Psychosocial processes influencing weight management among persons newly prescribed atypical antipsychotic medications.

The purpose was to generate a theory of the psychosocial processes influencing weight management among persons newly prescribed atypical antipsychotic medications. A grounded theory research design was used to guide the study. Semi-structured interviews were the method of data collection, and analysis was performed using constant comparison. Using theoretical sampling, a sample of 11 participants with first-episode psychosis prescribed atypical antipsychotics for at least 8 weeks, and five participants with a diagnosis of chronic schizophrenia prescribed atypical antipsychotic medication for at least 3 years were recruited from an outpatient psychiatric programme. Contextual factors influencing weight management were: accessibility to resources, unstructured lifestyle, and others' perception of weight. Conditions influencing weight management were: rapid weight gain, insatiable hunger and lack of motivation boosters. Participants' early responses to weight gain included discontinuing medications, choosing lower-calorie foods, using walking in daily activities as exercise, accepting weight gain and trying to manage weight but giving up. The consequences revealed from data analysis were contemplating weight management and not trying, as the barriers to weight management exceeded the facilitators. The theoretical framework developed in this study can assist with the understanding and management of weight gain among this unique population.

Assessing health utilities in schizophrenia. A feasibility study.

BACKGROUND: Utility, a concept derived from economics, is the desirability or preference that individuals exhibit for a certain health state. Utility measurement could be viewed as an alternative means of appraising the quality of life of individuals affected by a chronic illness such as schizophrenia. Traditional techniques of utility measurement involve 2 steps: (i) identifying the different health states experienced by individuals during the course of an illness; and (ii) assigning them numerical values known as utilities. AIM: The study examined the feasibility issues and psychometric aspects of obtaining accurate health state descriptions and their utilities from symptomatically stable patients with schizophrenia. METHODS: The study used a cross-sectional, case-controlled design, with a study group consisting of 120 clinically stabilised patients with schizophrenia and a control group of 32 treated and recovered patients with major depression. Patients were asked to provide detailed descriptions of 3 distinct health states associated with their illness: current state, worst state experienced since the onset of illness and a perfect state desired in the future. Further, patients were asked to assign utilities to these health states with the aid of a purpose-built evaluation protocol comprising Magnitude Estimation (ME), Rating Scale (RS), Standard Gamble (SG), Time Trade-Off (TTO) and Willingness-to-Pay (WTP) techniques. The battery was repeated after a 1-week interval. Independent raters assessed symptom severity, insight and quality of life, and nurse-clinicians involved in their care were asked to provide the utility ratings of their clients' mental health state. Patients' opinions about the acceptability of utility measurement techniques, and the respondent burden were also ascertained. RESULTS: Compared with control patients with treated depression, patients with schizophrenia were able to distinguish and describe the specified health states with an equal degree of ease and accuracy. RS, TTO and WTP techniques emerged as the favoured methods of utility evaluation. The test-retest reliability of utility ratings (r = 0.87 to 0.97; p < 0.001) was high, and concurrent validity with the quality of life measures was acceptable. Reliability and validity of patients' appraisals were unaffected by symptoms severity and insight. The accuracy of nurse-clinicians' appraisals were dependent on their close familiarity with the patients and their illness. CONCLUSION: Clinically stabilised patients with schizophrenia can provide accurate health state descriptions and assign them utilities with a fair degree of reliability and validity. Utility evaluations based on patients' self-appraisals can be seen as potential tools in outcome studies and clinical trials involving patients with schizophrenia, but the methodology requires further refinement to accommodate the limitations imposed by the patients' disturbed mental status.

Acquired aplastic anemia secondary to perphenazine.

Aplastic anemia, defined by the presence of pancytopenia and hypocellular bone marrow in the absence of any abnormal blood cells, is a serious complication of antipsychotic drug treatment. While hematological side effects from antipsychotic medications are rare, recent experience with clozapine, an atypical antipsychotic agent, has raised the awareness of clinicians to the serious and potentially fatal hematological changes that can occur with antipsychotic medications. A case of perphenazine-induced aplastic anemia in a 23-year-old schizophrenic man is reported.

Lithium dosage and leukocyte counts in psychiatric patients.

OBJECTIVE: To evaluate differences in leukocyte counts among patients treated with either lithium alone, antipsychotic medications alone, or a combination of both. DESIGN: Retrospective study. SETTING: Long-stay psychiatric hospital. PATIENTS: Patients admitted between 1990 and 1993, and treated with lithium for at least 1 week and/or with antipsychotic medication for at least 2 weeks. Excluded from the study were those patients for whom complete blood counts at baseline and during therapy were not available, and those patients whose blood picture could primarily be accounted for by extraneous factors. Included in the study were 38 patients treated with lithium alone, 207 patients receiving antipsychotic medications alone, and 71 patients receiving both. OUTCOME MEASURES: Leukocyte, lymphocyte and granulocyte counts. RESULTS: Patients treated with lithium alone had significantly higher mean leukocyte and granulocyte counts than those treated with antipsychotic medication alone (analysis of variance, p < 0.05). None of the patients receiving lithium alone showed leukopenia. The dosage of lithium was significantly correlated with leukocyte count (r = 0.25, 95% confidence interval [CI] 0.14 to 0.35, p < 0.001,) and granulocyte count (r = 0.27, 95% CI 0.16 to 0.38, p < 0.001), but not with lymphocyte count (r = 0.06, p = 0.286, 95% CI -0.05 to 0.17). CONCLUSIONS: Lithium therapy is associated with higher leukocyte and granulocyte levels in psychiatric patients. This leukocytotic effect of lithium may be dose dependent.

The cytotoxicity of clozapine metabolites: implications for predicting clozapine-induced agranulocytosis.

BACKGROUND: Therapy of schizophrenia with clozapine is associated with the unpredictable development of severe neutropenia and agranulocytosis in 1% to 2% of patients. The mechanism of this effect is unknown but may involve reactive products of clozapine generated by either hepatic metabolism or oxidation by the peroxidase-peroxide system of activated neutrophils. METHODS: Involvement of reactive metabolites was tested with in vitro cytotoxicity assays with use of peripheral blood mononuclear cells isolated from 3 groups of subjects: normal control subjects, patients with schizophrenia who tolerated clozapine therapy (control patients), and patients with schizophrenia in whom agranulocytosis developed while taking clozapine (patients with agranulocytosis). Cell viability was determined after incubations with clozapine and rat liver microsomes or clozapine and horseradish peroxidase-peroxide (HRP-H2O2). RESULTS: In microsomal incubations, clozapine significantly increased the cell death in all groups: control subjects (8.8%+/-1.6%), control patients (7.4%+/-0.4%), and patients with agranulocytosis (9.1%+/-1.5%). However, differences between mean values were not statistically significant. In similar incubations with HRP-H2O2, clozapine significantly increased toxicity (P < .05) in cells from patients with agranulocytosis (22%+/-4.6%) compared with those from normal control subjects (7.7%+/-4.1%) or control patients (6.5%+/-4.4%). CONCLUSIONS: These results suggest that both generating systems metabolized clozapine to toxic products. Some products may play a role in clozapine-induced agranulocytosis. Of diagnostic relevance is the observation the HRP-H2O2 produces significantly greater toxicity in cells from patients with agranulocytosis than in cells from control patients. Although the exact mechanism(s) of drug activation in vivo remains unclear, the bioactivation of clozapine by HRP-H2O2 may be a useful in vitro tool for predicting which patients are at risk for agranulocytosis before initiation of therapy.

The treatment of negative symptoms: a clinical and methodological study.

The primary objective of this study was to evaluate the efficacy, safety and tolerability of remoxipride (controlled release) versus haloperidol in patients with negative symptoms. The study comprised a multicentre, randomised, double-blind, parallel-group clinical trial. Two hundred and five patients were randomised to either remoxipride or haloperidol. Patients eligible for this study were aged 18-65 years, met the DSM-III-R diagnosis for chronic schizophrenia and the Positive and Negative Symptoms Scale (PANSS) criteria for predominant negative symptoms. There was a statistically significant reduction in the PANSS scores of at least 20% from baseline to last rating for 39 remoxipride (49.4%) and 45 haloperidol (47.6%) treated patients. There were no statistical differences found between the two treatment groups with respect to improvement of negative symptoms and adverse events. The PANSS data suggest that both remoxipride and haloperidol improve the cluster of negative symptoms concerned with social functioning. In addition, the design of the study provides a methodology that is appropriate to the study of primary negative symptoms in schizophrenia.

Will routine therapeutic drug monitoring have a place in clozapine therapy?

Clozapine is an atypical antipsychotic medication with proven efficacy in the management of refractory schizophrenia. It is also recommended for patients who do not tolerate the extrapyramidal adverse effects of traditional antipsychotic medications. However, the therapeutic promise of clozapine has been limited by a higher incidence of agranulocytosis. Currently, plasma clozapine concentrations are not routinely used in clinical management. Therapeutic effects are monitored empirically during a 6 to 8 week titration period in which the dosage is raised to 300 to 450 mg/day. Clozapine nevertheless fulfils a number of criteria which make it a candidate for therapeutic monitoring. These include an identifiable therapeutic range, an unpredictable dose-concentration relationship between patients, a potential for clinically relevant pharmacokinetic interaction with other drugs and a high probability of patient noncompliance. The therapeutic threshold plasma concentration appears to be about 400 micrograms/L. Concentrations above 1000 micrograms/L increase the risk of adverse effects on the central nervous system (confusion, delirium and generalised seizures). There is no evidence to link increased concentrations of clozapine or its metabolite to the development of agranulocytosis. We conclude that therapeutic drug monitoring can play a useful role in the clinical management of patients treated with clozapine. The clinician is advised to primarily use clinical judgement during dosage escalation, but intermittent monitoring is recommended to quickly optimise a therapeutic dosage for each patient. At steady state, occasional measurements could be made when clinical signs indicate possible toxicity or lack of effect (possibly caused by a lack of compliance or drug interaction). Long term monitoring would, in our view, not be necessary.

Can low-dose clozapine pharmacokinetics predict steady-state plasma concentration?

Plasma concentrations of clozapine at a given dose vary considerably between patients, but drug levels are not routinely monitored during the normal 4- to 8-week dose escalation period at the beginning of therapy. We hypothesized that the dose required to give a putative threshold therapeutic concentration of 350 micrograms/L could be individualized using pharmacokinetic predictions made at the beginning of normal dose escalation. Low-dose clozapine (25-75 mg every 12 h) was administered to 21 treatment-resistant patients with schizophrenia who had been split into three groups. In group A (six patients), individual target doses were predicted from area under the concentration-time curve data after a single 50-mg dose. In group B (five patients), predictions were made as in group A but at steady state. In group C (10 patients), predictions were based on trough clozapine levels obtained at steady state immediately before dose increase. Dosage was increased, if tolerated, by 25 mg twice daily three times a week for 4-8 weeks according to established clinical practice. Clozapine concentrations were measured weekly, and actual target doses were determined for each patient from dose-concentration plots. In groups A and B, the correlation between actual and predicted target dose was not significant (r = 0.18, p = 0.59). In group C, however, it was significant (r = 0.86, p = 0.0016). These results suggest that individualized doses of clozapine for treatment-resistant patients with schizophrenia can be conveniently predicted from trough drug levels at the start of therapy. Such information would facilitate a more rapid, individualized, and consistent attainment of therapeutic doses than is now the case in clinical practice.

Famotidine as an adjunct treatment of resistant schizophrenia.

Some patients suffering from schizophrenia fail to respond to or tolerate adequate doses of available antipsychotic medications. Thus, innovative pharmacotherapeutic approaches, such as augmentation strategies, play an important role in the management of these treatment-resistant patients. A recent case report suggested that the administration of famotidine to a patient suffering from schizophrenia with peptic ulcer disease was associated with improvement in the deficit symptoms of schizophrenia. Famotidine is a potent highly selective H2 receptor antagonist which crosses the blood-brain barrier. Impressed by this finding, famotidine was prescribed to some of our treatment-resistant patients suffering from schizophrenia who demonstrated significant deficit symptoms of schizophrenia. The subjects were 12 (eight male, four female) treatment-resistant psychotic patients whose antipsychotic medications were augmented with famotidine in an open trial. They ranged in age from 21 to 48 years with a mean age of 32.75 years. Seven of the 12 subjects made significant improvement resulting in discharge from hospital. Paranoid disturbances as well as absence of comorbid substance use were predictors of good response to famotidine augmentation of the antipsychotic medications. The results implied that H2 receptor activity in the brain might play a role in the pathogenesis of deficit syndromes in schizophrenia. Further studies of this strategy are recommended, since it may open a window of understanding of the negative (deficit) syndrome and its treatment.

Electroconvulsive therapy in Nigeria: psychiatrists attitudes, knowledge and skills.

A survey by a fixed alternative questionnaire of the attitudes, skills and knowledge of Nigerian psychiatrists and trainees was conducted to provide a comprehensive national information on the use of electroconvulsive therapy, ECT, in Nigeria. The response rate to the mailed questionnaire was 44.3%, a moderate but informative response because it is nationally representative. The findings indicate that Nigerian psychiatrists view the use of ECT favourably. About half of the respondents endorse the use of ECT with children under 16 years of age. Compared to other diagnostic categories, Nigerian psychiatrists showed higher preference for the use of ECT with major depression, schizophrenia and manic excitement. The importance of cross-cultural surveys of the attitude to various treatment modalities are highlighted.

Abnormal eating attitudes among a group of Nigerian youths: I. Bulimic behaviour.

The prevalence of bulimic behaviour, a form of abnormal attitude to eating, was investigated among three different samples of Nigerian youths. Using the Binge-Eating questionnaire, a total of 649 females comprising high-school (n = 196), university undergraduate (n = 333) and college of education (n = 120) students were surveyed. A significant proportion of the total student population engaged in bulimic behaviours of bingle-eating (21.16%) and vomiting (22.20%). The various weight control methods they used include diet pills (4.70%), diuretics (6.60%), laxatives (19.50%) and vomiting (26.20%). These findings suggested that bulimic behaviour may be as much a non-western phenomenon as it is a western phenomenon.

Abnormal eating attitudes among a group of Nigerian youths: II. Anorexic behaviour.

A survey of a total of 644 female Nigerian high-school, college and university undergraduate students was conducted to examine abnormal eating attitudes associated with anorexic behaviour. Using a cut-off score of 20 on the Eating Attitudes Test-26 (EAT-26), overall prevalence of disordered eating attitudes was found to be 14.1%. Prevalence figures for the high-school, university, and college samples were 18.6%, 9.1% and 21.7% respectively. These findings are comparable to those from western countries and suggests that nowadays abnormal eating attitudes associated with anorexia behaviour may be a universal phenomenon that transcends cultural boundaries, contrary to the earlier notion that they were restricted to western countries.

Psychiatric emergency services in a Canadian city: I. Prevalence and patterns of use.

The patterns of use of psychiatric emergency services in Saskatoon, Saskatchewan were studied. A total of 576 patients who had received psychiatric emergency care from any of the four major health care facilities in Saskatoon during a three month period were included in the study. Visits for psychiatric emergency services during the study period represented 2.32% of the total number of visits to emergency facilities. Most patients with psychiatric emergencies went to hospitals with psychiatric units. The characteristics of patients served by the four facilities and those who visited the psychiatric emergency services on more than one occasion during the study period are reported. The implications of these findings for health care planning are discussed.

Psychiatric emergency services in a Canadian city: II. Clinical characteristics and patients' disposition.

The clinical characteristics of patients seen at the psychiatric emergency facilities in a Canadian city and the determinants of decisions regarding their treatment were investigated. A total of 544 patients who sought psychiatric emergency services from the three hospitals in Saskatoon during a three month period were studied. Cognitive disturbance, past psychiatric history, previous psychiatric hospitalization and diagnoses of substance use disorders, affective disorders, anxiety disorders and schizophrenic disorders were associated with psychiatric emergencies. Psychiatric diagnoses and availability of social support were significantly associated with disposition. The implications of these findings for psychiatric emergency services are discussed.

Inpatient adolescent psychiatry in a teaching hospital in Nigeria.

The sociodemographic and clinical characteristics of 84 adolescents admitted to the psychiatric unit of a teaching hospital in Nigeria were studied. Their ages ranged from 12-20 years (mean 17). The pattern of psychiatric disorders in this population reflected the pattern in the adult population. Major psychoses comprising schizophrenia (44%), organic brain syndrome (23%), and affective disorders (16%) predominated. Infections and drug abuse are preventable causes of organic brain syndrome. Male adolescents were as likely to be hospitalized for a major psychiatric disorder as female adolescents. The peak period for psychopathology is late adolescence. The contributions of such factors as rural-urban migration, birth order, family size, polygamy and genetics to the etiology of major mental disorders in this population require further investigations. Understanding the prevalence and pattern of presentation of mental disorders in all age groups is essential for effective mental health planning.

Treatment of major affective disorder with fluvoxamine.

A placebo-controlled, double-blind study of 63 inpatients with major affective disorder was performed to compare the safety and efficacy of fluvoxamine and imipramine. Results indicate that fluvoxamine and imipramine are superior to placebo and demonstrate a trend toward superiority of fluvoxamine over imipramine. Fluvoxamine was generally well tolerated in most patients.