Eesha Sharma

Long-term outcome of obsessive-compulsive disorder in adults: a meta-analysis.

OBJECTIVE To study the long-term rate and predictors of remission in adults with obsessive-compulsive disorder (OCD), using meta-analysis. DATA SOURCES The MEDLINE database was searched to May 2013 using the search terms obsessive-compulsive disorder, prospective, outcome study, clinical course, remission, prognosis, follow-up, and long-term and limits for language (English), species (humans), and age (adults). This was supplemented by manual bibliographic cross-referencing. STUDY SELECTION English-language studies from peer-reviewed journals on adults with DSM-III-R, DSM-IV, DSM-IV-TR, ICD-9, or ICD-10 diagnosis of OCD followed up for ≥ 1 year and treated with serotonin reuptake inhibitors and/or cognitive-behavioral therapy that reported rate of remission (Yale-Brown Obsessive Compulsive Scale [YBOCS] score < 16 at longest follow-up) were included. DATA EXTRACTION Data were gathered as numbers/means/percentages/categories on sample size, study design, follow-up duration, age at assessment, illness duration, age at illness onset, gender, marital status, inpatient/outpatient status, family history, baseline YBOCS score, comorbidities, and remission. RESULTS Seventeen studies (pooled N = 1,265) fit the selection criteria and were used for the meta-analysis. The pooled sample had a mean follow-up duration 4.91 years and was predominantly male and outpatient and had onset of illness in the second decade, illness duration more than 10 years, and moderate-to-severe OCD. Pooled remission rate was 53% (95% CI, 42%-65%). Prospective studies showed higher pooled remission rate than retrospective studies (55% [95% CI, 45%-65%] vs 50% [95% CI, 27%-73%], P < .001). Indian studies showed higher pooled remission rate than others (71% [95% CI, 59%-83%] vs 48% [95% CI, 37%-59%], P < .001). Age at onset (t = -7.08, P = .019), illness duration (t = -8.13, P = .015), baseline YBOCS score (t = -6.81,P = .021), and male gender (t = -5.92, P = .027) had significant negative association with remission on meta-regression. CONCLUSION A high long-term remission rate found in this meta-analysis is contrary to generally held beliefs about poor outcome of individuals with OCD. Multicenter, prospective, long-term studies should systematically examine course and outcome in larger samples, emphasizing symptomatic and functional recovery.

Beneficial effects of add-on raloxifene in schizophrenia

The role of estrogens in schizophrenia has been proposed from the observation of schizophrenia occurring later and with symptom severity being lesser in women. Utility of estrogens in treatment of psychoses, though seen to be useful, comes with inherent risks of neoplasias, given its agonistic action on breast and endometrium. This risk can be overcome with use of selective estrogen receptor modulators, like raloxifene. Raloxifene has been used in schizophrenia, with improvement in symptoms and cognitive functions. We report the use of raloxifene as an adjunctive treatment, with risperidone, in treatment-resistant form of schizophrenia. The patient, a 29-year-old woman, over a 7-month follow-up period, showed significant improvement in socio-occupational functioning, with reduction in symptom severity.

Late-onset clozapine-induced agranulocytosis in a patient with comorbid multiple sclerosis

The risk of clozapine-induced agranulocytosis is highest in the initial 6 months after onset of treatment. There have been very few reports of neutropenia and agranulocytosis after this period. We report a unique case of delayed clozapine-induced agranulocytosis in a patient with preexisting multiple sclerosis (MS) which was treated with granulocyte colony-stimulating factor. Both MS and clozapine-induced agranulocytosis have an underlying autoimmune immune mechanism. This case highlights the need for frequent blood count monitoring on clozapine even after the initial 6 months of starting treatment especially in patients with a past history of drop in white blood cell counts as well as with a comorbid autoimmune disorder.

Antipsychotic induced metabolic changes & treatment response: A prospective study

BACKGROUND Metabolic side effects of antipsychotics contribute to morbidity and non-compliance in treatment of psychosis. Multiple studies suggest that metabolic side effects correlate with response to antipsychotic treatment. However, few studies have systematically looked at this. We conducted an exploratory, naturalistic, prospective, trans-diagnostic study to examine this association. METHODS 100 patients with psychosis, initiated on antipsychotic treatment alone, were assessed on Brief Psychiatric Rating Scale (BPRS), visual analog scale for appetite, anthropometric measurements (weight, waist circumference, body mass index), and fasting serum lipid and glucose profiles at baseline, 2-4 weeks (n=71) and 8-12 weeks (n=39). RESULTS Subjects who dropped out at first/second follow-ups did not differ from those who followed-up, in age, sex, illness duration and BPRS scores. On forward stepwise multiple linear regression analysis, early (2-4 weeks) increase in appetite and triglyceride levels (R(2)=0.257; p=0.003) together predicted 26% variance in treatment response (BPRS score reduction) at first follow-up. At second follow-up 16% of variance in treatment response was predicted by early (2-4 weeks) increase in triglyceride levels (R(2)=0.169; p=0.009). CONCLUSIONS Early appetite and triglyceride changes predicted antipsychotic treatment response. Involvement of dopaminergic, serotonergic and histaminergic neural pathways could explain the association between appetite and treatment response. Insulin signaling pathways have been implicated in lipid changes with antipsychotics. Study findings suggest metabolic side effects may be early predictors of antipsychotic response. These findings warrant further examination to elucidate the interaction between metabolic pathways and psychotic illnesses, and possibly mechanism of action of antipsychotics beyond dopamine blockade.

Entorhinal cortex volume in antipsychotic-naïve schizophrenia

Background: Entorhinal cortex (ERC), a multimodal sensory relay station for the hippocampus, is critically involved in learning, emotion, and novelty detection. One of the pathogenetic mechanistic bases in schizophrenia is proposed to involve aberrant information processing in the ERC. Several studies have looked at cytoarchitectural and morphometric changes in the ERC, but results have been inconsistent possibly due to the potential confounding effects of antipsychotic treatment. Materials and Methods In this study, we have examined the entorhinal cortex volume in antipsychotic-naïve schizophrenia patients (n=40; M:F=22:18) in comparison with age, sex, and handedness, matched (as a group) with healthy subjects (n=42; M:F=25:17) using a valid method. 3-Tesla MR images with 1-mm sections were used and the data was analyzed using the SPSS software. Results: Female schizophrenia patients (1.25±0.22 mL) showed significant volume deficit in the right ERC in comparison with female healthy controls (1.45±0.34 mL) (F=4.9; P=0.03), after controlling for the potential confounding effects of intracranial volume. However, male patients did not differ from male controls. The left ERC volume did not differ between patients and controls. Conclusions: Consistent with the findings of a few earlier studies we found a reduction in the right ERC volume in patients. However, this was limited to women. Contextually, our study finding supports the role for ERC deficit in schizophrenia pathogenesis — perhaps mediated through aberrant novelty detection. Sex-differential observation of ERC volume deficit in schizophrenia needs further studies.

Successful treatment of co-morbid schizophrenia and multiple sclerosis

Multiple sclerosis (MS) has both neurological and psychiatric manifestations. Though depression, bipolar disorder and la belle indifference are commonly described, schizophrenia-like-psychosis is not widely reported with MS. Drug interactions and side effects make treatment, in such scenario, challenging. We, for the first time, report a patient with MS and paranoid schizophrenia successfully treated with concurrent use of clozapine and risperidone with interferon-beta-1a.

Association between antipsychotic-induced metabolic side-effects and clinical improvement: a review on the evidence for metabolic threshold: author's response.

We thank Dr. Sahoo for the interest in the topic and response to our paper titled ‘Association between antipsychotic-induced metabolic side-effects and clinical improvement: A review on the evidence for metabolic threshold’ (Sharma et al., 2013). Dr. Sahoo has reiterated some of the points already mentioned in the paper; there are exceptions to the metabolic threshold concept and in fact we have stated in the introduction of our paper that in the meta analysis by Leucht et al. (2013) ‘‘. . .exceptions like amisulpiride which has lesser propensity for weight gain but better efficacy’’. However we differ with Dr. Sahoo’s contention that haloperidol is ‘‘extremely’’ efficacious as the meta-analysis by Leucht et al. suggested standardized mean difference of 0.45 for haloperidol less than olanzapine and risperidone (Leucht et al., 2013). Moreover, the concept of metabolic threshold is not specific to weight gain and the absence of weight gain with a drug does not automatically preclude the occurrence of other metabolic changes, which might be occurring without phenotypic manifestation of weight gain. As suggested by Dr. Sahoo leptin increase is seen with both clozapine and conventional antipsychotics which actually further strengthens our hypothesis and lends credence to the view that leptin may actually be involved in the mechanistic pathway of antipsychotics. We also would like to clarify that we did not suggest clozapine’s superior efficacy to be due to higher increase in leptin. We agree that the evidence for leptin and insulin changes following antipsychotic treatment are preliminary and we have stated the same in our paper. As stated in the paper, we would like to point out that at this stage we only ‘‘speculate’’ the association with improvement in psychosis and further studies are needed. We thank Dr. Sahoo for reiterating our stand that confounding factors

Obsessive Compulsive Disorder Masquerading as Psychosis

Obsessive compulsive disorder (OCD) is commonly regarded as a disorder with good insight. However, it has now been recognized that insight varies in these patients. Pathological beliefs seem to lie on a continuum of insight, with full insight at one end and delusion at the other. This can indeed pose a considerable challenge, especially in a scenario where the phenomenon is difficult to discern. We report a case of OCD, which was initially diagnosed as psychosis.

Gender differences in obsessive-compulsive disorder: Findings from a multicentric study from India

Obsessive-compulsive disorder (OCD) is phenotypically heterogeneous. Gender is an important factor mediating this heterogeneity. We examined gender differences in a large sample (n = 945) of OCD patients under a multi-centric study in India. Cross-sectional assessments were done on consecutive adult (>18 years) treatment-seeking patients with a DSM-5 diagnosis of OCD. Subjects were assessed on Structured Clinical Interview for DSM-5-Research Version for comorbid psychiatric illnesses, Yale Brown Obsessive Compulsive Scale for OCD phenomenology and symptom severity, Brown Assessment of Beliefs Scale for insight, Becks Depression Inventory for severity of depressive symptoms, and the Obsessive Beliefs Questionnaire. On multivariate backward Wald logistic regression analysis, males (59.7%) had more years of education, had a higher rate of checking compulsions and comorbid substance use disorders. Women were more likely to be married, more commonly reported precipitating factors, had a higher rate of hoarding compulsions and comorbid agoraphobia. Findings from this large study validate gender as an important mediator of phenotypic heterogeneity in OCD. The mechanistic basis for these differences might involve complex interactions between biological, cultural and environmental factors.