High Doses Of Neuroleptics Research Articles

When bipolar was still called manic depression: Getting sick in the era of the DSM–II.

This article is a first-person account of what it was like to be bipolar in the late 1970s, in the final days of the DSM-II. The field was on the verge of transitioning from psychodynamic psychiatry to biological psychiatry. During this period, nosology and etiology were confounded, and there was little diagnostic agreement across practitioners. Psychiatric admissions often lasted 6 months or more. Available treatments and conditions were sometimes harsh and iatrogenic: being housed with lobotomized people, rodent-infested municipal hospitals, prolonged periods in restraints and solitary confinement, cold wet sheets, high doses of neuroleptics or the withholding of medication, inadequate access to medication upon discharge, and even sexual misconduct by clinicians. This is also an account of resilience, the life-saving benefit of good treatment. It stresses the need to treat the persons trapped within the disease and to help clients become an active agent in their own recovery. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Spotlight on Oculogyric Crisis: A Review.

Background:Oculogyric crisis (OGC) is a form of acute dystonia characterized by sustained dystonic, conjugate, and upward deviation of the eyes. It was initially reported in patients with postencephalitic parkinsonism. But later, other factors such as medications, movement disorders, metabolic disorders, and focal brain lesions were also found to be associated with OGC.Methods:The literature regarding OGC was searched via PubMed, Google Scholar, and through citations in relevant articles till December 2019, with keywords including OGC, oculogyric eye movements, tonic eye movement, neuroleptics and OGC, antipsychotics and OGC, and all combinations of these. Only original articles (abstract or full text) that were published in the English language were reviewed.Results:Hypodopaminergic state is implicated in the pathogenesis of OGC. Common risk factors are younger age, male sex, severe illness, high neuroleptic dose, parenteral administration of neuroleptics, high potency of neuroleptic drugs, abrupt discontinuation of anticholinergic medication, and family history of dystonia.Conclusion:OGC is an acute dystonic reaction leading to tonic upward deviation of eyes. It is associated with various neurometabolic, neurodegenerative, and movement disorders and medications such as antipsychotics, antiemetics, antidepressants, antiepileptics, and antimalarials. OGC can adversely impact the compliance and prognosis of the primary illness. Hence, it needs to be managed at earlier stages with appropriate medication, primarily anticholinergics.

Neuroleptic Malignant Syndrome, a Sequalae of Multiple Administration of Antipsychotics: A Case Report

Neuroleptic malignant syndrome (NMS) is a lethal adverse drug reaction (ADR) that is often attributed to the administration of dopamine blockers, antiemetic agents as well as anti-parkinsonism medication withdrawal. We describe a challenging case of NMS, with malignant catatonia as a differential diagnosis, who was difficult to respond to treatment. The patient developed severe complications following her exposure to rapid titration using high doses of olanzapine, which was abruptly converted to chlorpromazine due to lack of efficacy, in addition to administering multiple as needed (PRN) medications for agitation. Hyperthermia, muscle rigidity, dysautonomia, mental status changes, catatonia, and some laboratory derangement were reported in this case. It is possible that factors such as naïve patients, high doses of neuroleptics, a switch from one agent to another, rapid escalation, and the increased use of parenteral therapy for managing of agitation acted collectively or individually as risk factors for developing NMS. Health care professionals should be cautious about the cumulative dose of antipsychotics used per day, including PRN medications. The delay in recognizing the early symptoms of NMS could put patients at higher risk of mortality. Lastly, it is pivotal to exclude other infectious or autoimmune etiologies before treating as NMS case.

High-Dose Neuroleptics and Neuroleptic Rotation for Agitated Delirium Near the End of Life

Agitated delirium presents unique challenges for hospice and palliative care clinicians. Haloperidol, the recommended neuroleptic, may be ineffective at low dose, or poorly tolerated at higher doses. This article reports on two patients with refractory agitated delirium. Both developed extrapyramidal symptoms from haloperidol and required rotation to an alternate neuroleptic. Patient #1 received 2000 mg/day oral chlorpromazine. Patient #2 received greater than 200 mg/day sublingual olanzapine. Control of agitation was achieved, though the doses were substantially higher than has previously reported in the literature. Each patient experienced considerable sedation, though this was an acceptable side effect for the family. Each patient was transferred from the acute care hospital to a location of family preference. There they died within a week of transfer. Agitated delirium is a palliative care emergency. High doses of neuroleptic medications, with rotation to an alternate neuroleptic when side effects occur with standard haloperidol, may effectively palliate agitated delirium. This remedy can provide the patient with a peaceful dying in a place of their choosing.

Schizophrénie et violence : incidence et facteurs de risque à propos d’une population tunisienne

Schizophrenia appears to be the mental pathology the most associated with violence. The aim of this study is to show the incidence and the different risk factors of violence among schizophrenics. We have compared a group of 30 violent schizophrenic inpatients with another group of 30 nonviolent schizophrenic inpatients hospitalised during the same period. These two groups have been matched according to age and gender. The comparison concerned: sociodemographic parameters, family and personal psychiatric history, legal antecedents, social insertion, clinic, Clinical Global Impressions (CGI), Global Impairment Scale (GIS) and Positive And Negative Syndrome Scale (PANSS) scores for admissions, familial support and insight, compliance to treatment, administered treatments, and awareness degree. Violent schizophrenics represent 18.07% of all hospitalisations and 26.08% of schizophrenic patients. When compared to violent schizophrenic patients, nonviolent schizophrenic patients have a better socioeconomic level (77% versus 43%), better professional adaptation (67% versus 10%) and familial support (60% versus 10%), better insight (87% versus 23%) and therapeutic control (70% versus 17%). Differences are significant. We found significantly more personal antecedents of inflicted violence within violent schizophrenics (50% versus 13%), more addictive behavior (53% versus 13%), and more paranoid and indifferentiated forms (87% versus 47%) than in nonviolent schizophrenics. The average of CGI scores was significantly higher within violent schizophrenics (5.27+/-0.8 versus 3.77+/-0.5). Conversely, the average of EGF scores was lowest (37.6+/-6.5 versus 47.8+/-5.6). The comparison of PANSS scores revealed that violent schizophrenic subjects are characterised by the existence of more positive signs and more general symptoms (34.4+/-4.7 versus 20.2+/-4.5; 55.1+/-11.4 versus 46.1+/-6.9). Violent schizophrenics are characterised by higher neuroleptic doses (2375+/-738 mg/d versus 1610+/-434 mg/d). Differences here are also significant. Addictive behaviour seems to considerably increase the risk of turning to violence. Thus in our study, 53% of violent patients showed an addictive behaviour. These results have also been reported by other authors. It is obvious that alcohol and drug abuse double the risk of violence among schizophrenic subjects. Psychotic decompensation and rich symptomatology increase the violent potential among the schizophrenics. In our study, the PANSS scores were higher among violent subjects. Nonviolent schizophrenic subjects have a lesser symptomatology of psychiatric disorders and a better outcome as shown by the CGI and EGF scores. In our study, the group of violent subjects needed higher neuroleptic doses and were noncompliant. Compliance permits the acquisition, and then maintains, the stability of the mental status and plays an essential role in decreasing dangerousness. In fact, violent schizophrenics exhibit low insight, implying diminished awareness of the legal implications of their acts, and are little aware of their illness and its dangerousness. In our study, we noted better familial support among nonviolent subjects. According to the literature, violent schizophrenics are characterised by a particularly hostile and rejecting familial environment. Awareness of these factors will allow us to provide improved prevention of violence within schizophrenic subjects.

The reliability of compliance assessments performed by doctors and patients during neuroleptic treatment: a comparison of compliance ratings

Objective: To compare compliance assessments made by doctors and patients during neuroleptic drug treatment and to detect any variables explaining the discrepancies between their ratings. Method: Compliance reports regarding neuroleptic medication were collected from 100 in-patients and out-patients and from their doctors. Re-ratings were performed after 1–2 weeks. Compliance ratings were compared with demographic, treatment and symptom-related variables and with the Attitudes to Neuroleptic Treatment (ANT) questionnaire using logistic regression analysis. Results: The doctors' and patients' compliance ratings showed good test–retest reliability (r=0.80, doctors; r=0.81, patients) and concordance (79% of the cases within the limits of ±25%-units deviation). Variables explaining discrepancies between the ratings included female gender, a low level of education, the diagnosis of mania, a high neuroleptic dose and several items from the ANT scale. Conclusion: Manic episodes, negative attitudes to neuroleptic medication and a high-dose treatment increase the risk for deviating views of compliance in the doctor–patient relationship.

Mortalité et causes de décès dans la schizophrénie : étude prospective entre dix et 14 ans d’une cohorte de 150 sujets

The aim of this study was to quantify the mortality risk in chronic schizophrenic patients, ten to 14 years after the initial evaluation. Furthermore, using sociodemographical, clinical and psychometrical variables evaluated at inclusion, predictors of global or mortality by suicide were explored. One hundred and fifty subjects meeting the research diagnostic criteria (RDC) for chronic schizophrenia were included in the study between 1991 and 1995. At the initial assessment, the following variables were assessed: sex, age, level of education, number of hospitalisations, mean duration of the illness, scores on the physical anhedonia scale, the brief psychiatric rating scale (BPRS), the positive and negative syndrome scale (PANSS), and Beck's depression inventory (BDI). In May 2005, all the subjects were assessed using direct or indirect methods. Survival analysis was conducted using the Kaplan-Meier product-limit estimator and a standardized mortality ratio (SMR) was calculated. Multivariate Cox regression was performed to detect predictive factors associated with mortality. The absolute mortality rate was of 18.57% and the RSM of 4.83. The absolute mortality rate for suicide was 6.98%. Multivariate Cox regression analyses showed that two factors (high rate of males, high dose of antipsychotics) were related to an increase in global mortality risk. Moreover, high dose of antipsychotics and a high rate of "positive" subjects, as evaluated by the PANSS, were related to an increase in mortality risk by suicide. High dose of neuroleptics could characterize the severe form of schizophrenia, the risk of mortality of which was higher than that of the less severe forms. Another explanation was that high doses of neuroleptics could lead to severe side effects and thus an increase in the vulnerability of schizophrenics to organic diseases. Positive, contrary to negative, symptoms could increase the risk of suicide. This 14-year follow-up study confirmed the increased mortality rates by natural and non natural causes observed in chronic schizophrenic subjects.

NEUROLEPTIC MALIGNANT SYNDROME IN CHILDREN

Objectives: Neuroleptic Malignant Syndrome (NMS) is a potentially life threatening condition, uncommon in children, characterized by hyperthermia, muscle rigidity, elevated creatine kinase (CK) levels, and autonomic instability. It is often precipitated by use of high dose neuroleptics. The purpose of this study is to raise awareness of the course and prognosis of NMS in a pediatric population to optimize strategies for early diagnosis and effective interventions.

Cigarette smoking in long-term schizophrenia

Purpose. – Cigarette smoking is a great health problem and prevalent among subjects with schizophrenia. Our aim was to investigate the prevalence and associations of cigarette smoking in patients with long-term schizophrenia. Methods. – Seven hundred and sixty schizophrenia patients were interviewed and their cigarette smoking was recorded. Results. – Smoking was more prevalent men than in women patients. In logistic regression analysis, male gender, duration of illness (DUI) from 10 to 19 years, being divorced or separated, lower education and high daily doses of neuroleptics (DDN) associated significantly with regular smoking. Heavy smoking associated, in men, with hospital treatment. Conclusions. – In schizophrenia patients, smoking is associated with long DUI, high DDN and institutional care. Interventions for cessation and/or reduction of cigarette smoking should be a part of the treatment for patients with schizophrenia.

Older people with schizophrenia: a community study in a rural catchment area

An increasing number of older people with schizophrenia are living in the community but we still have little data on their clinical presentation, service use and functioning. All patients over the age of 60 years with a primary diagnosis of a non-affective psychotic disorder who were known to health services were identified in a rural area of East England. Subjects were interviewed with the Present State Examination and other standardised interview instruments. Seventy-two subjects fulfilled study inclusion criteria. Forty-six of these had first become ill before the age of 60 years and 26 after (the very late onset group (VLO)). Eighty per cent were women and 26% had never married. Eighty-seven per cent lived in their own homes and 51% alone. In the preceding month, 41% of the sample had experienced psychotic symptoms and 15% depressive symptoms. Twenty-seven per cent of the sample were cognitively impaired. The earlier onset group had significantly higher rates of tardive dyskinesia and negative symptoms of schizophrenia and were treated with higher doses of neuroleptics. The VLO group had higher rates of hearing impairment (54% vs 15% p = 0.001) and of partial or no insight (93% vs 55% p = 0.004). Despite significant differences in presentation, elderly patients with schizophrenia and very late onset schizophrenia-like psychosis have much in common. Both groups are vulnerable with high levels of psychopathology, poor insight, sensory impairment and social isolation. The needs of older people with schizophrenia must be taken into account when services for older adults are planned.

Risk factors in neuroleptic malignant syndrome. A case-control study.

To determine whether environmental temperature, agitation, neuroleptic use, mental retardation, and affective disorders were risk factors for neuroleptic malignant syndrome (NMS). Cases and age- and sex-matched psychiatric controls admitted to a regional acute psychiatric unit over a 10-year period. Both uni- and multivariate analysis revealed statistically significant differences between patients with NMS (n=15) and controls (n=45) with regard to the presence of mental retardation, psychomotor agitation, and a number of variables relating to neuroleptic use (newly introduced or increased, intramuscular administration, and dosage). We found no differences between NMS patients and psychiatric controls in respect of changes in environmental temperature. Our study supports the need for caution when using intramuscularly administered, abruptly increasing, high-dose neuroleptics, particularly in mentally retarded or agitated patients, regardless of environmental temperature.

High dose neuroleptics – who gives them and why?

Aims and MethodNeuroleptic medication is often used in excess of the BNF maximum. The purpose of this study was to examine the relationship of neuroleptic dose to patient, prescriber and environmental factors, by using a cross sectional ‘snapshot’ study of psychiatric in-patient prescriptions combined with a retrospective case note survey.ResultsIt was found that certain consultants prescribe higher doses of neuroleptics than others. Patients with a history of aggression had a nine and a half times higher chance of being prescribed higher doses of neuroleptics. Patients with a greater than 5-year history of neuroleptic prescription received higher doses.Clinical ImplicationsHigh neuroleptic prescription is related more to patients' past reputation and prescriber differences than to patients' current behaviour.

Off-label prescribing by psychiatrists

A questionnaire was sent to 200 psychiatrists asking them about their off-label prescribing in the preceding month. One hundred and sixteen replies (58%) were obtained. Seventy-six (65%) respondents had prescribed medication off-label within the past month. Only 5 (4%) had ever received a complaint from patients related to their off-label prescribing. If this region is typical, off-label prescribing is common amongst psychiatrists. No formal guidelines exist except for the use of high dose neuroleptics. A suggested guideline is given in this article.

Atypical antipsychotics in ordinary clinical practice: a pharmaco-epidemiologic survey in a south London service

The introduction of atypical antipsychotics has triggered a reevaluation of treatment strategies in schizophrenia. Although research findings inform about the efficacy and safety of drugs, it is the decisions made daily in ordinary practice that affect the vast majority of patients. The aim of this paper was to examine the use of atypical antipsychotics in clinical care, by means of a survey of prescribing practices for clozapine, risperidone, olanzapine, sertindole and quetiapine for all patients treated for DSM-IV schizophrenia within a psychiatric service. Seventy-five (26%) of the 286 patients identified were on atypical antipsychotics. Patients on clozapine were mostly male, had more than 15 years of contact with psychiatric services and were poor responders. Patients prescribed other atypicals had responded to prior treatment with typical neuroleptics and had less than five years of contact with psychiatric services. Gender distribution was equal in this group. The use of research criteria for treatment resistance identified only one patient, as prolonged use of high-dose neuroleptics was uncommon. The new atypical antipsychotics appear to be replacing older neuroleptics as the first-line treatment of schizophrenia while clozapine is mostly reserved for poor responders. Clinicians' definition of treatment resistance was variable and below the threshold used in research.

Dosage of conventional neuroleptic medication and subjective cognitive functioning in schizophrenia

Subjective cognitive and perceptual disturbances as assessed with the Frankfurt Complaint Questionnaire (FCQ) were correlated with chlorpromazine equivalents in 40 schizophrenic inpatients, who were treated with conventional neuroleptics. In line with previous research using 'objective' neuropsychological tests, both correlations and partial correlations (controlling for the effects of psychopathology, extrapyramidal symptoms and length of illness) confirmed that higher neuroleptic doses significantly worsen several cognitive and perceptual domains (r = 0.44 -0.54; P < or = 0.005 -0.05) with the possible exception of mnestic functions (r = 0.21 -0.24, n.s.) and language (r = 0.37 -0.38, P < 0.1). The clinical importance of self-report scales for evaluating both the risks and benefits of neuroleptic treatment is discussed.

High-dose antipsychotic medication in maximum security

This study compares patients in an English Special Hospital treated on high doses of neuroleptics with a matched group of patients on standard doses. High-dose patients had significantly more psychiatric morbidity and side-effects than controls. They were also rated as more aggressive, but psychosis rather than aggression best predicted antipsychotic dose. This study adds support to the case that there is little benefit from the use of high-dose antipsychotics.

Drugs That Induce Delirium

Drug-induced delirium is often seen in clinical practice. Most knowledge about delirium-inducing drugs comes from reports on side effects, and few systematic studies have been done in the field. Delirium is strongly associated with anticholinergic activity; drugs of different classes, including tricyclic antidepressants and traditional high-dose neuroleptics, constitute a high-risk group. A large number of drugs, including benzodiazepines, sedatives, dopamine-activating drugs, antiepileptics, histamine H2 receptor blockers, digitalis and analgesics, are less frequently associated with delirious reactions and constitute a medium-high-risk group. Some of these drugs do not have anticholinergic effects but in vitro have shown to bind to muscarine receptors. The risk of inducing delirium in frail elderly and demented persons clearly suggests that drugs which might induced delirium should be avoided.

QUALYOP project 2: monitoring the dismantling of Italian psychiatric hospitals. Psychotropic drug use in 1072 inpatients.

This study describes the use of psychotropic drugs in a sample of eight Italian psychiatric hospitals. A cross-sectional approach was used to collect information about sociodemographic and clinical characteristics of the inpatient population, and about medications prescribed. Prescribing behaviour in the hospitals was compared using three indicators: the number of patients taking psychotropic drugs, the use of high doses of neuroleptics and the use of multiple neuroleptics. More than a thousand patients were resident in the eight hospitals on the census day, 56% of them males. Half the population had an ICD-X diagnosis of schizophrenia, one third of mental retardation. Sixty-nine percent of the sample was on neuroleptic therapy, nearly 47% on benzodiazepines and 4% on antidepressants. Twenty percent of the sample did not take any psychotropic drug on the census day. After adjustment for sociodemographic and clinical variables, setting-related variables resulted as determinants of psychotropic drug use. These data call for continuing education in psychopharmacology towards a more rational use of drugs; longitudinal audits of clinical practice should be implemented to guide clinicians toward a more rational use of psychotropic drugs.

D(2)- and 5-HT(2) receptor occupancy in high-dose neuroleptic-treated patients.

Individual schizophrenic patients are sometimes reported to benefit from unusually high doses of neuroleptics. Such patients may have poor drug penetration into the brain or ultra-rapid metabolism. Alternately, very high doses may be required to induce occupancy of 5-HT(2) receptors, which have been suggested as mediators of atypical effects. Five schizophrenic patients treated with high doses of fluphenazine decanoate (100-250 mg/wk) and adjunct medications were examined with positron emission tomography and [(11)C]raclopride to measure D(2) receptor occupancy and [(11)C]NMSP to measure 5-HT(2) receptor occupancy. All patients were rated globally as 'markedly' to 'severely' ill and had high scores on all subscales of the Positive and Negative Syndrome Scale for schizophrenia. However, according to retrospective clinical evaluation, there was improved social function and reduced distress following high-dose treatment, an effect that deteriorated after previous explorative dose reduction. Extrapyramidal symptoms were modest. D(2) receptor occupancy was very high (89-97%). 5-HT(2) receptor occupancy was also high (76-105%). Plasma concentrations of fluphenazine were 5-37 nm. No patient had a cytochrome P450 CYP2D6 genotype associated with ultra-rapid drug metabolism. The findings suggest almost complete saturation of D(2) receptors, and do not support poor drug availability in the brain as the basis of the apparent high-dose requirement. The high 5-HT(2) receptor occupancy may have contributed to the apparent clinical improvement and modest degree of EPS. However, it is likely that the treatment used also induced occupancy of other neuroreceptors.

Clinical and pharmacologic risk factors for neuroleptic malignant syndrome: a case–control study

Background: Pharmacologic and clinical risk factors for neuroleptic malignant syndrome have been suggested. High neuroleptic dose, rapid dosage increase, and parenteral administration were identified as risk factors in a case–control study; however, there are limited data regarding potential clinical risk factors. Methods: To examine potential clinical risk factors, we conducted a case–control study, comparing 12 cases to 24 controls, all treated with neuroleptics at our center. In addition to examining previously postulated pharmacologic risk factors, we also assessed for presence of psychomotor agitation, confusion, disorganization, and catatonia. Results: Significant differences were found between cases and controls for psychomotor agitation, confusion, disorganization, catatonia, mean and maximum neuroleptic dose, parenteral neuroleptic injections, neuroleptic dose increase within 5 days of the episode, magnitude of neuroleptic dose increase from initial dose, and extrapyramidal signs. Conclusions: This study demonstrated that psychopathological features such as psychomotor agitation, confusion, disorganized behavior, and catatonia may be risk factors for the neuroleptic malignant syndrome, in addition to pharmacologic risk factors and extrapyramidal signs, including akathisia. In clinical practice, careful monitoring for prodromal signs of neuroleptic malignant syndrome is required during neuroleptic treatment of patients with psychomotor agitation, confusion, and/or disorganization, while in the presence of catatonia these drugs should be avoided.