Use of maintenance ECT for elderly depressed patients.
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Biomedical subjects
Publications and source records attributed to A Galinowski.
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In order to assess the predictive value of somatic and biological factors in antidepressant trials, non specific parameters, i.e. natural course of illness, life events, placebo effect ... have to be controlled by means of studies vs placebo. Among somatic factors, retardation seems to predict a positive response to antidepressants. The predictive value of other endogenous signs--like insomnia or weight loss--is still questioned. Few biochemical parameters appear relevant when metabolites of central monoamines, their precursors and the enzymatic processes involved are considered. The serotoninergic system is the focus of many studies. Among the neuroendocrine indices, the DST proved too poorly specific of depression. Among the physiological parameters, some characteristics of sleep EEG, like a shortening of REM latency, seem promising. Pharmacological challenges, for instance response to stimulant drugs, gave inconsistent results and should be discussed on ethical grounds. Many studies have been undertaken but presently no routine reliable biological index is available to predict a response to antidepressants.
The thyrotropin-releasing hormone (TRH) test was performed in 100 depressed patients, including 73 patients with a major depressive episode (MDE) according to DSM-III. Thirty-one patients subsequently received an antidepressant with a predominant serotoninergic action (indalpine or citalopram), and 27 patients received a noradrenergic antidepressant (maprotiline). The diagnostic value of the TRH test was not conclusive for any of the subgroups of depressed patients: MDE, MDE with melancholia or MDE in bipolar patients. Similarly, the value of the TRH test in the choice of antidepressant treatment according to the monoaminergic action was not convincing. These results are discussed in the light of the data of the international literature.
ECT is a reliable treatment of serious affective disorders more efficacious than antidepressants either used alone or combined with mood stabilizers or neuroleptics. Recurrent affective disorders refractory to all treatments presently available have been tentatively treated by prophylactic ECT since the beginning of ECT. In this study, 16 cases of recurrent affective disorders treated with maintenance ECT are discussed. Six continue to show a good response to maintenance ECT. Six remain improved although they discontinued ECT. ECT failed to improve 4 patients. Indications and inclusion criteria of maintenance ECT are defined. Good responses in cases refractory to all other treatment strategies are promising but still require prospective studies, difficult to implement, in order to confirm the efficacy of maintenance ECT.
It has recently been suggested that the plasma level of homovanillic acid (HVA) may provide an index of central dopaminergic activity in humans. Clinical studies have shown that in schizophrenic patients, plasma HVA levels increase with the severity of psychopathology. However, these studies only considered the plasma free HVA fraction whereas investigations on conjugated HVA in humans are sparse and results remain controversial. The aim of this study was to measure both plasma free and conjugated HVA in healthy volunteers and drug-free schizophrenic patients. The mean values and the ranges of plasma free HVA in volunteers and patients were similar to those described in the literature. A substantial and significant increase in plasma free HVA was observed in schizophrenic patients compared with normal subjects. In contrast, plasma conjugated HVA was significatively decreased in schizophrenics. The plasma total HVA was nevertheless higher in schizophrenics compared with controls. No significant correlations were observed between plasma HVA levels and the clinical features of schizophrenic patients rated by various psychiatric scales. These findings suggest that there is an imbalance between plasma free and conjugated HVA in schizophrenic patients, who present an increase in total HVA when compared with controls. Paranoid schizophrenic patients, who present mainly positive symptoms, show the most marked plasma free/conjugated HVA imbalance.
The authors examined the immune status at the cellular and humoral levels of 16 untreated schizophrenic patients. No abnormality in the distribution of T cell subsets (CD4+, CD8+) was detected. The proliferative response to the T cell mitogen phytohemagglutinin was normal. No increase in the number of T cells showing activation markers, such as human leukocyte antigens and interleukin-2 receptors, was noted. Conversely, function studies revealed a clear deficiency in interleukin-2 production by purified T cells. This lower production was probably intrinsic to the patients' T cells, since interleukin-2 production showed normal sensitivity to prostaglandin E2-mediated down-regulation by autologous monocytes.
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Abnormalities of noradrenaline metabolism and of the activity of hypothalamic-pituitary adrenal axis (HPA) have been reported in depression. To study the possible relationship between these 2 parameters, urinary excretion of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and Dexamethasone Suppression Test (DST) were analyzed in 58 depressed patients. A positive correlation was found between the age of depressed patients and 24-h urinary excretion of MHPG. Twenty-two patients (38%) were DST non suppressors. Pre-DST plasma cortisol levels were significantly higher in non suppressors than suppressors. No difference was found however between urinary MHPG levels in suppressors and non suppressors. There was no correlation between pre-DST plasma cortisol and levels of urinary excretion of MHPG. These results do not support the hypothesis of a relationship between these 2 parameters. However, when depressed patients were separated into two groups according to urinary excretion of MHPG ("high MHPG" and "low MHPG"), the "high MHPG" group included significantly more non suppressors then the "low MHPG" one. This result is not sufficient to demonstrate of link between HPA system activity and central noradrenaline metabolism.
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In schizophrenia, various modifications of the immune system have been reported. A decrease of interleukin-2 production by T lymphocytes and an increase of IL-2 receptors were observed by several authors. Not only cellular but humoral immunity seems to be modified: apart from the viral hypothesis, an auto-immune hypothesis holds that auto-antibodies may play a role in the biology of schizophrenia. Natural auto-antibodies, preexisting any antigenic stimulation, may also be involved, particularly in the response to neuroleptic drugs.
Bulimia has been treated with various drugs. MAOI and heterocyclic non MAOI antidepressants have proved efficacious in controlled studies. Whereas Benzodiazepines, Lithium and antiepileptic medications appear less promising or have not yet been widely assessed in methodologically valid studies. Serotoninergic compounds are particularly specific of bulimic disorders. The links of bulimia with depressive states are briefly discussed.
A case of status epilepticus with transient motor deficit is reported in a 66 year old male treated with fluvoxamine. Fluvoxamine is supposed to induce few epileptic seizures. The patient had no previous history of epilepsy. Two factors seem to have favoured the occurrence of epilepsy: presence of an incipient arteriopathic impairment, cortical and subcortical brain atrophy and perhaps drug overdosage causing a tremor in the days before the epileptic fit.
Four cases of recurrent affective disorders received a long term treatment by maintenance ECT in order to control relapses which were not otherwise controlled by antidepressant or mood stabilizing drugs. The efficacy of maintenance ECT makes it possible to use this therapeutic method under certain conditions.
Among brief psychotherapies of depression, cognitive therapy, a theoretical model which was proposed by A.T. Beck as early as the sixties, holds that depression comes from a distorted view of the environment: depressed patients view themselves, the world and the future negatively (cognitive triad). This conception is based upon cognitions, preconscious schemes and faulty information processing, that cognitive therapy corrects, using in a pragmatic way cognitive and behavioral techniques requiring an active collaboration of the patient. Cognitive therapy is indicated, alone or combined with anti-depressants, in neurotic depressions (DSM-II) and in most of major depressions (DSM-III) treated on an outpatient basis. Comparative outcome studies prove the effectiveness of cognitive therapy.
The Social Adjustment Scale Self-Report (SAS-SR) is a simple and inexpensive method, which allows the routine assessment of the patient's social adjustment, especially in the case of depression. Compared with other scales based on an interview with the patient, the SAS-SR is more sensitive to change in the patient's clinical status. The SAS-SR is a useful method as part of the detection of even mild depressions, regular aftercare evaluation of out-patients or as an outcome measure in longitudinal studies. A French version of the SAS-SR is now available and is currently under evaluation in a large-scale randomized therapeutic trial.
In this review the authors propose to study the impact of antidepressants on attention, memory and motor functions in healthy volunteers and depressed patients on single and long-term administration. After reviewing the principal cognitive functions, we examine the actual investigation means to conclude that the Critical Flicker Fusion Test (CFFT) is one of the most drug-sensitive tests. It permits a categorization in: sedative antidepressants that in single administration lower CFFT; compounds with no effect on CFFT and no deleterious cognitive effect; and finally substances that raise CFFT and may have psychostimulating properties. On single administration amitriptyline is the most sedative antidepressant on attention or motor level. It seems to produce negative effects on memory level. However, experimental trials give contradictory results. Imipramine in single administration also has sedative effects on memory and car driving capacity. However divergent results of experimental trials do not allow any conclusions of a clearcut negative cognitive effect. Memory impairments with imipramine appear at administration levels of 150 mg. Mianserin has a sedative impact on attention and motor level at low doses (10 mg). Among the tricyclics, nortriptyline has a highly dose dependent sedative effect that has been shown on attention tests (Time Reaction:TR, Digit Symbol Substitution Test: DSST). Among non-tricyclic compounds, doxepine lowers attention and motor performances. Maprotiline (75 mg) lowers CFFT and has a dose dependent effect. Trazodone also has a negative impact on attention tests. Finally viloxazine lowers CFFT but does not impair other attention or motor tests on a 100 mg doses. Buspirone, lofepramine, midalcipran and zimelidine are antidepressants with no effect on CFFT and do not have any positive or negative cognitive effect. On the other hand nomifensine, paroxetine and fluoxetine raise CFFT in healthy volunteers on single administration. Improvement of CFFT performances was found in an isolated manner for nomifensine and paroxetine on 30 mg doses with no other memory or motor effects. MAO-Inhibitors do not impair attention or motor function; thus moclobemide has no negative impact on memory, attention or car driving tests. Cognitive impact of antidepressants in depressive patients seems the same with those of healthy volunteers on single administration. In long-term administration antidepressants have different effects in healthy and depressed subjects. In healthy volunteers cognitive effects of most compounds are normalized after the second week of treatment. However, attention and motor performances with amitriptyline are normalized after 3 weeks of treatment. Sedative motor or cognitive effects of imipramine do not exceed 8 days.(ABSTRACT TRUNCATED AT 400 WORDS)