studies' titles and abstracts for inclusion, and both read all the included studies. We systematically gathered information on the following aspects of each study: title; author(s); year of publication; sample size; mean age; sample characteristics; study set-ting; whether participants were treatment-seeking; study design; craving measures; study interventions; drop-out rates; and other relevant outcomes.
RESULTS
Overall, we appraised 130 clinical trials, including 8137 participants. We further considered the drugs from the studies that scored equal to or greater than six points in the quality assessment. There was a correlation between craving and cocaine use outcomes (self-reports, timeline follow-back or urinary benzoylecgonine) in the vast majority of studies. In the short-term treatment, acute phenylalanine-tyrosine depletion, clonidine, fenfluramine, meta-chlorophenylpiperazine (m-CPP) and mecamylamine presented promising effects. In the long term, amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone presented promising anti-craving effects. Unfortunately, the highly tested medications were not successful in most of the trials, as follows: propranolol in the short term; amantadine, aripiprazole, bromocriptine, citicoline, ketamine, modafinil, olanzapine, topiramate in the long term. The remaining 52 medications had no positive anti-craving outcomes.
LIMITATIONS
Our review was limited by high heterogeneity of craving assessments across the studies and by a great range of pharmacotherapies. Further, the majority of the studies considered abstinence and retention in treatment as the main outcomes, whereas craving was a secondary outcome and some of the studies evaluated patients with cocaine use disorder with comorbidities such as opioid or alcohol use disorder, schizophrenia, bipolar disorder or attention deficit hyperactivity. Lastly, most of the studies also included non-pharmacological treatments, such as counseling or psychotherapy.
CONCLUSIONS
There is a direct association between craving and cocaine use, underscoring craving as an important treatment target for promoting abstinence among persons with cocaine use disorder. Clonidine, fenfluramine and m-CPP showed to be promising medications for cocaine craving in the short-term treatment, and amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone in the long-term treatment.
PubMed: 36421870
DOI: 10.3390/brainsci12111546 -
PCN Reports : Psychiatry and Clinical... Dec 2022This review aimed to clarify whether antimanic agents used in Japan are superior to placebo for the treatment of acute mania, based on reports of randomized controlled... (Review)
Review
This review aimed to clarify whether antimanic agents used in Japan are superior to placebo for the treatment of acute mania, based on reports of randomized controlled trials (RCTs) conducted in Japan and other East Asian countries. A literature search was conducted using the MEDLINE, PubMed, and Ichushi databases from their dates of inception to July 31, 2021, for studies written in English or Japanese with a primary diagnosis of bipolar I disorder, comparing any of the following active drugs to treat acute mania in adults: aripiprazole, carbamazepine, chlorpromazine, haloperidol, lithium, olanzapine, sultopride, timiperone, and zotepine. A random-effects network meta-analysis was performed within a frequentist framework. The quality of each included study was evaluated using the revised Cochrane risk-of-bias tool for randomized trials. The outcomes adopted were the response rate for efficacy and dropout rate for tolerability during 3 weeks from baseline. Eleven RCTs, totaling 1148 participants, were reviewed. The pooled odds ratio (OR) (±95% confidence interval [CI]) was calculated. Timiperone (OR = 4.53, CI 1.09-18.80), sultopride (OR = 3.76, CI 1.08-13.05), and aripiprazole (OR = 1.99, CI 1.22-3.24) were significantly more effective than placebo. Olanzapine (OR = 0.51, CI 0.29-0.90) was significantly superior in acceptability to placebo. The results showed no significant differences from placebo for carbamazepine, chlorpromazine, haloperidol, lithium, and olanzapine. These results suggest that noninferiority trials alone cannot always confirm the antimanic drug efficacy and that direct placebo-controlled trials are necessary to verify the antimanic efficacy of the drugs.
PubMed: 38868658
DOI: 10.1002/pcn5.60 -
EClinicalMedicine Dec 2022Acute mania is a psychiatric emergency requiring rapid management. However, randomised controlled trials (RCTs) have shown considerable individual differences in...
Variability and efficacy in treatment effects on manic symptoms with lithium, anticonvulsants, and antipsychotics in acute bipolar mania: A systematic review and meta-analysis.
BACKGROUND
Acute mania is a psychiatric emergency requiring rapid management. However, randomised controlled trials (RCTs) have shown considerable individual differences in treatment effects on manic symptoms with antimanic drugs.
METHODS
We searched the MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov to identify RCTs without language restrictions from inception to April 19, 2022. We included double-blind RCTs of oral antimanic monotherapy versus placebo in adult patients. The primary outcome was variability in improvement of manic symptoms (assessed using the coefficient of variation ratio [CVR]). The secondary outcomes were overall improvement of manic symptoms and acceptability (i.e., discontinuation for any reason). The pooled effects of outcomes were calculated by random-effects meta-analyses using restricted maximum likelihood methods. The quality of the included studies was assessed using the Cochrane Risk of Bias (ROB) Assessment Tool. This study was registered with OSF (DOI:10.17605/OSF.IO/G4JNY).
FINDINGS
We included 39 RCTs (N=12150; mean age=39·9 years, interquartile range [IQR]=38·7-41·1; mean proportion of female=48·6%, IQR=42·3%-52·3%) and investigated 14 antimanic drugs. We found that eight antimanic drugs compared to placebo were associated with lower CVRs (95% confidence interval [CI]; I), including risperidone (0·51; 0·37-0·70; 0%), haloperidol (0·54; 0·44-0·67; 4%), olanzapine (0·59; 0·44-0·79; 47%), ziprasidone (0·61; 0·53-0·71; 0%), lithium (0·63; 0·52-0·76; 0%), quetiapine (0·65; 0·48-0·87; 2%), aripiprazole (0·68; 0·56-0·84; 25%), and cariprazine (0·70; 0·49-0·99; 28%). There were nine antimanic drugs associated with greater efficacy than placebo, including risperidone (reported as standardised mean difference; 95% CI; I: 0·64; 0·31-0·97; 15%), haloperidol (0·57; 0·29-0·85; 64%), cariprazine (0·51; 0·24-0·78; 0%), olanzapine (0·44; 0·30-0·58; 0%), lithium (0·42; 0·29-0·55; 0%), ziprasidone (0·42; 0·26-0·58; 0%), quetiapine (0·40; 0·13-0·67; 0%), asenapine (0·40; 0·13-0·67; 0%), and aripiprazole (0·32; 0·14-0·49; 53%). Ziprasidone (reported as risk ratio; 95% CI; I: 0·83; 0·79-0·89; 0%) and olanzapine (0·63; 0·49-0·80; 35%) were associated with better acceptability relative to placebo. Among the 39 RCTs, none had a high ROB.
INTERPRETATION
We demonstrated that eight antimanic drugs were associated with lower variability and better efficacy than placebo, suggesting that these antimanic drugs were associated with more homogenous and predictable improvements of manic symptoms in patients with acute mania.
FUNDING
The study was supported by from the Ministry of Science and Technology (MOST-110-2314-B-016-035, MOST-111-2314-B-016-054), Medical Affairs Bureau (MND-MAB-D-111102), and Tri-service General Hospital (TSGH-E-111229).
PubMed: 36247926
DOI: 10.1016/j.eclinm.2022.101690 -
Psychopharmacology Nov 2022While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges.
OBJECTIVES
Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders.
METHODS
The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated.
RESULTS
Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120-270 ng/ml and 180-380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders.
CONCLUSIONS
High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers.
Topics: Humans; Aripiprazole; Schizophrenia; Reference Values; Antipsychotic Agents; Cytochrome P-450 CYP2D6
PubMed: 36195732
DOI: 10.1007/s00213-022-06233-2 -
Frontiers in Psychiatry 2022To study the similarities and differences in the clinical efficacy of aripiprazole and quetiapine in Chinese patients with bipolar depression through meta-analysis....
OBJECTIVE
To study the similarities and differences in the clinical efficacy of aripiprazole and quetiapine in Chinese patients with bipolar depression through meta-analysis. Additionally, to provide evidence of aripiprazole in treatment for bipolar depression.
METHODS
We searched Chinese literature related to the study of aripiprazole and quetiapine in treatment for bipolar depression, among which results such as comments, letters, reviews, and case reports were excluded. The clinical efficacy between aripiprazole and quetiapine was synthesized and discussed.
RESULT
A total of 1,546 subjects were included in 17 studies. The random effect model was used to review the data by RevMan 5.2. The results showed that there was no significant difference in the remission rate between patients treated with aripiprazole and quetiapine evidenced by the scale used to evaluate the patients being treated for bipolar depression (221/501 vs. 193/501, Z = 1.12, = 0.26). But the results also showed that the remission rate of aripiprazole with lithium carbonate was significantly higher than quetiapine with lithium carbonate in the treatment of bipolar depression (111/232 vs. 69/232, Z = 3.92, < 0.0001). The results showed that the effective rate of aripiprazole was similar to quetiapine (426/572 vs. 386/572, Z = 2.70, = 0.007). Overall, there was no difference in the Hamilton Rating Scale for Depression (HAMD) score between patients treated with aripiprazole and quetiapine (Z = 1.68, = 0.09). The results also show that the drop-out rate of aripiprazole was similar to quetiapine in the treatment of patients with bipolar depression (Z = 1.80, = 0.07).
CONCLUSION
As an atypical antipsychotic, aripiprazole may be similar to quetiapine for treating bipolar depression with similar drop-out and higher remission rates when combined with lithium carbonate. However, the results of this study need to be read with caution given the poor quality of collected/analyzed literature.
PubMed: 36159936
DOI: 10.3389/fpsyt.2022.850021 -
Molecular Psychiatry Jan 2023People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical...
The impact of pharmacological and non-pharmacological interventions on physical health outcomes in people with mood disorders across the lifespan: An umbrella review of the evidence from randomised controlled trials.
OBJECTIVE
People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population.
METHODS
Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age).
RESULTS
Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES).
CONCLUSIONS
Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.
Topics: Adult; Humans; Aged; Adolescent; Fluoxetine; Olanzapine; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Aripiprazole; Longevity; Glycated Hemoglobin; Antipsychotic Agents; Antidepressive Agents; Bipolar Disorder; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic
PubMed: 36138129
DOI: 10.1038/s41380-022-01770-w -
CNS Drugs Oct 2022Preliminary results from randomized controlled studies as well as identified molecular, cellular, and circuit targets of select psychedelics (e.g., psilocybin) suggest...
BACKGROUND
Preliminary results from randomized controlled studies as well as identified molecular, cellular, and circuit targets of select psychedelics (e.g., psilocybin) suggest that their effects are transdiagnostic. In this review, we exploit the Research Domain Criteria (RDoC) transdiagnostic framework, to synthesize extant literature on psilocybin.
OBJECTIVE
We aimed to identify RDoC-based effects of psilocybin and vistas for future mechanistic and interventional research.
METHODS
A systematic search in electronic databases (i.e., PubMed, Scopus, PsycINFO, and Web of Science) performed in January and February 2021 identified English articles published between 1990 and 2020 reporting the effects of psilocybin on mental health measures. Data from included articles were retrieved and organized according to the RDoC bio-behavioral matrix and its constituent six main domains, namely: positive valence systems, negative valence systems, cognitive systems, social processes, sensorimotor systems, and arousal and regulatory systems.
RESULTS
The preponderance of research with psilocybin has differentially reported beneficial effects on positive valence systems, negative valence system, and social process domains. The data from the included studies support both short-term (23 assessments) and long-term (15 assessments) beneficial effects of psilocybin on the positive valence systems. While 12 of the extracted outcome measures suggest that psilocybin use is associated with increases in the "fear" construct of the negative valence systems domain, 19 findings show no significant effects on this construct, and seven parameters show lowered levels of the "sustained threat" construct in the long term. Thirty-four outcome measures revealed short-term alterations in the social systems' construct namely, "perception and understanding of self," and "social communications" as well as enhancements in "perception and understanding of others" and "affiliation and attachment". The majority of findings related to the cognitive systems' domain reported dyscognitive effects. There have been relatively few studies reporting outcomes of psilocybin on the remaining RDoC domains. Moreover, seven of the included studies suggest the transdiagnostic effects of psilocybin. The dashboard characterization of RDoC outcomes with psilocybin suggests beneficial effects in the measures of reward, threat, and arousal, as well as general social systems.
CONCLUSIONS
Psilocybin possesses a multi-domain effectiveness. The field would benefit from highly rigorous proof-of-mechanism research to assess the effects of psilocybin using the RDoC framework. The combined effect of psilocybin with psychosocial interventions with RDoC-based outcomes is a priority therapeutic vista.
Topics: Hallucinogens; Humans; Psilocybin
PubMed: 36097251
DOI: 10.1007/s40263-022-00944-y -
Canadian Journal of Psychiatry. Revue... Jan 2023Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for... (Review)
Review
OBJECTIVE
Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder.
METHODS
A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria.
RESULTS
Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient.
CONCLUSIONS
There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.
Topics: Humans; Hallucinogens; Psilocybin; Depressive Disorder, Major; Canada; Anxiety; Neoplasms
PubMed: 35975555
DOI: 10.1177/07067437221111371 -
Neuropsychiatric Disease and Treatment 2022The pharmacological management of Autism Spectrum Disorder (ASD) in children remains a challenge due to limited effective management options and the absence of approved... (Review)
Review
PURPOSE
The pharmacological management of Autism Spectrum Disorder (ASD) in children remains a challenge due to limited effective management options and the absence of approved drugs to manage the core symptoms. This review aims to describe and highlight effective pharmacological management options employed in managing the core symptoms and comorbidities of ASD from eligible studies over the past decade.
METHODS
A search of databases; PubMed, Scopus, Science Direct, and PsychInfo for pharmacotherapeutic options for ASD was conducted in this systematic review. Duplicate studies were removed by utilizing the EndNote citation manager. The studies were subsequently screened independently by two authors. Eligible studies from 01 January 2012 to 01 January 2022 were included based on established eligibility criteria. A narrative synthesis was used for data analysis.
RESULTS
The systematic review provides a comprehensive list of effective management options for ASD comorbidities and core symptoms from 33 included studies. The management options for ASD comorbidities; insomnia, hyperactivity, irritability and aggression, gastrointestinal disturbances, and subclinical epileptiform discharges, were reviewed. Risperidone, aripiprazole, methylphenidate, guanfacine, levetiracetam, and atomoxetine are examples of effective pharmacological drugs against ASD comorbidities. Additionally, this review identified various drugs that improve the core symptoms of ASD and include but are not limited to, bumetanide, buspirone, intranasal oxytocin, intranasal vasopressin, and prednisolone.
CONCLUSION
This review has successfully summarized the pharmacological advancements made in the past decade to manage ASD. Although there is still no pharmacological cure for ASD core symptoms or additional drugs that have obtained regulatory approval for use in ASD, the availability of promising pharmacological agents are under evaluation and study.
PubMed: 35968512
DOI: 10.2147/NDT.S371013