Vanteemar S. Sreeraj

A Critical Appraisal of Long Acting Injectable Antipsychotics: Translating Research to Clinics

Long acting injections (LAI) are an effective alternative mode of administration of antipsychotics, less commonly used in clinical practice. Gap in knowledge base is an important source of attitudinal bias. Current article is focused on reviewing the literature for the principles underlying the choice, initiation, maintenance, switch and termination of an LAI; historical, pharmacological and clinical factors implicating the rationale of using LAI against oral agents and older against newer LAIs. Evidences available in clinical and basic psychopharmacological researches are critically appraised, highlighting the lacunae in our understanding. It is endeavored to open the window for the studies to be carried forward in the future answering critical questions which could lay a stronger base for clinical utility of different LAIs. Thus, this article tries to acquaint clinicians with the translatable knowledge imparted from the research and riposte queries for the researchers to explore in relation to LAI.

Efficacy of fronto-temporal transcranial direct current stimulation for refractory auditory verbal hallucinations in schizophrenia: A randomized, double-blind, sham-controlled study

Persistent auditory verbal hallucinations (AVH) that are refractory to antipsychotic medications are reported in about 20-30% of schizophrenia patients. Transcranial Direct Current Stimulation (tDCS), a non-invasive and safe neuromodulatory technique, has attracted significant interest as an add-on treatment for refractory AVH in schizophrenia. Studies examining the efficacy of tDCS for refractory AVH in schizophrenia have reported inconsistent findings. In this study, using a randomized, double-blind, sham-controlled design (RCT), we sought to examine the effect of add-on tDCS [anode corresponding to left dorsolateral prefrontal cortex and cathode to left temporo-parietal junction; 2-mA, twice-daily sessions for 5-days] to treat refractory AVH in schizophrenia patients (N=25); following this RCT phase, patients that had <30% reduction in AVH severity were offered an open-label extension (OLE) active stimulation to evaluate the effect of cross-over to verum tDCS. In the RCT phase, repeated measures ANOVA with tDCS type [verum (N=12) vs. sham (N=13)] as between subjects factor demonstrated a significant tDCS-type X time-point interaction [F=21.5, p<0.001, partial-η2=0.48] with significantly greater reduction of AVH score in verum tDCS group as compared to sham group. In the OLE phase, sham-to-verum crossed over patients (N=13) showed significantly greater reduction in AVH severity than their corresponding change during RCT phase (t=2.9; p=0.01). Together, these observations add further support to the beneficial effects of add-on tDCS to treat refractory AVH schizophrenia.

Donepezil for Compulsive Behavior in Degenerative Dementia: Case Series

Diagnosing and managing dementia, presenting with compulsions is challenging. Presented are three cases, a possible representative subset of the Donepezil responders. Selective degeneration of dorsolateral prefrontal cortex networking striatum leading to compulsions would be amenable to cholinergic modulation.

High-definition transcranial direct current simulation (HD-tDCS) for persistent auditory hallucinations in schizophrenia

Conventional transcranial Direct Current Stimulation (tDCS) has been reported to alleviate persistent auditory hallucinations (AH) in schizophrenia as an add-on intervention. High-Definition tDCS (HD-tDCS), an optimized form of tDCS, has the potential for more focalized neuromodulation. In this study, add-on HD-tDCS (5 days twice daily session with 2-mA cathodal current on left temporo-parietal junction) using 4 × 1 ring montage significantly reduced persistent AH (t = 3.6;p < 0.01) in schizophrenia patients (N = 19). Add-on HD-tDCS has promising potential to treat persisting AH in schizophrenia. This needs further systematic research.

Gene polymorphisms and response to transcranial direct current stimulation for auditory verbal hallucinations in schizophrenia

Abstract Objective Recent observations demonstrate a significant ameliorative effect of add-on transcranial direct current stimulation (tDCS) on auditory verbal hallucinations (AVHs) in schizophrenia. Of the many SNPs, NRG1 rs35753505 and catechol-o-methyl transferase (COMT) rs4680 polymorphisms have shown to have a strong association with neuroplasticity effect in schizophrenia. Methods Schizophrenia patients (n=32) with treatment resistant auditory hallucinations were administered with an add-on tDCS. The COMT (rs4680) and NRG1 (rs35753505) genotypes were determined. The COMT genotypes were categorised into Val group (GG; n=15) and Met group (GG/AG; n=17) and NRG1 genotypes were categorised into AA group (n=12) and AG/GG group (n=20). Results The reduction in auditory hallucination sub-scale score was significantly affected by COMT-GG genotype [Time×COMT interaction: F(1,28)=10.55, p=0.003, ɳ2=0.27]. Further, COMT-GG effect was epistatically influenced by the co-occurrence of NRG1-AA genotype [Time×COMT×NRG1 interaction: F(1,28)=8.09, p=0.008, ɳ2=0.22]. Irrespective of genotype, females showed better tDCS response than males [Time×Sex interaction: F(1,21)=4.67, p=0.04, ɳ2=0.18]. Conclusion COMT-GG and NRG1-AA genotypes aid the tDCS-induced improvement in AVHs in schizophrenia patients. Our preliminary observations need replication and further systematic research to understand the neuroplastic gene determinants that modulate the effect of tDCS.

Feasibility of online neuromodulation using transcranial alternating current stimulation in schizophrenia

Abnormalities in resting and event-related brain oscillations are known to be associated with cognitive deficits in schizophrenia. Transcranial alternating current stimulation (tACS) modulates these rhythms across the neuronal circuits and could have a potential therapeutic role in psychiatric disorders. In this report, we describe, for the first time, application of online tACS in a schizophrenia patient with working memory deficits. This case report supports the feasibility and potential utility of online tACS in schizophrenia, which needs further systematic research.

Auditory false perception in schizophrenia: Development and validation of auditory signal detection task

Auditory hallucinations constitute an important symptom component in 70-80% of schizophrenia patients. These hallucinations are proposed to occur due to an imbalance between perceptual expectation and external input, resulting in attachment of meaning to abstract noises; signal detection theory has been proposed to explain these phenomena. In this study, we describe the development of an auditory signal detection task using a carefully chosen set of English words that could be tested successfully in schizophrenia patients coming from varying linguistic, cultural and social backgrounds. Schizophrenia patients with significant auditory hallucinations (N=15) and healthy controls (N=15) performed the auditory signal detection task wherein they were instructed to differentiate between a 5-s burst of plain white noise and voiced-noise. The analysis showed that false alarms (p=0.02), discriminability index (p=0.001) and decision bias (p=0.004) were significantly different between the two groups. There was a significant negative correlation between false alarm rate and decision bias. These findings extend further support for impaired perceptual expectation system in schizophrenia patients.