Behavioral Activation Contributed to the Total Reduction of Depression Symptoms in the Smartphone-based Cognitive Behavioral Therapy: A Secondary Analysis of a Randomized, Controlled Trial.

Objective: The contribution of components in cognitive behavior therapy (CBT) to the total reduction of depression symptoms has not been well elucidated, and previous studies couldn't exclude the human factors in the therapy. Design: This is a secondary analysis of a randomized, controlled trial comparing automated smartphone CBT without human factors plus antidepressant switch against antidepressant switch alone among patients with antidepressant-resistant depression. The present CBT consisted of self-monitoring, behavioral activation, and cognitive restructuring. We used linear regression to predict the overall pre- to post-symptom improvement based on improvement achieved by sessions teaching each cognitive or behavioral skill. The overall improvement was measured with the Beck Depression Inventory-II and the session-to-session improvement with K6. Results: Of the 164 participants originally enrolled in the study, 94 participants who completed all K6 evaluation were included in the primary analyses. The results indicated that K6 score reduction in the first half of behavioral activation significantly predicted BDI-II score reduction. The sensitivity analysis including 162 participants did not change the result. K6 score reductions after other CBT sessions did not significantly predict BDI-II score reduction. Conclusion: The behavioral activation seems to contribute to the total reduction of depressive symptoms even if human factors are excluded by using automated smartphone CBT.

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.

Predicting recurrence of depression using lifelog data: an explanatory feasibility study with a panel VAR approach.

BACKGROUND: Although depression has a high rate of recurrence, no prior studies have established a method that could identify the warning signs of its recurrence. METHODS: We collected digital data consisting of individual activity records such as location or mobility information (lifelog data) from 89 patients who were on maintenance therapy for depression for a year, using a smartphone application and a wearable device. We assessed depression and its recurrence using both the Kessler Psychological Distress Scale (K6) and the Patient Health Questionnaire-9. RESULTS: A panel vector autoregressive analysis indicated that long sleep time was a important risk factor for the recurrence of depression. Long sleep predicted the recurrence of depression after 3 weeks. CONCLUSIONS: The panel vector autoregressive approach can identify the warning signs of depression recurrence; however, the convenient sampling of the present cohort may limit the scope towards drawing a generalised conclusion.

Correction: Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/jmir.8602.].

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.

Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial.

BACKGROUND: In the treatment of major depression, antidepressants are effective but not curative. Cognitive behavioral therapy (CBT) is also effective, alone or in combination with pharmacotherapy, but accessibility is a problem. OBJECTIVE: The aim is to evaluate the effectiveness of a smartphone CBT app as adjunctive therapy among patients with antidepressant-resistant major depression. METHODS: A multisite, assessor-masked, parallel-group randomized controlled trial was conducted in 20 psychiatric clinics and hospitals in Japan. Participants were eligible if they had a primary diagnosis of major depression and were antidepressant-refractory after taking one or more antidepressants at an adequate dosage for four or more weeks. After a 1-week run-in in which participants started the medication switch and had access to the welcome session of the app, patients were randomized to medication switch alone or to medication switch plus smartphone CBT app via the centralized Web system. The smartphone app, called Kokoro-app ("kokoro" means "mind" in Japanese), included sessions on self-monitoring, behavioral activation, and cognitive restructuring presented by cartoon characters. The primary outcome was depression severity as assessed by masked telephone assessors with the Patient Health Questionnaire-9 (PHQ-9) at week 9. The secondary outcomes included the Beck Depression Inventory-II (BDI-II) and Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER). RESULTS: In the total sample (N=164), 81 participants were allocated to the smartphone CBT in addition to medication change and 83 to medication change alone. In the former group, all but one participant (80/81, 99%) completed at least half, and 71 (88%) completed at least six of eight sessions. In the intention-to-treat analysis, patients allocated the CBT app scored 2.48 points (95% CI 1.23-3.72, P<.001; standardized mean difference 0.40) lower on PHQ-9 than the control at week 9. The former group also scored 4.1 points (95% CI 1.5-6.6, P=.002) lower on BDI-II and 0.76 points (95% CI -0.05 to 1.58, P=.07) lower on FIBSER. In the per-protocol sample (comfortable with the smartphone app, still symptomatic, and adherent to medication with mild or less side effects after run-in), the intervention group (n=60) scored 1.72 points (95% CI 0.25-3.18, P=.02) lower on PHQ-9, 3.2 points (95% CI -0.01 to 6.3, P=.05) lower on BDI-II, and 0.75 points (95% CI 0.03-1.47, P=.04) lower on FIBSER than the control (n=57). The treatment benefits were maintained up to week 17. CONCLUSIONS: This is the first study to demonstrate the effectiveness of a smartphone CBT in the treatment of clinically diagnosed depression. Given the merits of the mobile mental health intervention, including accessibility, affordability, quality control, and effectiveness, it is clinically worthwhile to consider adjunctive use of a smartphone CBT app when treating patients with antidepressant-resistant depression. Research into its effectiveness in wider clinical contexts is warranted. TRIAL REGISTRATION: Japanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984 (Archived by WebCite at http://www.webcitation.org/6u6pxVwik).

Cognitive training for divergent thinking in schizophrenia: a pilot study.

Individuals with schizophrenia demonstrate deficits in divergent thinking. This ability is indispensable for generating creative solutions and navigating the complexities of social interactions. In a pilot study, seventeen stable schizophrenia outpatients were randomly assigned to a training program for divergent thinking or a control program on convergent thinking. After eight weeks of training, participants in the divergent thinking program had significantly greater improvements on measures of idea fluency, negative symptoms, and interpersonal relations than did participants receiving the control program. These preliminary results suggest that interventions for divergent thinking in schizophrenia may lead to improvements in patients' social functioning.

Subjective assessments of the quality of life, well-being and self-efficacy in patients with schizophrenia.

AIM: The present study examined three kinds of subjective assessment scales in the same patient group with schizophrenia to analyze the correlations among scores obtained in relation to the background data. METHOD: Thirty-six patients with schizophrenia were examined with the 26-item short form of the World Health Organization Quality of Life (WHO-QOL 26), Subjective Well-being under Neuroleptic drug treatment: Short Japanese version (SWNS) and Self-Efficacy for Community Life scale (SECL) for subjective assessment scales, five kinds of neurocognitive tests, Positive and Negative Syndrome Scale (PANSS) for clinical symptom, Social Functioning Scale (SFS), and Global Assessment of Functioning (GAF) scale for social functioning. RESULT: The scores for delusions (components of positive syndrome), anxiety and depression (components of general psychopathology) on the PANSS significantly correlated with QoL and subjective well-being scores. In contrast, the scores for components of negative syndrome were not correlated with the subjective assessment scores. Furthermore, none of the clinical symptom scores were correlated with the score in self-efficacy scale. The SFS and GAF scores were significantly correlated with the subjective assessment scores. There were significant correlations among the scores on the three subjective assessment scales. CONCLUSION: Each scale has different features and should be utilized depending upon the expected effect of treatment or the purpose of assessment. The treatments provided to patients must be directed at improving both psychological and social impairments, in order to enhance the social functioning and QoL of patients.

Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on risperidone metabolism in patients with schizophrenia.

OBJECTIVE: Risperidone is converted to 9-hydroxyrisperidone by CYP2D6. Two parameters were used to examine the influences of CYP2D6 polymorphism and of co-medication on risperidone metabolism: the risperidone:9-hydroxyrisperidone concentration ratio (R:9-OHR ratio) and the sum of the risperidone and 9-hydroxyrisperidone concentrations divided by the dose (C:D ratio). We evaluated the effect of the CYP2D6*10 allele, which is a prevalent mutant allele among East Asians. METHODS: Genotyping using the P450 microarray system was performed for 89 Japanese patients with schizophrenia receiving risperidone. The patients with CYP2D6*1/*1, *1/*2, or *2/*2 were classified as Group 1, those with one CYP2D6*10 allele (CYP2D6*1/*10 or *2/*10) were classified as Group 2, and those with two CYP2D6*10 alleles were classified as Group 3. The R:9-OHR and C:D ratios were analyzed using two-way ANOVAs with the CYP2D6 genotype and co-medication with CYP2D6-dependent drugs as independent variables. RESULTS: Both the "genotype" and the "co-medication" factors had significant impacts on the R:9-OHR ratio (p = 0.011, p < 0.001). The "genotype" factor also had a significant impact on the C:D ratio (p = 0.032). However, the "co-medication" factor did not have a significant impact on the C:D ratio (p = 0.129). CONCLUSIONS: The CYP2D6*10 polymorphism and the presence of co-medication exerted significant influences on the pharmacokinetics of risperidone.

Association between duration of untreated psychosis, premorbid functioning, and cognitive performance and the outcome of first-episode schizophrenia in Japanese patients: prospective study.

OBJECTIVE: The aim of the present study was to identify the relationship between duration of untreated psychosis (DUP), premorbid functioning, and cognitive dysfunction and the outcome of first-episode schizophrenia. METHOD: Thirty-four neuroleptic-naïve patients who consulted hospitals in Tokyo and who were treated by psychiatrists for the first time were evaluated with regard to DUP, premorbid functioning, psychiatric symptoms, and global functioning. The neuropsychological test battery consisted of the Letter Cancellation Test, Trail-Making Test, Digit Span and Verbal Fluency Test. One year later, 24 of the subjects were reassessed for psychiatric symptoms, global functioning, and social functioning, and the relationships between DUP, premorbid functioning, and cognitive performance and the outcome was investigated. RESULTS: Short DUP, good premorbid functioning, and good Letter Cancellation Test, Digit Span and Verbal Fluency Test scores were significantly associated with good outcome. CONCLUSIONS: The present results in a Japanese sample are consistent with previous international evidence that delay of initial treatment, premorbid functioning, and cognitive deficits are associated with outcome. A major limitation of the present study was the small size of the subject group. But because the subjects were relatively homogeneous and not influenced by psychoactive substances, the results reflect the essence of the disorder.

Relation between social functioning and neurocognitive test results using the Optional Thinking Test in schizophrenia.

The current study investigated the relationship between clinical evaluations of social functioning and neurocognitive test results, including various fluency tests for assessing divergent thinking, in patients with schizophrenia. The Optional Thinking Test (OTT) was used to measure the ability of individuals to conceive of alternatives. This test assesses alternative thinking, or the capacity to generate solutions to problems. The current study examined 36 schizophrenia patients and 25 normal subjects using the Mini-Mental State Examination (MMSE), the Rey Auditory Verbal Learning Test (RAVLT), the Letter Cancellation Test (LCT), the Letter and Category Fluency Tests, and the OTT for neurocognitive assessment, as well as the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF), the Social Functioning Scale (SFS), and the Life Assessment Scale for the Mentally Ill - Interpersonal Relations (LASMI-I) for clinical measures. The schizophrenia patients had significantly poorer performances on the MMSE, RAVLT, LCT (time), fluency tests, and OTT than the controls. In the OTT, the proportions of classified strategies were indistinguishable between the schizophrenia patients and the controls. Alternative thinking, as measured by the OTT, was correlated with verbal fluency and attention but was not correlated with the social functioning scores (GAF, SFS, LASMI-I), whereas the Means-Ends Problem-Solving was correlated with the GAF in schizophrenia. Patients with schizophrenia could conceive of the same categories of alternatives as healthy people, but could not conceive as many alternatives.