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Asian Journal of Psychiatry Jan 2023To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for... (Meta-Analysis)
Meta-Analysis
Pharmacological and nonpharmacological augmentation treatments for clozapine-resistant schizophrenia: A systematic review and network meta-analysis with normalized entropy assessment.
OBJECTIVE
To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS).
METHODS
Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking.
RESULTS
We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93).
CONCLUSION
Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).
Topics: Humans; Clozapine; Network Meta-Analysis; Entropy; Memantine; Mirtazapine; Antipsychotic Agents; Schizophrenia
PubMed: 36470132
DOI: 10.1016/j.ajp.2022.103375 -
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 -
Acta Neuropsychiatrica Apr 2023Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs) have evaluated the efficacy of different strategies to augment clozapine. This systematic review and meta-analysis reviewed the available RCTs that have evaluated the clinical efficacy of various pharmacological agents, non-pharmacological strategies (occupational therapy, cognitive behaviour therapy), and somatic treatment [electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, etc.)] as augmenting agents to clozapine.
METHODS
Data were extracted using standard procedures, and risk of bias was evaluated. Effect sizes were computed for the individual studies.
RESULTS
Forty-five clinical trials were evaluated. The pooled effect size for various antipsychotic medications was 0.103 (95% CI: 0.288-0.493, < 0.001); when the effect size was evaluated for specific antipsychotics for which more than one trial was available, the effect size for risperidone was -0.27 and that for aripiprazole was 0.57. The effect size for lamotrigine was 0.145, and that for topiramate was 0.392. The effect size for ECT was 0.743 (CI: 0.094-1.392). Risk of bias was low (mean Jadad score - 3.93). Largest effect sizes were seen for mirtazapine (effect size of 5.265). Most of the studies can be considered underpowered and limited by small sample sizes.
CONCLUSIONS
To conclude, based on the findings of the present systematic review and meta-analysis, it can be said that compared to other treatment strategies, clozapine non-responsive patients respond maximum to mirtazapine followed by ECT.
Topics: Humans; Clozapine; Schizophrenia; Mirtazapine; Antipsychotic Agents; Risperidone
PubMed: 36380513
DOI: 10.1017/neu.2022.30 -
Molecular Psychiatry Jan 2023A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.
Topics: Female; Humans; Adult; Depressive Disorder, Major; Duloxetine Hydrochloride; Sertraline; Citalopram; Venlafaxine Hydrochloride; Vortioxetine; Fluoxetine; Paroxetine; Mirtazapine; Amitriptyline; Desvenlafaxine Succinate; Fluvoxamine; Reboxetine; Network Meta-Analysis; Antidepressive Agents; Randomized Controlled Trials as Topic
PubMed: 36253442
DOI: 10.1038/s41380-022-01824-z -
Case Reports in Obstetrics and... 2022Hyperemesis gravidarum (HG) is a rare condition (1.1%) characterized by excessive vomiting, malnutrition, dehydration, and laboratorial alterations. Herein, we describe...
Hyperemesis gravidarum (HG) is a rare condition (1.1%) characterized by excessive vomiting, malnutrition, dehydration, and laboratorial alterations. Herein, we describe the even rarer and serious presentation of refractoriness to the usual treatment of antiemetics and parenteral nutrition, with improvement only after the use of olanzapine and mirtazapine. Two subsequent pregnancies of the same woman with HG are described, which were associated with severe weight loss, anemia, hyponatremia, hypokalemia, and mild dysfunction of liver enzymes. In the third pregnancy, the usual treatment for HG was not successful, requiring enteral nutrition and the introduction of olanzapine. In the fourth pregnancy, the patient refused to use enteral nutrition for refractory HG. Hence, the patient was started on mirtazapine at an initial dose of 15 mg/day, which was gradually increased to 30 mg/day. The patient responded well to the new regimen, as demonstrated by the decrease in symptoms, the gain of 10 kg in the pregnancy, and delivering a healthy newborn. A systematic review of literature showed 11 articles and 30 cases that successfully used mirtazapine in HG. Good clinical outcomes were seen with 4 days of the treatment and at an initial dose of 15 mg/day. However, most of these reports were from psychiatric profiles, with a predominance of depression and anxiety symptoms, and a poor description of the obstetric conditions and the disease progression itself. Pulmonary hypertension was described in one case and neonatal hyperexcitability in another. The case described in this paper reinforces the idea that mirtazapine and olanzapine can be considered in refractory HG, with good results. In the world literature, this is the second case of HG that has been successfully treated with olanzapine and the first in Latin America treated with mirtazapine.
PubMed: 36105926
DOI: 10.1155/2022/7324627 -
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 -
Cost Effectiveness and Resource... Apr 2022This study aims to synthesize the empirical economic evidence of pharmaceutical therapies for people with dementia. (Review)
Review
OBJECTIVES
This study aims to synthesize the empirical economic evidence of pharmaceutical therapies for people with dementia.
STUDY DESIGN
Systematic review and meta-analysis. Literature evaluating the costs and effects of drug therapies for dementia was indexed until December 2021. Quality of study was assessed using the Cochrane Risk of Bias Tool and Consensus on Health Economic Criteria list. Cost data were standardized to 2020 US dollars and analyzed from healthcare service and societal perspectives. Random-effects models were used to synthesize economic and clinical data, based on mean differences (MDs) and standardized MDs.
RESULTS
Ten unique studies were identified from 11,771 records. Acetylcholinesterase inhibitors (AChEIs) and memantine improved dementia-related symptoms, alongside nonsignificant savings in societal cost (AChEIs: MD-2002 [- 4944 ~ 939]; memantine: MD-6322 [- 14355 ~ 1711]). Despite decreases in cost, antidepressants of mirtazapine and sertraline and second-generation antipsychotics were limited by their significant side effects on patients' cognitive and activity functions. Subgroup analysis indicated that the impacts of AChEIs on cost were affected by different analytical perspectives, follow-up periods, and participant age.
CONCLUSIONS
AChEIs and memantine are cost-effective with improvements in dementia-related symptoms and trends of cost-savings. More empirical evidence with non-industrial sponsorships and rigorous design in different settings is warranted.
PubMed: 35443684
DOI: 10.1186/s12962-022-00354-3 -
Progress in Neuro-psychopharmacology &... Jul 2022Sleep quality disturbances are a common occurrence in post-traumatic stress disorder (PTSD) and may remain after evidence-based treatment for PTSD has been implemented.... (Meta-Analysis)
Meta-Analysis Review
Efficacy, acceptability, and tolerability of antidepressants for sleep quality disturbances in post-traumatic stress disorder: A systematic review and network meta-analysis.
Sleep quality disturbances are a common occurrence in post-traumatic stress disorder (PTSD) and may remain after evidence-based treatment for PTSD has been implemented. If left untreated, sleep disturbance can perpetuate or aggravate the disorder. A systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) was conducted comparing efficacy, acceptability, and tolerability among antidepressants for sleep quality improvement in PTSD, using Cochane's RoB2.0 and GRADE approach for NMA. The Cochrane Library, LILACS, PsycINFO, PTSDpubs, and PubMed Central databases were searched from inception to November 29, 2020, leading to the retrieval of 3733 reports. After the selection process, seven RCTs were included in the review (N = 600). We found low certainty of evidence (LCE) that sertraline may improve sleep quality (measured by PSQI) in adult patients with PTSD (MD -0.48, 95% CrI -0.63 to -0.32). Sertraline was as well accepted (RR 1.12, 95% CrI -0.83 to 1.52, very low certainty [VLCE]) and as well tolerated as placebo (RR 0.58, 95% CrI 0.28 to 1.14, LCE). Mirtazapine (MD -3.35, 95% CrI -9.06 to 2.39, LCE), paroxetine (MD -3.13, 95% CrI -7.47 to 1.26, VLCE), nefazodone (MD -0.25, 95% CrI -5.95 to 5.38, VLCE), and bupropion (MD -2.28, 95% CrI -4.75 to 0.21, VLCE) were similar to placebo for improving sleep quality. These antidepressants resulted in little or no benefit for sleep in PTSD. Although the NMA suggested that sertraline may improve sleep in PTSD compared to placebo, due to the low certainty, these estimates are not robust enough to guide clinical decisions.
Topics: Adult; Antidepressive Agents; Humans; Network Meta-Analysis; Sertraline; Sleep Quality; Sleep Wake Disorders; Stress Disorders, Post-Traumatic
PubMed: 35395322
DOI: 10.1016/j.pnpbp.2022.110557 -
The Cochrane Database of Systematic... Mar 2022Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed... (Review)
Review
BACKGROUND
Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment.
OBJECTIVES
To assess the effects of medication for reducing PTSD symptoms in adults with PTSD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 11, November 2020); MEDLINE (1946-), Embase (1974-), PsycINFO (1967-) and PTSDPubs (all available years) either directly or via the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR). We also searched international trial registers. The date of the latest search was 13 November 2020.
SELECTION CRITERIA
All randomised controlled trials (RCTs) of pharmacotherapy for adults with PTSD.
DATA COLLECTION AND ANALYSIS
Three review authors (TW, JI, and NP) independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. We contacted investigators to obtain missing data. We stratified summary statistics by medication class, and by medication agent for all medications. We calculated dichotomous and continuous measures using a random-effects model, and assessed heterogeneity.
MAIN RESULTS
We include 66 RCTs in the review (range: 13 days to 28 weeks; 7442 participants; age range 18 to 85 years) and 54 in the meta-analysis. For the primary outcome of treatment response, we found evidence of beneficial effect for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.59 to 0.74; 8 studies, 1078 participants), which improved PTSD symptoms in 58% of SSRI participants compared with 35% of placebo participants, based on moderate-certainty evidence. For this outcome we also found evidence of beneficial effect for the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine: (RR 0.45, 95% CI 0.22 to 0.94; 1 study, 26 participants) in 65% of people on mirtazapine compared with 22% of placebo participants, and for the tricyclic antidepressant (TCA) amitriptyline (RR 0.60, 95% CI 0.38 to 0.96; 1 study, 40 participants) in 50% of amitriptyline participants compared with 17% of placebo participants, which improved PTSD symptoms. These outcomes are based on low-certainty evidence. There was however no evidence of beneficial effect for the number of participants who improved with the antipsychotics (RR 0.51, 95% CI 0.16 to 1.67; 2 studies, 43 participants) compared to placebo, based on very low-certainty evidence. For the outcome of treatment withdrawal, we found evidence of a harm for the individual SSRI agents compared with placebo (RR 1.41, 95% CI 1.07 to 1.87; 14 studies, 2399 participants). Withdrawals were also higher for the separate SSRI paroxetine group compared to the placebo group (RR 1.55, 95% CI 1.05 to 2.29; 5 studies, 1101 participants). Nonetheless, the absolute proportion of individuals dropping out from treatment due to adverse events in the SSRI groups was low (9%), based on moderate-certainty evidence. For the rest of the medications compared to placebo, we did not find evidence of harm for individuals dropping out from treatment due to adverse events.
AUTHORS' CONCLUSIONS
The findings of this review support the conclusion that SSRIs improve PTSD symptoms; they are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence. The NaSSA mirtazapine and the TCA amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence. In addition, we found no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence. There remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amitriptyline; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Humans; Middle Aged; Mirtazapine; Paroxetine; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic; Young Adult
PubMed: 35234292
DOI: 10.1002/14651858.CD002795.pub3 -
Frontiers in Psychiatry 2022Consistent evidence suggests residual depressive symptomology are the strongest predictors of depression relapse following cognitive-behavioral therapy (CBT) and...
A Systematic Review and Individual Patient Data Network Analysis of the Residual Symptom Structure Following Cognitive-Behavioral Therapy and Escitalopram, Mirtazapine and Venlafaxine for Depression.
OBJECTIVE
Consistent evidence suggests residual depressive symptomology are the strongest predictors of depression relapse following cognitive-behavioral therapy (CBT) and antidepressant medications (ADM's). Psychometric network models help detecting and understanding central symptoms that remain post-treatment, along with their complex co-occurrences. However, individual psychometric network studies show inconsistent findings. This systematic review and IPD network analysis aimed to estimate and compare the symptom network structures of residual depressive symptoms following CBT, ADM's, and their combination.
METHODS
PsycINFO, PsycArticles, and PubMed were systematically searched through October 2020 for studies that have assessed individuals with major depression at post-treatment receiving either CBT and/or ADM's (venlafaxine, escitalopram, mirtazapine). IPD was requested from eligible samples to estimate and compare residual symptom psychometric network models post-CBT and post-ADM's.
RESULTS
In total, 25 from 663 eligible samples, including 1,389 patients qualified for the IPD. Depressed mood and anhedonia were consistently central residual symptoms post-CBT and post-ADM's. For CBT, fatigue-related and anxiety symptoms were also central post-treatment. A significant difference in network structure across treatments (CBT vs. ADM) was observed for samples measuring depression severity using the MADRS. Specifically, stronger symptom occurrences were present amongst post-CBT (vs. ADM's) and amongst post-ADM's (vs. CBT). No significant difference in global strength was observed across treatments.
CONCLUSIONS
Core major depression symptoms remain central across treatments, strategies to target these symptoms should be considered. Anxiety and fatigue related complaints also remain central post-CBT. Efforts must be made amongst researchers, institutions, and journals to permit sharing of IPD. A protocol was prospectively registered on PROSPERO (CRD42020141663; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=141663).
PubMed: 35178002
DOI: 10.3389/fpsyt.2022.746678