Shyam Sundar Arumugham

Augmentation strategies in obsessive–compulsive disorder

Around 40–60% of patients with obsessive–compulsive disorder do not show adequate response to selective serotonin reuptake inhibitors (SSRIs). Augmentation strategies are recommended in people who show partial response to SSRI treatment or poor response to multiple SSRIs. In this article, the authors review the evidence for augmentation strategies. The available evidence is predominantly based on small-scale, randomized controlled trials, open-label trials and case series. Antipsychotic augmentation, especially risperidone, haloperidol, aripiprazole and cognitive-behavior therapy have shown the best evidence. Ondansetron, memantine, riluzole, clomipramine, mirtazapine and repetitive transcranial magnetic stimulation over supplementary motor area show some preliminary evidence. Ablative neurosurgery or deep brain stimulation may be tried in carefully selected treatment refractory patients.

Genetic substrates of psychosis in patients with Parkinson's disease: A critical review

Patients with Parkinsons disease (PD) may develop several non-motor symptoms such as psychosis, depression, cognitive impairment, autonomic disturbances and sleep disturbances. Psychosis is one of the common non-motor symptoms, which commonly manifests as visual hallucinations and minor hallucinations such as sense of passage and presence. Though long-term dopaminergic therapy, longer duration of PD and cognitive impairment have been described as risk factors for emergence of psychosis in PD, predicting psychosis in PD remains challenging. Multiple studies have explored the genetic basis of psychosis in PD by studying polymorphisms of several genes. Most of the studies have focused on apolipoprotein E polymorphism followed by polymorphisms in cholecystokinin (CCK) system, dopamine receptors and transporters, HOMER gene, serotonin, catechol-o-methyltransferase, angiotensin converting enzyme and tau. Other than the studies on polymorphisms of CCK, most of the studies have reported conflicting results regarding association with psychosis in PD. Three out of four studies on CCK polymorphism have reported significant association of -45C>T polymorphism with the presence of hallucinations. The discrepancies in the results across the studies reviewed are possibly due to racial differences as well as differences in the patient characteristics. This review critically analyzes the published studies on genetic polymorphisms in patients with PD and psychosis.

Pattern of cognitive impairment in patients with Parkinson's disease and psychosis: A critical review

Psychosis is one of the debilitating non-motor symptoms (NMS) of Parkinsons disease (PD). Cognitive impairment is considered to be a risk factor for emergence of psychosis in PD. Early detection of relevant cognitive impairment may serve as a predictor for development of psychosis, with implications for prevention and early intervention. However, the exact pattern of cognitive impairment associated with psychosis is not clear. In this article, we aim to critically review the literature on case-control studies in PD patients with and without psychosis in order to understand the pattern of cognitive impairment in those with psychosis. Majority of studies conducted till date have focused on executive and visuospatial functions. Despite some inconsistencies, most of the studies found significant impairment in these domains in PD patients with psychosis compared to those without psychosis. Studies assessing for other cognitive functions such as attention, language and memory in PD patients have also found worse performance in those with psychosis. Although there is enough evidence to suggest that PD patients with psychosis have poor cognitive functioning, it is unclear if these deficits are generalized or specific. The available evidence, which is primarily in the form of cross-sectional studies assessing for specific cognitive deficits, is not adequate to indicate a clear demarcating pattern of cognitive deficits, which differentiates PD patients with and without psychosis. Longitudinal studies with extensive cognitive assessment are warranted.

Adverse Effects of Electroconvulsive Therapy.

Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs.

Efficacy and safety of combining clozapine with electrical or magnetic brain stimulation in treatment-refractory schizophrenia

ABSTRACT Introduction: A substantial proportion (40-70%) of patients with treatment-resistant schizophrenia experience persistent symptoms despite an adequate clozapine trial. Brain stimulation techniques (BST) such as electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) have shown promise in medication-refractory schizophrenia. However, their co-administration with clozapine raises some safety concerns. Areas covered: We conducted a systematic literature search through Pubmed and cross-references for relevant publications evaluating the safety and efficacy of combining BST with clozapine. Expert commentary: Evidence from a randomized controlled trial and open-label trials suggest that ECT is an effective intervention in clozapine-refractory schizophrenia. There is limited evidence that the combination is safe. However, until sufficient data accumulate, it would be prudent to be vigilant against adverse effects related to lowered seizure threshold, cognitive impairment, and cardiovascular events. Both high frequency rTMS over the dorsolateral prefrontal cortex and low frequency rTMS over the temporoparietal cortex have been safely administered in patients receiving clozapine. However, rTMS efficacy in clozapine-refractory patients remains uncertain. The evidence for tDCS-clozapine combination is in the form of case reports and needs to be evaluated in controlled trials. Newer methods of brain stimulation and refinement of existing BSTs hold promise for the future.

Comparison of clinical characteristics of familial and sporadic obsessive-compulsive disorder.

BACKGROUND Obsessive-compulsive disorder (OCD) is a heterogeneous condition with evidence of familiality in a considerable proportion of patients. A classification into familial and sporadic forms has been proposed to explain the heterogeneity. The current study aims to compare the demographic, clinical and comorbidity patterns of patients with and without a family history of OCD in first-degree relatives. METHOD 802 consecutive patients who consulted a specialty OCD Clinic at a tertiary care psychiatric hospital in India were evaluated with the Mini-International Neuropsychiatric Interview, the Yale-Brown Obsessive-Compulsive Scale, and the Clinical Global Impression Scale. Family history was assessed by interviewing patients and at least one first-degree relative. RESULTS Family history of OCD was seen in 152 patients (19%). Family history was associated with juvenile onset (Χ(2)=19.472, p<0.001), obsessions of contamination (Χ(2)=6.658, p=0.01), hoarding (Χ(2)=4.062, p=0.032), need for symmetry (Χ(2)=3.95, p=0.047), washing compulsion (Χ(2)=7.923, p=0.005), ordering compulsions (Χ(2)=6.808, p=0.009), repeating compulsions (Χ(2)=4.950, p=0.026) and compulsions by proxy (Χ(2)=7.963, p=0.005). Family history was also associated with greater severity of OCD (t=-2.31, p=0.022) and compulsions (t=-3.09, p=0.002) and longer duration of illness at presentation (t=-2.93, p=0.004). CONCLUSION Our findings suggest that familial OCD may have distinctive clinical features. Studying familial forms of OCD may offer unique insight in to understanding the genetic basis of OCD.

Aripiprazole augmentation in highly treatment-resistant obsessive–compulsive disorder – experience from a specialty clinic in India

Abstract Objective: To study the effectiveness and tolerability of aripiprazole augmentation in patients with highly treatment-resistant obsessive–compulsive disorder (OCD) in a real-world scenario. Methods: We conducted a chart review of patients who were initiated on aripiprazole augmentation at a specialty OCD clinic in India between 2004 and 2014. Primary outcome measure was all-cause discontinuation. Results: 23 patients were eligible for analysis. Patients had not achieved symptom remission despite a mean of over 3 prior SRI trials. Aripiprazole was continued to be used in seven patients (30%) at the time of last follow-up. Thirteen patients (57%) discontinued the drug due to side effects, and three patients (13%) discontinued aripiprazole citing no improvement. Six patients (26%) were noted to have ≥25% reduction on the Yale-Brown Obsessive–Compulsive Scale. Conclusions: The study demonstrated, in a real-world setting, that aripiprazole may be a useful augmenting agent in a proportion of patients with highly treatment-resistant OCD. However, side effects may lead to premature discontinuation in many of them.

Effectiveness of Risperidone Augmentation in Obsessive-Compulsive Disorder: Experience From a Specialty Clinic in India.

Abstract Risperidone is the most widely used augmenting agent in the treatment of obsessive-compulsive disorder (OCD). However, a recent controlled study found risperidone to be no different from placebo, raising doubts about its effectiveness. In this context, we sought to examine the real-world effectiveness of risperidone from the large database of an OCD clinic in India. A total of 1314 consecutive patients who registered at the OCD clinic between 2004 and 2014 were evaluated with structured interviews and scales. Patients with OCD initiated on risperidone augmentation without concurrent cognitive behavior therapy and who were on stable and adequate doses of serotonin reuptake inhibitors for at least 12 preceding weeks were included for analysis. The primary outcome measure was all-cause discontinuation. Logistic regression was performed to identify the factors predicting improvement with risperidone augmentation. A total of 92 patients were eligible for analysis. Risperidone continued to be used in 23 patients (25%) at the time of last follow-up, and the remaining discontinued either because of ineffectiveness or intolerability. The fall in the Yale-Brown Obsessive-Compulsive Scale scores was significantly greater in patients who continued to take risperidone when compared with those who did not (41.6% vs 3.7%, t = 6.95, P < 0.001). A total of 22 patients (24%) were noted to have at least a 25% reduction on the Yale-Brown Obsessive-Compulsive Scale scores. On regression analysis, no predictors of improvement with risperidone augmentation could be identified. The study demonstrated, in a real-world setting, that risperidone may be a useful augmenting agent in a proportion of patients with partial/poor response to serotonin reuptake inhibitors.

Predictors of response to serotonin reuptake inhibitors in obsessive-compulsive disorder

ABSTRACT Introduction: 40–60% of patients with obsessive compulsive disorder (OCD) do not respond adequately to serotonin reuptake inhibitors (SRIs). It is important to identify predictors of response to help individualize treatment and identify refractory patients early in the course of treatment. Areas covered: We review the current literature on predictors of response to SRIs in adult patients with OCD including clinical features, neuropsychological profile, neuroimaging, genetics and other biological factors. We conducted a literature search in PUBMED database using the MeSH terms ‘Obsessive-Compulsive Disorder’, ‘drug therapy’, ‘treatment outcome’, ‘neuroimaging’, ‘genetics’ ‘cytokines’ and obtained 60 articles. Expert commentary: Poor-insight into obsessions, symmetry/hoarding and contamination/washing dimension and the presence of certain personality disorders are associated with poor response to SRIs. Orbitofrontal cortex, anterior cingulate cortex, caudate, putamen and thalamus volume changes in structural imaging studies and altered activity in the same regions in functional imaging studies were found predictive of poor response. However, there is inconsistency with regards to direction of change. Genes involving serotonergic and glutamatergic signalling pathways have emerged as predictors in recent studies. Studies with large sample size, standardised methodology and rigorous statistical analyses are required before predictors can be utilised in routine clinical practice.

Diminished modulation of motor cortical reactivity during context-based action observation in schizophrenia

BACKGROUND Deficient mirror neuron system (MNS)-activity is associated with social cognition deficits in schizophrenia. However, it is not known how socio-emotional contexts modulate the MNS-response. In a Transcranial Magnetic Stimulation (TMS)-experiment, we aimed to compare putative MNS-responses to action observation stimuli with and without a context, in patients with schizophrenia and healthy subjects. METHOD TMS-evoked motor cortical reactivity was measured by single and paired [short interval intracortical inhibition (SICI) and facilitation (ICF)] pulse-paradigms in schizophrenia patients (n = 39) and healthy subjects (n = 28) while they observed three experimental-blocks: a static image, a neutral hand action (NA) and a context-based hand action (CA). The degree of cortical reactivity facilitation with the two action observation blocks, relative to the static block provided indirect measures of premotor MNS-activity. A subset of patients (n = 31) also underwent comprehensive social cognition assessments. RESULTS RMANOVA demonstrated significantly higher cortical reactivity during the CA-block in both groups (all TMS-paradigms); albeit significantly less pronounced in patients (SICI and ICF paradigms). MNS-activity during the CA-block was significantly higher compared to that during the NA-block in both groups (all TMS-paradigms), but significantly less pronounced in patients (SICI and single-pulse paradigms). MNS-activity during the CA-block measured by the ICF paradigm was positively correlated with social cognition performance. CONCLUSION Providing a context to the action modulates MNS-activity. This modulation is diminished in schizophrenia patients, suggestive of a diminished sensorimotor associative learning process. This novel, ecologically valid paradigm to tap into the MNS may serve as a neuro-marker of social cognition performance in schizophrenia.