C L Katona

Publications (70)351.24 Total impact

• Article: Psychotropics and drug interactions in the elderly patient.

  C L Katona
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  ABSTRACT: This short paper attempts to provide a framework to aid the old-age psychiatrist in choosing psychotropic drugs in a way that minimizes the risks of adverse drug reactions. It concentrates on the clinical problems most frequently encountered in old-age psychiatric practice. Older people are at risk of adverse drug interactions because of their higher rate of physical morbidity and increased likelihood of receiving polypharmacy, as well as due to age-related change in drug handling. The strongest evidence for relevant interactions in older people relates to changes in renal excretion (particularly relevant for lithium) and cytochrome P450 (relevant for a wide range of psychotropic and other drugs). Awareness of potential interactions is important in ensuring safe prescribing practice for older people with mental health problems.
  International Journal of Geriatric Psychiatry 01/2002; 16 Suppl 1:S86-90. · 2.42 Impact Factor
• Article: Altered brain protein kinase C in depression: a post-mortem study.

  M A Coull, S Lowther, C L Katona, R W Horton
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  ABSTRACT: [(3)H]Phorbol 12,13-dibutyrate (PDBu) binding was measured in soluble and particulate fractions of frontal cortex and hippocampus from suicides, with a firm retrospective diagnosis of depression, and individually matched controls. Suicides were divided into those who had been free of antidepressant drugs for at least 3 months and those in whom prescription of antidepressants was clearly documented. In frontal cortex, there was a significantly higher number (by 75%) of [(3)H]PDBu binding sites in the soluble fraction in antidepressant-free suicides compared to controls; significant differences were also seen in the proportion of sites in the soluble and particulate fractions. Higher numbers of [(3)H]PDBu binding sites in the particulate fraction of hippocampus in antidepressant-free suicides was restricted to those who died by violent means. No significant differences in the number of [(3)H]PDBu binding sites were found in antidepressant-treated suicides compared to controls. This study provides evidence for the involvement of protein kinase C in the pathophysiology of depression.
  European Neuropsychopharmacology 08/2000; 10(4):283-8. · 4.05 Impact Factor
• Article: Three years survival in patients with a clinical diagnosis of dementia with Lewy bodies.

  Z Walker, R L Allen, S Shergill, E Mullan, C L Katona
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  ABSTRACT: The majority of information available on the prognosis of dementia with Lewy bodies (DLB) is based on retrospective data from autopsy series, which are subject to selection bias due to the specific reasons patients are referred for post-mortem studies. The earlier studies comparing DLB patients with patients with Alzheimer's disease (AD) suggest that the mean duration of illness is shorter in DLB patients than in patients with AD. However, more recent studies have not observed significant differences between DLB and AD in age of onset, age at death or duration of illness. We report a 3 year follow-up of a cohort of 114 consecutive patients with dementia, referred to an old age psychiatric service and diagnosed using ICD 10 criteria and the McKeith and Byrne DLB criteria. The case notes of all patients were reviewed to determine the date of onset of symptoms and the date of first presentation to the psychiatric services. Information about outcome was gathered from case notes, hospital files and general practitioner (GP) records. Of the original sample of 114 patients, 106 could be traced. Sixty-four had died and 42 were still alive at the time of the follow-up. Thirty-two patients had originally been assigned the diagnosis of DLB, 43 the diagnosis of AD, 31 vascular dementia and other diagnoses. There were no differences between the AD and DLB group in age at onset, age at death or survival. We have not found any evidence that the prognosis of clinically diagnosed DLB patients is worse than that of patients with a clinical diagnosis of AD.
  International Journal of Geriatric Psychiatry 04/2000; 15(3):267-73. · 2.42 Impact Factor
• Article: In-vivo demonstration of dopaminergic degeneration in dementia with Lewy bodies.

  Z Walker, D C Costa, P Ince, I G McKeith, C L Katona
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  ABSTRACT: With the dopaminergic presynaptic ligand FP-CIT and single photon emission tomography we have shown a severe dopaminergic degeneration in a patient with a necropsy confirmed diagnosis of dementia with Lewy bodies (DLB). We suggest that functional imaging of the nigrostriatal dopamine pathway helps to distinguish DLB from Alzheimer's disease during life.
  The Lancet 09/1999; 354(9179):646-7. · 38.28 Impact Factor
• Article: Outcome in refractory depression.

  S S Shergill, M M Robertson, G Stein, M Bernadt, C L Katona
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  ABSTRACT: Failure to respond to first-line antidepressant treatment can occur in up to 40% of patients with depressive illness. A proven strategy for managing this refractory depression is lithium augmentation. The long-term outcome and optimal management of patients treated with lithium augmentation remains unclear. We describe a 4-8 year naturalistic follow-up of patients treated with lithium augmentation in two controlled studies of its efficacy in refractory depression. Cases were followed up with personal interview where possible, and by telephone and general practitioner contact otherwise. Lifetime clinical status was ascertained using the Schedule for Affective Disorders and Schizophrenia-Lifetime (SADS-L). We obtained outcome data on 53 of the original eligible 76 patients. There was a good outcome in 38 (72%) patients. Good outcome was associated with a less endogenous nature of depression and an absence of previous hospitalisations. There do not seem to be any specific prognostic indicators of long-term outcome to lithium augmentation beyond those recognised to be relevant in the outcome of depression generally. The conclusions are limited by incomplete follow-up of the total original sample and lack of objective illness and medication data for the intervening period.
  Journal of Affective Disorders 09/1999; 54(3):287-94. · 3.52 Impact Factor
• Article: Olanzapine in dementia with Lewy bodies: a clinical study.

  Z Walker, J Grace, R Overshot, S Satarasinghe, A Swan, C L Katona, I G McKeith
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  ABSTRACT: Dementia with Lewy bodies (DLB) is now a well-recognized form of dementia in which psychosis and behavioural disturbance are common. Treatment with conventional neuroleptics is often very poorly tolerated. Olanzapine, a newly introduced atypical neuroleptic which binds to multiple receptor types with relatively low affinity for D2 receptors, may be a useful treatment option in DLB. The Behavioural Pathology in Alzheimer's Disease Rating Scale, The Neuropsychiatric Inventory, Unified Parkinson's Disease Rating Scale and The Webster Disability Scale. We present the results of eight DLB patients with associated psychotic and behavioural difficulties. All patients were given olanzapine 2.5-7.5 mg. Their psychotic phenomena and behavioural and extrapyramidal symptoms were monitored at 2-weekly intervals. Three out of the eight patients could not tolerate olanzapine even at the lowest available dose. Two patients had clear improvement in psychotic and behavioural symptoms. Three patients were able to tolerate olanzapine but gained only minimal benefit. Olanzapine at the doses used conferred little advantage over conventional neuroleptics and should only be given with great caution to patients with DLB. The utility of smaller doses deserves further evaluation.
  International Journal of Geriatric Psychiatry 07/1999; 14(6):459-66. · 2.42 Impact Factor
• Article: [3H] imipramine binding in brain samples from depressed suicides and controls: 5-HT uptake sites compared with sites defined by desmethylimipramine.

  K M Lawrence, M Kanagasundaram, S Lowther, C L Katona, M R Crompton, R W Horton
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  ABSTRACT: Using desmethylimipramine (DMI) defined and Na+ dependent [3H]imipramine binding, we have examined both 5-HT uptake sites and sites unrelated to 5-HT uptake, in frontal cortex, putamen and substantia nigra of suicides with a firm retrospective diagnosis of depression and matched controls. No differences were seen between antidepressant-free suicides and controls, although [3H]imipramine binding sites were significantly lower in putamen of the subgroup of non-violent suicides. The number of DMI defined [3H]imipramine binding sites was also significantly lower in putamen of antidepressant-treated suicides.
  Journal of Affective Disorders 02/1998; 47(1-3):105-12. · 3.52 Impact Factor
• Article: A double-blind comparison of the efficacy and safely of paroxetine and imipramine in the treatment of depression with dementia.

  C L Katona, B N Hunter, J Bray
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  ABSTRACT: To compare the efficacy of paroxetine and imipramine prospectively in patients with coexisting depression and dementia. An 8-week, double-blind, parallel group trial comparing paroxetine 20-40 mg/day with imipramine 50-100 mg/day in 198 patients aged 60 years or over with a Montgomery-Asberg Depression Rating Scale (MADRS) score > or = 20 and a Folstein mini-mental state evaluation score of 17-23 points after a 3- to 7-day placebo run-in period. Both paroxetine and imipramine reduced the MADRS and the Clinical Global Impression (CGI) severity-of-illness and global improvement scores at weeks 2, 4, 8 and at endpoint, with no significant differences between treatment groups at any timepoint (MADRS, p > or = 0.368; cgi, p > or = 0.286). There was a statistically significant difference in favour of paroxetine at both the week 4 and week 8 timepoints (analysis of variance, p < or = 0.049) in the Cornell scale for depression in dementia: at endpoint there was no significant difference between treatments (p = 0.103). Treatment-emergent adverse experiences were reported by 51.5% (51/99) of patients treated with paroxetine and 50.5% (50/99) of patients treated with imipramine. Anticholinergic adverse experiences (paroxetine 6.1%; imipramine 13.1%) and serious non-fatal adverse experiences (paroxetine 4.0%; imipramine 8.1%) were reported by more patients in the imipramine group than in the paroxetine group. Paroxetine and imipramine were both effective in the treatment of depression in elderly subjects with co-existing dementia, and no significant differences were detected between the groups. There were trends suggesting that paroxetine was better tolerated than imipramine in terms of anticholinergic adverse experiences and serious non-fatal adverse experiences.
  International Journal of Geriatric Psychiatry 02/1998; 13(2):100-8. · 2.42 Impact Factor
• Article: Neuropsychological and imaging differences in dementia with Lewy bodies and Alzheimer's disease.

  R L Allen, Z Walker, C L Katona
  The British Journal of Psychiatry 12/1997; 171:486-7. · 6.62 Impact Factor
• Article: Dopamine uptake sites, labelled with [3H]GBR12935, in brain samples from depressed suicides and controls.

  C Bowden, S C Cheetham, S Lowther, C L Katona, M R Crompton, R W Horton
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  ABSTRACT: We have quantitated dopamine uptake sites, labelled with [3H]GBR12935, in caudate, putamen and nucleus accumbens of suicides with a retrospective diagnosis of depression, and age and gender-matched controls. Suicides were subdivided into those who had been free of antidepressant drugs for at least three months, and those in whom prescription of antidepressant drugs was clearly documented. We found no significant differences between controls and suicides overall, or when the suicides were divided on the basis of antidepressant treatment or violence of death. A significant negative correlation between the number of dopamine uptake sites and age was found in each region studied. Our results suggest dopamine uptake sites are not critically involved in depression or antidepressant drug action.
  European Neuropsychopharmacology 12/1997; 7(4):247-52. · 4.05 Impact Factor
• Article: Corticotropin-releasing factor binding sites in cortex of depressed suicides.

  D Hucks, S Lowther, M R Crompton, C L Katona, R W Horton
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  ABSTRACT: Corticotropin-releasing factor (CRF) receptors were measured by saturation binding in frontal and motor cortex of suicides with a firm retrospective diagnosis of depression, and matched controls. The suicides were divided into those who were free of antidepressant drugs, and those in whom prescription of antidepressant drugs was clearly documented. There were no differences in the number or affinity of CRF receptors between antidepressant-free or antidepressant-treated suicides and matched controls in either brain region. When suicides were divided according to violence of death, again there were no differences between violent or non-violent suicides and controls.
  Psychopharmacologia 12/1997; 134(2):174-8. · 4.08 Impact Factor
• Article: Reduced dopamine turnover in the basal ganglia of depressed suicides.

  C Bowden, S C Cheetham, S Lowther, C L Katona, M R Crompton, R W Horton
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  ABSTRACT: We have measured the concentrations of dopamine, and the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), in five brain regions from suicide victims with a firm retrospective diagnosis of depression, and matched controls. The suicides were divided into those free of antidepressant drugs and those in whom prescription of antidepressant drugs was clearly documented. DOPAC concentrations were significantly lower in caudate, putamen and nucleus accumbens of antidepressant-free suicides compared to controls. In antidepressant-treated suicides, lower concentrations of DOPAC were observed in the basal ganglia, reaching statistical significance in caudate. Lower DOPAC concentrations were largely restricted to those suicides who died by non-violent methods. There were no significant differences in dopamine and HVA concentrations in either suicide group compared to controls, although there was a trend for HVA concentrations to be lower in suicides. This study provides evidence for reduced dopamine turnover, as judged from reduced DOPAC levels, in depressed suicides, although we cannot exclude the possibility that this may be due to ingestion of toxic agents.
  Brain Research 10/1997; 769(1):135-40. · 2.73 Impact Factor
• Article: 5-HT1D and 5-HT1E/1F binding sites in depressed suicides: increased 5-HT1D binding in globus pallidus but not cortex.

  S Lowther, C L Katona, M R Crompton, R W Horton
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  ABSTRACT: 5-HT1D and 5-HT1E/1F receptor binding sites were measured in brain samples obtained at postmortem from suicide victims with a firm retrospective diagnosis of depression, and matched controls. In antidepressant-free suicides a significantly higher number of 5-HT1D receptors was found in globus pallidus. This was largely restricted to those suicides who died by violent means. This effect was not observed in antidepressant-treated suicides. No differences or trends in 5-HT1D binding were found in putamen, parietal or frontal cortex, in antidepressant-free or antidepressant-treated suicides. There were no differences in the number of 5-HT1E/1F receptors in any of the regions studied.
  Molecular Psychiatry 08/1997; 2(4):314-21. · 13.67 Impact Factor
• Article: Dementia with lewy bodies: a study of post-synaptic dopaminergic receptors with iodine-123 iodobenzamide single-photon emission tomography.

  Z Walker, D C Costa, A G Janssen, R W Walker, G Livingstone, C L Katona
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  ABSTRACT: Dementia with Lewy bodies (DLB) can at present only be diagnosed with certainty by neuropathological examination. Diagnosis during life remains at best probable, based on the presence of symptoms known from autopsy studies to be frequently associated with DLB. The greatest practical clinical problem lies in distinguishing DLB and Alzheimer's disease (AD). In DLB there is a considerable degeneration of nigral neurones with depletion of striatal dopamine. In contrast, AD is not associated with significant changes in dopamine metabolism. Iodine-123 iodobenzamide single-photon emission tomography (IBZM-SPET) measures post-synaptic dopamine D2 neuroreceptor availability in the corpus striatum, but is nevertheless a method for assessing the integrity of the nigrostriatal dopaminergic pathway. Sixteen clinically diagnosed DLB patients, 15 normal controls and 13 AD patients underwent IBZM-SPET. All subjects were scanned 1.5-2 h after intravenous injection of 185 MBq of 123I-IBZM. Circular regions of interest were employed to calculate radioactivity ratios in each hemisphere as follows: caudate nucleus/frontal cortex, putamen/frontal cortex and caudate nucleus/putamen. The DLB patients had significantly lower left caudate/putamen ratios (95% confidence intervals: DLB 0.893-0.965, AD 0.972-1.175, controls 1.031-1.168) than either controls or AD patients, and significantly lower right caudate/putamen ratios (95% confidence intervals: DLB 0.926-1.019, AD 0.954-1.103, controls 1. 027-1.144) than controls. Our data suggest that patients with DLB diagnosed by clinical criteria have changes in striatal post-synaptic D2 receptors. This may be of value in distinguishing DLB from AD during life.
  European Journal of Nuclear Medicine 07/1997; 24(6):609-14.
• Article: Brain alpha-adrenoceptors in depressed suicides.

  F De Paermentier, J M Mauger, S Lowther, M R Crompton, C L Katona, R W Horton
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  ABSTRACT: alpha1-Adrenoceptors and alpha2-adrenoceptors were measured by radioligand binding to homogenates of brain samples obtained at post-mortem from suicides with a retrospective diagnosis of depression, and age and gender-matched controls. Suicides were subdivided into those who had been free of antidepressant drugs for at least three months, and those in whom prescription of antidepressant drugs was clearly documented. The number of alpha1-adrenoceptors (or alpha1A + alpha1D-adrenoceptors) did not differ significantly between antidepressant-free or antidepressant-treated suicides and controls. In antidepressant-free suicides, the number of alpha2-adrenoceptors was significantly higher in temporal cortex (Ba 21/22). alpha2A-Adrenoceptors did not differ significantly from controls in this brain region, suggesting the involvement of other alpha2-adrenoceptor subtypes. In antidepressant-treated suicides, significantly lower numbers of alpha2-adrenoceptors were found in occipital cortex and hippocampus (and for alpha2A-adrenoceptors in caudate and amygdala) compared to controls.
  Brain Research 06/1997; 757(1):60-8. · 2.73 Impact Factor
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  Article: Brain 5-hydroxytryptamine uptake sites labeled with [3H]paroxetine in antidepressant drug-treated depressed suicide victims and controls.

  K M Lawrence, F De Paermentier, S Lowther, M R Crompton, C L Katona, R W Horton
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  ABSTRACT: Saturation binding of [3H]paroxetine was performed in 10 brain regions from a group of suicide victims who had a firm, retrospective diagnosis of depression and who had been prescribed antidepressant drugs, as well as in a group of controls. The number of binding sites did not differ significantly between suicide victims and controls, apart from in putamen, where a lower number of sites was found in the suicide victims. Higher dissociation constant (Kd) values were found in suicide victims dying by antidepressant overdose and also in those dying by other means when compared with controls.
  Journal of psychiatry & neuroscience: JPN 06/1997; 22(3):185-91. · 5.34 Impact Factor
• Article: Brain [3H]cAMP binding sites are unaltered in depressed suicides, but decreased by antidepressants.

  S Lowther, C L Katona, M R Crompton, R W Horton
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  ABSTRACT: Saturation binding of [3H]cAMP to the regulatory subunit of cAMP-dependent protein kinase (PKA) was measured in the soluble fraction of brain samples, obtained at post-mortem, from suicides with a firm retrospective diagnosis of depression and individually matched controls. Suicides were subdivided into those who had been free of antidepressant drugs for at least 3 months and those in whom prescription of antidepressants was clearly documented. In antidepressant-free suicides, we found no significant differences in the number or affinity of [3H]cAMP binding sites in the five regions studied. In antidepressant-treated suicides however, Bmax values were lower in all regions, reaching statistical significance in parietal cortex and amygdala. Kd values for antidepressant-treated suicides were significantly higher in parietal cortex, temporal cortex and amygdala. These results suggest the regulatory subunit of PKA is unaltered in depression, but is influenced by antidepressant drugs.
  Brain Research 06/1997; 758(1-2):223-8. · 2.73 Impact Factor
• Article: Pharmacological choices after one antidepressant fails: a survey of UK psychiatrists.

  S S Shergill, C L Katona
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  ABSTRACT: At least 30% of depressed patients fail to respond to adequate first-line anti-depressant medication. Several pharmacological strategies have been suggested to treat such refractory depression. There has been no survey of United Kingdom psychiatrists' treatment preferences for refractory depression. This study was carried out to determine both experience and preference of various strategies for management of refractory depression. A total of 300 fellows, members and inceptors of the Royal College of Psychiatrists were randomly selected and approached by postal questionnaire. They were asked to comment on management of a detailed clinical vignette of a case of depression with initial treatment failure. The response rate was 63% (n = 175). The most popular treatment choices were increasing dosage of tricyclic medication and change of medication of SSRI. The most rarely selected were augmentation with triiodothyronine (T3) and augmentation with tryptophan or MAOIs. Treatment choice was significantly influenced by previous experience. A large number (39%) of psychiatrists were not confident in treating refractory depression. Surprisingly few psychiatrists chose to use the best proven pharmacological treatments such as augmentation with lithium or T3. In view of this and the considerable proportion of psychiatrists lacking confidence in the management of refractory depression, this topic deserves priority as a topic for continuing professional development (CPD) courses.
  Journal of Affective Disorders 04/1997; 43(1):19-25. · 3.52 Impact Factor
• Article: Dopamine D1 and D2 receptor binding sites in brain samples from depressed suicides and controls.

  C Bowden, A E Theodorou, S C Cheetham, S Lowther, C L Katona, M R Crompton, R W Horton
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  ABSTRACT: Dopamine D1 and D2 receptors were measured (by saturation binding of [3H]SCH23390 and [3H]raclopride) in caudate, putamen and nucleus accumbens, obtained at post-mortem from suicide victims with a firm retrospective diagnosis of depression, and matched controls. There were no differences in the number or affinity of D1 or D2 receptors between suicides who had been free of antidepressants for at least three months prior to death, and controls. Increased numbers and decreased affinity of D2 receptors were however found in each brain region of antidepressant-treated suicides. We argue that these increases are related to concurrent treatment with neuroleptics rather than a direct effect of antidepressants. Increased numbers of D1 receptors in antidepressant-treated suicides were seen only in nucleus accumbens. This increase could not be clearly attributed to neuroleptics and may be related to antidepressant treatment.
  Brain Research 04/1997; 752(1-2):227-33. · 2.73 Impact Factor
• Article: 5-HT1A receptor binding sites in post-mortem brain samples from depressed suicides and controls.

  S Lowther, F De Paermentier, S C Cheetham, M R Crompton, C L Katona, R W Horton
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  ABSTRACT: 5-HT1A receptor binding sites were measured, by saturation binding with [3H]8-OH-DPAT, in frontal and occipital cortex, hippocampus and amygdala obtained at post-mortem examination from suicide victims with a firm retrospective diagnosis of depression, and matched controls. The number of 5-HT1A binding sites did not differ significantly between suicides and controls, either in the total sample or when the suicides were divided on the basis of violence of death or recent antidepressant treatment.
  Journal of Affective Disorders 03/1997; 42(2-3):199-207. · 3.52 Impact Factor