Clinical Research Directory

Effectiveness of Exercise Alone and tDCS+Exercise on Cognitive Function Improvement in Patients With Treatment Resistant Schizophrenia

Cognitive impairment is a major determinant of disability in schizophrenia. Aerobic exercise improves global cognition in schizophrenia, particularly working memory and attention/vigilance. Transcranial direct current stimulation (tDCS) targeting frontal regions has shown promise for cognitive deficits, including working memory improvements in some studies. This randomized 2×2 factorial trial will test the independent and combined effects of supervised aerobic exercise and prefrontal tDCS on cognition in treatment resistant schizophrenia, measured using the MATRICS Consensus Cognitive Battery (MCCB).

Τhe Combination of Pharmacotherapy With RECOVERYTRSGR and RECOVERYTRSBDGR.

The effectiveness and efficacy of the combination of pharmacotherapy with the two new recovery-oriented programs, RECOVERYTRSGR for patients with treatment- resistant schizophrenia and RECOVERYTRSBDGR for patients with treatment- resistant bipolar disorder.

Magnetic Seizure Therapy for Schizophrenia - Trial

This trial aims to assess the clinical effects and tolerability of Magnetic Seizure Therapy (MST) as an alternative to electroconvulsive therapy (ECT) for Treatment Resistant Schizophrenia (RS).

Maintenance ElectroConvulsive Therapy in Clozapine RESISTant Schizophrenia - the MECT-RESIST Trial

Schizophrenia is one of the most severe and costliest mental disorders in terms of human suffering and societal expenditure. About 15-30% of patients do not respond to all known antipsychotics, including clozapine, the current gold-standard in these cases. Hence, a recent Cochrane review stated that the quality of the existing studies is too poor to recommend any intervention in addition to clozapine and that new, randomized controlled trials independent from the pharmaceutical industry need to be performed to substantially improve patient care. Although electroconvulsive therapy (ECT) was initially used to treat schizophrenia, it is nowadays by far underused in the therapy of schizophrenia in many countries. ECT is well known to be highly effective in clozapine-treatment-resistant schizophrenia (CRS), and synergistic effects of clozapine and ECT have been demonstrated. However, relapse rates after successful courses of ECT are still very high, and evidence for maintenance ECT (mECT) in CRS is scarce at best. In a multi-center trial the investigators aim to examine the effectiveness of mECT in treatment-resistant patients with schizophrenia who improved after a course of routine ECT. If mECT will lead to a later timepoint of relapse and/or to a higher proportion of relapse-free patients compared to those undergoing treatment as usual, this trial would have an enormous impact on therapeutic strategies for "treatment-resistant" patients and would induce a profound change of current treatment guidelines, where ECT still ranks at the level of ultima ratio, despite accumulating evidence suggesting otherwise.

Reduction of Auditory-Verbal Hallucinations in Schizophrenia Through Cortical Neuromodulation

Approximately 1% of the general population will be affected by schizophrenia over the course of their lives, with life expectancy being reduced by 20 years on average and quality of life being severely diminished in affected individuals. One third of patients suffering from schizophrenia will evolve towards a resistant form of the disease, amongst which many will suffer from auditory-verbal hallucinations (AVH) that current therapeutic approaches struggle to alleviate. Previous work from our team has demonstrated the possibility of robustly inferring the periods of occurrence of AVH from fMRI data, paving the way for the development of a closed-loop neuromodulation system comprised of an electrode array positioned in Broca's area, which would detect AVH in real time, and effector electrodes which would stimulate the temporo-parietal cortex to interrupt them. The aim of this project is to assess the feasibility of this system. To do so, we will first test the ability of transcranial magnetic stimulation of the "continuous theta burst" (cTBS) type, applied at the time of AVH onset, to reduce their duration and intensity, and assess whether this is associated with therapeutic response to the current gold standard rTMS protocol for AVH reduction through neuroplasticity induction. Demonstrating the feasibility of acute suppression of AVH by cortical neurostimulation is an essential element in the feasibility of a closed-loop reactive neuromodulation system. The research project comprises two phases: -Phase 1: randomized controlled clinical trial (1 weekly session per patient over 12 weeks: 6 active stimulation sessions and 6 sham sessions) evaluating the phasic effects of rTMS on AVHs as they appear during the sessions. Phase 2: open-label study offering patients a routine rTMS protocol which has demonstrated its effects on AVH (10 TMS sessions over one workweek - twice daily with 1-hour intervals, MULTIMODHAL study, NCT01373866).

Effect of Atenolol Versus Ivabradine on HRV in TRS Patients on Clozapine With Tachycardia: A Randomised Control Trial.

Clozapine is the only drug approved for Treatment Resistant Schizophrenia. However, it has been associated with many adverse drug reactions including agranulocytosis, myocarditis, sialorrhea, constipation, orthostasis, tachycardia. There are many factors that have impacted the use of clozapine in TRS patients including physician hesitation, patient denial, stopping of drug due to Adverse drug reactions. Although Tachycardia should not be the reason to stop clozapine, but data shows that it leads to discontinuation of drugs in significant patient population. If patient on clozapine develops tachycardia; first orthostasis, myocarditis and systemic infection should be ruled out. Tachycardia traditionally have been treated with B1 adrenergic blockers such as Atenolol. But the problem with beta blocker medications is that significant proportion develops hypotension. Recently developed Ivabradine slows heart rate via I(f) current, and is not associated with much cardiac adverse effects. Recent Clinical trials have been carried out to show its effects on Clozapine associated tachycardia which shows promising results. Some studies suggest using Ivabradine in patient population that have contraindication for beta blockers. Although both of these drugs are used widely in clinical practice, but as Ivabradine is relatively new drug there have been no head-to-head comparison with Atenolol. A recent meta-analysis tried to compare treatment efficacy in these patients, but found no studies that met their inclusion criteria. This current study attempts to make such comparison and guide further research.