Treatment-resistant depression (TRD) is an important clinical challenge and may present differently between age groups.

A total of 893 depressed patients recruited within the framework of the European research consortium “Group for the Studies of Resistant Depression” were assessed by generalized linear models regarding age effects (both as numerical and factorial predictors) on treatment outcome, number of lifetime depressive episodes, hospitalization time, and duration of the current episode. Effects of age as numerical predictor on the severity of common depressive symptoms, measured with Montgomery–Åsberg Depression Rating Scale (MADRS) for two-time points, were assessed by linear mixed models, respectively, for patients showing TRD and treatment response. A corrected p threshold of 0.001 was applied.

Overall symptom load reflected by MADRS (p < 0.0001) and lifetime hospitalization time (p < 0.0001) increased with age in TRD patients but not treatment responders. In TRD, higher age was predicting symptom severity of inner tension, reduced appetite, concentrations difficulties, and lassitude (all p ≤ 0.001). Regarding clinical significance, older TRD patients were more likely to report severe symptoms (item score > 4) for these items both before and after treatment (all p ≤ 0.001).

In this naturalistic sample of severely ill depressed patients, antidepressant treatment protocols were equally effective in addressing TRD in old age. However, specific symptoms such as sadness, appetite, and concentration showed an age-dependent presentation, impacting residual symptoms in severely affected TRD patients and calling for a precision approach by a better integration of age profiles in treatment recommendations.

Although numerous effective antidepressant (AD) strategies are available for the treatment of major depressive disorder (MDD), many patients do not achieve satisfactory treatment response.

The aims of the present European, cross-sectional, multicenter, naturalistic study were (1) to determine the proportion of patients suffering from primary MDD who received additional psychotherapy to their ongoing psychopharmacotherapy and (2) to identify the associated socio-demographic and clinical patterns.

Patients receiving both treatments were compared to those lacking concomitant additional psychotherapy that was manual-driven psychotherapy (MDP) in all cases.

While 68.8% of a total of 1279 MDD patients received exclusively psychopharmacotherapy, 31.2% underwent a psychopharmacotherapy-MDP combination. The latter patient population was rather younger, higher educated, employed, exhibited an earlier mean age of MDD onset, lower severity of current depressive symptoms with lower odds of suicidality and higher rates of melancholic features, and comorbid asthma and migraine, and was generally treated with lower daily doses of their first-line ADs. Whereas agomelatine was more commonly dispensed in these patients, selective serotonin reuptake inhibitors were more often prescribed in MDD patients lacking additional MDP. No significant between-group differences were detected in terms of treatment outcome.

The fact that the employment of additional MDP was not related to better treatment outcome in MDD represents our major and clinically most relevant finding. Generally, MDP was employed in a minority of our patients who experienced rather beneficial socio-demographic and clinical characteristics. This might reflect an inferior accessibility of these psychotherapeutic techniques for patients who are more severely ill and less socio-economically privileged.

References Bartova L, Fugger G, Dold M, Swoboda MMM, Zohar J, Mendlewicz J, Souery D, Montgomery S, Fabbri C, Serretti A, Kasper S. Combining psychopharmacotherapy and psychotherapy is not associated with better treatment outcome in major depressive disor

Wellbeing has a fundamental role in determining life expectancy and major depressive disorder (MDD) is one of the main modulating factors of wellbeing. This study evaluated the modulators of wellbeing in individuals with lifetime recurrent MDD (RMDD), single-episode MDD (SMDD) and no MDD in the UK Biobank.

Scores of happiness, meaningful life and satisfaction about functioning were condensed in a functioning-wellbeing score (FWS). We evaluated depression and anxiety characteristics, neuroticism-related traits, physical diseases, lifestyle and polygenic risk scores (PRSs) of psychiatric disorders. Other than individual predictors, we estimated the cumulative contribution to FWS of each group of predictors. We tested the indirect role of neuroticism on FWS through the modulation of depression manifestations using a mediation analysis.

We identified 47 966, 21 117 and 207 423 individuals with lifetime RMDD, SMDD and no MDD, respectively. Depression symptoms and personality showed the largest impact on FWS (variance explained ~20%), particularly self-harm, worthlessness feelings during the worst depression, chronic depression, loneliness and neuroticism. Personality played a stronger role in SMDD. Anxiety characteristics showed a higher effect in SMDD and no MDD groups. Neuroticism played indirect effects through specific depressive symptoms that modulated FWS. Physical diseases and lifestyle explained only 4–5% of FWS variance. The PRS of MDD showed the largest effect on FWS compared to other PRSs.

This was the first study to comprehensively evaluate the predictors of wellbeing in relation to the history of MDD. The identified variables are important to identify individuals at risk and promote wellbeing.

Sexual dysfunction (SD) is an important underestimated adverse effect of antidepressant drugs. Patients, in fact, if not directly questioned, tend to scarcely report them. The aim of the present meta-analysis was to quantify SD caused by antidepressants on the basis of studies where sexual functioning was purposely investigated through direct inquiry and specific questionnaires.

A literature search was conducted using MEDLINE, ISI Web of Knowledge, and references of selected articles. Selected studies performed on patients without previous SD were entered in the Cochrane Collaboration Review Manager (RevMan version 4.2). Our primary outcome measure was the rate of total treatment-emergent SD. Our secondary outcome measures were the rates of treatment-emergent desire, arousal, and orgasm dysfunction.

Our analyses indicated a significantly higher rate of total and phase-specific treatment-emergent SD compared with placebo for the following drugs in decreasing order of impact: sertraline, venlafaxine, citalopram, paroxetine, fluoxetine, imipramine, phenelzine, duloxetine, escitalopram, and fluvoxamine, with SD ranging from 25.8% to 80.3% of patients. No significant difference with placebo was found for the following antidepressants: agomelatine, amineptine, bupropion, moclobemide, mirtazapine, and nefazodone.

Treatment-emergent SD caused by antidepressants is a considerable issue with a large variation across compounds. Some assumptions, such as the inclusion of open-label studies or differences in scales used to assess SD, could reduce the significance of our findings. However, treatment-emergent SD is a frequent adverse effect that should be considered in clinical activity for the choice of the prescribed drug.

Mindfulness meditations (MM) are a group of meditation practices which are recently receiving growing attention. Following the increasing interest towards the neural correlates of meditation, particularly Mindfulness meditations (MM), the aim of the present work is to review current findings about the neural correlates of MM and compare such findings to those of further specific and non specific treatments.

A literature search was undertaken using MEDLINE, ISI web of knowledge, the Cochrane database and references of retrieved articles. Studies which focused on the functional neural correlates of MM, psychotherapy, pharmacotherapy and placebo published up to August 2009 were screened by the reviewers in order to be considered for the inclusion.

Main findings suggest that long term MM practice could allow a more flexible emotional regulation by engaging frontal cortical structures to dampen automatic amygdala activation when it is needed. A great overlap could exist between cerebral areas activated during MM, psychotherapy,pharmacotherapy and those activated by expectancy in placebo studies. However, while MM, psychotherapy and placebo could act through a top-down regulation, antidepressants could act through a bottom-up process.

MM could target specific brain areas related to emotions and emotional regulation. Consistent similarities could exist between MM and other interventions, particularly psychotherapy. Despite these promising findings, however, further research is needed in order to extend current findings, to more deeply compare MM to other treatments and to better investigate the neurochemical correlates of MM.

Mindfulness based Cognitive Therapy (MBCT) is a standardized meditation program which has been proposed as a therapeutic option for the prevention of relapses in patients suffering from major depression (MD). The aim of the present review and meta-analysis is to provide an estimate of the efficacy of MBCT for MD patients.

A literature search was undertaken using MEDLINE, ISI web of knowledge, the Cochrane database, Google scholar and references of retrieved articles. Controlled studies investigating the efficacy of MBCT for MD were entered in the Cochrane Collaboration Review Manager Software (RevMan version 5.0).

Reviewed data showed that MBCT in adjunct to usual care was significantly better than usual care alone for reducing MD relpases in patients with 3 or more past episodes of MD. MBCT plus gradual discontinuation of maintenance antidepressants was similar to continuation of antidepressants alone with respect to relapse prevention. The augmentation of MBCT could be useful for patients with current residual symptoms of depression as well.

Current studies showed preliminary evidence about the efficacy of MBCT for patients with 3 or more past episodes of depression and for currently depressed patients with residual symptoms. However, methodological shortcomings of reviewed studies including small sample size, frequent lack of replications and the absence of studies comparing MBCT to control groups designed to distinguish specific from non specific effects of meditation imply the necessity for further research.

The purpose of this study is to contribute to the knowledge of the clinical characteristics of the bipolar spectrum by examining factors associated to course of symptoms in BP patients. We evaluated differences between acutely depressed versus subthreshold mixed patients.

90 depressed patients (Group 1, HDRS: 18.2±4.6, YMRS: 1.4±2.9) and 41 patients presenting a mixed subthreshold symptomathology (Group 2, HDRS: 9.1±3.2, YMRS: 9.6±6.4) were included in the study. All patients underwent structured diagnostic interviews for axis I and axis II disorders (SCID-I, SCID-II) and have been submitted to psychometric assessment with Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Young Mania Rating Scale (YMRS), Global Assessment Scale (GAS), Social Adjustment Self-reported Scale (SASS), Quality of Life Scale (QoL), at baseline and repeated follow-up (1, 3, 6, 12 months). Personality dimensions were evaluated by Temperament and Character Inventory (TCI-R).

The most important result is the slight increase in depressive symptoms in subthreshold mixed patients after 3 months of treatment. These patients were more likely diagnosed as BP-I, were non-SUD patients and/or non-comorbid for axis II personality disorders and had a shorter duration of current episode prior intake. Measures of social and functional adjustment were not different in the two groups, though a slight trend for depressed patients to report a poorer quality of life. No difference in personality traits were observed among the two samples.

Our study confirms the importance of considering subthreshold symptoms in the evaluation and treatment of patients with Bipolar Disorder.

Increasing evidence suggests that symptoms of Attention Deficit Hyperactivity disorder (ADHD) could persist into adult life in a substantial proportion of cases. The aim of the present study is to investigate the impact of 1) adverse events, 2) personality traits and 3) genetic variants chosen on the basis of previous findings and 4) their possible interactions on adult ADHD severity in a sample of 110 Caucasian patients.

One hundred and ten individuals diagnosed with adult ADHD were evaluated for occurrence of adverse events in childhood and adulthood, and personality traits by the Temperament and Character Inventory (TCI). Common polymorphisms within a set of nine important candidate genes (SLC6A3, DBH, DRD4, DRD5, HTR2A, CHRNA7, BDNF, PRKG1 and TAAR9) were genotyped for each subject. Life events, personality traits and genetic variations were analyzed in relationship to severity of current symptoms, evaluated by the Brown Attention Deficit Disorder Scale (BADDS).

Genetic variations were not significantly associated with severity of ADHD symptoms and life stressors displayed only a minor effect as compared to personality traits. Indeed, symptoms’ severity was significantly correlated with the temperamental trait of Harm avoidance and the character trait of Self directedness.

The results of the present work are in line with previous evidence of a significant correlation between some personality traits and adult ADHD. However, several limitations such as the small sample size and the exclusion of patients with other severe comorbid psychiatric disorders could have influenced the significance of present findings.

Mindfulness meditations (MM) are an important group of meditative practices which have received growing attention. The aim of the present paper is to systematically review current evidence on the neurobiological changes and on the clinical benefits related to MM practice in psychiatric disorders, physical illnesses and in healthy subjects.

A literature search was undertaken using MEDLINE, ISI web of knowledge, the Cochrane collaboration database and references of retrieved articles. Controlled and cross-sectional studies with controls published in English up to November 2008 were included.

Electroencephalographic studies found a significant increase in alpha and theta activity during meditation. Neuro-imaging studies showed that MM practice activates the prefrontal cortex, the anterior cingulate cortex and that long term meditation practice is associated to an enhancement of cerebral areas related to attention. From a clinical point of view, Mindfulness based Stress Reduction showed efficacy for many psychiatric and physical conditions as well as for healthy subjects, Mindfulness based Cognitive Therapy was mainly efficacious in reducing relapses of depression in patients with 3 or more episodes, Zen meditation significantly reduced blood pressure and Vipassana meditation showed efficacy in reducing alcohol and substance abuse in prisoners. However, given the low quality designs of current studies it is difficult to establish whether clinical outcomes are due to specific or non specific effects of MM.

Despite encouraging findings, several limitations including small sample size, absence of randomization and inappropriate control groups affect the significance of current evidence and further better designed studies are required.

The aim of the present review and meta analysis is to evaluate the efficacy of new noradrenergic antidepressants (NAD) in the treatment of panic disorder (PD).

A literature search was conducted using MEDLINE, ISI web of knowledge and references of selected articles. Data from fourteen papers focusing on venlafaxine, mirtazapine and reboxetine were entered in RevMan 4.2.10 Our primary outcome measures were the rate of response, remission and side effects of NAD compared to placebo. Further analysis included the end-point mean number of panic attacks, the Panic and Anticipatory Anxiety Scale and the Hamilton Scale for Anxiety’ values.

We found a significant higher rate of response (OR = 3.2, 95% CI=2.61 to 3.92), remission (OR = 2.14, 95% CI=1.72 to 2.66) and side effects (OR = 1.41, 95% CI=1.11 to 1.78) for NAD compared to placebo, even though the studies were very heterogeneous. Analysis performed on the three drugs individually showed higher rate of response for patients treated with venlafaxine and mirtazapine whereas no statistical difference was found between reboxetine and placebo. The number of panic attacks and the values of all scales measuring the intensity of panic disorder at the end of trial were significantly lower for patients treated with a NAD.

Although the small sample size of some studies and limiting statistical assumptions could reduce the significativity of our findings, both venlafaxine and mirtazapine showed a significant efficacy for the treatment of PD which was comparable to selective serotonine reuptake inhibitors. Further studies on reboxetine are needed.

Serotonin and dopamine neurotransmitters have been extensively studied in association with temperamental and character traits.

In the present study we considered the association between 1A, 2A and 2C serotonin receptor and COMT SNPs and personality traits, as measured by the Temperament and Character Inventory (TCI), in a sample of suicide patients and controls. The SNPs considered were for 1A receptor rs1423691, rs878567 and rs6295, for 2A receptor rs643627, rs594242, rs6311 and rs6313, for 2C receptor rs547536, rs2192372, rs6318, rs2428707, rs4272555 and rs1801412, and for COMT rs737865, rs4680 and rs165599.

The sample was composed of three groups: two German samples, consisting of a healthy control group of 289 subjects (42.6% males, mean age: 45.2±14.9) and a psychiatric patient group of 111 suicide attempters (38.7% males, mean age: 39.2±13.6), and an Italian sub-sample, composed of 70 mood disorder patients (44.3% males, mean age: 42.9±14.4).

Controlling for sex, age and educational level, single markers and haplotypes were not or only marginally associated with personality dimensions.

Our study does not support 1A, 2A, 2C and COMT role on personality traits.

Few studies have been conducted looking at clinical features associated to treatment resistant depression (TRD) defined as failure to at least two consecutive antidepressant trials. The objective of this study was to identify clinical and demographic factors associated to TRD in a large sample of depressed patients who failed to reach response or remission after at least two consecutive adequate treatments.

A total of 702 patients with unipolar major depression were included in the analysis. 346 patients were considered as non resistant. The remaining 356 patients were considered as resistant with a HAM-D-17 score remaining ≥ 17 after 2 consecutive adequate trials. Cox regression models were used to examine the association between individual clinical variables and TRD.

Eleven variables were found to be associated with TRD. Anxiety comorbidity (p<0.001, OR=2.6), comorbid panic disorder (p<0.001, OR=2.6) and social phobia (p<0.008, OR=2.1), personality disorder (p<0.049, OR=1.7), suicidal risk (p<0.001, OR=2.2), severity (p<0.001, OR=1.7), melancholia (p<0.018, OR=1.5), a number of hospitalizations > 1 (p<0.003, OR=1.6), recurrent episodes (p<0.009, OR=1.5), early age of onset (p<0.009, OR=2.0) and non response to the first antidepressant received lifetime (p<0.019, OR=1.6).

Our findings provide a set of eleven relevant clinical variables associated to TRD which can be explored at the clinical level. The statistical model used in this analysis allowed for a hierarchy of these variables (based on the OR) showing that comorbid anxiety disorder is the most powerful clinical factor associated to TRD.