Henrik Lublin

Behavioural effects of dopamine D-1 and D-2 receptor agonists in monkeys previously treated with haloperidol

The effects of dopamine D-1 and D-2 receptor agonists were evaluated in five Cebus apella monkeys. During a previous haloperidol treatment (2 years), three of the monkeys had developed oral tardive dyskinesia (tongue protrusion and/or chewing). The partial D-1 agonist, SKF 38393, induced/aggravated oral dyskinesia and slight sedation, but no non-oral repetitive movements. Conversely, the selective D-2 agonist, LY 171555, produced non-oral repetitive movements and increased reactivity (arousal), but no significant change in the oral movements. Apomorphine (a mixed D-1/D-2 agonist) induced non-oral repetitive movements, increased reactivity, and increased oral dyskinesia. Pretreatment with SKF 38393 inhibited the LY 171555-induced non-oral repetitive movements, while in four monkeys the SKF 38393-induced oral movements were inhibited by LY 171555. The results suggest that oral dyskinesia (tardive dyskinesia) is more related to D-1 receptor stimulation than to D-2 receptor supersensitivity.

Assessment of patient satisfaction with psychiatric care. Development and clinical evaluation of a brief consumer satisfaction rating scale (UKU-ConSat)

Quality management and quality control of health services has become increasingly important. Central to the concept of quality of care is the patients (the health care consumers) own view of the care provided and the treatment outcome. UKU (Udvalg for Kliniske Undersøgelser; that is, Committee for Clinical Trials), a working group within the Scandinavian Society for Psychopharmacology (SSP), has designed a brief consumer satisfaction rating scale, the UKU-ConSat. Based on an extensive literature review, a number of principles related to content, assessment, interview techniques, documentation and standardisation steered the design of the rating scale. UKU-ConSat consists of six items related to the structure and process of treatment care, and two items related to outcome and well-being. A manual accompanies the rating scale with guidelines for how to solicit information from the patient and how to rate each item. A first field trial of the rating scale in 135 inpatients at multiple clinical sites in Finland and Sweden showed that it could be applied to several relevant patient categories (psychotic, affective, neurotic, organic and alcohol and substance abuse disorders). According to both patients and staff the rating scale promises to become useful both for research and for improvement of routine psychiatric services.

Drug therapy of dementia in elderly patients. A review.

Today drug therapy of dementia in elderly patients is possible. Owing to a huge increase in the number of elderly people throughout the Western world in the coming years, evidence-based treatment of dementia in this group is needed. The article reviews double-blind, randomized trials on the effect in dementia of donepezil, galantamine, rivastigmine and memantine up to 2003. A total of 27 studies were included. Donepezil, galantamine, rivastigmine and memantine improve cognition and the global level of functioning in mild to moderate Alzheimers disease (AD). Most evidence exists for donepezil and galantamine. The effect of rivastigmine is best documented in Lewy body dementia (LB). Galantamine, memantine and donepezil may improve cognition in vascular dementia (VD). Galantamine may improve behavioural psychological symptoms of dementia (BPSD). No solid evidence for drug therapy in severe dementia exists. Elderly patients with mild to moderate AD should be offered drug therapy. One should also consider expanding the indication of dementia treatment to LB and VD. An international consensus on what primary efficacy variables to use is needed.

Effekt af ketotifen (en histamin-antagonist) ved tardive dyskinesier hos aber

Lublin H, Gerlach J. Effect of ketotifen (a histamine antagonist) in tardive dyskinesia in monkeys.Ketotifen (a histamine H-1 antagonist) was given to 8 Cebus monkeys, which previously had received haloperidol for 2 years. Five monkeys had mild tardive dyskinesia. In rodents ketotifen has been shown to reduce haloperidol-induced hypersensitivity. In the present study ketotifen (single dose, 0.5-10.0 mg/kg, and multiple dose, 2 mg × 2/kg/day for 14 days) did not influence tardive dyskinesia. The monkeys were sedated, and locomotor activity was reduced. Ketotifen did not change the effects of haloperidol (a dopamine D-2 antagonist) or apomorphine (a mixed dopamine D-1/D-2 agonist). The results suggest that the only behavioral changes induced by ketotifen were sedation and decreased locomotion, caused by sedation.

Adfærdsmæssig interaktion mellem en ny glutamat-antagonist, FG 9065, og dopamin-agonister hos aber

Lublin H, Gerlach J. Behavioral interaction between a new glutamate antagonist, FG 9065, and dopamine agonists in monkeys.Glutamatergic mechanisms have been found to be involved in regulation of the dopaminergic system. The effects of glutamate are mediated by two groups of receptors: the N-rnethyl-D-aspartate (NMDA) receptors and the non-NMDA receptors, one of the latter being of the quisqualate type. FG 9065 (a quisqualate antagonist) was evaluated in eight Cebus monkeys, which previously had received haloperidol for 2 years. Five monkeys had mild oral tardive dyskinesia, consisting of tongue protrusions and/or chewing movements. FG 9065 was evaluated alone and in combination with methylphendiate (dopamine-releasing and uptake-inhibiting drug), SKF 38393 (partial dopamine D-1 agonist), and quinpirole (LY 171555, selective dopamine D-2 agonist). FG 9065 induced/aggravated oral tardive dyskinesia. Otherwise no behavioral effects were found. Methylphenidate increased locomotor activity, stereotypy, and rea...

Samtidige EKG-forandringer, Ieverpåvirkning og vaegtstigning under behandling med klozapin

Lublin H, Kistrup K. Samtidige EKG-forandringer, leverpavirkning og vaegtstigning under behandling med klozapin.A 32-year-old man simultaneously developed electrocardiographic (ECG) changes, disturbed liver function and weight increase (18 kg) during clozapine treatment. The connection with clozapine treatment was established through reappearance of the reactions to repeated exposure. The ECG changes disappeared soon after treatment withdrawal, and the changes in the liver function normalized slowly during the subsequent months. The pathophysiology and clinical importance of the ECG changes during neuroleptic treatment are still not clear, so any ECG changes have to be evaluated individually to determine the potential clinical impact and to minimize the risk for the patient.Clozapine, ECG changes, Liver function, Weight gain

Effekten av Dopamin D-1 og D-2 receptor agonister på aber: Et adfærdsmæssigt korrelat til D-1 og D-2 receptor stimulation. Dopamin D-1 og D-2 agonister hos aber

The effect of dopamine (DA) D-1 and D-2 receptor agonists was evaluated in five Cebus monkeys previously treated with haloperidol for two years. Three monkeys had developed oral tardive dyskinesia. The behavioural effects of the D-1 agonist SKF 38393, the D-2 agonist LY 171555 and apomorphine, a combined D-1/D-2 agonist, were investigated. Apomorphine induced oral hyperkinesia, non-oral stereotyped, repetitive movements of head, limbs and trunk and increased reactivity. SKF 38393 induced oral hyperkinesia and slight sedation. No non-oral stereotyped, repetitive movements were seen. Conversely LY 171555 produced non-oral stereotyped, repetitive movements, increased reactivity and inhibited the oral movements. Pretreatment with SKF 38393 produced an inhibition of the LY 171555-induced non-oral stereotyped, repetitive movements, and conversely, the SKF 38393-induced oral movements were inhibited by LY 171555. Pretreatment with SKF 38393 produced an inhibition of the apomorphine-induced stereotyped, repetitiv...