Эффективность использования высоких доз антидепрессантов

Higher doses than those currently used might be modestly more effective, but come with higher risks of adverse effects.

Before writing medications off as ineffective or only partially effective, clinicians strive to optimize dosing. To better identify optimal doses for six selective serotonin reuptake inhibitors (SSRIs), investigators applied meta-analytic techniques to 40 studies involving 10,039 patients with major depression in placebo-controlled randomized trials who were treated with fluoxetine, (N=2386), fluvoxamine (N=910), paroxetine (N=3424), sertraline (N=865), citalopram (N=1349), or escitalopram (N=1105).

Focusing on efficacy and tolerability, investigators calculated number needed to treat (NNT) and number needed to harm (NNH). They used published dose ranges to convert SSRI doses to imipramine equivalents, with 100 mg of imipramine equivalent to:

Sertraline, 120 mg

Fluvoxamine, 100 mg

Paroxetine, 20 mg

Fluoxetine, 20 mg

Citalopram, 33.3 mg

Escitalopram, 16.7 mg

Statistical modelling adjusted for lag times of medication-effect onsets and for doses used in the trials (100–400 mg of imipramine equivalents). In dose-by-time interaction analyses, higher doses yielded greater therapeutic responses. Greatest efficacy was seen for 200–250-mg imipramine equivalents, compared with higher and lower ranges (NNTs: compared with placebo, 3; in lower-dose comparisons, 14–16). Compared with low doses, higher dose was associated with greater likelihood of dropout due to adverse effects (NNHs, 45–48), but all-cause dropouts were fewer at higher doses, presumably due to efficacy. Fluvoxamine, approved for depression in other countries but not by the FDA, was excluded in some analyses, which yielded similar overall results.

Comment

These findings generally support the use of higher dose ranges for several SSRIs for major depression that did not respond or only partially responded to SSRIs. Most clinicians treating obsessive-compulsive disorder and bulimia nervosa are already comfortably using these higher doses. However, distinctions among SSRIs are warranted; for example, the FDA has issued warnings about QTc interval prolongation with higher doses of citalopram.

 Optimal Doses for SSRIs in Treating Depression: Meta-Analytic Results

Микрофлора кишечника и депрессия

Abstract

Purpose of review With depressive disorders the leading source of disability globally, the identification of new targets for prevention and management is imperative. A rapidly emerging field of research suggests that the microbiome–gut–brain axis is of substantial relevance to mood and behaviour. Similarly, unhealthy diet has recently emerged as a significant correlate of and risk factor for depression. This review provides evidence for the gut microbiota as a key factor mediating the link between diet and depressive illness.

Recent findings The development of new technologies is affording a better understanding of how diet influences gut microbiota composition and activity and how this may, in turn, influence depressive illness. New interventions are also suggesting the possible utility of pre and probiotic formulations and fermented food in influencing mental health.

Summary Although in its early stages, the emerging field of research focused on the human microbiome suggests an important role for the gut microbiota in influencing brain development, behaviour and mood in humans. The recognition that the gut microbiota interacts bidirectionally with other environmental risk factors, such as diet and stress, suggests promise in the development of interventions targeting the gut microbiota for the prevention and treatment of common mental health disorders.

The Gut Microbiome and Diet in Psychiatry: Focus on Depression

Самидорфан и оланзапин

Topline results from a phase 2 study show that treatment with a novel oral antipsychotic was as effective as treatment with the antipsychotic olanzapine (multiple brands) with far less weight gain in patients with schizophrenia, the company developing the drug announced today.
The drug currently known as ALKS 3831, from Alkermes, combines samidorphan, a novel, potent mu-opioid antagonist, with olanzapine.

Positive Topline Phase 2 Results for Novel Schizophrenia Drug