Effectiveness of cognitive remediation in depression:a meta-analysis

Background Preliminary evidence suggests beneficial effects of cognitive remediation in depression. An update of the current evidence is needed. The aim was to systematically assess the effectiveness of cognitive remediation in depression on three outcomes. Methods The meta-analysis was pre-registered on PROSPERO (CRD42019124316). PubMed, PsycINFO, Embase and Cochrane Library were searched on 2 February 2019 and 8 November 2020 for peer-reviewed published articles. We included randomized and non-randomized clinical trials comparing cognitive remediation to control conditions in adults with primary depression. Random-effects models were used to calculate Hedges' g, and moderators were assessed using mixed-effects subgroup analyses and meta-regression. Main outcome categories were post-treatment depressive symptomatology (DS), cognitive functioning (CF) and daily functioning (DF). Results We identified 5221 records and included 21 studies reporting on 24 comparisons, with 438 depressed patients receiving cognitive remediation and 540 patients in a control condition. We found a small effect on DS (g = 0.28, 95% CI 0.09-0.46, I2 40%), a medium effect on CF (g = 0.60, 95% CI 0.37-0.83, I2 44%) and a small effect on DF (g = 0.22, 95% CI 0.06-0.39, I2 3%). There were no significant effects at follow-up. Confounding bias analyses indicated possible overestimation of the DS and DF effects in the original studies. Conclusions Cognitive remediation in depression improves CF in the short term. The effects on DS and DF may have been overestimated. Baseline depressive symptom severity should be considered when administering cognitive remediation

Augmenting neurocognitive remediation therapy to Preventive Cognitive Therapy for partially remitted depressed patients:protocol of a pragmatic multicentre randomised controlled trial

Introduction Major depressive disorder (MDD) affects 163 million people globally every year. Individuals who experience subsyndromal depressive symptoms during remission (ie, partial remission of MDD) are especially at risk for a return to a depressive episode within an average of 4 months. Simultaneously, partial remission of MDD is associated with work and (psycho)social impairment and a lower quality of life. Brief psychological interventions such as preventive cognitive therapy (PCT) can reduce depressive symptoms or relapse for patients in partial remission, although achieving full remission with treatment is still a clinical challenge. Treatment might be more effective if cognitive functioning of patients is targeted as well since cognitive problems are the most persisting symptom in partial remission and predict poor treatment response and worse functioning. Studies show that cognitive functioning of patients with (remitted) MDD can be improved by online neurocognitive remediation therapy (oNCRT). Augmenting oNCRT to PCT might improve treatment effects for these patients by strengthening their cognitive functioning alongside a psychological intervention. Methods and analysis This study will examine the effectiveness of augmenting oNCRT to PCT in a pragmatic national multicentre superiority randomised controlled trial. We will include 115 adults partially remitted from MDD with subsyndromal depressive symptoms defined as a Hamilton Depression Rating Scale score between 8 and 15. Participants will be randomly allocated to PCT with oNCRT, or PCT only. Primary outcome measure is the effect on depressive symptomatology over 1 year. Secondary outcomes include time to relapse, cognitive functioning, quality of life and healthcare costs. This first dual approach study of augmenting oNCRT to PCT might facilitate full remission in partially remitted individuals as well as prevent relapse over time. Ethics and dissemination Ethical approval was obtained by Academic Medical Center, Amsterdam. Outcomes will be made publicly available

Brain tumor location influences the onset of acute psychiatric adverse events of levetiracetam therapy: an observational study.

To explore possible correlations among brain lesion location, development of psychiatric symptoms and the use of antiepileptic drugs (AEDs) in a population of patients with brain tumor and epilepsy. The medical records of 283 patients with various types of brain tumor (161 M/122 F, mean age 64.9 years) were analysed retrospectively. Patients with grade III and IV glioma, previous history of epileptic seizures and/or psychiatric disorders were excluded. Psychiatric symptoms occurring after initiation of AED therapy were considered as treatment emergent psychiatric adverse events (TE-PAEs) if they fulfilled the following conditions: (1) onset within 4 weeks after the beginning of AED therapy; (2) disappearance on drug discontinuation; (3) absence of any other identified possible concurrent cause. The possible influence of the following variables were analysed: (a) AED drug and dose; (b) location and neuroradiologic features of the tumor, (c) location and type of EEG epileptic abnormalities, (d) tumor excision already or not yet performed; (e) initiation or not of radiotherapy. TE-PAEs occurred in 27 of the 175 AED-treated patients (15.4%). Multivariate analysis showed a significant association of TE-PAEs occurrence with location of the tumor in the frontal lobe (Odds ratio: 5.56; 95% confidence interval 1.95-15.82; p value: 0.005) and treatment with levetiracetam (Odds ratio: 3.61; 95% confidence interval 1.48-8.2; p value: 0.001). Drug-unrelated acute psychiatric symptoms were observed in 4 of the 108 AED-untreated patients (3.7%) and in 7 of the 175 AED-treated patients (4%). The results of the present study suggest that an AED alternative to levetiracetam should be chosen to treat epileptic seizures in patients with a brain tumor located in the frontal lobe to minimize the possible onset of TE-PAEs

The Treatment of Hallucinations in Schizophrenia Spectrum Disorders

This article reviews the treatment of hallucinations in schizophrenia. The first treatment option for hallucinations in schizophrenia is antipsychotic medication, which can induce a rapid decrease in severity. Only 8% of first-episode patients still experience mild to moderate hallucinations after continuing medication for 1 year. Olanzapine, amisulpride, ziprasidone, and quetiapine are equally effective against hallucinations, but haloperidol may be slightly inferior. If the drug of first choice provides inadequate improvement, it is probably best to switch medication after 2-4 weeks of treatment. Clozapine is the drug of choice for patients who are resistant to 2 antipsychotic agents. Blood levels should be above 350-450 mu g/ml for maximal effect. For relapse prevention, medication should be continued in the same dose. Depot medication should be considered for all patients because nonadherence is high. Cognitive-behavioral therapy (CBT) can be applied as an augmentation to antipsychotic medication. The success of CBT depends on the reduction of catastrophic appraisals, thereby reducing the concurrent anxiety and distress. CBT aims at reducing the emotional distress associated with auditory hallucinations and develops new coping strategies. Transcranial magnetic stimulation (TMS) is capable of reducing the frequency and severity of auditory hallucinations. Several meta-analyses found significantly better symptom reduction for low-frequency repetitive TMS as compared with placebo. Consequently, TMS currently has the status of a potentially useful treatment method for auditory hallucinations, but only in combination with state of the art antipsychotic treatment. Electroconvulsive therapy (ECT) is considered a last resort for treatment-resistant psychosis. Although several studies showed clinical improvement, a specific reduction in hallucination severity has never been demonstrated

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

BACKGROUND: Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. DISCUSSION: A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. SUMMARY: A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons

Effectiveness of cognitive remediation in depression: a meta-analysis

BACKGROUND: Preliminary evidence suggests beneficial effects of cognitive remediation in depression. An update of the current evidence is needed. The aim was to systematically assess the effectiveness of cognitive remediation in depression on three outcomes. METHODS: The meta-analysis was pre-registered on PROSPERO (CRD42019124316). PubMed, PsycINFO, Embase and Cochrane Library were searched on 2 February 2019 and 8 November 2020 for peer-reviewed published articles. We included randomized and non-randomized clinical trials comparing cognitive remediation to control conditions in adults with primary depression. Random-effects models were used to calculate Hedges' g, and moderators were assessed using mixed-effects subgroup analyses and meta-regression. Main outcome categories were post-treatment depressive symptomatology (DS), cognitive functioning (CF) and daily functioning (DF). RESULTS: We identified 5221 records and included 21 studies reporting on 24 comparisons, with 438 depressed patients receiving cognitive remediation and 540 patients in a control condition. We found a small effect on DS (g = 0.28, 95% CI 0.09-0.46, I2 40%), a medium effect on CF (g = 0.60, 95% CI 0.37-0.83, I2 44%) and a small effect on DF (g = 0.22, 95% CI 0.06-0.39, I2 3%). There were no significant effects at follow-up. Confounding bias analyses indicated possible overestimation of the DS and DF effects in the original studies. CONCLUSIONS: Cognitive remediation in depression improves CF in the short term. The effects on DS and DF may have been overestimated. Baseline depressive symptom severity should be considered when administering cognitive remediation