Impact of sedative and appetite-increasing properties on the apparent antidepressant efficacy of mirtazapine, selective serotonin reuptake inhibitors and amitriptyline: an item-based, patient-level meta-analysis.

Background: In an influential network meta-analysis, the tricyclic antidepressant (TCA) amitriptyline was found to be the most efficacious of 21 antidepressants, hence outranking selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs). The alpha/5HT///H antagonist mirtazapine was ranked as the second most effective and appeared at least as effective as the SSRIs and SNRIs that followed next. Since the most common effect parameter in depression trials-the sum score of the Hamilton Depression Rating Scale (HDRS-17-sum)-includes three items measuring sleep and two measuring appetite and weight, this outcome could be the result of amitriptyline and mirtazapine being more sedative and orexigenic.

Anxiolytic-like effects of acute serotonin-releasing agents in zebrafish models of anxiety: experimental study and systematic review.

Though commonly used to model affective disorders, zebrafish display notable differences in terms of the structure and function of the brain serotonin system, including responses to pharmacological interventions, as compared to mammals. For example, elevation of brain serotonin following acute administration of serotonin reuptake inhibitors (SRIs) generally has anxiogenic effects, both in the clinical situation and in rodent models of anxiety, but previous research has indicated the opposite in zebrafish. However, several issues remain unresolved.

[Psychedelic psychiatry].

In the last 20 years there has been an increased interest in research on psychedelic compounds for treatment of psychiatric conditions such as depression, anxiety and substance use disorders. Despite existing treatments being efficacious for many patients, this is not the case for up to a third of the patients with depression. Additionally, treatments are often long and associated with side effects.

Initial severity of the Positive and Negative Syndrome Scale (PANSS)-30, its main subscales plus the PANSS-6, and the relationship to subsequent improvement and trial dropout: a pooled participant-level analysis of 18 placebo-controlled risperidone and paliperidone trials.

Greater initial severity on the 30-item Positive and Negative Syndrome Scale (PANSS-30) correlates positively with antipsychotic-placebo separation and trial dropout, but it is unknown whether these associations are present also on PANSS-derived subscales. We assessed the relationship between initial severity and antipsychotic-placebo separation as measured by PANSS-30 and four PANSS symptom subscales: the positive (PANSS-POS), negative (PANSS-NEG), general (PANSS-GEN) and 6-item (PANSS-6) subscales, using patient-level data from 18 placebo-controlled risperidone and paliperidone trials. Analysis of covariance in the intention-to-treat population (last-observation-carried-forward) was used to assess antipsychotic-placebo separation and trial dropout.

The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective.

The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed and is still not entirely understood. This study aimed to determine the direct and indirect effects of SSRIs relative to a placebo control condition on clinical symptoms of depression. We included data of 8262 adult patients with major depression participating in 28 industry-sponsored US Food and Drug Administration (FDA) registered trials on the efficacy of SSRIs.

Performance of 3 Sets of Criteria for Potentially Inappropriate Prescribing in Older People to Identify Inadequate Drug Treatment.

Importance: Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) are used in research to reflect the quality of drug treatment in older people and have been suggested for inclusion in core outcome sets for evaluation of interventions for improved prescribing. Their validation so far, however, is primarily restricted to expert opinion-based processes.

Objective: To evaluate the performance of 3 explicit PIM/PPO criteria sets as diagnostic tools to identify inadequate drug treatment in older patients.

The efficacy of transcranial magnetic stimulation (TMS) for negative symptoms in schizophrenia: a systematic review and meta-analysis.

Several trials have shown preliminary evidence for the efficacy of transcranial magnetic stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia.

Impact of chosen cutoff on response rate differences between selective serotonin reuptake inhibitors and placebo.

Response defined as a 50% reduction in the sum score of the Hamilton Depression Rating Scale (HDRS-17-sum) is often used to assess the efficacy of antidepressants. Critics have, however, argued that dichotomising ratings with a cutoff close to the median may lead to scores clustering on either side, the result being inflation of miniscule drug-placebo differences. Using pooled patient-level data sets from trials of three selective serotonin reuptake inhibitors (SSRIs) (citalopram, paroxetine and sertraline) (n = 7909), and from similar trials of duloxetine (n = 3478), we thus assessed the impact of different cutoffs on response rates.

Antipsychotic-placebo separation on the PANSS-6 subscale as compared to the PANSS-30: a pooled participant-level analysis.

In order for measurement-based care to be implemented, there is a need for brief rating instruments that can be administered in a short amount of time, but that are still sufficiently informative. Here, we assessed the drug-placebo sensitivity of the six-item subscale (PANSS-6) of the 30-item Positive and Negative Syndrome Scale (PANSS-30) using a large collection of patient-level data (n = 6685) from randomized controlled trials of risperidone and paliperidone. When analyzing the data by study, we found no material difference in mean effect sizes (ES) between the two measures (PANSS-30 ES = 0.

Determining maximal achievable effect sizes of antidepressant therapies in placebo-controlled trials.

Objective: Antidepressants outperform placebo with an effect size of around 0.30. It has been suggested that effect sizes as high as 0.

Do side effects of antidepressants impact efficacy estimates based on the Hamilton Depression Rating Scale? A pooled patient-level analysis.

The Hamilton Depression Rating Scale (HDRS-17) measures symptoms that may overlap with common antidepressant side effects (e.g., sexual dysfunction), thus making it possible that side effects of antidepressant treatment are erroneously rated as symptoms of depression, and vice versa.

Low SSRI dosing in clinical practice-a register-based longitudinal study.

Objective: Since several recent meta-analyses report a dose-response relationship for the antidepressant effect of the selective serotonin reuptake inhibitors (SSRIs), we investigated how these drugs are dosed in clinical practice.

Methods: Through linkage of nation- or region-wide registers, we describe SSRI doses in 50,365 individuals residing in Region Västra Götaland, Sweden, with an incident diagnosis of depression and initiating SSRI treatment between 2007 and 2016. The primary question was to elucidate to what extent these individuals had been prescribed a daily dose that according to recent meta-analyses is required to elicit the maximum antidepressant effect, that is >20 mg citalopram, >10 mg escitalopram, >10 mg fluoxetine, >10 mg paroxetine or >50 mg sertraline.

The efficacy of repetitive transcranial magnetic stimulation (rTMS) for bipolar depression: A systematic review and meta-analysis.

Background: Repetitive transcranial magnetic stimulation (rTMS) has established efficacy in the treatment of unipolar depression and a growing evidence base in the treatment of bipolar depression. The objective of this study was to provide an estimate of the efficacy of rTMS in bipolar depression as an up to date synthesis of this literature is lacking.

Methods: We conducted a systematic review of the sham-controlled randomized controlled trial (RCT) literature examining rTMS in bipolar depression.

Pre-diagnostic and post-diagnostic psychopharmacological treatment of 16 288 patients with bipolar disorder.

Objectives: The aim was to describe the pre-diagnostic and post-diagnostic psychopharmacological treatment of bipolar disorder over the past two decades.

Methods: We identified all 16 288 individuals aged ≥ 18 years, who received their first diagnosis of bipolar disorder at a psychiatric hospital in Denmark between 1997 and 2014. For each calendar year, we calculated the proportion of patients (with index date in the respective calendar years) who were prescribed psychopharmacological treatment in the 2 years preceding and the 2 years following the date of the first diagnosis of bipolar disorder.