Doses Of Neuroleptics Research Articles

Simplified high-performance liquid chromatographic method for determination of risperidone and 9-hydroxyrisperidone in serum from patients comedicated with other psychotropic drugs

A HPLC method was developed for determination of risperidone and its therapeutically active main metabolite 9-hydroxyrisperidone in serum. After a single-step liquid-liquid extraction the analytes were separated on a C 18 column and measured by UV detection at 280 nm. Inter-day coefficient of variation was <7% for both compounds at serum levels occurring in patients treated with ordinary doses. Studies of analytical interference showed that the most commonly coadministered antidepressants and benzodiazepines did not interfere. Some conventional low dose neuroleptics and clozapine did interfere, but this is of minor importance, because risperidone is intended as an alternative to these drugs.

Case-control study of neuroleptic malignant syndrome.

The authors performed a case-control study of neuroleptic malignant syndrome to identify potential risk factors. Twenty-five patients with neuroleptic malignant syndrome were matched with 50 comparison subjects on age, sex, primary psychiatric diagnosis, and time of admission to the hospital. The records of all subjects were reviewed independently by two researchers for information on postulated risk factors. Exploratory direct comparisons of the two groups were followed by a conditional logistic regression analysis. Patients with neuroleptic malignant syndrome were more likely to be agitated or dehydrated before the development of neuroleptic malignant syndrome, often needed restraint or seclusion, and received larger doses of neuroleptics soon after hospitalization. Previous treatment with ECT increased vulnerability. The prevalence of neuroleptic malignant syndrome may be reduced by avoiding large doses of neuroleptics over short periods in the management of acute psychosis and by paying adequate attention to the patient's hydration and electrolyte status.

Incidence and risk factors for severe tardive dyskinesia in older patients.

Severe tardive dyskinesia (TD) represents a serious and potentially disabling movement disorder, yet relatively little is known about the incidence of and risk factors for severe TD. We report the results of a longitudinal prospective incidence study of severe TD in 378 middle-aged and elderly neuropsychiatric patients. Psychiatric, neuropsychological, pharmacological and motor variables were obtained at intake and at regular intervals for 36 months. The cumulative incidence of severe TD was 2.5% after one year, 12.1% after two years, and 22.9% after three years. Individual univariable Cox regression analyses were conducted to identify demographic, psychiatric, motor and pharmacological predictors of severe TD. Results indicated that higher daily doses of neuroleptics at study entry, greater cumulative amounts of prescribed neuroleptic, and greater severity of worsening negative symptoms were predictive of severe TD. These findings suggest that conventional neuroleptics may be prescribed to older patients only when necessary and at the lowest effective dosage. Additional caution is recommended in patients exhibiting negative symptoms.

Chronic neuroleptic exposure in bipolar outpatients.

Although the chronic use of neuroleptic medications is generally discouraged in patients with bipolar disorder, data on the actual extent of this practice are relatively scarce. All bipolar patients receiving treatment at the Connecticut Mental Health Center on September 1, 1994, were identified through a computerized administrative database; the medical record was then examined. Patients were included in the study if (1) the last two recorded diagnoses in the chart were concordant for bipolar disorder and (2) the patient had not been hospitalized in the past year. Of 49 patients meeting review criteria, 33 (67%) met criteria for chronic neuroleptic exposure. The mean +/- SD continuous neuroleptic dosage for these 33 outpatients was 416 +/- 527 mg/day chlorpromazine (CPZ) equivalents. The dosage distribution was skewed, with 17 (52%) receiving < or = 200 mg/day CPZ [corrected] equivalents. Chronic neuroleptic administration occurred frequently in our sample of nonhospitalized bipolar outpatients.

Relationship between negative symptoms in chronic schizophrenia and neuroleptic dose, plasma levels and side effects

The negative symptoms of schizophrenia are often difficult to distinguish from the side effects of antipsychotic medication. In this study, we tried to clarify this issue by studying a group of patients in a clinic setting where a wide range of antipsychotic doses were being prescribed. Thirty-one patients meeting DSM-III-R criteria for schizophrenia or schizoaffective disorder were studied. Clinical ratings were carried out to assess the positive and negative symptoms of schizophrenia, parkinsonism, akathisia and tardive dyskinesia. Plasma levels were also measured for the majority of patients. Antipsychotic plasma levels were found to be highly correlated with dose. Antipsychotic dose and plasma levels were not correlated with the severity of negative symptoms, akathisia or parkinsonism. However, the severity of positive symptoms and tardive dyskinesia were positively correlated with both dose and plasma level. These findings do not support the hypothesis that higher doses of antipsychotic medication are associated with more severe negative symptoms.

Side effects of low dose neuroleptics and their impact on clinical outcome in generalized anxiety disorder

1. 1. The present study was designed to determine the impact of neuroleptic side effects on clinical outcome in generalized anxiety disorder. 2. 2. 205 outpatients entered the study. In an open label design fluspirilene 1.5mg per week was administered for a period of 6 weeks. 3. 3. Consistent with previous studies fluspirilene demonstrated again anxiolytic properties and was in general tolerated well. 4. 4. However, in responders significantly less side effects were observed than in nonresponders. The interaction between tolerability and clinical outcome is the main finding of the present study. 5. 5. In conclusion, the data suggest, that neuroleptic treatment of generalized anxiety disorder should be guided by paying more attention to potential side effects. If under neuroleptic treatment of generalized anxiety disorders side effects are observed, pharmacotherapy should be discontinued, because this fact predicts an unfavourable clinical outcome.

Neuroleptic dosing in chronic schizophrenia: a 10-year follow-up.

To evaluate neuroleptic dosing patterns in individuals with schizophrenia over a 10-year interval. Changes in neuroleptic dosing between 1980 and 1990 were followed in 65 patients with a diagnosis of chronic schizophrenia. According to more recent dosing guidelines, doses were already high at the time of initial evaluation, yet overall they continued to increase during the next decade of treatment for both males and females. Patients were almost equally divided, however, by those who underwent an increase (n = 33) and those whose dose remained stable (n = 4) or was decreased (n = 28). A considerable number of patients with schizophrenia appear to receive progressively higher neuroleptic doses over the course of their illness, despite a lack of empirical data to support such an approach. Results are discussed in terms of current dosing recommendations and factors influencing dose changes.

Utilization of neuroleptic drugs in Italian mental health services: a survey in Piedmont.

This survey describes neuroleptic prescribing practices in Italian mental health services 15 years after implementation of a mental health reform law that shifted the focus of care from mental hospitals to community services. The authors conducted a cross-sectional survey of neuroleptic prescribing practices in several psychiatric services throughout the Piedmont region in northern Italy. The relationship between dosing patterns and patients' characteristics was assessed using multiple regression analysis. Sixty-six community mental health services and 14 psychiatric wards in general hospitals participated in the survey in 1991. Among the 3,823 psychiatric patients seen in these settings for whom survey data were available, 67 percent of outpatients and 84 percent of inpatients were prescribed neuroleptic drugs. Twenty-eight percent of outpatients and 45 percent of inpatients received more than one neuroleptic. The average daily dose of neuroleptics was low to moderate; 89 percent of outpatients and 67 percent of inpatients received 500 mg of chlorpromazine equivalents or less. The neuroleptic dose was significantly associated with patients' age, education, diagnosis, length of treatment, and receipt of polypharmacy. This survey confirms the low to moderate neuroleptic dosing in Italian mental health services, both in outpatient and inpatient settings. However, it also documents the widespread use of polypharmacy, a pattern that has remained largely unchanged over the past 15 years.

Effect of smoking on neuroleptics in schizophrenia

The effect of smoking on daily doses and plasma levels of neuroleptics prescribed for schizophrenic patients was studied. 90 outpatients with schizophrenic disorder (DSM-III-R) who were on a stable regimen of psychotropic medication and showed a stable clinical state were included in a double-blind placebo-controlled trial. Data were collected and blood tests taken at the baseline interview. The plasma levels were obtained for 52 patients. Daily neuroleptic doses converted to chlorpromazine equivalents correlated significantly (r = 0.436) with the plasma levels of their unmetabolised fractions. The neuroleptic doses increased with age in smokers, while in nonsmokers they decreased. Neither sex, age nor smoking had a significant association with the neuroleptic plasma levels. Smoking seems to lead to increased neuroleptic dosages in postmenopausal schizophrenics by increasing hepatic metabolism and renal excretion of the drugs and possibly enhancing dopamine release. It is also possible that older smoking patients form a selected group of heavy smoker and they, therefore, need exceptionally high neuroleptic doses.

Correlations between standard auditory evoked potentials and symptomatology in a group of 50 schizophrenic patients

Standard auditory evoked potentials (AEP) were recorded in 50 schizophrenic patients and 47 normal controls. All patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Positive and Negative Syndrome Scale (PANSS), and were classified in three groups (positive-type [n = 10], negative-type [n = 23]and mixed-type [n = 17]patients) according to the normative criteria suggested by Kay. The mean latencies of AEP components (N1, P2, N2) and mean peak-to-peak amplitudes (N1P2, P2N2) did not correlate with age, duration of illness, length of hospitalisation or neuroleptic dosage. The evoked response did not differ between the three groups of patients (positive, negative and mixed). There was only a trend (P = 0.075) to a longer N1 latency in the negative-type group and a shorter one in the positive-type group than in the mixed-type and the control groups. The latency of N1 component correlated significantly with negative symptoms of schizophrenia (SANS scores). This correlation was related to the severity of a depressive dimension of the disorder reflected by the "depressive factor" of BPRS or "affective flattening" and "avolition" subscales of SANS.

Treatment of tardive dyskinesia.

Although the new generation of atypical antipsychotic agents could some day eliminate concerns about tardive dyskinesia (TD), this disorder remains a significant clinical problem for both patients and physicians. Fortunately, many, if not most, cases of TD are mild. For patients with mild to moderate TD, therapeutic efforts are primarily directed at minimizing neuroleptic exposure or, when possible, changing to atypical agents. Most cases of TD do not seem to progress, suggesting that the risk of remaining on typical neuroleptics is probably small. Patients with moderate to severe forms of TD present greater challenges. These patients frequently require medication to suppress their dyskinesias. A variety of suppressive agents have been tried with limited success. No treatment strategy has emerged that is clearly superior or even successful in most patients. Increasing doses of typical neuroleptics may be useful for short-term suppression; however, the long-term efficacy and risk of this strategy have not been studied carefully. Data on atypical neuroleptics are scant. Clozapine's short-term suppressive effects seem, at best, weak, but patients may improve with long-term treatment. Medications with relatively few side effects that may have suppressive efficacy for some patients include calcium channel blockers, adrenergic antagonists, and vitamin E. Gamma-amino-butyric acid agonists agents and dopamine depleters are frequently useful, but have troubling side effects of their own. A variety of other medications have been employed, but are not well studied. For patients with tardive dystonia, anticholinergic agents or botulinum toxin has been particularly effective. Efforts to understand the neurobiology of TD may shed light on this persistent clinical conundrum.

Neuroleptics in acute mania: a pharmacoepidemiologic study.

To provide an epidemiologic descriptive analysis of the acute drug treatment of inpatients with bipolar mania in state psychiatric facilities in 1990. We surveyed the first 3 weeks of drug treatment of all inpatients with bipolar mania who were admitted to 22 New York State adult psychiatric facilities during a 6-month period (n = 528). Almost all patients with mania were treated with neuroleptics. The mean +/- SD neuroleptic dosage was 684 +/- 543 mg/d chlorpromazine equivalents. Sixty-one percent of the patients received lithium and 12% received carbamazepine or valproate. Neuroleptic dosage was related to age, with older patients receiving lower dosages. Patients receiving combination treatment of a neuroleptic with either lithium, an anticonvulsant, or a benzodiazepine received a mean neuroleptic dosage similar to that of patients treated with a neuroleptic alone. Although their use has been widely discouraged for mood disorders, neuroleptics have been the standard treatment for acute mania.

Lack of gender differences in neuroleptic response in patients with schizophrenia

Objective: The authors sought to determine if there were gender differences in neuroleptic response in male and female patients with schizophrenia who were matched for clinical and demographic variables and participated in a double-blind trial of traditional antipsychotic drugs. Methods: 24 males (m) and 20 females (f) with schizophrenia or schizoaffective disorder who did not differ in clinical characteristics (age of onset, course of illness, prior hospitalizations, premorbid functioning) participated in an extended drug-free period followed by a neuroleptic trial under double-blind, placebo-controlled conditions. Results: Males and females showed significant improvement in total, positive and negative BPRS symptoms during neuroleptic treatment. However, there were no significant differences in treatment response between sexes. No sex differences were found in baseline drug-free symptomatology, neuroleptic dose or dosage by weight. Conclusions: There were no significant sex differences in neuroleptic treatment response in male and female patients well-matched for clinical, treatment and demographic characteristics. Methodological issues which distinguish this study from prior studies reporting gender differences in neuroleptic response are examined.

Drug treatment of schizophrenia and delusional disorder in late life.

As people live longer, an increasing proportion of patients with schizophrenia and delusional disorder will be elderly. Little has been published on treatment response, effective treatment strategies, or the use of atypical neuroleptics in this group. This review of the literature explores documented response rate, route and dose of neuroleptic, indicators of poor response, and the use of novel drugs. Despite great variation in the neuroleptic dose ranges employed, patients with late-onset disease often continue to experience psychotic symptoms. Compliance with treatment is the most important determinant of outcome. Atypical neuroleptics are specifically indicated for patients with visual hallucinations or extrapyramidal symptoms. Elderly psychotic patients should be treated as vigorously and with as wide a range of neuroleptics as their younger counterparts. Physicians should not restrict drug doses to modest levels in all cases as long as patients are monitored frequently for the emergence of side effects.

Micro-titration of depot neuroleptic dosages

Depot neuroleptic treatments can be compromised by side-effects unacceptable to users or, more seriously, by tardive dyskinesia (TD). Neuroleptic dosages can be lowered to increase acceptability and decrease the Incidence of TD, but with a greater likelihood of relapse. One argument proposes that many patients changing to lower dosages break down because withdrawal from a neuroleptic is stressful in itself. Research suggests that withdrawal regimes should be radically cautious. A computer tool is offered which can aid clinicians in calculating small reductions.

Blink rate, neurocognitive impairments, and symptoms in schizophrenia

This study addresses the relationship between blink rate (as a measure of central dopaminergic activity), symptoms, neuropsychological performance, as well as neurological signs in schizophrenia. Blink rate between schizophrenic patients and a matched control group was compared in both "relaxed" and "attentive" conditions. Blink rate was increased in schizophrenic patients in the "relaxed" condition but not in the "attentive" condition. The relationship between blink rate and clinical variables was examined in a larger sample of 204 patients. In both "relaxed" and "attentive" conditions, blink rate was related to "hallucinations," "anxiety," negative symptoms, and neuroleptic dosage. Attention was a significant predictor only in the "relaxed" condition. No other significant correlation was found between blink rate, neuropsychological impairments, and neurological signs. These findings suggest that blink rate is not related to neurocognitive impairments in schizophrenia.

Lithium and neuroleptics in combination: is there enhancement of neurotoxicity leading to permanent sequelae?

Neurotoxicity in relation to concomitant administration of lithium and neuroleptic drugs, particularly haloperidol, has been an ongoing issue. This study examined whether use of lithium with neuroleptic drugs enhances neurotoxicity leading to permanent sequelae. The Spontaneous Reporting System database of the United States Food and Drug Administration and extant literature were reviewed for spectrum cases of lithium/neuroleptic neurotoxicity. Groups taking lithium alone (Li), lithium/haloperidol (LiHal) and lithium/ nonhaloperidol neuroleptics (LiNeuro), each paired for recovery and sequelae, were established for 237 cases. Statistical analyses included pairwise comparisons of lithium levels using the Wilcoxon Rank Sum procedure and logistic regression to analyze the relationship between independent variables and development of sequelae. The Li and Li-Neuro groups showed significant statistical differences in median lithium levels between recovery and sequelae pairs, whereas the LiHal pair did not differ significantly. Lithium level was associated with sequelae development overall and within the Li and LiNeuro groups; no such association was evident in the LiHal group. On multivariable logistic regression analysis, lithium level and taking lithium/haloperidol were significant factors in the development of sequelae, with multiple possibly confounding factors (e.g., age, sex) not statistically significant. Multivariable logistic regression analyses with neuroleptic dose as five discrete dose ranges or actual dose did not show an association between development of sequelae and dose. Database limitations notwithstanding, the lack of apparent impact of serum lithium level on the development of sequelae in patients treated with haloperidol contrasts notably with results in the Li and LiNeuro groups. These findings may suggest a possible effect of pharmacodynamic factors in lithium/neuroleptic combination therapy.

Proton magnetic resonance spectroscopy of the basal ganglia in patients with schizophrenia: a preliminary report

To examine metabolic changes in the left basal ganglia in chronic schizophrenia, we performed proton magnetic resonance spectroscopy ( 1H-MRS) in 21 medicated schizophrenic patients and 21 gender- and age-matched normal controls. Compared to the normal subjects, the schizophrenic patients showed a significantly increased level of choline-containing compounds (Cho) ( t=2.60, p ⩽ 0.05) and ratio of Cho to N-acetylaspartate (NAA) ( t=2.46, p ⩽ 0.05) in the left basal ganglia. No significant correlation was observed between the 1H-MRS measurements in the left basal ganglia and clinical symptom scores as evaluated using the Brief Psychiatric Rating Scale (BPRS). The chlorpromazine-equivalent neuroleptic dosage was positively correlated with the level of NAA ( r=0.38, p ⩽ 0.05) and negatively correlated with the Cho/NAA ratio ( r = −0.34, p ⩽ 0.05). These findinds suggest that these changes in metabolites in the left basal ganglia may reflect some of the functional and morphological abnormalities reported previously for the brain in schizophrenia.

Neuroleptic-Induced Parkinsonism in Elderly Patients Diagnosed With Psychotic Major Depression and Dementia of the Alzheimer Type

The authors prospectively examined elderly patients diagnosed with major depression with psychotic features (MD-P) and patients diagnosed with dementia of the Alzheimer Type (DAT) for neuroleptic-induced parkinsonism (NIP) during perphenazine treatment. Baseline parkinsonian symptoms did not differ between groups. With treatment, mean NIP score doubled in DAT patients but remained unchanged in the MD-P group. The difference between groups was highly significant and remained so after the effects of age, perphenazine dose, and duration of perphenazine treatment were controlled. Although the mechanisms underlying these differences in NIP development remain to be determined, clinical guidelines for neuroleptic dosages in elderly patients need to account for variability in neuroleptic tolerance between diagnostic groups.

Does minimizing neuroleptic dosage influence hyponatremia?

Neuroleptic dosage was reduced by 10% every 2 weeks in five male hyponatremic polydipsic patients with schizophrenia. Mean dose fell from 1980 ± 1289 to 631 ± 135 chlorpromazine equivalents/day over a mean of 12.2 weeks until behavioral relapse occurred. During this time, serum sodium did not vary from baseline levels (132.9 ± 4.9 mEq/1), suggesting that minimizing neuroleptic dose does not alter the severity of hyponatremia in these patients.