Papers by Kuldeep Chengappa
Asian Journal of Psychiatry, 2009
India representing over a sixth of the world's population is a po... more India representing over a sixth of the world's population is a popular venue for clinical trials, including those of psychotropic agents. In this commentary, we have focused on the rating scales employed to assess major depressive disorder, especially the Hamilton Depression Rating Scale (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS) in the Indian clinical setting. The prominence given to somatic symptoms in the HAM-D scale may be appropriate for the less "westernized" Indian patients who do not speak English fluently, while the MADRS with more emphasis on cognitive symptoms may be better suited for the urban and westernized Indian subjects. Research into the prevalence of "persecutory ideation" or "fearful mood" or "decreased interest in religious activity" should be undertaken to determine if some of the individual items enquired in these scales require change and/or modification. Finally, even though these are observer rated scales, translations into various Indian languages will likely result in improved quality and validity of clinical trials of major depressive disorder conducted in India. This commentary may be relevant to other non-English speaking populations as well.
Background. Tardive dyskinesia is a serious adverse event, which is associated mainly with the us... more Background. Tardive dyskinesia is a serious adverse event, which is associated mainly with the use of the first-generation antipsychotic agents. Convergent data from clinical trials suggest that second-generation antipsychotic agents are less likely to cause tardive dyskinesia. However, the data with regard to the effect of switching from first-to second-generation antipsychotic agents on pre-existing dyskinetic symptoms during routine clinical care is sparse. Methods. Sixty-three patients with DSM-IV schizophrenia or schizoaffective disorder (n=61) or bipolar I disorder (n=2) consecutively admitted to a state hospital, who were treated either with olanzapine (n=35) or conventional antipsychotic agents (n=28) by physician choice, were enrolled in the study. The severity and frequency of tardive dyskinetic symptoms using the Abnormal Involuntary Movement Scale were assessed in the two medication groups at baseline, 8 weeks, and 6 months. Results. There were statistically significant reductions in the prevalence and severity of dyskinetic symptoms at 8 weeks and 6 months for the group treated with olanzapine but not for those treated with conventional agents. Conclusions. These preliminary data suggest that olanzapine may be a treatment option for subjects with tardive dyskinesia. However, the question whether olanzapine treats, ameliorates, or masks preexisting tardive dyskinesia was difficult to answer, as no dosage reduction or withdrawal was undertaken.
American Journal of Psychiatry, Nov 9, 2014
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2000
To evaluate the impact of risperidone on seclusion and restraint in patients at a state psychiatr... more To evaluate the impact of risperidone on seclusion and restraint in patients at a state psychiatric facility, shortly after risperidone's release. Patients who were in the hospital for at least 3 months prior to receiving risperidone and subsequently received risperidone for at least 3 months formed the cohort. A mirror-image design was used with duration to a maximum of 1 year before and 1 year after initiation of risperidone. The hospital population that did not receive either risperidone or clozapine during the same time period was used for comparison of trends of seclusion and restraint. Seventy-four patients (most with schizophrenia) met the inclusion criteria of the risperidone group. There were statistically significant decreases in the number of seclusion hours (2.2 [SD 5.5] to 0.26 [SD 0.06]) and of events (0.23 [SD 0.59] to 0.05 [SD 0.14]) per person per month during risperidone treatment, compared with the prerisperidone treatment period (P = 0.01). The comparison gro...
Current Psychiatry Reports, 2007
Patients with bipolar disorder are at high risk of gaining weight and developing metabolic illnes... more Patients with bipolar disorder are at high risk of gaining weight and developing metabolic illnesses, and pharmacologic treatment for the disorder may significantly increase this risk. This paper reviews the literature on the metabolic consequences of the medications used in bipolar disorder and describes the possible strategies to prevent, monitor, and treat the common metabolic illnesses that patients with bipolar disorder may develop during treatment.
The Journal of clinical psychiatry, 1994
Akathisia is a common side effect of traditional neuroleptic drugs and is associated with medicat... more Akathisia is a common side effect of traditional neuroleptic drugs and is associated with medication refusal and impulsive behavior. While our previous experience indicates that clozapine is effective in treating persistent akathisia, two controlled studies indicate vastly different prevalence rates of akathisia (7% vs. 40%) in patients receiving clozapine. We used the Barnes Rating Scale for Drug-Induced Akathisia to estimate the prevalence of akathisia in patients receiving stable doses of clozapine alone (N = 29) in a state hospital. Measurements were also made of manifest psychopathology (Brief Psychiatric Rating Scale) and tardive dyskinesia (Abnormal Involuntary Movement Scale). Two patients (6.8%) receiving clozapine were rated as having akathisia. Only 4 (28.6%) of the 14 subjects with a history of moderate-to-severe tardive dyskinesia on traditional neuroleptic drugs continued to show current evidence of tardive dyskinesia, and in 10 patients (71.4%) there was no evidence o...
Schizophrenia Research, 1992
A total of 57 schizophrenic patients (of which 17 were first-episode, neuroleptic naive) and 76 h... more A total of 57 schizophrenic patients (of which 17 were first-episode, neuroleptic naive) and 76 healthy controls were screened for anti-histone IgG antibodies using an enzyme immunoassay (ELISA). All patients had significantly higher anti-histone antibody titers than controls (t = 3.1, p less than 0.003). Previously medicated patients had significantly higher titers than neuroleptic-naive first episode patients (t = 2.87, p less than 0.006). This study suggests that neuroleptic medications are associated with anti-histone antibodies.
Schizophrenia Research, 2003
Objective: The study was carried out to assess the neuropsychological and psychopathological impa... more Objective: The study was carried out to assess the neuropsychological and psychopathological impact of treatment with olanzapine in non-refractory schizophrenic patients (DSM-IV) previously treated with typical antipsychotic drugs. Method: Eleven patients with diagnosis of schizophrenia by SCID-DSM-IV were sumbitted to a prospective naturalistic pilot study with olanzapine (5-20rag qd) and evaluated with a comprehensive neuropsychologic battery before and after 6 months of treatment and with the PANSS every 2 months. The indexes of global, verbal and visual memory, indexes of attention/concentration (WMS-R), global, verbal and manipulative IQ (WAIS-R) and verbal fluency were comparatively analyzed. The psychopathological symptoms were grouped for analysis according to the model of the mean components (positive, negative, excitement, depressive and cognitive) of the PANSS. The results were analyzed statistically (mean, sd and t-test [significance level adopted p<0.05]). Results: All neuropsychological indexes improved after 6 months of treatment, especially the verbal memory index, which showed significant improvement, suggesting a specific effect of the established treatment on this function. The positive, negative and general psychopathological symptoms, as well as positive, negative, depressive and cognitive components measured by the PANSS improved significantly. Conclusion: The study shows cognitive and psychopathological benefits obtained by the use of olanzapine in relation to the performance in the previous treatment with typical antipsychotic drugs.
Psychological Medicine, 1994
SynopsisSerum concentrations of anti-hippocampal antibodies and in vitro production of the lympho... more SynopsisSerum concentrations of anti-hippocampal antibodies and in vitro production of the lymphokine interleukin-2 (IL-2) in response to phytohaemagglutinin (PHA) stimulation were determined using an enzyme immunoassay in 49 schizophrenic patients and 41 healthy controls. Decrease in IL-2 production, a finding frequently associated with many autoimmune diseases, was associated with an elevation in anti-hippocampal antibody optical density (AHA-OD) in schizophrenic patients. Although some control subjects had elevated antibody levels, this elevation was not associated with decreased IL-2 production. Low IL-2 production is well known to be a state marker associated with active autoimmune disease. We suggest that production of hippocampal antibody is a trait marker of vulnerability to autoimmune diseases. Thus, our finding of low IL-2 production in patients with high concentrations of hippocampal antibody is compatible with the possibility that such patients have an ongoing autoimmune...
Psychiatry Research, 1994
Using an enzyme immunoassay (ELBA), we measured serum interleukin-6 (IL-6) concentration in 128 s... more Using an enzyme immunoassay (ELBA), we measured serum interleukin-6 (IL-6) concentration in 128 schizophrenic patients (24 of whom were never medicated) and in 110 normal control subjects. Mean serum IL-6 concentration was significantly higher in the schizophrenic patients as compared with the control subjects (p = 0.009). Comparisons within the patient group revealed that serum IL-6 was significantly correlated with duration of illness (r = 0.32, p = 0.0004). After covariation for duration of illness, there was no relationship between IL-6 levels and the production of autoantibodies, clinical state, or medication status. Thus, elevated serum IL-6 levels in schizophrenia develop during the course of illness and may be related to treatment or to disease progression.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2002
Concomitant medications are frequently used in the treatment of resistant psychiatric conditions ... more Concomitant medications are frequently used in the treatment of resistant psychiatric conditions to augment the primary psychotropic agent or to ameliorate side effects. The present study evaluated the prescription of concomitant psychiatric medications for psychiatric inpatients that were prescribed either olanzapine at its first commercial availability or another first-line antipsychotic agent. Sixty-nine newly admitted patients (mainly with schizophrenia) who were prescribed either olanzapine (n = 35) or another first-line antipsychotic agent (n = 34) were assessed (for the prescription of other concomitant psychotropic drugs) before (2-4 weeks prior to study) and following 8 weeks of treatment (unless discharged sooner). The results indicate that significantly fewer olanzapine-treated subjects were prescribed anticholinergic agents as compared to those prescribed other first-line antipsychotic agents, and a similar trend was noted in the prescription of mood stabilizers as well. Olanzapine-treated subjects used less as needed (PRN) antipsychotic medication compared to pre-olanzapine treatment period. Olanzapine-treated subjects used more anxiolytic agents compared to the control group in the early stages of treatment, probably due to the greater baseline severity of illness. These data suggest that olanzapine use is associated with less use of anticholinergic and moodstabilizing agents as compared to older antipsychotic agents. These results also suggest that there is less need for PRN antipsychotic medication following olanzapine treatment. More severely ill subjects may require more anxiolytics during olanzapine initiation. The need for less anticholinergic and mood-stabilizing agent use with olanzapine could lead to greater adherence to long-term treatment and perhaps decreased cost (i.e. use of blood and organ system monitoring with mood stabilizers). At the end of treatment, olanzapine-treated subjects had statistically significantly lesser concomitant medicine usage compared to control subjects.
Neuroscience Research, 1994
Serum interleukin-6 (IL-6) was measured in picograms/ml (pg/ml) using an immunoassay (ELISA) in h... more Serum interleukin-6 (IL-6) was measured in picograms/ml (pg/ml) using an immunoassay (ELISA) in healthy individuals (n = 148), of whom 128 were classified as dextral and 20 as non-dextral, as per a laterality questionnaire. Only 3 (15%) non-dextral individuals had serum IL-6 levels above the lower limit of the assay sensitivity as compared to 59 (46%) of dextral individuals (P < 0.013). There were no significant correlations between previously determined mitogen stimulated interleukin-2 production and autoantibodies in a subset of the same individuals. While this data does not provide casual information, it adds to the evidence of the asymmetric regulation of immune functions by the cerebral hemispheres.
Journal of Psychiatric Practice, 2001
Obesity and associated medical conditions may have an impact on morbidity and even mortality in p... more Obesity and associated medical conditions may have an impact on morbidity and even mortality in patients with psychiatric disorders. The authors present the results of a survey of the prevalence of obesity and selected medical conditions among 420 consecutively admitted psychiatric inpatients at a long-stay facility and compare these data with those reported in the literature. Female psychiatric subjects had considerably higher rates of being either overweight or obese (69%) as compared to women in the general U.S. population (51%). Male psychiatric subjects did not differ significantly from their counterparts in the general population in being overweight or obese (nearly 55%). The majority of psychiatric subjects with essential hypertension, diabetes mellitus, dyslipidemias, cardiovascular disease, or sleep apnea were either overweight or obese (72%-87%). In this cross-sectional study, no associations could be deduced between psychotropic drug classes and specific medical conditions. No specific psychiatric diagnostic category was associated with a significantly greater prevalence of any specific medical condition, except that subjects with schizoaffective disorder appeared to have a higher prevalence of type II diabetes mellitus (11.6%). Subjects with predominant substance or alcohol abuse or dependence disorders had a lower prevalence of obesity and associated medical conditions. Obesity-either independently or additively along with a sedentary lifestyle, unhealthy dietary habits, and nicotine dependence-may have a serious impact on coexisting medical comorbidity in psychiatric patients. Judicious monitoring for obesity and rapid pharmacological and nonpharmacological intervention, where appropriate, by concerned clinicians may improve several coexisting medical conditions in psychiatric patients and thereby improve patients' overall quality of life.
Journal of Clinical Psychopharmacology, 2000
This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective d... more This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who were receiving either olanzapine (N = 12) or clozapine (N = 12) at standard clinical doses in a naturalistic setting. Serum anticholinergic levels were determined in adult male and female subjects using a radioreceptor binding assay. The Udvalg for Kliniske Undersogelser Scale was used to evaluate anticholinergic side effects clinically, and the Mini-Mental State Examination provided a global cognitive measure. Patients had achieved target doses that were stable at the time at which blood samples were obtained, and no other concomitant medicine with known anticholinergic potential was allowed. Patients receiving olanzapine (average dose, 15 mg/day) had serum anticholinergic levels of 0.96 (+/-0.55) pmol/ atropine equivalents compared with levels of 5.47 (+/-3.33) pmol/atropine equivalents for those receiving clozapine (average dose, 444 mg/day) (p &lt; 0.001). Rates of increased and decreased salivation were significantly more common among the clozapine- and olanzapine-treated patients, respectively, whereas constipation, urinary disturbances, and tachycardia/palpitations were significantly more common among clozapine-treated patients. Neither group showed any global cognitive deficits. Olanzapine-treated patients had serum anticholinergic levels that were less than one fifth those of the clozapine-treated patients. Furthermore, clinical evaluations confirmed that clozapine-treated patients experienced more frequent and severe anticholinergic side effects (except dry mouth). However, none of the patients in either group expressed any desire to discontinue these medications as a result of the anticholinergic side effects.
Journal of Clinical Psychopharmacology, 2008
Individuals with bipolar disorder smoke cigarettes at higher rates (31%-67%) than the U.S. genera... more Individuals with bipolar disorder smoke cigarettes at higher rates (31%-67%) than the U.S. general population (∼20%) (1, 2), have a more difficult time with smoking cessation (1), and smoking is related to greater severity of both manic and depressive symptoms (2, 3). However, there have been no controlled studies of nicotine dependence treatments in this subset of psychiatric smokers. The sustained release (SR) formulation of bupropion (BUP) is a weak catecholamine reuptake inhibitor (4) and a potent non-competitive ion channel site antagonist at the nicotinic acetylcholine receptor (nAChR), which was approved as an aid to smoking cessation in the U.S. in 1997 (5). While bupropion is safe and improves smoking cessation rates for smokers with schizophrenia [e.g., (6)], this agent has not been tested for smokers with bipolar disorder. This report describes the first controlled evaluation of bupropion in smokers with bipolar disorder on short-term smoking abstinence rates. Participants in this pilot study were clinically stable outpatients with DSM-IV diagnoses of bipolar I disorder and nicotine-dependent cigarette smokers consuming at least 10 cigarettes per day (cpd), with expired breath carbon monoxide (CO) levels ≥10 parts per million
Journal of Ayurveda and Integrative Medicine, 2011
Expert Review of Neurotherapeutics, 2004
Acute manic episodes in bipolar disorder require rapid and effective relief. Pharmacotherapy has ... more Acute manic episodes in bipolar disorder require rapid and effective relief. Pharmacotherapy has traditionally involved mood stabilizers such as lithium or divalproex. Evidence for the efficacy of atypical antipsychotics to treat bipolar mania, either as monotherapy or in combination with traditional mood-stabilizing agents, has increased in recent years. Since the combination of an atypical agent and a traditional mood stabilizer is generally well tolerated, it represents a first-line approach for the treatment of severe and treatment-resistant mania. Atypical antipsychotics have a superior neurological tolerability profile compared with typical antipsychotics and are preferentially recommended in most treatment guidelines. The atypical agents, olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole, have demonstrated efficacy in bipolar mania in large randomized, controlled studies, and offer efficacy across a broader range of symptoms than typical antipsychotics, and may even have mood-stabilizing properties traditionally associated with lithium and divalproex. Olanzapine, risperidone and quetiapine have been shown to be effective for manic episodes both as monotherapy and in combination with other agents such as lithium and divalproex. Although the tolerability profiles of atypicals as a class are superior to those of conventional antipsychotics, there are differences among the atypical agents in their propensity to cause certain adverse events such as extrapyramidal symptoms (EPS) and weight gain, particularly in the long-term. The ultimate choice of the atypical agent will depend on the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s individual needs, but atypical antipsychotics are clinically effective options for achieving mood stabilization in the treatment of acute bipolar mania.
European Psychiatry, 2004
The combination of clozapine and other potentially leukopenic drugs may pose a greater risk for n... more The combination of clozapine and other potentially leukopenic drugs may pose a greater risk for neutropenia. However, neutropenia may not always be due to clozapine. When adding potentially leukopenic drugs, clinicians should look for possible alternatives especially as clozapine is often a drug used as the last resort in treatment refractory schizophrenia.
Clinical Therapeutics, 2002
Subsets of psychiatric patients gain excess body weight while receiving mood-stabilizing agents s... more Subsets of psychiatric patients gain excess body weight while receiving mood-stabilizing agents such as lithium carbonate or valproate sodium. Patients who gain excess weight may discontinue therapy, with severe consequences. Among the newer anticonvulsant agents, topiramate is a candidate agent for bipolar disorder and is associated with weight loss when used as adjunctive treatment. This open-label, nonrandomized, chart-review study assessed changes in body weight and body mass index (BMI) in patients receiving topiramate, lithium, or valproate. Data were extracted from the medical charts of patients admitted in 1999 and 2000 to a state psychiatric hospital with either schizophrenia, schizoaffective disorder, bipolar disorder, or other psychiatric diagnoses who were prescribed valproate, lithium, or topiramate and were reviewed for changes in body weight and BMI. The use of concomitant psychotropic medicines was recorded (eg, antipsychotic agents, antidepressant agents, other mood stabilizers such as gabapentin or carbamazepine). Continuous variables were analyzed using a factorial analysis of variance and the Student t test. Contingency statistics were used to analyze categorical variables. A total of 214 patients were included in the chart review (123 men, 91 women; mean age, 39.4 years). Significantly more women than men received topiramate (P = 0.004). Patients receiving either lithium or valproate gained a mean (SD) of 6.3 (9.0) kg and 6.4 (9.0) kg, respectively, whereas patients receiving topiramate lost a mean 1.2 (6.3) kg (F = 11.54, df = 2,198; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Lithium- or valproate-treated patients experienced an increase in BMI (mean, 2.1 [3.0] for both groups), whereas topiramate-treated patients experienced a reduction in BMI (mean, -0.5 [2.4]); this result was statistically significant (F = 11.40, df = 2,198; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Finally, lithium- or valproate-treated patients gained &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;8% of their baseline body weight (8.2% [11.5%] for lithium-treated patients and 8.5% [11.9%] for valproate-treated patients), whereas topiramate-treated patients lost 0.7% (7.2%) of their body weight (F = 9.93, df= 2,198; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Controlled studies for the efficacy of topiramate therapy in various psychiatric conditions are awaited. These data indicate that patients receiving topiramate experience body weight loss and a reduction in BMI. This advantage of topiramate may promote long-term adherence to treatment among psychiatric patients and possibly decrease the medical risks associated with obesity.
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Papers by Kuldeep Chengappa