The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients

Background

A reciprocal relationship between diabetes risk and depression has been reported. There are few studies investigating glucose–insulin homeostasis before and after short-term antidepressant treatment in drug-naïve major depressive disorder (MDD) patients.

Methods

This study included 104 healthy controls and 50 drug-naïve MDD patients diagnosed according to the DSM-IV criteria. These MDD patients were randomly assigned to receive fluoxetine or venlafaxine for six weeks. Depressive symptoms, body mass index, fasting plasma levels of glucose and insulin were measured.

Results

Compared to the healthy controls, the fasting plasma insulin and the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) was significantly lower in the MDD patients before antidepressant treatment (7.7±4.8 μIU/mL vs. 5.1±4.2 μIU/mL, p=0.006; 114.2±72.3% vs. 74.8±52.0%, p=0.005, respectively). However, these indices were not correlated with depression severity. After 6 weeks of fluoxetine or venlafaxine treatment, the level of HOMA-β borderline significantly increased (108.1±75.5%, p=0.059).

Limitations

The study was limited by the follow-up duration and lack of a placebo group.

Conclusions

Antidepressants might affect insulin secretion independently of the therapeutic effects on MDD. Further studies are needed to investigate the long-term effects of antidepressants on insulin regulation in MDD patients.     

The utilization of psychopharmacological treatment and medication adherence among Medicaid enrolled children and adolescents with bipolar depression

Background

To examine the psychotropic medication utilization and compare adherence to treatment regimens in pediatric bipolar depression patients.

Methods

2003–2007 MAX data from four geographically diverse states were used. According to the regimen received by the patients (6–18 years) in the first month after the index bipolar depression diagnosis, patients were categorized into six mutually exclusive groups. The month to month change of treatment regimen in each group was then assessed during the 6 month post-index bipolar depression diagnosis. Adherence to each regimen was measured as continuation of the initial regimen, switch to a new regimen, augmentation with medication from a different therapeutic category, and discontinuation of all pharmacotherapies. Repeated measure analysis was conducted to compare the trend of each adherence measure across the study groups.

Results

Of the 5,460 subjects identified, 15.39% received antipsychotic monotherapy, 9.43% received mood stabilizer monotherapy, 5.77% received antidepressant monotherapy, 26.48% received mood stabilizer–antipsychotic polytherapy, 22.51% received antidepressant polytherapy, and 19.89% received antipsychotic–mood stabilizer–antidepressant polytherapy. At the end of the follow-up period, over 50% of the 1st month polytherapy users and less than 50% of the monotherapy users were continuing their initial regimen. Repeated measure analysis using antipsychotic monotherapy as the reference group suggested differences in trend slopes (p<0.05).

Limitations

In absence of structured clinical evaluation, bipolar disorder diagnoses cannot be ascertained in this study.

Conclusions

Bipolar depression patients were predominantly treated with combinations of psychotropic drugs. Potentially questionable practice, such as antidepressant monotherapy was used only in a small fraction of patients. Combination regimens had better adherence as compared to monotherapies.     

Predictors of relapse in patients with major depressive disorder in a 52-week,fixed dose,double blind,randomized trial of selegiline transdermal system (STS)

Objective

We investigated patient and disease characteristics predictive of relapse of MDD during a 52-week placebo controlled trial of selegiline transdermal system (STS) to identify patient characteristics relevant for STS treatment.

Method

After 10 weeks of open-label stabilization with STS, 322 remitted patients with MDD were randomized to 52-weeks of double-blind treatment with STS (6 mg/24 h) or placebo (PLB). Relapse was defined as Hamilton Depression Rating Scale (HAMD-17) score of ≥14 and a CGI-S score of ≥3 with at least 2-point increase from the beginning of the double blind phase on 2 consecutive visits. Cox's proportional hazards regression was used to examine the effect of potential predictors (age, sex, age at onset of first MDD, early response pattern, number of previous antidepressant trials, severity of index episode, number of previous episodes, melancholic features, atypical features and anxious feature) on outcome. Exploratory analyses examined additional clinical variables (medical history, other psychiatric history, and individual items of HAM-D 28) on relapse.

Results

For all predictor variables analyzed, treatment Hazard Ratio (HR=0.48~0.54) was significantly in favor of STS (i.e., lower relapse risk than PLB). Age of onset was significantly predictive of relapse. Type, duration, and severity of depressive episodes, previous antidepressant trials, or demographic variables did not predict relapse. In additional exploratory analysis, eating disorder history and suicidal ideation were significant predictors of relapse after controlling for the effect of treatment in individual predictor analysis.

Conclusions

While age of onset, eating disorder history and suicidal ideation were significant predictors, the majority of clinical and demographic variables were not predictive of relapse. Given the post-hoc nature of analysis, the findings need confirmation from a prospective study. It appears that selegiline transdermal system was broadly effective in preventing relapse across different subtypes and symptoms clusters of MDD.     

Kétamine,psilocybine, et antidépresseurs d'action rapide : de nouvelles promesses pour la psychiatrie?

The hypothesis of monoaminergic deficiency has long dominated the conceptual framework for the development of new antidepressant strategies, but the limits of conventional antidepressant treatments targeting monoaminergic signaling have motivated the search for new antidepressant pathways. The success of ketamine in the management of depressive disorders has provoked a renewed interest in hallucinogenic substances such as psilocybin targeting the serotonergic signaling 5HT^2A and neurosteroid allosteric modulator of γ-aminobutyric acid (GABAA) receptors such as brexanolone. Unlike conventional treatments, these modulators of glutamatergic, serotonergic and GABAergic systems exert a rapid antidepressant effect ranging from 24 hours to a week. Apart from their clinical interest and the fantasized search for a “miracle” molecule that jointly meets the expectations of patients and clinicians, these new targets could lead to the identification of potential new biomarkers for the development of rapid-acting antidepressants and redefine therapeutic strategies in mood disorders.     

Interactive effects of systemic inflammation and life stressors on treatment response of depressive disorders

Inflammation is an important contributor in the pathophysiology of depression and recent evidence suggests that systemic inflammation and life stressors have interactive roles in depression onset. The aim of the present study was to investigate the individual and interactive effects of systemic inflammation and life stressors with short- and long-term treatment responses in outpatients with depressive disorders in a naturalistic one-year prospective design.Serum high-sensitivity C-reactive protein (hsCRP) levels were measured and number of stressful life events (SLEs) during the last 3 months were ascertained from 1094 patients at baseline. These patients received initial antidepressant monotherapy, then, for patients with an insufficient response or uncomfortable side effects, next treatment with alternative strategies were administered at every 3 weeks in the acute treatment phase (3, 6, 9, and 12 weeks) and at every 3 months in the continuation treatment phase (6, 9, and 12 months). 12-week and 12-month remission was estimated, defined as a Hamilton Depression Rating Scale score of ≤ 7.In multivariable logistic regression analyses, individual effects were found only between higher baseline serum hsCRP levels (≥1.0 vs. < 1.0 mg/L) and 12-week non-remission. Significant interactive effects between higher hsCRP levels and higher number of SLEs (≥2 vs. < 2) on both 12-week and 12-month non-remission were observed.Combining serum hsCRP levels and number of SLEs might therefore be a useful predictor for short- and long-term treatment responses in patients with depressive disorders receiving pharmacotherapy.     

A naturalistic study on the criteria of choice of second-generation antidepressants: A comparison of venlafaxine and SSRIs in depressed inpatients

INTRODUCTION: The objective of this study was to compare, in a naturalistic setting, the efficacy and tolerability of selective serotonin reuptake inhibitors (paroxetine, sertraline, citalopram) and venlafaxine, in 120 depressed inpatients. This paper attempts to review which variables may influence a physician's choice of a specific antidepressant for a specific patient. METHOD: Patients were assessed using the Hamilton Psychiatric Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), the Clinical Global Impression (CGI) and the Symptoms Check List (SCL-90). The two groups under assessment were comparable in all socio-demographic characteristics. We used logistic regression analyses to identify variables that differentiate the two groups at baseline. This, in turn, would represent those variables with the potential to influence a physician's selection of an antidepressant. RESULTS: Venlafaxine patients reported significantly worse scores on MADRS at baseline, but any difference was no longer present at discharge. We found no significant variation in the efficacy of the antidepressants under study and there were no differences in the incidence and profiles of adverse events between the groups of patients. CONCLUSION: The degree of severity of the actual depressive picture appears to influence choice in favour of venlafaxine. However, it appears that the choice of SSRIs is more closely linked to patients who present a previous history of non-mood psychiatric symptoms.     

CLINICAL NOTE

Regional cerebral hypoperfusion is found in depression. Favorable therapeutic effect of antidepressant drugs usually leads to flow normalization. In our patients, cerebral blood flow correlated well with clinical findings. Clinical and scintigraphic improvement was observed after 3 weeks of therapy in all patients. On follow up after 6 months, psychiatric and scintigraphic normalization was noted in all but one patient who committed suicide shortly after the last examination. In the described case, a tendency toward baseline clinical and scintigraphic findings was observed after initial partial response to medication. Noncompliance to medication was suspected and confirmed after her suicide.