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Biomedical subjects

K N Chengappa

Publications and source records attributed to K N Chengappa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Topiramate as add-on treatment for patients with bipolar mania.

OBJECTIVE: Anticonvulsant agents such as carbamazepine and valproate are alternatives to lithium in treating subjects with bipolar disorder. Topiramate (Topamax), a new antiepileptic agent, is a candidate drug for bipolar disorder. We evaluated topiramate as adjunctive treatment for bipolar patients. METHODS: Eighteen patients with DSM-IV bipolar I disorder [mania (n = 12), hypomania (n = 1), mixed episode (n = 5), and rapid cycling (n = 6)], and two subjects with schizoaffective disorder bipolar type, resistant to current mood-stabilizer treatment were initiated on topiramate, 25 mg/day, increasing by 25-50 mg every 3 7 days to a target dose between 100 and 300 mg/day, as other medications were held constant for 5 weeks. The Young Mania Rating Scale (Y-MRS), Hamilton Depression Rating Scale (Ham-D), and Clinical Global Impression-Bipolar Version Scale (CGI-BP) were used to rate subjects weekly. RESULTS: By 5 weeks, 12 (60%) subjects were responders, i.e., 50% reduction in the Y-MRS scores and a CGI of 'much' or 'very much improved'. Three subjects were 'minimally improved', four showed no change, and one was 'minimally worse'. Six subjects had parasthesia, three experienced fatigue, and two had 'word-finding' difficulties; in all cases, side effects were transient. All patients lost weight with a mean of 9.4 lb in 5 weeks, and a significant reduction in body mass index (BMI) occurred too. CONCLUSIONS: Topiramate appears to have efficacy for the manic and mixed phases of bipolar illness. Other preliminary data suggest antidepressant efficacy too. Among obese bipolar subjects, the weight loss potential of topiramate may be beneficial. If controlled trials confirm these initial results, topiramate may be a significant addition to the available treatments for bipolar disorder.

Acetates↗
PubMed1999

Cerebrospinal cytokine levels in patients with acute depression.

There is increasing evidence for an association between the alteration of cytokine concentrations in blood and the pathophysiology of depressive disorders. Studies in humans have not investigated CSF cytokine concentrations and their relationship to depressive disorders. This study reports on the association of the CSF concentration of proinflammatory cytokines, IL-1beta, IL-6 and TNFalpha, and major depressive disorders. CSF samples were obtained from 13 hospitalized patients with acute unmedicated severe depression and were compared with 10 control subjects. Compared to the control group, the depressed patient group had higher CSF concentrations of IL-1beta, lower IL-6 and no change in TNFalpha. A positive correlation was found between serum IL-1beta and the severity of depression. These results indicate a unique profile for CSF proinflammatory cytokines in acute depression. These findings merit further investigation and if replicated may possibly offer immunological treatment options for depression.

Acute Disease↗
PubMed1999

Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group.

OBJECTIVE: The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania. METHOD: The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score. RESULTS: The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group. CONCLUSIONS: The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania.

Acute Disease↗
PubMed1999

Clozapine reduces severe self-mutilation and aggression in psychotic patients with borderline personality disorder.

BACKGROUND: Clozapine has been reported to be effective in diminishing violence toward others in psychotic patients. This article describes the impact of clozapine on severe self-mutilation among patients with the dual diagnoses of borderline personality disorder and persistent psychoses. METHOD: Seven subjects known to the authors were selected for careful chart audits. These subjects had been admitted to 2 state psychiatric hospitals owing to severe self-mutilation and/or violence and subsequently treated with clozapine. A mirror-image design anchored to the start date of clozapine treatment and extending in either direction to a maximum of 1 year was used to extract data. Data extracted included incidents of self-mutilation (restraint), seclusion, the as and when needed (p.r.n.) use of medications, injuries to staff and peers, hospital privileges, and Global Assessment of Functioning (GAF) scores. RESULTS: The subjects were all white women with a mean age of 37 years. All subjects carried DSM-III-R or DSM-IV borderline personality disorder diagnoses and an Axis I disorder diagnosis. They had received trials of several psychotropic agents, often in combination and mostly without benefit. After clozapine treatment, there were statistically significant reductions in incidents of self-mutilation (restraint), seclusion, the use of p.r.n. antianxiety medications, and injuries to staff and peers. These subjects received higher levels of hospital privileges, and their GAF scores nearly doubled following clozapine treatment. Four subjects were subsequently discharged from hospital. CONCLUSION: These preliminary but nonetheless favorable results suggest that clozapine deserves careful consideration for a controlled study in patients with borderline personality disorder and psychoses, especially if the clinical issues include severe self-mutilation, aggression, and violence. Until such studies are done, the risk-to-benefit ratio of clozapine treatment needs to be carefully evaluated on an individualized basis in such subjects.

Adult↗
PubMed1999

Risperidone use at a state hospital: a clinical audit 2 years after the first wave of risperidone prescriptions.

BACKGROUND: In spite of some inherent limitations, naturalistic data can provide information on populations that have greater heterogeneity than can controlled clinical trials and on functional outcomes that may be especially important in clinical practice. In the present retrospective naturalistic study, we evaluated key clinical outcomes among the first wave of risperidone-treated patients at a state psychiatric hospital. METHOD: Outcome data were extracted from the charts of 142 patients 2 years after initiation of treatment with risperidone. Their diagnoses included DSM-III-R schizophrenia (57%), schizoaffective disorder (22%), dementia and other organic conditions (7%), bipolar disorder (5%), and other psychiatric disorders (9%). RESULTS: During the 2-year period, 92 of 142 patients were discharged from the hospital: 61 (43%) were discharged on risperidone treatment and 31 (22%) were discharged on treatment with other drugs. At the time of the study, 50 of 142 patients were still in the hospital: of these, 18 (13%) were still receiving risperidone. The modal maximum daily dose of risperidone was 4.1 mg in patients discharged on risperidone treatment and 7.5 mg in patients still in the hospital. All groups were granted more ward privileges after starting risperidone, the most being granted to patients discharged from the hospital on risperidone treatment (p<.05 versus patients discharged on treatment with other drugs) and those still receiving risperidone in the hospital. Significantly fewer patients discharged on risperidone treatment than on treatment with other drugs were readmitted to the hospital within 2 years after discharge (p<.01). CONCLUSION: Improved privilege levels and a reduced readmission rate indicate that risperidone was an effective antipsychotic agent among a heterogeneous patient population in a state hospital. These factors may be especially important to justify use of this agent in the current fiscal climate.

Adult↗
PubMed1998

Clozapine withdrawal-emergent dystonias and dyskinesias: a case series.

BACKGROUND: Severe psychotic decompensation during clozapine withdrawal has been reported previously. Less attention has been paid to movement disorders following abrupt clozapine withdrawal. This report describes 4 subjects who experienced severe dystonias and dyskinesias upon abrupt clozapine withdrawal. METHOD: Current and past medical records of 4 subjects with DSM-IV schizophrenia or schizo-affective disorder were reviewed. RESULTS: All subjects had a history of neuroleptic-induced extrapyramidal symptoms, 1 had a history of severe dystonias, and 1 had neuroleptic malignant syndrome. All had mild orolingual tardive dyskinesia prior to clozapine treatment. All subjects had received clozapine for several months, and 3 of the 4 subjects stopped clozapine abruptly. Two subjects experienced cholinergic rebound symptoms within hours, which resolved quickly. These subjects had severe limb-axial and neck dystonias and dyskinesias 5 to 14 days after clozapine withdrawal. Two subjects were unable to ambulate, and 1 had a lurching gait. Two gagged while eating or drinking. Two subjects were returned to clozapine, 1 was started on low-dose risperidone treatment, and 1 was started on olanzapine treatment. All experienced significant improvements in their mental state and movement disorders. CONCLUSION: Severe movement disorders, which may be worse than the movements prior to clozapine treatment, and cholinergic rebound symptoms may occur upon abrupt clozapine withdrawal and must be recognized in addition to the severe psychotic decompensation noted in some patients. Patients, families, and caregivers must be alerted to this possibility. Where possible, a slow clozapine taper, the use of anticholinergic agents, and symptomatic treatment may help minimize these withdrawal symptoms, and reintroduction of clozapine or treatment with the newer atypical agents can help in the clinical management of these symptoms.

Acute Disease↗
PubMed1997

The effects of clozapine on negative symptoms in patients with schizophrenia with minimal positive symptoms.

The effectiveness of clozapine in the treatment of the negative symptoms of schizophrenia remains controversial, as improvements in negative symptoms are invariably accompanied by improvements in positive symptoms and neurological side effects. We examined the effectiveness of treatment with clozapine on negative symptoms in a cohort of patients with minimal positive symptoms. Improvements in positive and negative symptoms were measured by BPRS ratings in a subgroup of schizophrenic patients (n=17, from a state hospital cohort of 75) with minimal positive symptoms, who had received clozapine for 6 months. In this subgroup, significant improvements were noted by a composite score on the three negative symptom items of emotional withdrawal, blunted affect, and motor retardation. Positive and depressive symptoms remained unchanged. The remaining cohort (n=58) showed improvements in overall psychopathology including positive, negative, and depressive symptoms. Interestingly, nearly 50% of each group were discharged from the hospital. These findings suggest that clozapine may be beneficial in the treatment of core negative symptoms, even in the absence of other improvements in psychopathology. This effect of clozapine may be a function of its unique pharmacological profile.

Adult↗
PubMed1996

The treatment of clozapine-associated agranulocytosis with granulocyte colony-stimulating factor (G-CSF).

During a 5-year period, 6 patients with clozapine-associated agranulocytosis who received granulocyte colony-stimulating factor (G-CSF) were compared with 5 subjects who did not receive this treatment. Seven patients were asymptomatic, and the weekly leukocyte count alone indicated agranulocytosis. The average duration of agranulocytosis was not significantly different between the treated and untreated groups (6.5 vs. 6.6 days), though the treated group had a significantly shorter average duration of hospitalization (8.2 vs. 13.5 days). G-CSF administration was well tolerated, and no adverse effects were noted. Incidentally noted was the recent addition of ranitidine (with the potential for bone marrow toxicity) to clozapine for 2 patients. Currently, weekly white cell and differential counts remain the main tools for detecting incipient or occurring agranulocytosis. Until efficacy studies prove otherwise, G-CSF administered soon after the diagnosis of clozapine-associated agranulocytosis may shorten the duration of hospitalization and thus prove cost-effective.

Adult↗
PubMed1996

Obsessive-compulsive symptoms in schizophrenia: a comparison of olanzapine and placebo.

The antipsychotic drug olanzapine is similar to clozapine and risperidone in potent serotonergic antagonism. We assessed obsessive-compulsive symptoms during olanzapine treatment because these symptoms have been reported during risperidone and clozapine treatment. Obsessions and compulsions were measured in 25 subjects with schizophrenia before and after a 6-week double-blind trial comparing two olanzapine doses to placebo. At baseline, 8 subjects had mild or moderate obsessions, and 6 had mild compulsions. There was no significant difference in the course of obsessive-compulsive symptoms among the three treatment groups. We found that olanzapine did not appear to cause obsessive-compulsive symptoms in patients with schizophrenia. Our sample size, the dose and duration of olanzapine treatment, and assessment methods limit the extent to which this finding can be generalized. Though emerging obsessive-compulsive symptoms have been reported for 13 clozapine-treated and 2 risperidone-treated patients with schizophrenia, this phenomenon has not yet been demonstrated in a controlled study.

Adult↗
PubMed1995

Obstetric complications and autoantibodies in schizophrenia.

Our hypothesis stated that patients with schizophrenia who had obstetric complications (OC) were more likely to have autoimmune abnormalities than those without OC. OC were rated using a checklist. Anti-brain autoantibodies were measured in serum using an enzyme immunoassay. Autoantibodies to non-CNS tissues were detected using serological procedures. There were no significant differences between the groups with respect to anti-brain antibodies, but patients with OC (n = 24) had a significantly higher prevalence of autoantibodies to non-CNS tissues than patients without OC (n = 25). Both groups were receiving neuroleptic drugs. OC may contribute to autoimmune abnormalities among patients with schizophrenia.

Adult↗
PubMed1995

Assessment of changes in both weight and frequency of use of medications for the treatment of gastrointestinal symptoms among clozapine-treated patients.

Clozapine has an unusual profile of adverse effects; among them, gastrointestinal (GI) side effects are important management concerns. The charts of patients in a state hospital who received clozapine for at least 3 months were reviewed. We compared the pre- and post-clozapine weights and changes in frequency and intensity of use of drugs prescribed for gastrointestinal symptoms for each subject (n = 99). There were statistically significant increases in the use of antacids (p < 0.02) and both bulk and non-bulk laxatives (p < 0.05, p < 0.03). Seventy-three percent of patients gained weight, of whom 27% gained over 10% body weight. This study confirms clozapine's association with weight gain, constipation, and upper GI symptoms. The literature concerning weight gain, and the mechanisms underlying GI adverse effects were reviewed.

Adult↗
PubMed1995

Clozapine use in female geriatric patients with psychoses.

This study was undertaken to evaluate the clinical response of geriatric patients with psychoses to the atypical neuroleptic drug, clozapine. Records of patients over 60 years of age (n = 12, all female) who had received clozapine over a 30-month period from selected hospitals in Western Pennsylvania were reviewed. Among the six patients who were rapidly titrated (300 mg/day in 3 weeks), none are currently receiving clozapine, while four patients who received a slower titration and lower dosage (range, 25 mg/day to 300 mg/day; mean, 150 mg/day) remain clinically improved on stable doses of clozapine. Postural hypotension affected seven patients, and was the reason for discontinuation of clozapine in five patients. One patient experienced nonfatal agranulocytosis, and one subject experienced leukopenia. One patient died from causes unrelated to clozapine. This retrospective study suggests both a low-dose and slow-titration strategy for initiating clozapine among elderly patients, similar to the use of other psychotropic drugs in the elderly, as well as close attention to postural hypotension, agranulocytosis, and drug interactions.

Aged↗
PubMed1994

Serum interleukin-6 concentration in schizophrenia: elevation associated with duration of illness.

Using an enzyme immunoassay (ELISA), 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.

Adult↗