Group Of Depressed Patients Research Articles

Restless Legs Syndrome Induced by Mirtazapine

Article AbstractLetter to the EditorSir: Mirtazapine is a novel antidepressant, known as a noradrenergic and specific serotonergic antidepressant (NaSSA). It is an antagonist of presynaptic α2-autoreceptors and α2- heteroreceptors, resulting in an increased release of both norepinephrine and serotonin, and it also enhances noradrenergic and serotonergic neurotransmission. However, mirtazapine potently blocks 5-HT2 and 5-HT3 receptors. Although there are several studies in the literature that examine the effects of mirtazapine on sleep parameters, further study of larger groups of depressed patients is clearly needed.

Typus melancholicus Personality Type and the Five-Factor Model of Personality

Personality traits are significant factors in the development and course of depression. Apart from the classical five-factor model of personality, other personality constellations, such as Tellenbach’s Typus melancholicus, have been described in association with depressive disorder. Several instruments have been developed to assess the Typus melancholicus personality (TMP). A systematic comparison of these instruments has not been done to date. The goal of this study was the comparison of four questionnaires used in assessing TMP. Four TMP questionnaires were compared and their relationship to the five-factor model of personality was examined among 264 psychiatric patients and normal controls. It was found that the TMP type represents a trait distinct from those of the five-factor model. TMP inventories had only moderate concurrent validity. The single TMP scales focus on different aspects of the TMP, despite their common core. Both the five-factor personality traits and the TMP scales were able to differentiate a group of depressed patients from control groups. The results show that TMP is not one trait but a personality trait constellation. This leads to the conclusion that a number of dimensions must be taken into consideration in the construction of a TMP inventory. This multidimensionality contributes to the refinement of the TMP concept and differentiates its therapeutic implications.

Normalization of Frontal Cerebral Perfusion in Remitted Elderly Major Depression: A 12-Month Follow-Up SPECT Study

We examined global and regional cerebral blood flow abnormalities in a group of unmedicated nondemented elderly late-onset unipolar major depressed patients in acute depression and in remission (after a 12-month follow-up period). 35 somatic treatment remitter patients over the age of 60 years and 20 sex-, age-, and vascular risk factor-matched healthy controls were imaged with single photon emission computed tomography, using technetium-99m hexamethylpropylene amine oxime as a tracer. In depression, the depressed group had significantly lower uptake in the left anterior frontal region than the control group. In remission, the left frontal cerebral perfusion abnormalities disappeared, and there were no significant differences in uptake between controls and patients. No significant correlations were found between baseline clinical characteristics of patients and their regional cerebral perfusion at baseline or after a 12-month follow-up. These findings are consistent with the hypothesis that certain neuroanatomic regions of the central nervous system may be functionally and reversibly involved in unipolar major depression, particularly in the late-onset subgroup.

Clinical-Trial Criteria Leave Limited Study Population

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessClinical-Trial Criteria Leave Limited Study PopulationJim RosackJim RosackSearch for more papers by this authorPublished Online:17 May 2002https://doi.org/10.1176/pn.37.10.0028For patients with depression, some days it seems as though absolutely nothing is going their way. Then along comes a new clinical trial for the latest antidepressant medication, and they begin to hope that they can become subjects. Psychiatrists can feel free to disabuse them of that notion: A new study of inclusion and exclusion criteria has determined that the vast majority of patients with depression would never be enrolled in a clinical trial. They simply don’t “fit” the rules.“Studies establishing the effectiveness of antidepressants are based on highly selective samples of depressed patients,” according to researchers from Brown University. In a report appearing in the March American Journal of Psychiatry, the group said that as many as 85 percent of depressed patients treated in an outpatient setting would be excluded from the typical study approved by the federal Food and Drug Administration to determine whether a new antidepressant medication works.The report was supported by grants from the National Institute of Mental Health.“When you take any medicine, you assume it’s been found to be effective for your condition,” said Mark Zimmerman, M.D., an associate professor of psychiatry and human behavior at Brown University and director of outpatient psychiatry at Rhode Island Hospital, in a press release. “But no one knows for sure whether antidepressants are effective for most of the patients that we treat.”Zimmerman and his colleagues reviewed inclusion and exclusion criteria in 31 antidepressant clinical trials published from 1994 to 1998 in five leading psychiatric journals. The majority excluded patients who had psychotic features, a history of manic episodes, any risk of suicide, unstable medical illness, or a history of drug or alcohol use. Several of the studies reviewed also excluded subjects with such comorbid diagnoses as eating disorders, obsessive-compulsive disorder, or any form of panic or anxiety disorder.Almost all of the studies excluded patients who did not meet a cutoff score on a measure of symptom severity—most commonly the Hamilton Depression Scale—even though they may have met DSM diagnostic criteria for major depressive disorder.The researchers then conducted diagnostic evaluations of 346 patients at Rhode Island Hospital’s outpatient practice. When they excluded patients with any feature commonly used in the clinical trials, two-thirds of the patients would have been excluded from taking part in an antidepressant trial. If patients with a comorbid anxiety or panic disorder were also excluded, 85 percent would not have qualified for a drug trial.Yet more than 90 percent of those patients for whom prescribing information was available were being treated with an antidepressant medication at the time of the review.Zimmerman said that drug companies define patient criteria narrowly in antidepressant trials to minimize any confounding effects on results of the efficacy of the drug being studied, including attempting to minimize the placebo effect.“But the current practice of limiting studies to only ‘pure’ moderate to severely ill depressive patients may actually skew the findings of the drug trials as well,” Zimmerman said. If antidepressants are not effective for some of the large subgroups of depressed individuals who have comorbid disorders, prescribing an antidepressant would incur an unjustifiable exposure of risks and side effects, he added.“Drug companies have been very correct in assuming that if they show their medicine works for a highly select group of depressed patients, physicians will use it for all patients,” Zimmerman concluded.An abstract of “Are Subjects in Pharmacological Treatment Trials of Depression Representative of Patients in Routine Clinical Practice?” is posted on the Web at http://ajp.psychiatryonline.org/cgi/content/abstract/159/3/469. ▪ American Journal of Psychiatry 159 469 ISSUES NewArchived

Relationship Between Clinical Variables and Symptomatic Anxiety in Late-Life Depression

The authors asked whether anxiety that is symptomatic of late-life depression is associated with clinical variables besides depression and, if so, how much of the variance is explained by this association. Severity of anxiety in 101 elderly patients with major depression was measured at index assessment and at antidepressant response. The following clinical variables were selected to determine whether they were associated with severity of anxiety: depression severity, burden of chronic physical illness, cognitive functioning, negative life events, life difficulties, and intensity of psychosocial support. Anxiety had a statistically significant association with severity of depression and life events at index assessment and with severity of depression and life difficulties at antidepressant response. In linear-regression models, depression severity accounted for the largest proportion of the variance in anxiety at both index assessment and response; life events and life difficulties accounted for only 3% and 4% of variance, respectively. In this group of elderly depressed patients, medical burden, cognitive impairment, and negative psychosocial circumstances did not contribute in a clinically significant way to variance in severity of symptomatic anxiety.

Neuropsychological dysfunction in depressed suicide attempters.

Neuropsychological deficits in the context of psychiatric disease may be associated with suicide risk. In this study, neuropsychological performance was compared among depressed patients with at least one prior suicide attempt of high lethality, depressed patients with low-lethality prior attempts, depressed patients with no prior suicide attempts, and nonpatients. Fifty unmedicated patients in a major depressive episode (21 with no history of suicide attempts and 14 and 15 patients with previous attempts of low and high lethality, respectively) and 22 nonpatients were assessed. Groups were comparable in age, education, occupational level, and estimated premorbid intelligence. The neuropsychological battery produced scores within five composite domains: general intellectual functioning (current), motor functioning, attention, memory, and executive functioning. Patients whose prior suicide attempts were of high lethality performed significantly worse than all groups on tests of executive functioning and were the only group to perform significantly worse than nonpatients on tests of general intellectual functioning, attention, and memory. A discriminant function analysis revealed two prominent dimensions in the data: one that discriminated high-lethality suicide attempters from all other groups (primarily associated with performance on tests of executive functioning) and another that discriminated all depressed patient groups from nonpatients (associated with performance on measures of attention and memory). For the patients with high-lethality prior suicide attempts, deficits did not appear to reflect diffuse brain damage from past attempts, since the results of tests commonly affected by diffuse injury were not selectively impaired. Neuropsychological deficits in depressed patients with high-lethality prior suicide attempts suggest impairment of executive functioning beyond that typically found in major depression. This more extensive neuropsychological impairment in the context of depression may be a risk factor for severe suicide attempts.

Raised levels of plasma interleukin‐1β in major and postviral depression

Interleukin-1beta (IL-1beta) is released as part of the acute phase immune response and can directly stimulate the release of corticotrophin-releasing hormone and thus induce hypothalamic pituitary adrenal axis hyperactivity. Major depression has been shown to be accompanied by both an acute phase immune response, including raised IL-1beta production and hypothalamic pituitary adrenal axis hyperactivity. In this study the possible role of IL-1beta in major depression and postviral depression was investigated. Plasma IL-1beta levels were measured in four groups; patients suffering from postviral depression (n= 17), patients with major depression (n = 20), subjects who were postviral and euthymic (n= 12) and normal controls (n = 20). IL-1beta serum concentrations were significantly elevated in both groups of depressed patients compared to controls. The serum concentrations of IL-1beta were higher in the postviral group than in the major depression group; this difference was not significant. These data confirm previous suggestions of elevated IL-1beta levels in major depression and postviral depression. IL-1beta is known to induce depressive symptoms as well as sickness behaviour and may contribute to the hypothalamic pituitary adrenal axis hyperactivity found in mood disorders.

PLASMA INFLAMMATORY CYTOKINE RESPONSE TO SURGICAL TRAUMA IN CHRONIC DEPRESSED PATIENTS

We investigated inflammatory cytokine response in chronic depressed patients during abdominal surgery. Twenty-five major depressed patients (Group D) and twenty-five patients (Group C) as the control were studied. Plasma interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor-alpha (TNF-α) concentrations were measured before and at 15 min after induction of anesthesia, the end of surgery, 24h and 3 days after the operation. Plasma IL-6 concentrations in Group D at the end of the operation and 24h after surgery were significantly lower than those of Group C. The plasma IL-6 concentration (87.1±55.3pg/ml) of patients scoring more than 18 points in the Hamilton depression-rating score at the end of the operation was significantly higher than 57.5±76.7pg/ml of patients scoring less than 18 points. Plasma IL-8 concentration (6.1±3.2pg/ml) in Group D at the end of the operation was significantly lower than 8.7±4.2pg/ml of Group C. We conclude that plasma IL-6 and IL-8 response to surgical trauma is inhibited in chronic depressed patients. The IL-6 response to surgical trauma is depending on the clinical state of depression.

Paroxetine in Parkinson's disease: effects on motor and depressive symptoms.

Selective serotonin reuptake inhibitors have been used in the treatment of depression in patients with PD. Conflicting data as to whether selective serotonin reuptake inhibitors worsen parkinsonian motor symptomatology have been reported. In this study, the additional 6 months therapy with paroxetine 20 mg/d in a group of depressed patients with PD did not modify parkinsonian motor function (Unified Parkinson's Disease Rating Scale scores); however, in one patient, fully reversible worsening of tremor was observed. Depression, as evaluated by Beck Depression Inventory and Hamilton Depression Rating Scale, improved from baseline to final visit (p < 0.05 by analysis of variance).

Reduced Leptin Levels in Human Narcolepsy

Recently, hypocretins have been implicated in the pathophysiology of narcolepsy, a sleep disorder characterized particularly by the occurrence of excessive daytime sleepiness and cataplexy. Hypocretins, which stimulate food intake, have been reported to be absent in the cerebrospinal fluid (CSF) of the majority of patients suffering from narcolepsy. Because these patients also display an increased body mass index (BMI), it has been suggested that disturbances in metabolism and food intake regulation may be present. To further investigate these presumed alterations, we studied the production of leptin, a fat-cell-derived hormone signaling to the brain the size of the adipose tissue. We measured the levels of leptin in serum and CSF from 15 narcoleptic patients and compared the results to those from age-, sex- and BMI-matched control groups of depressive patients and patients suffering from a noninflammatory neurological disorder. Compared to both control groups, leptin levels in serum, but not in the CSF, were significantly reduced in narcoleptic patients by more than 50%. These results support the hypothesis that human narcolepsy is accompanied by complex alterations of the regulation of food intake and metabolism. The significance of these alterations for the core symptomatology of narcolepsy should be a target of future research.

Hippocampal volume in geriatric depression

Background: There is a growing literature on the importance of hippocampal volume in geriatric depression. Methods: We examined hippocampal volume in a group of elderly depressed patients and a group of elderly control subjects ( N = 66 geriatric depressed patients and 18 elderly nondepressed control subjects) recruited through Duke’s Mental Health Clinical Research Center for the Study of Depression in the Elderly. The subjects received a standardized evaluation, including a magnetic resonance imaging scan of the brain. Patients had unipolar major depression and were free of comorbid major psychiatric illness and neurologic illness. Differences were assessed using t tests and linear regression modeling. Results: Accounting for the effects of age, gender, and total brain volume, depressed patients tended to have smaller right hippocampal volume ( p = .014) and left hippocampal volume ( p = .073). Among depressed patients, age of onset was negatively but not significantly related to right hippocampal volume ( p = .052) and to left hippocampal volume ( p = .062). We noted that among subjects with either right or left hippocampal volume of 3 mL or less, the vast majority were patients rather than control subjects. Conclusions: These results support a role for hippocampal dysfunction in depression, particularly in late-age onset depression. Longitudinal studies examining both depressive and cognitive outcomes are needed to clarify the relationships between the hippocampus, depression, and dementia.

Effect of Nortriptyline and Paroxetine on Extrapyramidal Signs and Symptoms: A Prospective Double-Blind Study in Depressed Elderly Patients

Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been reported to induce extrapyramidal signs and symptoms (EPS). The authors examined the change from baseline EPS, measured by an objective rating scale, in a group of elderly depressed patients participating in an ongoing randomized, double-blind comparison of nortriptyline and paroxetine. Mild baseline EPS were present in both groups. After 6 weeks of antidepressant treatment, patients in the nortriptyline group showed a significant decrease in total EPS scores. Patients in the paroxetine group showed a similar decrease in EPS from baseline, which did not reach statistical significance. There was no significant difference between nortriptyline and paroxetine in the change in EPS.

Treatment for chronic depression: cognitive behavioral analysis system of psychotherapy (CBASP)

Chronic depression is a common disorder in secondary care. Treatment results for this group of depressed patients are often disappointing and the existing treatment protocols are insufficiently tailored to chronic MDD. For this reason, an effective psychotherapeutic treatment will constitute a welcome addition to the range of treatments currently available for chronically depressed patients.To describe 'cognitive behavioral analysis system of psychotherapy' (CBASP), the first form of psychotherapy specifically designed for the treatment of chronic depression.This article describes the evidence, rational and the most important techniques of CBASP.In the United States CBASP has proven to be effective in one trial. As a result of these findings, CBASP is recommended in the Dutch treatment guidelines as an evidence-based treatment option for chronic depression. However, the findings have not yet been replicated and little is known about possible ways of implementing CBASP in the Netherlands. For this reason a randomised controlled trial on the effectiveness of CBASP has started in three psychiatric hospitals in the Netherlands.CBASP is recommended as a treatment option for chronic depression in the Dutch treatment guidelines, but evidence should be further supported by additional research.

Costing depression and its management: an Australian study.

To examine the cost impact of referral to a Mood Disorders Unit (MDU), by comparing pre-service and post-service costs, and MDU and control samples. We studied tertiary referral MDU patients and a control group of consultants' depressed patients, with the principal comparison intervals being: (i) 12 months prior to and (ii) 6 months following baseline assessment, with costs annualised to allow the impact of assessment and treatment recommendation to be determined. In addition, we assessed any 'personal cost' of depression. Following baseline assessment, MDU referrals showed a reduction in costs, while controls' costs increased, largely driven by contrasting directions in hospitalisation and social welfare costs. We identify variables associated with high and increased costs, including features of the earlier stages of the disorder, whether social welfare was received, diagnostic subtype and personality dysfunction, with multivariate analyses refining the variable sets. Self-report data indicated that patients judged the 'personal cost' of depression to exceed more formal cost parameters, so that to experience depression is itself depressogenic. This first Australian attempt to cost depression and its management in the clinical setting more provides a methodology for wider application in service evaluation studies rather than delivers an unequivocal answer to whether a specialist Mood Disorders Unit is cost efficient or not.

Increased cerebrospinal fluid glutamine levels in depressed patients

Background: There is increasing evidence for an association between alterations of brain glutamatergic neurotransmission and the pathophysiology of affective disorders. Methods: We studied the association between cerebrospinal fluid (CSF) metabolites, including glutamine, in unipolar and bipolar depressed patients versus control subjects using a proton magnetic resonance spectroscopy technique. Cerebrospinal fluid samples were obtained from 18 hospitalized patients with acute unmedicated severe depression without medical problems and compared with those of 22 control subjects. Results: Compared with the control group, the depressed patient group had significantly higher CSF glutamine concentrations, which correlated positively with CSF magnesium levels. Conclusions: These findings suggest an abnormality of the brain glial–neuronal glutamine/glutamate cycle associated with N-methyl- d-aspartate receptor systems in patients with depression.

The citalopram challenge test in patients with major depression and in healthy controls

Neuroendocrine challenge tests in depressed patients have revealed a blunted hormonal reaction to serotonergic stimuli. In the present study, citalopram was chosen as the serotonergic agent for neuroendocrine stimulation. Compared to earlier challenge agents, citalopram has the advantage of serotonergic selectivity, its application is well tolerated and the possibility of intravenous application reduces pharmacokinetic interference. Sixteen patients suffering from an acute episode of major depression and 16 healthy controls underwent the stimulation procedure with 20 mg of citalopram and placebo. Whereas significant differences in the secretion of prolactin and cortisol between citalopram and placebo challenge were observed in the control group, no differences were found in the group of depressed patients. Comparison of depressed patients and controls showed a significantly blunted prolactin secretion in patients. Differences in cortisol secretion following serotonergic stimulation with citalopram did not become significant. The stimulation procedure was well tolerated in all subjects, although a higher number of side effects was observed in the control group. The amount of side effects did not correlate with the hormone responses. These results are in line with the hypothesis of serotonergic hypofunction in depressed patients. In conclusion, the 20-mg citalopram challenge test is thought to be a promising tool for further investigation of serotonergic function in psychiatric illness.

Cerebrospinal Cytokine Levels in Patients with Acute Depression

There is increasing evidence for an association between the alteration of cytokine concentrations in blood and the pathophysiology of depressive disorders. Studies in humans have not investigated CSF cytokine concentrations and their relationship to depressive disorders. This study reports on the association of the CSF concentration of proinflammatory cytokines, IL-1β, IL-6 and TNFα, and major depressive disorders. CSF samples were obtained from 13 hospitalized patients with acute unmedicated severe depression and were compared with 10 control subjects. Compared to the control group, the depressed patient group had higher CSF concentrations of IL-1β, lower IL-6 and no change in TNFα. A positive correlation was found between serum IL-1β and the severity of depression. These results indicate a unique profile for CSF proinflammatory cytokines in acute depression. These findings merit further investigation and if replicated may possibly offer immunological treatment options for depression.

Depressive Symptoms in Koreans, Korean-Chinese and Chinese: A Transcultural Study

We compared symptoms among three groups of depressed patients: 60 Koreans residing in Seoul, Korea; 42 Korean-Chinese in Yanbien, China; and 31 Chinese in Yanbien, China, using Hamilton’s Rating Scale for Depression and Beck’s Depression Inventory. Korean depressives manifested the highest scores in depressive mood, dissatisfaction, feelings of guilt, and loss of work and interest, whereas the Chinese scored highest in loss of work and interest, loss of libido, insomnia, delayed insomnia and agitation. The Korean-Chinese had prominent symptoms of agitation, retardation and hypochondriasis. The findings suggest that Korean depressives are characterized by psychological symptoms, Chinese depressives are characterized by somatic symptoms and Korean-Chinese depressives lie between the other two groups on a somatic–psychological continuum. The results are discussed in the context of cultural differences between Korea and China and the cultural pluralism of the Korean-Chinese.

Follow-up study of depression in the elderly. Clinical and SPECT data.

Imaging studies in depression of the elderly are often small and highly selective. To investigate a large group of elderly depressed patients in order to assess changes in clinical, imaging and neuropsychological variables at follow-up. Patients (n = 175, age range 65-91 years) with clinical depression were identified from consecutive local referrals. Clinical interviews, neuropsychological tests and SPECT scans were carried out at referral and at two-year follow-up. Of 84 re-examined patients, 46.5% were well, 9.5% were ill, 33% partially recovered and 11% had developed dementia. Duration of illness before index assessment was the only factor to predict outcome. Thirty-nine patients could be scanned and followed up. There were no differences between patients with good or poor depressive outcome on SPECT. Ten clinically improved patients could be re-examined with SPECT. There were relative increases in right cingulate gyrus and right cerebellum at follow-up. The patients group was comparable with other studies showing high levels of residual depressive symptoms. Activity changes in limbic cortex are implicated in depression of old age.

MECHANISMS OF ACTIONS OF ANTIDEPRESSANTS

The advent of the selective serotonin (5-HT) reuptake inhibitors (SSRIs) has resulted, perhaps, in norepinephrine (NE) becoming the “forgotten” monoamine with respect to the mechanism of action of antidepressants. This is unfortunate as it has been clear for many years that drugs that acutely alter NE function selectively can be antidepressants (e.g., desipramine). This presentation focuses on the mechanisms of action of all types of antidepressants as well as the pharmacodynamic reasons for differences in their side-effect profile. For example, the improved side-effect and toxicity profile seen with the SSRIs, as well as newer drugs such as venlafaxine, is due, at least in part, to their inability to block muscarinic cholinergic, (1 adrenergic, or H1 histamine receptors, nor to inhibit myocardial conduction. With respect to mechanism of action, it is of interest that different types of antidepressants have comparable efficacy in treating heterogeneous groups of depressed patients. Drugs that selectively block the uptake of serotonin (e.g., fluoxetine, sertraline) or norepinephrine (desipramine, the investigational compound reboxetine) or both monoamines (imipramine, venlafaxine) cause a similar extent of improvement in nonselected depressed patients. Whether this holds true for subgroups of depressed patients is currently under investigation. Relevant to this issue is whether drugs that are selective in vitro retain their selectivity in vivo, especially under repeated administration. Both preclinical and clinical data will be presented that address this. For example, repeated administration of NE reuptake inhibitors to rats does not affect certain serotonergic parameters (e.g., 5-HT1A receptor sensitivity) in the same way as SSRIs. On the other hand, SSRIs do not downregulate β1 adrenergic receptors, but antidepressants that affect noradrenergic function do this. Also, the clinical efficacy of NE reuptake inhibitors does not seem to be dependent on the presence of 5-HT, nor is the efficacy of SSRIs dependent on the presence of NE. By contrast, new in vivo voltammetric data are presented demonstrating that NE reuptake inhibitors alter the clearance of 5-HT in certain brain areas. Also, treatment of depressed patients with desipramine causes, over time, a reduction of the content of 5-HT in their platelets. Thus, there is evidence for both selective and nonselective effects of various types of antidepressants on monoamine function in vivo.