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The International Journal of... Oct 2021The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but...
BACKGROUND
The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review, we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine oxidase-inhibitors, antipsychotics, and psychostimulants.
METHODS
MEDLINE and Web of Science were searched.
RESULTS
Twenty-four studies were included. For lithium, no significant interactions with ketamine were reported. Two out of 5 studies on lamotrigine indicated that the effects of ketamine were attenuated. Benzodiazepines were repeatedly shown to reduce the duration of ketamine's antidepressant effect. For the monoamine oxidase-inhibitor tranylcypromine, case reports showed no relevant changes in vital signs during concurrent S-ketamine use. One paper indicated an interaction between ketamine and haloperidol, 2 other studies did not. Four papers investigated risperidone, including 3 neuroimaging studies showing an attenuating effect of risperidone on ketamine-induced brain perfusion changes. Clozapine significantly blunted ketamine-induced positive symptoms in patients with schizophrenia but not in healthy participants. One paper reported no effect of olanzapine on ketamine's acute psychotomimetic effects.
CONCLUSION
Current literature shows that benzodiazepines and probably lamotrigine reduce ketamine's treatment outcome, which should be taken into account when considering ketamine treatment. There is evidence for an interaction between ketamine and clozapine, haloperidol, and risperidone. Due to small sample sizes, different subject groups and various outcome parameters, the evidence is of low quality. More studies are needed to provide insight into pharmacodynamic interactions with ketamine.
Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Depression; Drug Interactions; Female; Haloperidol; Humans; Ketamine; Lithium; Male; Olanzapine; Psychotropic Drugs; Risperidone; Schizophrenia; Treatment Outcome
PubMed: 34170315
DOI: 10.1093/ijnp/pyab039 -
Journal of Psychopharmacology (Oxford,... Jun 2022Rasagiline monotherapy is approved in early Parkinson's disease (PD) for motor benefit. However, the efficacy and optimal rasagiline dosage in improving Unified... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rasagiline monotherapy is approved in early Parkinson's disease (PD) for motor benefit. However, the efficacy and optimal rasagiline dosage in improving Unified Parkinson's Disease Rating Scale (UPDRS) subscale scores between Japanese and Caucasian individuals remain uncertain.
AIMS
To investigate the efficacy of rasagiline monotherapy and evaluate differences between early PD patients in Eastern and Western countries.
METHODS
The study design involved the meta-analysis of randomized controlled trials identified using electronic databases.
RESULTS
The mean difference (MD) in total UPDRS scores indicated no significant difference between the 1 and 2 mg rasagiline (MD = -0.00, 95% confidence interval (CI) = -0.82 to 0.81). Compared with the placebo, the MD of UPDRS part I scores significantly improved in the 1 mg (MD = -0.33, 95% CI = -0.57 to -0.10) but not in the 2 mg. For UPDRS part II scores, the MD significantly improved in the 1 mg (MD = -0.87, 95% CI = -1.48 to -0.27) and 2 mg (MD = -0.98, 95% CI = -1.28 to -0.68). Regarding the UPDRS part III, the MD significantly improved in both (1 mg: MD = -2.41, 95% CI = -3.26 to -1.56; 2 mg: MD = -2.05, 95% CI = -2.64 to -1.46). The most commonly reported adverse events were headaches, back pain, and dizziness, with no statistical difference between the 1 mg rasagiline and placebo groups. Subgroup analysis revealed similar effects between Asian and Western participants.
CONCLUSION
Rasagiline monotherapy at 1 mg per day is recommended for patients with early PD because of the benefits for motor, nonmotor functions, and safety.
Topics: Databases, Factual; Humans; Indans; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 35546511
DOI: 10.1177/02698811221093795 -
Revista Brasileira de Psiquiatria (Sao... 2020Ayahuasca is a South American psychoactive plant brew used as traditional medicine in spiritual and in cultural rituals. This is a review of the current understanding...
Ayahuasca is a South American psychoactive plant brew used as traditional medicine in spiritual and in cultural rituals. This is a review of the current understanding about the pharmacological mechanisms that may be interacting in ayahuasca. Searches were performed using PubMed, PsycINFO, and Web of Science databases and 16 papers were selected. As hypothesized, the primary narrative in existing research revolved around prevention of deamination of N,N-dimethyltryptamine (N,N-DMT, also referred to as DMT) by monoamine oxidase inhibitors (MAOIs) in ayahuasca. Two of the constituents, DMT and harmine, have been studied more than the secondary harmala alkaloids. At present, it is unclear whether the pharmacological interactions in ayahuasca act synergistically or additively to produce psychoactive drug effects. The included studies suggest that our current understanding of the preparation's synergistic mechanisms is limited and that more complex processes may be involved; there is not yet enough data to determine any potential synergistic interaction between the known compounds in ayahuasca. Our pharmacological understanding of its compounds must be increased to avoid the potential risks of ayahuasca use.
Topics: Banisteriopsis; Harmine; Humans; N,N-Dimethyltryptamine; Plant Extracts; Psychotropic Drugs
PubMed: 32638916
DOI: 10.1590/1516-4446-2020-0884 -
Journal of Affective Disorders Mar 2021Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants.
METHODS
In this systematic review, network meta-analysis was used to investigate the comparative efficacy and acceptability of MAOIs for depressive disorders. Overall, the network meta-analysis included 52 double-blind, randomized controlled trials (RCTs) that compared 14 antidepressants or placebo. Across studies, the mean arm size was n = 58 participants from a total N = 6462 (5309 active drug; 1153 placebo).
RESULTS
Except fluvoxamine, all antidepressants demonstrated superior efficacy to placebo, and none demonstrated substantially better or worse all-cause dropout rates. Phenelzine demonstrated superior evidence for efficacy compared to all other treatments, and clomipramine demonstrated superior evidence for acceptability compared to all other treatments.
LIMITATIONS
The study is primarily limited by low estimate precision due to a relative paucity of studies for some of the included treatment conditions. Further evidence is required to study the relative efficacy of MAOIs against newer antidepressants.
CONCLUSIONS
The results of this analysis largely support the re-evaluation of the use of MAOIs as antidepressant agents in the treatment algorithm of depression.
Topics: Antidepressive Agents; Depressive Disorder; Humans; Monoamine Oxidase Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 33601690
DOI: 10.1016/j.jad.2021.01.021 -
Fitoterapia Sep 2019Depressive disorders remain a current public health problem whose prevalence has increased in the past decades. In the constant search for new therapeutic alternatives,...
Depressive disorders remain a current public health problem whose prevalence has increased in the past decades. In the constant search for new therapeutic alternatives, β-carboline alkaloids have been identified as good candidates for new antidepressant drugs. In this systematic review, we summarized all pre-clinical investigations involving the use of natural or semisynthetic β-carboline in depression models. A literature search was conducted in August 2018, using PubMed, Scopus and Science Direct databases. All reports were carefully analyzed, and data extraction was conducted through standardized forms. Methodological quality assessment of in vivo studies was also performed. The entire systematic review was performed according to PRISMA statement. From a total of 373 articles, 26 met all inclusion criteria. In vitro and in vivo studies have evaluated a wide variety of β-carbolines through enzymatic and binding assays, and acute or chronic animal models. Most of the in vivo and in vitro studies is concentrated on two molecules: harman and harmine. They have been investigated in several animal models and some mechanisms of action have been proposed for their antidepressant activity. In general, β-carbolines modulate 5-HT and GABA systems, promote neurogenesis, induce neuroendocrine response and restore astrocytic function, being effective when administrated acutely or chronically in different animal models, including chronic mild stress protocols. In short, β-carbolines are multi-target antidepressant compounds and may be useful in the treatment of depressive disorders.
Topics: Alkaloids; Animals; Antidepressive Agents; Carbolines; Depression; Drug Evaluation, Preclinical; Harmine
PubMed: 31175948
DOI: 10.1016/j.fitote.2019.104196 -
Frontiers in Medicine 2021Roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), has been used to treat anemia in patients with chronic kidney disease (CKD). However, its...
Roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), has been used to treat anemia in patients with chronic kidney disease (CKD). However, its safety and efficacy remain controversial. The PubMed, EMBASE, Science Citation Index, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries databases were searched for relevant studies published up to April 2021. We identified randomized controlled trials (RCTs) comparing roxadustat with placebo or erythropoiesis-stimulating agents (ESAs) in anemia patients with CKD with or without dialysis. Eleven studies including 6,631 patients met the inclusion criteria. In non-dialysis-dependent (NDD-) and dialysis-dependent (DD-) CKD patients, the total adverse events were not significantly different between the roxadustat and control (placebo for NDD-CKD patients and ESA for DD-CKD patients) groups [relative risk (RR) = 1.02, 95% confidence interval (CI) = 1.00, 1.04, = 0.08, and RR = 1.22, 95% CI = 0.91, 1.64, = 0.18, respectively], and the trial sequential analysis (TSA) confirmed the result in the NDD-CKD groups. No significant differences in hyperkalemia and infection incidences were found between roxadustat and placebo in the DD-CKD groups. The pooled results showed that roxadustat significantly increased the hemoglobin response rate compared with placebo in the NDD-CKD group and had an effect similar to that of ESA in the DD-CKD group. However, iron metabolism parameters did not seem to be obviously optimized by roxadustat. Roxadustat can be safely used in CKD patients. Oral roxadustat was more effective than placebo as a therapy for anemia in NDD-CKD patients and non-inferior to ESA in correcting anemia in DD-CKD patients. However, additional clinical trials are still needed to further prove whether roxadustat can optimize iron metabolism.
PubMed: 34532333
DOI: 10.3389/fmed.2021.724456 -
BMC Psychiatry Mar 2020Depression is one of the leading causes of the global burden of disease, and it has particularly negative consequences for elderly patients. Antidepressants are the most... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression is one of the leading causes of the global burden of disease, and it has particularly negative consequences for elderly patients. Antidepressants are the most frequently used treatment. We present the first single-group meta-analysis examining: 1) the response rates of elderly patients to antidepressants, and 2) the determinants of antidepressants response in this population.
METHODS
We searched multiple databases for randomized controlled trials on antidepressants in the elderly with major depressive disorder above 65 years (last search: December 2017). Response was defined as 50% improvement on validated rating scales. We extracted response rates from studies and imputed the missing ones with a validated method. Data were pooled in a single-group meta-analysis. Additionally, several potential moderators of response to antidepressants were examined by subgroup and meta-regression analyses.
RESULTS
We included 44 studies with a total of 6373 participants receiving antidepressants. On average, 50.7% of the patients reached a reduction of at least 50% on the Hamilton Depression Scale (HAMD). Subgroup and meta-regression analyses revealed a better response to treatment for patients in antidepressant-controlled trials compared to placebo-controlled trials. Mean age, study duration, percentage of woman, severity of illness at baseline, dose of antidepressants in fluoxetine equivalents, year of publication, setting (in- or out-patients), antidepressant groups (SSRI, TCA, SSNRI, α2-antagonist, SNRI, MAO-inhibitor), ITT (intention-to-treat) analysis vs completer analysis, sponsorship and overall risk of bias were not significant moderators of response.
CONCLUSIONS
Our findings suggest an improvement in symptoms can be found in about 50% of the elderly with major depressive disorder treated with antidepressants.
Topics: Aged; Antidepressive Agents; Depressive Disorder, Major; Female; Fluoxetine; Humans; Patients
PubMed: 32131786
DOI: 10.1186/s12888-020-02514-2 -
Neurological Sciences : Official... Jan 2020The aim of this report was to systematically evaluate the efficacy and safety of rasagiline (R) plus levodopa (L) (R + L) for the treatment of Parkinson's disease (PD)... (Comparative Study)
Comparative Study
OBJECTIVE
The aim of this report was to systematically evaluate the efficacy and safety of rasagiline (R) plus levodopa (L) (R + L) for the treatment of Parkinson's disease (PD) compared with that of L monotherapy, in order to provide a reference resource for rational drug use.
METHODS
Randomized controlled trials (RCTs) of R + L for PD published up to September 2018 were searched. Sensitivity analyses were also performed.
RESULTS
Fourteen RCTs with 2531 participants were included. Compared with L monotherapy, the pooled effects of R + L combination therapy on unified Parkinson's disease rating scale (UPDRS) score were (SMD - 0.50, 95% CI - 0.70 to - 0.30, P < 0.00001) for UPDRS motor score, (SMD - 0.59, 95% CI - 0.79 to - 0.39, P < 0.00001) for UPDRS activities of daily living (ADL) score, (SMD - 0.65, 95% CI - 0.81 to - 0.49, P < 0.00001) for UPDRS total score. R + L combination therapy was better than L monotherapy in reducing daily off-time (SMD - 1.15, 95% CI - 2.13 to - 0.17, P = 0.02), but there was a statistically nonsignificant result in daily on-time increase (SMD 1.39, 95% CI - 0.69 to 3.48, P = 0.19). There were no statistical differences in number of adverse events (OR 1.33, 95% CI 0.97 to 1.82, P = 0.07) and number of dropout (OR 0.88, 95% CI 0.65 to 1.19, P = 0.39) between R + L combination therapy and L monotherapy.
CONCLUSIONS
R + L combination therapy was superior to L monotherapy for improvement of UPDRS scores and off-time in PD patients. Moreover, R + L combination therapy and L monotherapy were similar in terms of safety and tolerability.
Topics: Antiparkinson Agents; Drug Therapy, Combination; Humans; Indans; Levodopa; Neuroprotective Agents; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 31446579
DOI: 10.1007/s10072-019-04050-8