Nandita Hazari

Combined use of clozapine and ECT: a review

Objective This paper aims to review the available evidence for the use of clozapine and electroconvulsive therapy (ECT) in combination. Methodology Electronic searches were carried out to identify reports describing the combined use of clozapine and ECT. Results Forty reports including 208 patients were identified. The majority of reports were in the form of case reports and case series, with few retrospective and open-label studies. The majority of patients were aged between 18 and 65 years and diagnosed with schizophrenia or schizoaffective disorder. Most of the patients refractory to clozapine were started on ECT as an augmentation therapy; however, in some reports, both ECT and clozapine were started concurrently, and in few cases clozapine was started after ECT. In terms of effectiveness, 37.5–100% patients improved in short-term, and sustained long-term improvement (3 weeks to 24 months) was described in few studies. In terms of the side-effect profile, five patients each had delirium and tachycardia and only four patients were described to have prolonged seizures. Overall, the combination was considered effective and safe. Conclusion There is evidence for the effectiveness and safety of the clozapine–ECT combination and it should be used in patients with treatment-resistant schizophrenia who do not respond to clozapine.

Delay in initiation of clozapine: a retrospective study from a tertiary care hospital in North India.

This study aimed to assess the delay in initiation of clozapine, number of adequate antipsychotic trials prior to starting clozapine and practice of polypharmacy prior to starting clozapine. A retrospective study design was followed. Treatment records of 200 patients started on clozapine during the period of January 2006-June 2014 were reviewed. The mean delay in clozapine initiation was 1.93 (S.D. 1.82) years and median was 1.5 years. Mean of 3 (S.D. 1.18) adequate antipsychotic trials was given prior to considering clozapine and 27.5% patients had received polypharmacy prior to clozapine. Factors related to delay in starting of clozapine included higher age, longer duration of illness, age more than 20 years of age, polypharmacy, use of an adequate trial of typical antipsychotic medication, patients from urban locality and those with onset of illness prior to introduction of clozapine into Indian market. Findings of the present study suggest that there is a delay of 1.5-2 years in starting of clozapine and about one-fourth of patients receive polypharmacy prior to receiving clozapine. These finding suggests that there is a need to change the prescribing habits to reduce the delay in starting of clozapine.

Predatory journals in psychiatry: A note of caution.

The birth of predatory publishers/journals in the past few years has become an important issue of concern in the scientific world. Predatory publishers/journals are defined as those publishers/ journals that unprofessionally abuse the author-pays publishing model for their own profit (Beall, 2013). Through the exploitation of open access model, predatory journals have raised doubts over the integrity of biomedical and scientific publishing and have raised questions over the transparency of the process of peer review and the validity of impact factor. Predatory journals, predatory publishing firms and fraudulent conferences are common phenomenon nowadays and cannot afford to be ignored by researchers (Bowman, 2014; Gutierrez et al, 2015). Good quality research studies form the foundation of evidence-based medicine, which are in turn the basis for new treatment guidelines, formulating policies and overall public health. The quality of published research will only be of a high standard if the peer review process is transparent and ethical/conflictual issues are addressed. However, predatory journals defeat this purpose, and the most important victims are newly developing scientific streams like psychiatry where research is still in nascent stages. Also, young researchers striving for employment, promotions and grants sham publications to enhance their resumes and to get a breakthrough in their career in an ever-increasing race for publications (Bartholomew, 2014). They are easy prey for predatory journals and a few stands to lose their creditability early in their career due to this. Predatory journals earn their revenue through hefty article processing charges from the authors. It is commonplace to receive emails inviting papers with assured publication in these journals. There will often be notifications like ‘‘call for paper’’ on their website. In most cases article processing charges are not revealed till the article is published or alternatively article processing charges are taken under the disguise of open access. Most importantly there is a faulty/nontransparent peer review process at the heart of the predatory journal where many papers with methodological flaws can get accepted. The famous example of the ‘‘spoof paper’’ on the ‘‘wonder’’ anticancer drug is quite obvious in this regard (Bohannon, 2013). In a developing branch like psychiatry where, there are still many unanswered questions, the new research is more important and anticipated. It is important from the perspective of patients as well as researchers to have access to genuine scientific research rather than fake, spurious, non-transparent publishing by the predatory journals (Beall, 2012). Young researchers, resident doctors, and auxiliary health workers in psychiatry are often the easy target of predatory

Management of tardive syndromes with clozapine: A case series

Tardive syndromes are among the most debilitating side effects associated with use of antipsychotics. In this case series we present 5 cases of drug induced tardive syndromes, who had not responded to many of the other therapeutic measures but responded to clozapine. The response rate with clozapine varied from 50% to 100% and the response was seen by week 3 in most cases. Over the long term follow-up of as long as 6 years the response to clozapine was sustained. In two cases clozapine could be stopped.

Relationship of obsessive compulsive symptoms/disorder with clozapine: A retrospective study from a multispeciality tertiary care centre

OBJECTIVE To study the prevalence, phenomenology and course of OCS/OCD in patients receiving clozapine. METHODOLOGY Case records of 220 patients who received clozapine for at least 3 months were reviewed. RESULTS One fifth (N=42; 19.1%) of patients had OCS/OCD, of which majority (13.2%) had onset of OCS/OCD prior to starting of clozapine and remaining 5.9% developed OCS/OCD after starting of clozapine. About one fourth of the patients with pre-existing OCS/OCD had worsening with clozapine while the remaining maintained at the same level (55.17%) or improved (20.7%). Majority of the patients who developed de novo OCS/OCD on clozapine were females and OCS/OCD emerged within 12 months (69.2%) of starting of clozapine. In those who developed OCS/OCD with clozapine, among obsessions, pathological doubts were most common, followed by obsessions with sexual content; among compulsions repetitive checking was the most common. SSRIs were required for management in half the patients, while the remaining improved spontaneously or with reduction in clozapine dose. CONCLUSION Clozapine can lead to aggravation or de novo presentation of OCS/OCD but these can be managed with reduction in dose or addition of SSRIs.

Effectiveness of electroconvulsive therapy in patients with treatment resistant schizophrenia: A retrospective study

This study aimed to evaluate the effectiveness of electroconvulsive therapy (ECT) among patients with treatment resistant schizophrenia (TRS). Records of patients who had received ECT were reviewed to identify patients with TRS who were administered ECT in combination with clozapine. Socio-demographic, clinical data and ECT details were extracted. The most common diagnosis was of paranoid schizophrenia (49%) followed by undifferentiated schizophrenia (36%). A-fifth (22%) of the patients were judged to have poor response to clozapine. The mean number of ECTs given were 13.97 (SD-7.67) and mean clozapine dose was 287.5mgs/day (SD-100.1). About two-thirds (63%) of the patients showed >30% reduction in scores on different symptom-rating scales with combined use of clozapine and ECT. Among clozapine non-responders, approximately 69% responded to the combination. Post-ECT rise in blood pressure was the most common side effect (16.9%) followed by prolonged seizures (7%). Long-term follow-up data was available for 47 out of the 59 patients. More than two-third (N=34; 72%) followed-up for an average of 30 months (SD 32.3; range: 1-120), maintained well with continued clozapine treatment. To conclude, results of this study further endorse the effectiveness, safety and long-term benefits of the clozapine-ECT combination in TRS and clozapine-refractory schizophrenia.

Stigma and its correlates among patients with bipolar disorder: A study from a tertiary care hospital of North India

This study aimed to assess stigma and its sociodemographic and clinical correlates among patients with bipolar disorder while in remission. 185 patients currently in remission were assessed on Internalized Stigma of Mental Illness Scale (ISMIS) for internalized stigma, Explanatory Model Interview Catalogue Stigma Scale for perceived stigma and Participation scale for restriction of activities. About 28% patients reported moderate to high level of self stigma as assessed by ISMIS total score. Discrimination experience (38.9%) was reported to be the most commonly experienced self stigma followed by alienation (28.6%) and social withdrawal (28.6%). On the participation scale, about two-fifth (42%) of the participants had severe restriction of activities. Internalized stigma was higher among those with lower age and lesser income. Higher level of stigma was associated with shorter mean duration of remission, income, mean duration of depressive episodes, higher severity of residual depressive symptoms and current level of functioning. Higher internalized stigma was associated with greater restriction in participation of activities. To conclude, present study suggests that self stigma is highly prevalent among patients with bipolar disorder in India and is associated with clinical variables like duration of depressive episodes and level of functioning.

Influence of religion and supernatural beliefs on clinical manifestation and treatment practices in patients with bipolar disorder

Abstract Background: Religious and supernatural beliefs influence help seeking and treatment practices in bipolar disorder, but these are rarely explored by clinicians. This study aimed to understand religiousness, magico-religious beliefs, prevalence of religious and supernatural psychopathology and treatment practices among patients with bipolar disorder in euthymic state. Methodology: A total of 185 patients of bipolar disorder currently in remission were assessed cross-sectionally for their clinical profile, current clinical status on the Hamilton Depression Rating Sscale (HDRS), Young Mania Rating Scale (YMRS) and the Global Assessment of Functioning (GAF). A semi structured instrument for magico-religious beliefs, aetiological models, treatment seeking and treatment practices was administered. Results: More than a third of patients (37.8%) had psychopathology with either religious or supernatural content or both in their lifetime. Almost half (45.4%) the patients believed in a supernatural/religious aetiology for their illness. Among the specific causes, planetary influences (13.5%) and God’s will (30.8%) were the most common supernatural and religious cause, respectively. Almost half (44.3%) of patients had first treatment contact with religious/supernatural treatment providers. More than 90% of patients reported belief in God, yet about 70% reported that their doctors did not ask them sufficient questions to understand their religiosity. Conclusion: Magico-religious beliefs are common in bipolar disorder and a large number of patients attribute these as aetiological factors for their illness. Consequently they tend to seek treatment from traditional practitioners prior to approaching medical practitioners and may continue treatment with them alongside medical management.

Metabolic disturbances, side effect profile and effectiveness of clozapine in adolescents

Introduction: Data on effect of clozapine on metabolic syndrome in adolescent patients with psychosis are limited. This study aimed to evaluate the prevalence and incidence of metabolic syndrome in children and adolescents with psychotic disorders prior to clozapine and while receiving clozapine. Secondary aims were to study the effectiveness and side effect profile of clozapine. Materials and Methods: Thirteen child and adolescent patients were evaluated at baseline, 3 months, and a follow-up beyond 6 months. Assessments were made for metabolic profile, effectiveness by positive and negative syndrome scale (PANSS), and side effects. Results: Prior to starting of clozapine, the prevalence of metabolic syndrome was 23%. After 3 months on clozapine, 38.5% (5/13) patients fulfilled criteria of metabolic syndrome and further on follow-up beyond 6 months (with last observation carried forward) 46.2% (6/13) had developed metabolic syndrome. There was a significant reduction in PANSS scores at 3 months and follow-up more so in those who developed metabolic syndrome at 3 months. Among the other side effects, hypersalivation was the most common side effect (100%) followed by sedation (69%). Conclusion: Half the prevalence of metabolic syndrome in adolescents on clozapine can be attributed to other factors prior to starting of clozapine, and another half can be attributed to clozapine. Clozapine is effective in an adolescent population.

Kynurenine pathway (KP) inhibitors: Novel agents for the management of depression:

Depression is a highly prevalent and severely disabling condition globally. Despite being a major cause of disability worldwide, little progress has been made in the last three decades in developing rational and novel pharmacological treatment options for the management of depression. Recently there has been growing interest in the role of kynurenine pathway in pathophysiology of depression. In this paper, the potential role of kynurenine pathway inhibitors in the management of depression particularly in secondary and reactive depression and the development of novel antidepressant drugs targeting kynurenine pathway are discussed.