Most people with major depressive episodes meet the criteria for the anxious distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feelings of tension, restlessness, difficulty concentrating, and fear that something awful may happen. This cross-sectional study was aimed at identifying clinical correlates of AD in people with unipolar or bipolar depression.

Inpatients with a current major depressive episode were included. Data on socio-demographic and clinical variables were collected. The SCID-5 was used to diagnose depressive episodes and relevant specifiers. The Montgomery–Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to assess the severity of depressive and manic (mixed) symptoms, respectively. Multiple logistic regression analyses were carried out to identify clinical correlates of AD.

We included 206 people (mean age: 48.4 ± 18.6 yrs.; males: 38.8%) admitted for a major depressive episode (155 with major depressive disorder and 51 with bipolar disorder). Around two-thirds of the sample (N = 137; 66.5%) had AD. Multiple logistic regression models showed that AD was associated with mixed features, higher YMRS scores, psychotic features, and a diagnosis of major depressive disorder (p < 0.05).

Despite some limitations, including the cross-sectional design and the inpatient setting, our study shows that AD is likely to be associated with mixed and psychotic features, as well as with unipolar depression. The identification of these clinical domains may help clinicians to better contextualize AD in the context of major depressive episodes.

Obsessive phenomena, when present, are usually seen in the depressive phase of bipolar disorder.

The peculiar case with aggravation in ruminative and obsessive thinking with simultaneous hypomania may widen our understanding of the phenomenology of antidepressant induced hypomanic symptoms.

We present a case of ruminative hypomania induced by high dose venlafaxine. Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D) and Yale Brown Obsessive Compulsive Scale (YBOCS) were used for symptom ratings.

The patient was 30 years old and she had treatment history of depression for 3 months. She had two consecutive suicide attempts with drugs in the week before she was hospitalized for suicidal risk. She was using venlafaxine 300 mg/day and olanzapin 2,5 mg/day; continuous ruminative thinking about the past and imaginary sexual affairs with former friends were apparent with an unremitting pattern, leading to intense psychomotor agitation and suicide attempts. Irritable mood, and increased energy was observed with continuous ruminations. She was diagnosed with bipolar-II-disorder, with mixed features and anxious distress (YMRS:17, HAM-D:22, YBOCS:34). After discontinuing venlafaxine and starting anti-manic treatment with haloperidol 10 mg/day in the first week, both affective symptoms and ruminations were improved (YMRS:2, HAM-D:4, YBOCS:8). Aripiprazol 20 mg/day and quetiapine 100 mg/day which were given for continuation treatment were also effective for preserving full remission.

When prescribing high dose venlafaxine for treatment resistant depression, it should be remembered that this may induce hypomanic symptoms and prominent ruminative thinking which can be ameliorated with anti-manic treatment.

No significant relationships.

Mixed states in mood disorders present significant clinical and prognostic challenges. Although the DSM-5 has broadened diagnostic criteria for mixed states with the development of the ‘mixed features’ specifier and its application to unipolar depressive disorders, some mixed episodes might still be overlooked.

to evaluate the frequency and the factors associated with mixed depression according to the broader Koukopoulos criteria in a sample of patients with a major depressive episode

We included 99 consecutive patients presenting for a major depressive episode of bipolar (n=10) or unipolar major depressive (n=89) disorder at our outpatient clinic. Major depression was ascertained using SCID- IV criteria, and mixed features were determined using Koukopoulos’ diagnostic criteria

Mean age of the sample was 35.5 years [14-58]. Women accounted for 63.6% of patients. Mixed features were found in 19.5% (n=19) of the sample, 80% (n=8) among patients with bipolar disorders (BD) and 12.3% (n=11) among those with major depressive disorder (MDD). Individuals with mixed features had more substance abuse (p=0.005) and more suicide attempts (p=0.01). Individuals receiving antipsychotics had a lower risk of mixed features (p=0.000) while antidepressant treatment did not have any affect. A family history of BD, psychosis, suicide and substance abuse were found in these patients. Mixed features in depression were more frequent in patients with BD than in MDD.

Our study showed a high frequency of mixed features in depression, especially bipolar depression when Koukopoulos criteria are applied. Special attention should be given to these patients given the association with substance use and suicidality

No significant relationships.

Epidemiological, clinical, and treatment response characteristics of major depression with anxious distress (ADS) are quite similar to those of mixed depression, but no study investigated the symptom interplay of these conditions.

To analyze the correlations among symptom criteria for major depression with ADS and for mixed depression using a network analysis.

Two hundred and forty-one outpatients with major depression were consecutively recruited. DSM-5 criteria for major depression with ADS or with mixed features (MF) and Koukopoulos’ criteria for mixed depression (MXD) were assessed using a structured clinical interview.

A total of 58.9% of patients met DSM-5 criteria for major depression with ADS, 48.5% for MXD, and 2.5% for major depression with MF, so that the symptoms of this specifier were excluded from the network analysis. The most frequent symptoms were difficulty concentrating due to worries (57.7%), feeling keyed up or on edge (51%) (major depression with ADS), and psychic agitation or inner tension (51%) (MXD). Psychic agitation or inner tension had a central position in the network and bridged MXD to major depression with ADS through feeling keyed up or on edge.

Criteria for major depression with ADS and for MXD are partially overlapping, with psychic agitation or inner tension and feeling keyed up or on edge that feature in both conditions and are difficult to distinguish in clinical practice. The clarification of the relationship between these two psychopathological conditions could bring important implications for diagnosis, prognosis, and treatment of depressive episodes.

Mixed presentations, defined by simultaneous occurrence of depressive and manic symptoms, are difficult to treat. Antidepressants, although commonly used, have weak evidence of efficacy and may increase risk of mood destabilization. The aim of this pooled post hoc analysis was to evaluate the efficacy of cariprazine in the treatment of bipolar depression with or without concurrent manic symptoms.

Patients from 3 randomized, double-blind, placebo-controlled studies who met DSM-IV-TR or DSM-5 criteria for bipolar I disorder with a current major depressive episode were identified to have concurrent manic symptoms by baseline Young Mania Rating Scale total score ≥4. Efficacy was assessed in cariprazine 1.5 and 3 mg/day dose groups versus placebo; analyses included the least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score.

Of 1383 patients randomized to treatment, 808 (58.4%) had concurrent manic symptoms. For patients with manic symptoms, mean reduction in MADRS total score from baseline to week 6 was significantly greater for both cariprazine 1.5 and 3 mg/day compared with placebo, with least squares mean differences (LSMDs) versus placebo of −2.5 (p = .0033) and −2.9 (p = .0010), respectively; for patients without manic symptoms, the LSMD was significant for 1.5 mg/day (−3.3; p = .0008), but not for 3 mg/day (−1.9; p = .0562).

The results of this post hoc analysis suggest that cariprazine may be an appropriate treatment option for patients with bipolar I depression with or without manic symptoms, with higher doses potentially more effective in patients with manic symptoms.

Although bipolar disorder (BD) is a fundamentally cyclical illness, a divided model of BD that emphasizes polarity over cyclicity has dominated modern psychiatric diagnostic systems since their advent in the 1980s. However, there has been a gradual return to conceptualizations of BD which focus on longitudinal course in the research community due to emerging supportive data. Advances in longitudinal statistical methods promise to further progress the field.

The current study employed hidden Markov modeling to uncover empirically derived manic and depressive states from longitudinal data [i.e. Young Mania Rating Scale and Montgomery–Asberg Depression Rating Scale responses across five occasions from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study], estimate participants’ probabilities of transitioning between these states over time (n = 3918), and evaluate whether clinical variables (e.g. rapid cycling and substance dependence) predict participants’ state transitions (n = 3229).

Analyses identified three empirically derived mood states (‘euthymic,’ ‘depressed,’ and ‘mixed’). Relative to the euthymic and depressed states, the mixed state was less commonly experienced, more temporally unstable, and uniquely associated with rapid cycling, substance use, and psychosis. Individuals assigned to the mixed state at baseline were relatively less likely to be diagnosed with BD-II (v. BD-I), more likely to present with a mixed or (hypo)manic episode, and reported experiencing irritable and elevated mood more frequently.

The results from the current study represent an important step in defining, and characterizing the longitudinal course of, empirically derived mood states that can be used to form the foundation of objective, empirical attempts to define meaningful subtypes of affective illness defined by clinical course.

The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating patients with major depressive disorder (MDD) with mixed features who present with mild and moderate-to-severe levels of anxiety.

The data in this analysis were derived from a study of patients meeting the DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/day (n=109) or placebo (n=100). Anxiety severity was evaluated using the Hamilton Anxiety Rating Scale (HAM–A). To evaluate the effect of baseline anxiety on response to lurasidone, the following two anxiety groups were defined: mild anxiety (HAM–A≤14) and moderate-to-severe anxiety (HAM–A≥15). Change from baseline in MADRS total score was analyzed for each group using a mixed model for repeated measures.

Treatment with lurasidone was associated with a significant week 6 change versus placebo in MADRS total score for patients with both mild anxiety (–18.4 vs. –12.8, p<0.01, effect size [ES]=0.59) and moderate-to-severe anxiety (–22.0 vs. –13.0, p<0.001, ES=0.95). Treatment with lurasidone was associated with a significant week 6 change versus placebo in HAM–A total score for patients with both mild anxiety (–7.6 vs. –4.0, p<0.01, ES=0.62), and moderate-to-severe anxiety (–11.4 vs. –6.1, p<0.0001, ES=0.91).

In this post-hoc analysis of an MDD with mixed features and anxiety population, treatment with lurasidone was associated with significant improvement in both depressive and anxiety symptoms in subgroups with mild and moderate-to-severe levels of anxiety at baseline.

This post-hoc analysis assessed rates of symptomatic and functional remission, as well as recovery (combination of symptomatic and functional remission), in patients treated with lurasidone for major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features).

Patients with MDD plus two or three manic symptoms (defined as per the DSM–5 mixed-features specifier) were randomly assigned to flexible-dose lurasidone 20–60 mg/day (n=109) or placebo (n=100) for 6 weeks, followed by a 3-month open-label, flexible-dose extension study for U.S. sites only (n=48). Cross-sectional recovery was defined as the presence of both symptomatic remission (Montgomery–Åsberg Depression Rating Scale score ≤ 12) and functional remission (all Sheehan Disability Scale [SDS] domain scores ≤3) at week 6, and at both months 1 and 3 of the extension study (“sustained recovery”).

A significantly higher proportion of lurasidone-treated patients (31.3%) achieved recovery (assessed cross-sectionally) compared to placebo (12.2%, p=0.002) at week 6. The number of manic symptoms at baseline moderated the effect size for attaining cross-sectional recovery for lurasidone treatment (vs. placebo) (p=0.028). Sustained recovery rates were higher in patients initially treated with lurasidone (20.8%) versus placebo (12.5%).

In this post-hoc analysis of a placebo-controlled study with open-label extension that involved patients with MDD and mixed features, lurasidone was found to significantly improve the rate of recovery at 6 weeks (vs. placebo) that was sustained at month 3 of the extension study. The presence of two (as opposed to three) manic symptoms moderated recovery at the acute study endpoint.