Psychiatry of the elderly: the WPA/WHO consensus statements.
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Aged↗
Biomedical subjects
C Katona
Publications and source records attributed to C Katona.
Who becomes depressed? The Islington community study of older people.
BACKGROUND: Depression in older people is common and debilitating and associated with physical ill health. This is the first study of risk factors for depression in a representative sample of older people selected for high vulnerability because of physical ill health. METHOD: Subjects identified in an epidemiological community survey of morbidity in people > or =65 years old, who had activity limitation (ADL) but no psychiatric morbidity were reinterviewed after 3 years. RESULTS: 79 (90%) of subjects were interviewed. Ten percent developed pervasive depression and 24% screened positive for depression. This latter group were more likely to consult doctors than others with similar levels of disability (P<0.005) mainly because of an acute physical illness. Frequent pain was associated with the development of depression (P<0.02). CONCLUSION: Older people who are ADL limited are known to be at high risk for depression. For the majority who do not become depressed, chronicity of illness does not lead to depression. Those who become depressed are most likely to be those with an acute illness and those who are in pain. They will usually increase their consultation rate with doctors but will not complain of depression. They may be undertreated for both pain and depression. Further studies are needed to confirm other risk factors.
Activities of Daily Living↗
Managing depression and anxiety in the elderly patient.
Depression in the elderly is under-recognised and under-treated, even more than in younger patients. Late-life depression is a chronic and disabling illness, but there is a common misconception that it is a normal feature of ageing. It can also be difficult to differentiate depression from coexisting anxiety and cognitive disorders. Antidepressants are as effective in acute treatment in older, as in younger, depressed adults. Maintenance antidepressant therapy also appears as effective in older patients. It may, however, be difficult to attain therapeutic levels of tricylic antidepressants (TCAs) in the elderly because of side effects. The selective serotonin re-uptake inhibitors (SSRIs) have more favourable safety and tolerability profiles, making them a suitable treatment option for older patients, who are more vulnerable to adverse effects. In selecting an SSRI for treating late-life depression, its pharmacokinetic profile and effects on coexisting illnesses that are prevalent in the elderly, such as anxiety, dementia and cardiovascular disease, also need to be considered.
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Long-term outcome of severe puerperal psychiatric illness: a 23 year follow-up study.
BACKGROUND: Although there have been many follow-up studies of severe puerperal psychiatric illness, few have been very long-term. METHODS: Sixty-four subjects from 85 (75.3%) in an unselected sample of women admitted to a psychiatric hospital within 6 months of childbirth were successfully followed up a mean of 23 years (range 17-28) later. Most subjects were interviewed in detail, with further information obtained from general practice and hospital records. Data included subsequent illnesses and diagnoses, subsequent childbirth, longitudinal social function, current symptoms and social function. RESULTS: Seventy-five per cent of subjects had further psychiatric illnesses, most of them unrelated to childbirth, and 37% had at least three subsequent episodes. The risk of puerperal psychiatric illness was 29% in subsequent pregnancies. At outcome interview the majority of subjects were well, with satisfactory social adjustment. Diagnoses in subsequent psychiatric illnesses showed considerable consistency with index diagnoses, with some shift to bipolar disorder. Further illnesses were less likely to occur where the index illness occurred with first child, onset was within 1 month of delivery, and where the index diagnosis was unipolar depression. CONCLUSIONS: There is a high risk of subsequent non-puerperal recurrences following severe puerperal psychotic illness, showing considerable diagnostic consistency with the index episode, but with good functional outcome. Puerperal illnesses showed strong continuities with non-puerperal illnesses in these women.
Adult↗
Drug treatment of older people with affective disorders in the community: lessons from an attempted clinical trial.
BACKGROUND: Depression and phobic anxiety disorders are the most common psychiatric disorders in people aged 65 and over. SSRI antidepressants are effective in treating both conditions in younger people, and in treating depression in hospital samples of older subjects. No studies have investigated the efficacy of SSRIs in older people with these conditions living in the community. OBJECTIVES: To evaluate the efficacy and feasibility of treating older people suffering from depression and/or phobic anxiety in the community with fluoxetine alone. DESIGN: Subjects identified as depressed and/or anxious at screening were offered open-label fluoxetine and were reassessed for affective illness at 3 and 6 months. MEASURES: Outcome was assessed using the depression subscale of the Short Comprehensive Assessment and Referral Evaluation (Short-CARE) Scale and the Anxiety Disorder Scale. RESULTS: Of 67 subjects with depression and/or phobic anxiety, 55 (81%) were eligible to take fluoxetine. Fifty-four (98%) of these agreed to follow-up but only six (11%) agreed to take medication. No subject was still taking medication by the end of the study. Among those subjects on whom follow-up data were available, 70% of subjects depressed at screening and 97% of those with phobic anxiety retained their diagnoses at 3 months; at 6 months, the figures were 65% and 92% respectively. CONCLUSIONS: Drug treatment alone is not acceptable to older patients in the community with depression and phobic anxiety disorders. Discussion of symptoms with an appropriate professional is insufficient therapy on its own. Further work is needed to evaluate the effectiveness of a key worker such as a mental health nurse in coordinating treatment of patients with these disorders.
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5-ethyl-2'-deoxyuridine, a modulator of both antitumour action and pharmacokinetics of 5-fluorouracil.
The aim of the present studies was to elucidate the effects and optimal modulatory conditions of 5-ethyl-2'-deoxyuridine (EtdUrd) on the antitumour efficacy, pharmacokinetics and catabolism of 5-fluorouracil (5-FU) on Colon-26 and Colon-38 murine tumours. HPLC and GC-MS techniques were used to measure the concentrations of 5-FU, dihydro-5-fluorouracil, EtdUrd, 5-ethyluracil and uridine in the plasma and that of 5-FU and 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) in the tumours. It was shown that EtdUrd, given 1 h before 5-FU, selectively enhanced the antitumour action of 5-FU, without significantly increasing its toxic side-effects, thus resulting in an approximately three times higher therapeutic index. Pharmacokinetic studies revealed that 1 h after 400 mg/kg EtdUrd administration - i.e. at the time of 5-FU treatment - the plasma concentration of EtdUrd was 269 microM, and that of 5-ethyluracil, as the major metabolite of EtdUrd, was 421 microM. It is of interest that EtdUrd pretreatment did not change the maximal plasma concentration of 5-FU; however, the half-life of the terminal elimination increased from 114.5 min to 171.2 min and thus the mean residence time of 5-FU rose significantly (P < 0.05). After the combined treatment, the maximal concentration of dihydro-5-fluorouracil in the plasma decreased from 61.06 microM to 29.70 microM (P < 0.01). The intratumoral concentrations of 5-FU were 34%-158% higher 6-96 h after the combined treatment than after the single 5-FU treatment. EtdUrd also caused a moderate increase in the intratumoral level of FdUMP. It is noteworthy, that EtdUrd increased the endogenous uridine concentration in the plasma from 18 microM to a maximum of 249 microM, and the level remained high for longer than 6 h. The present studies indicate that EtdUrd enhances the therapeutic index of 5-FU by reducing the catabolism, prolonging the plasma and intratumoral concentrations of 5-FU and, at the same time, offering protection to normal organs by increasing the endogenous uridine level.
Animals↗
Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial.
BACKGROUND: Depression in older people is often unrecognised and untreated or under-treated. Antidepressant treatment may itself exacerbate a pre-existing illness, interact with concomitant medications or produce undesirable cognitive and sedative side effects. Newer antidepressants may offer advantages in terms of a lesser burden of adverse effects. METHODS: The comparative tolerability of the unique selective noradrenaline reuptake inhibitor (selective NRI) reboxetine (4-6 mg/day; n = 176) and that of imipramine (50-100 mg/day; n = 171) was assessed in an elderly ( > 65 years) cohort of depressed or dysthymic patients in an 8-week, double-blind, multicentre trial. Comparative efficacy was also assessed. RESULTS: Overall, 68% of patients in the reboxetine group experienced adverse events compared with 71% in the imipramine group. Reboxetine-treated patients were less likely to develop hypotension and related symptoms (7% vs. imipramine 16%) or cardiovascular disorders (12.5% vs. imipramine 21.1%), while those treated with imipramine were less likely to experience insomnia (6.3% vs. 2.9%). Adverse events were more often assessed as related to treatment (43%) and moderate to severe in intensity (73%) with imipramine than with reboxetine (33% and 65%, respectively). Furthermore, there were fewer serious adverse events in the reboxetine-treated group (P = 0.019). The reduction in the Hamilton Rating Scale for Depression (HAM-D) was comparable between the treatment groups in the total population. At the last assessment, the majority of patients in both treatment groups were assessed as normal to borderline or mildly ill using the Clinical Global Impression (CGI) scale. In a subanalysis of the dysthymic patients a modest but significant difference in favour of imipramine was observed for both HAM-D and CGI assessments. This may have been a reflection of a trend towards more severe depressive symptoms at baseline in the reboxetine group. CONCLUSIONS: Reboxetine is as effective as imipramine in the treatment of depression in elderly patients but is at least as well tolerated with a lower risk of hypotension and related symptoms, fewer serious adverse events, adverse event-related withdrawals and treatment-related adverse events.
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Modulation of 5-fluorouracil by 5-ethyl-2'-deoxyuridine on cell lines expressing different dihydropyrimidine dehydrogenase activities.
The purpose of the present study was to clarify the significance of the inhibition of dihydropyrimidine dehydrogenase (DPD) in the modulation of 5-fluorouracil (5-FU) action by 5-ethyl-2'-deoxyuridine (EUdR). Four human cell lines, which differed in their susceptibility to 5-FU and in their DPD activity, were selected as biological objects. Several other enzymes of pyrimidine metabolism, i.e. thymidylate synthase (TS), thymidine kinase (TK) and pyrimidine nucleoside phosphorylase (PNP), which might be involved in the 5-FU action were also studied to elucidate their potential role in the modulation of 5-FU cytotoxicity. Two out of the four cell lines, i.e. COLO1 and SW620, showed low (57 and 28 pmol/min/mg protein) and the other two cell lines, i.e. CAL51 and CAL33, showed high (235 and 184 pmol/min/mg protein) DPD activity, respectively. In our study, contrary to our expectation, no correlation between the DPD and TS activity of the cell lines and their 5-FU sensitivity could be observed. EUdR alone was cytotoxic only on CAL33 cells in a concentration below 1 mM (IC50=194 microM) which might be due to the high TK activity (857 pmol/min/mg protein) measured in this cell line, favoring the formation of the phosphorylated nucleotides EdUMP and EdUTP indispensable for the inhibition of TS and DNA polymerase, respectively. Surprisingly, although EUdR by metabolizing to EUra was able to reduce the high activity of DPD in CAL33 and CAL51 cells by 47 and 55%, respectively, no potentiation of the 5-FU action occurred on these cell lines. On the contrary, enhancement of the 5-FU cytotoxicity was demonstrated on COLO1 and SW620 cells with low DPD activity. Our findings suggest that the 5-FU modulatory action of EUdR may be directed on other molecular targets than DPD as well, i.e. the augmentation of TS inhibition by EdUMP as demonstrated on SW620 cells might be one of these mechanisms.
Antimetabolites, Antineoplastic↗
[Therapeutic approach to depressive disorders in the elderly person].
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Aged↗
The expression of Fos within the suprachiasmatic nucleus of the diurnal rodent Arvicanthis niloticus.
Rhythms in the expression of the nuclear phosphoprotein Fos, have been demonstrated in the suprachiasmatic nucleus (SCN) of nocturnal rodents. When rats are housed in a 12:12-h light/dark (LD) cycle the number of Fos-immunoreactive (-IR) cells within the SCN is higher during the day than at night [9,23]. In the two experiments reported here, Fos-IR was examined in the SCN of a diurnal murid rodent, Arvicanthis niloticus. First, thirty-six adult male A. niloticus housed in a 12:12-h LD cycle were perfused at six equally spaced time points beginning 1 h after lights on (n=6 per time point). Brains were sectioned and treated with immunohistochemical procedures for the identification of Fos. The number of Fos-IR cells in the SCN varied significantly as a function of time, and was highest 1 h after lights on and decreased thereafter. The distribution of Fos-IR within the SCN overlapped with that of arginine-vasopressin-IR (AVP-IR) and vasoactive intestinal peptide-IR (VIP-IR), but not with that of gastrin-releasing peptide-IR (GRP-IR). In the second study, double-labeling techniques revealed extensive Fos expression within SCN neurons containing AVP-IR, but not neurons containing GRP-IR. In conclusion, although the overall rhythm of Fos-IR in the SCN is similar in diurnal and nocturnal rodents, differences may exist with respect to the relative distribution of Fos-immunoreacte cells within different SCN cell populations.
Animals↗
An informant interview for the diagnosis of dementia and depression in older adults (IDD-GMS).
BACKGROUND: There has been no instrument developed for the differential diagnosis of psychiatric conditions using an informant. The present study describes the development and validation of an informant interview for the diagnosis of dementia and depression in older adults (IDD-GMS). The IDD-GMs, as its name indicates, is based upon the well-established Geriatric Mental State Schedule (GMS). METHOD: Thirty older adults with psychiatric illnesses were identified. An informant/career was interviewed using the IDD-GMS. Questions from the GMS were altered to reflect the informant nature of interview. Validity was compared to ICD-10 diagnoses. Interrater reliability was determined. RESULTS: Using a hierarchical diagnostic system, receiver operating characteristics demonstrated one optimal cutpoint for sensitivity, > 13 for dementia and > 16 for depression, and one for specificity, > 13 for dementia and > 10 for depression. CONCLUSION: The validity and reliability of the IDD-GMS falls within acceptable limits and indicates that the IDD-GMS can be used as a diagnostic instrument for dementia and depression. The IDD-GMS represents the first informant interview to achieve this.
Adult↗
Do consultant home visits have a future in old age psychiatry?
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Do health and use of services differ in residents of sheltered accommodation? A pilot study.
OBJECTIVE: To compare the rates of mental health problems, disability and use of health and social services of older people living in sheltered accommodation with those of the rest of the community in the same age group. DESIGN: Door-to-door survey in randomly selected enumeration districts. The districts contained three sheltered accommodation complexes. Residents from these addresses were compared with the others. SETTING: London Borough of Islington. SUBJECTS: 700 men and women aged 65 or over. MAIN OUTCOME MEASURES: Short-CARE depression, dementia and activity scales; the Guy's/Age Concern anxiety scale; individual items detailing problems with mobility, vision and hearing; use of a number of health and social services. RESULTS: The only difference in mental health variables on univariate analysis was a greater severity of cognitive impairment and dementia symptoms in sheltered accommodation. When demographic differences were taken into account, the association with cognitive impairment became statistically insignificant. There were significant associations between residence in sheltered accommodation and several of the disability variables. Increased use of health and social services by sheltered residents remained significant after disability and living alone were taken into account. CONCLUSIONS: The residents of sheltered accommodation were more disabled than the general elderly population but, in contrast to those in residential care, did not have a great excess of mental health problems. Indeed, the possibility was raised that sheltered accommodation may protect against depression in people who live alone.
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The dexamethasone suppression test and treatment outcome in elderly depressed patients participating in a placebo-controlled multicenter trial involving moclobemide and nortriptyline.
The dexamethasone suppression test (DST) was conducted in 95 elderly DSM-III-R depressed patients randomized for treatment with moclobemide (MOC; 400 mg daily), nortriptyline (NT; 75 mg daily), or placebo (PBO) in a 7-week double-blind multicenter study. Patients were assessed weekly using various clinical scales, including the 17-item Hamilton Depression Rating Scale. The DST was administered at baseline and at the end of treatment. At baseline, no relationship was found between DST status and the various clinical scales used. At the end of treatment, suppressors (DST-) had significantly improved clinical ratings compared to nonsuppressors (DST+), and were mostly found among those treated with NT (71%) as compared to MOC (41%) or PBO (33%) (p < .03). On the other hand, baseline DST measures influenced treatment outcome; DST+ patients had a greater number of treatment responders to NT (48%) than MOC (19%) or PBO (20%) (p < .07). For DST- patients, the situation was reversed: NT, 7%; MOC, 31%. Postdexamethasone cortisol levels were lower in MOC responders (p < .07). An interaction was found between DST and drug-specific response. The DST may be a useful adjunct for predicting and evaluating the outcome of antidepressant therapy.
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[Determination of dihydropyrimidine dehydrogenase in the prediction of toxic side effects of 5-fluorouracil].
In the chemotherapy of colorectal cancers the most frequently given drug is 5-fluorouracil, which in certain cases reduces or delays the appearance of the local recurrence or metastasis. It is well known that the patient's response to 5-fluorouracil is very different concerning both, effects and side effects. More than 80% of the infused drug is catabolised in the first 20 minutes after the treatment. The first and rate limiting enzyme of the catabolism is dihydropyrimidine dehydrogenase, which has the highest activity in the liver and lymphocytes. The activity of this enzyme shows correlation with the blood level of 5-fluorouracil. The deficiency of this enzyme caused severe, in some cases lethal toxicity, its congenital deficiency is responsible for familial pyrimidinaemia. Authors intended to collect data about the dihydropyrimidine dehydrogenase activity of colorectal cancer patients, in order to screen enzyme deficiency or very low enzyme activity, which might be in connection with the appearance of severe side effects, moreover to determine the optimal dose of 5-fluorouracil before the treatment. Dihydropyrimidine dehydrogenase activity was determined in the lymphocytes of 48 colorectal cancer patients, treated by 5-fluorouracil, at the beginning of each cytostatic cycle. The enzyme activity of the patients was between 1.2 and 24.4 pmol/min/10(6) lymphocyte. The value of the enzyme activity fluctuated in a range, characteristic for the individual patients and this value was not modified by the 5-fluorouracil treatment. Dividing the patients in two groups, low (lower than 5 pmol/min 10(6) lymphocyte) and high (higher than 15 pmol/min 10(6) lymphocyte) dihydropirimidine dehydrogenase activity, we found that decrease in the white blood cell number and appearance of the side effects occurred with much higher frequency in the low activity group which resulted in the reduction of the dose or in more serious cases interruption of the treatment. Authors conclude that the determination of the dihydropyrimidine dehydrogenase activity in the lymphocytes is a valuable method in the prediction of the toxic side effects of 5-fluorouracil, in the screening of the congenital enzyme deficiency and in the individualization of the 5-fluorouracil dosage.
Adjuvants, Pharmaceutic↗
[Merkel cell tumor].
Merkel cell cancer is a rare carcinoma arising from the neuroendocrin cells of the skin. The diagnosis is based on the clinical behaviour, histopathologic and ultrastructural findings and immunohistochemical results. An unusual case of Merkel cell carcinoma is presented. Mass from the umbiculus and a right inguinal lymph node was excised in a 63-year-old female. The histologic features of a typical, primitive small cell tumor combined with the immunohistochemical evaluations established the diagnosis. Rare polynuclear giant cells were focally present in our case. Patient was treated with combination of chemotherapy (Cisplatin, Etoposid) and radiotherapy. Control examinations showed complete respond. One year later metastasis developed. Resection of all known metastasis were performed. Two months after the laparotomy she died of metastatic disease. The autopsy did not reveal any other primary tumor. The capricious nature of the clinical course and the differences between this tumor and other carcinomas is emphasized.
Carcinoma, Merkel Cell↗
Wheel-running rhythms in Arvicanthis niloticus.
Wheel-running behaviour of the Nile grass rat, Arvicanthis niloticus, was studied under a variety of lighting conditions to characterize circadian rhythms in this species. A series of lighting schedules was used to determine the nature of entrainment, the rates of reentrainment after 6-h phase shifts, and the stability of free-running rhythms in constant light (LL) and constant dark (DD). All 15 individuals showed peaks of activity around dawn and dusk, 11 were more likely to run when lights were on and 4 were more likely to run when the lights were off. Three of the latter animals were completely crepuscular, but 1 showed a distinctly different and relatively nocturnal pattern, remaining active well into the dark phase. All 7 animals that were exposed to 6-h phase advances and delays reentrained to both shifts within 9 days. Stable and precise free-running rhythms were exhibited by all animals in LL and DD, and periods were longer in LL than DD. The ratio of the active to the inactive phase was significantly higher in LL than in DD or LD conditions. We conclude that A. niloticus exhibit predominantly diurnal running rhythms, with peaks of activity occurring around dawn and dusk, and that their rhythms are stable and precise and respond rapidly and predictably to changes in lighting conditions.
Animals↗
Does a teaching programme improve general practitioners' management of depression in the elderly?
General Practitioners have a central role to play in the management of depression in their older patients. However, studies suggest that GPs tend to underdiagnose and undermanage depression in this age group. Continuing Medical Education is an important part of helping GPs keep up to date and improve their practice. We set out to see what effect a half a day postgraduate training course had on the views and knowledge of a group of local GPs on the management of depression in the elderly. Twenty-one general practitioners attended the course and of these fifteen completed a questionnaire with clinical vignettes before and six weeks after the course. Analysis of the questionnaire and vignette data showed significant improvements in a number of areas: in particular, GPs' knowledge about antidepressant treatment increased, as did their preference for cognitive behavioural therapy out of a range of psychological treatments. This study indicates that a teaching package on depression in the elderly can improve general practitioner's management knowledge. It also suggests that old age psychiatrists can play an important part in the education of their GP colleagues. Nevertheless, further studies are needed to ensure that educational programmes make an effective impact on the underdiagnosis and undertreatment of depression in the elderly.
Age Factors↗