Whose depression deteriorates during acute phase antidepressant treatment?

BACKGROUND: Few studies have investigated the proportion of patients with depression who experience worsening of depression symptoms during adequate antidepressant treatment. The current study aimed to investigate the proportion and predictors of worsening depression during antidepressant treatment in a multi-center randomized trial involving patients with major depression. METHODS: We defined the deterioration of depression using depression symptom severity evaluated by total Patient Health Questionnaire (PHQ-9) score increases from week 0 to week 9 during acute phase antidepressant treatment. Patients' baseline demographic and clinical data, change in PHQ-9 scores from week 0 to week 3, and side effects at week 3 were evaluated as potential predictors of subsequent deterioration of depression. RESULTS: Of 1,647 patients, 99 (6.0%) exhibited deterioration of depression, and this proportion was smaller when reliable change index criteria were applied. Logistic regression analysis revealed that the following factors were significantly associated with deterioration of depression: younger age at onset of first episode of major depressive disorder, current older age, and greater increase in PHQ-9 scores between week 0 and week 3. LIMITATIONS: The time of the primary endpoint might not have been sufficiently long. The present study did not include a placebo arm, and potentially relevant predictors might not have been comprehensively investigated. CONCLUSIONS: A small proportion of patients may experience deterioration of depression during acute phase antidepressant treatment. Age at onset at first depressive episode, current age, and early negative response to antidepressants may be useful predictors of subsequent worsening of depression.

Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUN☺D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial.

BACKGROUND: For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished. METHODS: This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates. RESULTS: Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), - 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects. CONCLUSIONS: In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01109693 . Registered on 23 April 2010.

A Validity and Reliability Study of the Japanese Version of the Geriatric Depression Scale 15 (GDS-15-J).

OBJECTIVE: The 15-item Geriatric Depression Scale (GDS-15) is one of the most widely used screening instruments for depression among the elderly. The aim of this study was to examine the validity and reliability of the Japanese version of the GDS-15 (GDS-15-J) in comparison with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for depression. METHODS: The study participants were 128 elderly outpatients (age range, 55 to 92 years) categorized into two groups (76 non-depressive patients, 52 depressive patients) based on the DSM-IV-TR criteria for depression. RESULTS: Logistic regression analysis showed that regardless of age and sex, the GDS-15-J score could be used to screen patients for depression (p < .001). The validity of the GDS-15-J for depression assessed against DSM-IV-TR criteria was excellent based on receiver operating characteristic analysis (optimal cutoff point: 6/7; sensitivity: .98; specificity: .86). The recommended optimal cutoff score when screening for depression is 6/7. To evaluate the constructive validity of the GDS-15-J, factor analysis was performed. Three factors were extracted. Cronbach's alpha reliability coefficient was .83 to the GDS-15-J scale, which indicated a high degree of internal consistency. CONCLUSION: The GDS-15-J is a clinically applicable screening instrument for depression. CLINICAL IMPLICATIONS: In this study this version of the GDS-15-J displayed excellent psychometric properties using a 6/7 cut off. Analyses suggest some items that might be removed in future studies of an abbreviated scale.

Acute psychosis during the postictal period in a patient with idiopathic generalized epilepsy: postictal psychosis or aggravation of schizophrenia? A case report and review of the literature.

Postictal psychoses are common comorbid conditions of temporal lobe epilepsy and are reported to be characterized by affective changes. However, postictal psychoses are rare among patients with idiopathic generalized epilepsy, and the causal relationship between postictal psychoses and idiopathic generalized epilepsy is unknown. Here, we report the case of a man who had idiopathic generalized epilepsy and experienced 4 episodes of schizophrenia-like interictal psychosis before the age of 41 years. At the age of 56 years, he experienced a generalized tonic-clonic seizure for the first time in 15 years and developed psychotic symptoms on the next day. Notably, in addition to the schizophrenia-like symptoms, the patient experienced mania-like symptoms such as elated mood, grandiose delusions, agitation, and pressured speech during the last psychotic episode in the postictal period. It was suspected that postictal neuronal processes and a predisposition to endogenous psychosis both contributed to the psychopathology of this episode.

Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in aortic tissue with Takayasu's arteritis.

To further investigate the immunological mechanisms involved, we analyzed the expression of costimulatory molecules in aortic tissue and their counterpart molecules on infiltrating cells of patients with Takayasu's arteritis. We also examined the expression of major histocompatibility complex (MHC) class I chain-related (MIC) A in aortic tissue, which is known to be induced by external stress, and its counterpart NKG2D receptors on infiltrating cells. Among these costimulatory molecules, strong expression of 4-1BBL and Fas was induced in the aortic tissue, and most of the infiltrating cells expressed 4-1BB and FasL, suggesting these pathways play critical roles in T-cell-mediated vascular injury. We also found that MICA was strongly induced in the aortic tissue and that at least part of the infiltrating cells expressed NKG2D receptors. Some infiltrating cells - but not vascular smooth muscle cells - seemed to have undergone apoptosis. Our findings strongly suggest that 4-1BB/4-1BBL and Fas/FasL pathways play important roles in vascular injury in Takayasu's arteritis. We assume that gammadelta T cells infiltrated aortic tissue recognizing MICA, resulting in the induction of MHC antigens and costimulatory molecules, and then alphabeta T-cells infiltrated recognizing some auto-antigens presented by MHC antigens, leading to chronic inflammation.