Are anxious and mixed depression two sides of the same coin? Similarities and differences in patients with bipolar I, II and unipolar disorders.

BACKGROUND: Diagnostic criteria are not always useful to discriminate major depression with anxious distress (ADS-D; Diagnostic and Statistical Manual for Mental Disorders, version-5 [DSM-5] criteria) from mixed depression (Koukopoulos' criteria; KMX-D). So, clinicians need alternative tools to improve their diagnostic ability and to choose the most appropriate treatment. The aim of the present study is to identify socio-demographic and clinical features that discriminate patients with ADS-D from those with KMX-D. METHODS: Two hundred and forty-one consecutive outpatients with unipolar (51%) and bipolar (49%) disorder, fulfilling DSM-5 criteria for a current major depressive episode (MDE) and with a 21-item Hamilton Depression Rating Scale score ≥ 14, were recruited and treated in a prospective observational study. RESULTS: Ten percent of patients met criteria for KMX-D, 22% ADS-D, and 37% for both. Irritable premorbid temperament, mixed depression polarity at onset, mixed depression recurrence, and a high number of mania symptoms at intake were typical features of patients with KMX-D. Depressive polarity at onset, a low number of mania symptoms at intake, and generalized anxiety disorder comorbidity were typical features of patients with ADS-D. Multinomial logistic regression confirmed that higher rate of irritable temperament and higher Young Mania Rating Scale total score differentiated patients with KMX-D from patients with pure MDE. CONCLUSION: Our findings suggest some clinical features that could help differentiate between ADS-D and KMX-D in patients meeting both conditions and to select the appropriate treatment. However, the small sample size may have limited the power to detect differences between the groups. Further research is needed to confirm the results of present study.

Which patients with bipolar depression receive antidepressant augmentation? Results from an observational multicenter study.

BACKGROUND: To identify demographic and clinical characteristics of bipolar depressed patients who require antidepressant (AD) augmentation, and to evaluate the short- and long-term effectiveness and safety of this therapeutic strategy. METHODS: One hundred twenty-two bipolar depressed patients were consecutively recruited, 71.7% of them received mood stabilizers (MS)/second-generation antipsychotics (SGA) with AD-augmentation and 28.3% did not. Patients were evaluated at baseline, and after 12 weeks and 15 months of treatment. RESULTS: The AD-augmentation was significantly higher in patients with bipolar II compared with bipolar I diagnosis. Patients with MS/SGA + AD had often a seasonal pattern, depressive polarity onset, depressive index episode with anxious features, a low number of previous psychotic and (hypo)manic episodes and of switch. They had a low irritable premorbid temperament, a low risk of suicide attempts, and a low number of manic symptoms at baseline. After 12 weeks of treatment, 82% of patients receiving ADs improved, 58% responded and 51% remitted, 3.8% had suicidal thoughts or projects, 6.1% had (hypo)manic switch, and 4.1% needed hospitalization. During the following 12 months, 92% of them remitted from index episode, 25.5% did not relapse, and 11% needed hospitalization. Although at the start advantaged, patients with AD-augmentation, compared with those without AD-augmentation, did not significantly differ on any outcome as well on adverse events in the short- and long-term treatment. CONCLUSION: Our findings indicate that ADs, combined with MS and/or SGA, are short and long term effective and safe in a specific subgroup for bipolar depressed patients.

Is short-term antidepressant treatment effective and safe in bipolar depression? Results from an observational multicenter study.

OBJECTIVES: To investigate the short-term effectiveness and the short-term and long-term safety of acute antidepressant (AD) treatment of bipolar depression in a naturalistic setting. METHODS: Patients with bipolar (n = 86) or unipolar (n = 111) depression were consecutively recruited and treated with AD (combined with mood stabilizer [MS] and/or second-generation antipsychotics in bipolar depression). Exclusion criteria were mixed depression, high mood instability, previous predominantly mixed depression (both bipolar and unipolar depression), rapid cycling course and previous switch AD-emerging (bipolar depression). RESULTS: After 12 weeks of treatment, no difference was found in remission, response and improvement rates between bipolar and unipolar depression. Concerning short-term safety, switching and suicidality did not differ significantly between the two groups, and no suicide attempt was observed. Concerning long-term safety, patients with bipolar depression had a significant reduction of depressive and total recurrences during the year of follow-up, compared to the year before entering the study, without significant changes in (hypo)mania and mixed depression recurrences, and suicide rates. CONCLUSIONS: Acute AD treatment of bipolar depression is effective in the short-term and safe in the short- and long-term, when administered in combination with MSs and/or second-generation antipsychotics, with a low risk of switch, mixed depression and cycle acceleration.

Lithium, valproate, and carbamazepine prescribing patterns for long-term treatment of bipolar I and II disorders: A prospective study.

OBJECTIVE: This study aims to describe the prescription patterns of the mood stabilizers most commonly used for the treatment of bipolar I and II disorders (lithium, valproate, and carbamazepine) and to analyze the treatment outcomes. METHODS: Two hundred and thirty-four outpatients with bipolar disorders receiving prophylactic treatment with lithium, valproate, carbamazepine, or their combination were followed up for at least 18 months in two Italian psychiatric centers specialized in mood disorders. RESULTS: The combination of lithium and valproate or carbamazepine was the most common prophylactic treatment (54.3%), followed by valproate or carbamazepine (24%) and lithium monotherapy (22%). Polytherapy was prescribed mainly to patients with bipolar I disorder, a high number of previous episodes and lifetime psychotic symptoms, whereas valproate or carbamazepine monotherapy was prescribed to patients with anxiety comorbidity. The annual frequency of recurrences decreased significantly after entering the study in the overall sample, and the reduction was significantly higher in patients on lithium plus valproate or carbamazepine compared with the valproate or carbamazepine group, but not with the lithium monotherapy group. The number of mixed recurrences during the follow-up was significantly higher in patients on lithium plus valproate or carbamazepine. CONCLUSIONS: Our findings may help clinicians to personalize long-term treatment to prevent relapses of bipolar disorder according to clinical presentation.

Predictors of recurrence during long-term treatment of bipolar I and II disorders. A 4 year prospective naturalistic study.

BACKGROUND: Despite the large number of treatments available for bipolar disorder (BD), more than one half of patients have a recurrence within 2 years, and over 90% experience at least one additional affective episode during their lifetime. METHODS: The aim of this study was to test the impact of a number of demographic and clinical features on the risk to recurrence in a real- word representative sample of 266 outpatients with BD-I or II treated in a naturalistic setting during a 4-years-follow-up period. RESULTS: We found that the number of episodes per year after study entry, compared to the number of episodes per year before study entry,significantly decreased and that about one third of patients had no recurrences during the observation period. The length of follow-up and the number of previous episodes, mainly depressive, predicted the risk of recurrence, while female gender, higher age at intake, and a higher frequency of past mixed episodes predicted a higher frequency of recurrences. LIMITATIONS: The study had some limitations to consider: i.e. the risk of poor reliability of information on the previous course of illness or the naturalistic treatment during the follow-up. CONCLUSIONS: Our study suggests that (a) an evidence-based long-term treatment, with regular follow-up visits could improve the course of disease and prognosis; (b) clinicians should carefully consider the presence of a high number of mixed episodes, to provide more targeted treatment strategies; (c) an appropriate use of antidepressants in selected patients did not worsen the course of illness.