Multiple sclerosis (MS) is a chronic, debilitating disease for which there is no cure; however, the recent introduction of injectable immunomodulating agents has reduced the rate of relapsing ...episodes and possibly slowed the progression of the disease. These disease‐modifying agents are recommended by the National MS Society, but their true potential cannot be realized if patients do not accept them and healthcare professionals do not promote them. Since MS has an unpredictable course, and treatments can produce side effects, adherence to the recommended therapy is a complex and challenging issue. Improved understanding of the obstacles to adherence and the identification of possible solutions should be of value to nurses, who have numerous opportunities to encourage patients to initiate and continue therapy. Part I of this article, published in the September/October 2001 issue of Rehabilitation Nursing, described the particular problems of treatment adherence in MS. Part II proposes that the transtheoretical model of behavior change can be a useful tool in achieving both patient acceptance and treatment goals. This model is founded upon the concept that readiness for change is crucial, and that attempts at intervention should be sensitive to the patients' changing conditions and states of mind.
The occupancy of the atypical neuroleptic quetiapine (Seroquel) at the D
2 dopamine receptor was investigated using the PET tracers
11Craclopride and
N-
11Cmethylspiperone in a group of five ...schizophrenic patients. A steady-state treatment condition was ensured by dosing the patients with 750 mg quetiapine daily during 3 weeks followed by a period of tapering off the dose. For each patient, PET examinations were performed with both tracers at two of the following doses: 750, 450, 300 and/or 150 mg. As control, a group of six healthy untreated volunteers was investigated. The D
2 binding potential in the putamen and the caudate nucleus was determined by using an evaluation method based on the method proposed by Patlak and Blasberg. The receptor occupancy was determined by assuming that the group of healthy volunteers is representative of untreated drug-naive schizophrenic patients. While a significant linear trend of increasing occupancy with increasing quetiapine dose (reaching 51%±10% occupancy at the 750 mg dose) was detected with
11Craclopride (
P<0.01), no such trend was apparent for
N-
11Cmethylspiperone (
P>0.09, maximal occupancy values were 2% ±3%, measured for the group of three patients on 450 mg). The study suggests that
N-
11Cmethylspiperone cannot be used for the assessment of D
2 receptor occupancy induced by quetiapine. The result is discussed in terms of endogenous dopamine, tracer kinetics and equilibrium dissociation constants.
Objective: Quetiapine is a novel antipsychotic agent with many atypical features, including low D
2 and higher 5HT
2A affinity in vitro, low propensity to induce extra-pyramidal side effects and ...minimal effects on prolactin levels. The purpose of this study was to investigate, using positron emission tomography (PET), the relationship between plasma concentrations of different doses of quetiapine and occupancy of D
2 and 5HT
2A receptors in schizophrenic patients.
Methods: Five patients were treated with quetiapine (titrated to 750 or 450 mg/day) for 28 days, subsequently reduced weekly in a descending-dose schedule. Dopamine D
2 and 5HT
2A occupancies were determined using
11C raclopride and
11C
N-methylspiperone as ligands, respectively, and PET imaging.
Results: Mean D
2 receptor occupancies of 41 and 30% were observed at quetiapine doses of 750 and 450 mg/day. At lower dose levels no occupancy could be determined. Quetiapine induced a consistently higher degree of 5HT
2A receptor occupancy, with mean occupancies of 74 and 57% at doses of 750 and 450 mg/day, respectively. No EPS emerged during the trial and most of the pre-trial EPS resolved during the study.
Conclusions: In clinically effective doses, quetiapine induced low occupancy at D
2 receptors, which is consistent with atypical antipsychotics such as clozapine, and probably explains the lack of EPS observed in this trial. Correlations between receptor occupancy and plasma concentrations of quetiapine could not be calculated, although receptor occupancy increased with higher plasma concentrations for the 450 and 750 mg doses.
Computed tomography (CT) measures and cerebrospinal fluid (CSF) levels of the monoamine metabolites homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid ...(5-HIAA) were determined in 43 healthy volunteers and in 26 patients with an acute psychosis of the schizophrenic type. There were no differences in the mean CSF levels of monoamine metabolites between the two groups. However, the patients had significantly wider lateral and third ventricles as compared to the volunteers. In the volunteers there were no significant correlations between ventricular sizes and monoamine metabolite levels, whereas in the patients a significant negative correlation was obtained between the size of the lateral ventricles and the levels of HVA and 5-HIAA in the CSF. These results may indicate that the enlargements of the brain ventricles found in a subgroup of schizophrenic patients may be associated with deficiencies in central monoamine transmission mechanisms.
![N-[ 11C]Methylspiperone PET...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0925-4927/small "N-[ 11C]Methylspiperone PET, in contrast to [ 11C]raclopride, fails to detect D 2 receptor occupancy by an atypical neuroleptic")
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