Recent studies have highlighted the increase in treatment resistant depression. Of particular concern is the rising trend of depression and suicide rates among Young Adults. Ketamine was approved for treatment resista...Recent studies have highlighted the increase in treatment resistant depression. Of particular concern is the rising trend of depression and suicide rates among Young Adults. Ketamine was approved for treatment resistant depression in 2019 by the US Food and Drug Administration. It received an additional indication for treatment of suicidality. While intranasal Ketamine is approved for depression, recent data about intravenous infusion of Ketamine in controlled inpatient settings has been promising. ECT has a long-standing trend for being used for resistant depression and recent comparison trials have revealed positive results when head-to-head comparisons are made with Ketamine. Future studies need to focus on patient selection and wherein treatment algorithm should Ketamine be selected as treatment modality.展开更多
Pramipexole is a dopamine agonist used in the treatment of Parkinson’s disease and Restless legs syndrome. Although off-label, the use of Pramipexole as an adjunct therapy in treatment resistant depression has recent...Pramipexole is a dopamine agonist used in the treatment of Parkinson’s disease and Restless legs syndrome. Although off-label, the use of Pramipexole as an adjunct therapy in treatment resistant depression has recently been documented in the literature with promising results. We present a 75-year-old male with MDD who has failed trials of SSRIs, SNRIs, TCAs, SGA, TMS, Ketamine, and ECT who was initiated on Pramipexole. We discuss, based on existing literature, the probability of a favorable long-term response to Pramipexole and the potential side effects for our patient. We also highlight the need for future studies designed to test the efficacy of Pramipexole in geriatric patients with TRD.展开更多
AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systemati...AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that the benefits of intraand cross-class switch do not significantly differ. Data on combination strategy are controversial regarding TCA-SSRI combination(positive results in old studies, negative in more recent study) and bupropion-SSRI combination(three open series studies but not three controlled trails support the useful of this combination) and positive regard mirtazapine(or its analogue mianserine) combination with ADs of different classes. As regards the augmentation strategy, available evidences supported the efficacy of TCA augmentation with lithium salts and thyroid hormone(T3), but are conflicting regard the SSRI augmentation with these two drugs(1 positive trial out of 4 for lithium and 3 out of 5 for thyroid hormone). Double-blind controlled studies showed the efficacy of AD augmentation with aripiprazole(5 positive trials out 5), quetiapine(3 positive trials out 3) and, at less extent, of fluoxetine augmentation with olanzapine(3 positive trials out 6), so these drugs received the FDA indication for the acute treatment of TRD. Results on AD augmentation with risperidone are conflicting(2 short term positive trials, 1 short-term and 1 long-term negative trials). Case series and open-label trials showed that AD augmentation with pramipexole or ropinirole, two dopamine agonists, could be an effective treatment for TRD(response rate to pramipexole 48%-74%, to ropinirole 40%-44%) although one recent double-blind placebo-controlled study does not support the superiority of pramipexole over placebo. Evidences do not justify the use of psychostimulants, omega-3 fatty acids, S-adenosil-Lmetionine, methylfolate, pindolol, lamotrigine, and sex hormone as AD augmentation for TRD. Combining the available evidences with our experience we suggest treating non-responders to one SSRI bupropion or mirtazapine trial by switching to venlafaxine, and nonresponders to one venlafaxine trial by switching to a TCA or, if TCA are not tolerated, combining mirtazapine with SSRI or venlafaxine. In non-responders to two or more ADs(including at least one TCA if tolerated) current AD regimen could be augmented with lithium salts(mainly in patients with bipolar depression or suicidality), SGAs(mostly aripiprazole) or DA-agonists(mostly pramipexole). In patients with severe TRD, i.e., non-responders to combination and augmentation strategies as well as to electroconvulsive therapy if workable, we suggest to try a combination plus augmentation strategy.CONCLUSION: Our study identifies alternative effective treatment strategies for TRD. Further studies are needed to compare the efficacy of different strategies in more homogeneous subpopulations.展开更多
The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression （TRD） and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diag...The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression （TRD） and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment.展开更多
As the global population gets older, depression in the elderly is emerging as an important health issue. A major challenge in treating geriatric depression is the lack of robust efficacy for many treatments that are o...As the global population gets older, depression in the elderly is emerging as an important health issue. A major challenge in treating geriatric depression is the lack of robust efficacy for many treatments that are of significant benefit to depressed working age adults. Repetitive transcranial magnetic stimulation(r TMS) is a novel physical treatment approach used mostly in working age adults with depression. Many TMS trials and clinics continue to exclude the elderly from treatment citing lack of evidence in this age group. In this review, we appraise the evidence regarding the safety and efficacy of rT MS in the elderly. A consistent observation supporting a high degree of tolerability and safety among the elderly patients emerged across the Randomised Controlled Trials and the uncontrolled trials. Further, there is no reliable evidence negating the utility of rT MS in the elderly with depression. We also identified several factors other than age that moderate the observed variations in the efficacy of rT MS in the elderly. These factors include but not limited to:(1) brain atrophy;(2) intensity and number of pulses(dose-response relationship); and(3) clinical profile of patients. On the basis of the current evidence, the practice of excluding elderly patients from TMS clinics and trials cannot be supported.展开更多
Background Depressive disorder is a well-known chronic, recurrent and disabling mental disease with high direct and indirect costs to society in both western and eastern cultures. Approximately 40% of depressed patien...Background Depressive disorder is a well-known chronic, recurrent and disabling mental disease with high direct and indirect costs to society in both western and eastern cultures. Approximately 40% of depressed patients show only partial or no response to initial or even multiple antidepressant medications and are usually called treatment-resistant depression （TRD） patients. The present work was to measure the features of sensory gating （SG） P50 in TRD patients with the intent of understanding the characteristics of this disease. Methods In 50 TRD patients, 39 non-treatment-resistant depression （NTRD） patients and 51 healthy controls （HC）, auditory evoked potential P50 was measured using the conditioning/testing paradigm presented with auditory double clicks stimuli, and 36 TRD patients had repeated measurements after an 8-week venlafaxine treatment course. Results All the depressive disorder patients, including the TRD and NTRD groups, showed an increased testing stimulus wave （$2-P50） amplitude compared to controls （P 〈0.01 and P 〈0.05）, but there was no significant difference between the TRD and NTRD groups （P 〉0.05）. There were significant differences in the ratio of testing stimulus （S2） and conditioning stimulus （S1） （S2/S1） and in the value of 100 × （1-S2/S1） among the three groups. Compared to the baseline, TRD patients had no significant changes of features and different expression of P50 after acute treatment （P 〉0.05）. Meanwhile, a statistically significant positive correlation of S2/S1 with the scores of the 17-item Hamilton Rating Scale for Depression （HAMD-17） （P 〈0.01）, and a significantly negative correlation of S1-S2, 100 × （1-S2/S1） with the scores of HAMD-17 （P 〈0.01） were observed in the TRD patients＇ baseline measurement, but there was no correlation after venlafaxine treatment （P 〉0.05）. Conclusions Both the TRD and NTRD patients had obvious SG deficits, with a more severe deficit in TRD patients. Although, with a correlated relationship to the severity of depressive symptoms, SG P50 deficit might be suggested as a trait marker for TRD, and a combination of S2/S1 ratio, S1-S2 and 100 × （1-S2/S1）, was recommended for electrophysiological measurement in TRD patients.展开更多
Comorbid anxiety with depression predicts poor outcomes with a higher percentage of treatment resistance than either disorder occurring alone. Overlap of anxiety and depression complicates diagnosis and renders treatm...Comorbid anxiety with depression predicts poor outcomes with a higher percentage of treatment resistance than either disorder occurring alone. Overlap of anxiety and depression complicates diagnosis and renders treatment challenging. A vital step in treatment of such comorbidity is careful and comprehensive diagnostic assessment. We attempt to explain various psychosocial and pharmacological approaches for treatment of comorbid anxiety and depression. For the psychosocial component, we focus only on generalized anxiety disorder based on the following theoretical models:(1) "the avoidance model";(2) "the intolerance of uncertainty model";(3) "the meta-cognitive model";(4) "the emotion dysregulation model"; and(5) "the acceptance based model". For depression, the following theoretical models are explicated:(1) "the cognitive model";(2) "the behavioral activation model"; and(3) "the interpersonal model". Integration of these approaches is suggested. The treatment of comorbid anxiety and depression necessitates specific psychopharmacological adjustments as compared to treating either condition alone. Serotonin reuptake inhibitors are considered first-line treatment in uncomplicated depression comorbid with a spectrum of anxiety disorders. Short-acting benzodiazepines(BZDs) are an important "bridging strategy" to address an acute anxiety component. In patients with comorbid substance abuse, avoidance of BZDs is recommended and we advise using an atypical antipsychotic in lieu of BZDs. For mixed anxiety and depression comorbid with bipolar disorder, we recommend augmentation of an antidepressant with either lamotrigine or an atypical agent. Combination and augmentation therapies in the treatment of comorbid conditions vis-à-vis monotherapy may be necessary for positive outcomes. Combination therapy with tricyclic antidepressants, gabapentin and selective serotonin/norepinephrine reuptake inhibitors(e.g., duloxetine) are specifically useful for comorbid chronic pain syndromes. Aripiprazole, quetiapine, risperidone and other novel atypical agents may be effective as augmentations. For treatment-resistant patients, we recommend a "stacking approach" not dissimilar from treatment of hypertension In conclusion, we delineate a comprehensive approach comprising integration of various psychosocial approaches and incremental pharmacological interventions entailing bridging strategies, augmentation therapies and ultimately stacking approaches towards effectively treating comorbid anxiety and depression.展开更多
Both type 2 diabetes and depression are common and are projected to increase.There is increasing evidence for a bidirectional relationship between the two.Diabetes is a risk factor for depression;contrariwise,individu...Both type 2 diabetes and depression are common and are projected to increase.There is increasing evidence for a bidirectional relationship between the two.Diabetes is a risk factor for depression;contrariwise,individuals with depression are at greater risk of developing diabetes.They are a burden for both the individual and the society.Co-existent depression worsens diabetic control because of obesity,insulin resistance and the adverse metabolic effects of anti-diabetes medicines.In addition,compliance to lifestyle measures required for diabetes is also compromised such as following a specific diet,taking proper medications on time,getting metabolic parameters assessed and maintaining a sleep cycle.Depression occurs in many grades;mild depression is more common in diabetes than frank or full-blown depression leading to suicide.Unfortunately,there are not enough trained and accessible mental health professionals such as psychologists or psychiatrists to deal with the increasing burden of depression in diabetes.Therefore,alternate models for management of mild to moderate depression are required.There is evidence that a team-approach by employing health care assistants can lower the risk of cardiac risk factors.INtegrating DEPrEssioN and Diabetes treatmENT study was carried out to determine whether the team-approach using non-health care professionals could be effective in managing mild to moderate depression and to study its effects on metabolic parameters among subjects with type 2 diabetes mellitus.The international study,carried out in four independent centers in India assessed the impact of a trained but not qualified non-psychiatrist in coordinating and forming a fulcrum between the patient,the family and the consultant endocrinologist/diabetologist.The interventions were fine-tuned to be culturally appropriate by qualitative interviews before they began.It was shown that the outcomes of both depression and diabetes could be improved by the employment of a clinical care coordinator.It is possible to scale up the studies to wider geographical areas and health-care organizations.展开更多
Corrosion of metal components constitutes a major challenge in many engineering systems, with appropriate design, proper material selection, and heat treatment as commonly used control strategies. In this study, the c...Corrosion of metal components constitutes a major challenge in many engineering systems, with appropriate design, proper material selection, and heat treatment as commonly used control strategies. In this study, the corrosion behaviour of heat-treated (annealed, normalised, hardened, and tempered) NST 37-2 steel in three concentrations (1.0, 1.5 and 2.0 M) of hydrochloric acid solution was investigated using weight loss and electrode-potential methods. Results showed that corrosion rate increased with increase in acid concentration. The decreasing order of corrosion resistance was Tempered > Annealed > Normalised > Hardened > Untreated. The surface pictures of the heat-treated and untreated samples showed uniform and pitting corrosion with the latter becoming more pronounced as concentration increased.展开更多
This brief review discusses the behavioral consequences of two pharmacologically selected lines of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats were selected on the basis of differential h...This brief review discusses the behavioral consequences of two pharmacologically selected lines of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats were selected on the basis of differential hypothermic and behavioral responses to the anticholinesterase, diisopropylfluorophosphate (DFP). FSL rats are more sensitive to the hypothermic effects of cholinergic, serotonergic, and dopaminergic agonists but less sensitive to the locomotor or stereotypic effects of dopamine agonists. FSL rats exhibit greater immobility in the forced swim test and reduced social interaction compared with FRL rats, but do not differ in saccharin intake, behavior in the elevated plus maze, or responses for rewarding brain self-stimulation. The exaggerated immobility and reduced social interaction are counteracted by chronic treatment with antidepressants. Because FSL rats were more sensitive to 5-HT1A receptor agonists, high (HDS) and low (LDS) 8-OH-DPATsensitive lines were selectively bred for differential hypothermic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). HDS rats were also more sensitive to the hypothermic effects of oxotremorine, a cholinergic agonist, but selection for this response did not diverge with later selection. HDS rats exhibited greater immobility in the forced swim test than LDS rats and this correlated response could be seen early in selection (generation 3). HDS rats also showed reduced social interaction compared to LDS rats, but did not differ in behavior in the elevated plus maze. These findings confirm that selection for hypothermic responses to pharmacological agents do have behavioral consequences, notably the production of depressive-like phenotypes, which can be counteracted by chronic antidepressant treatment. Because increased 5-HT1A receptor sensitivity was common to both selected lines (FSL and HDS), neurobiological processes dependent on this receptor could contribute to the abnormal behaviors that manifest in these rat lines and thus suggesting a mechanism underlying depressive behaviors in humans. However, available human data are inconsistent with this hypothesis and suggest that other mechanisms underlie these behavioral abnormalities in HDS and FSL rats. These mechanisms as well as additional behavioral testing in these rat lines will be discussed.展开更多
文摘Recent studies have highlighted the increase in treatment resistant depression. Of particular concern is the rising trend of depression and suicide rates among Young Adults. Ketamine was approved for treatment resistant depression in 2019 by the US Food and Drug Administration. It received an additional indication for treatment of suicidality. While intranasal Ketamine is approved for depression, recent data about intravenous infusion of Ketamine in controlled inpatient settings has been promising. ECT has a long-standing trend for being used for resistant depression and recent comparison trials have revealed positive results when head-to-head comparisons are made with Ketamine. Future studies need to focus on patient selection and wherein treatment algorithm should Ketamine be selected as treatment modality.
文摘Pramipexole is a dopamine agonist used in the treatment of Parkinson’s disease and Restless legs syndrome. Although off-label, the use of Pramipexole as an adjunct therapy in treatment resistant depression has recently been documented in the literature with promising results. We present a 75-year-old male with MDD who has failed trials of SSRIs, SNRIs, TCAs, SGA, TMS, Ketamine, and ECT who was initiated on Pramipexole. We discuss, based on existing literature, the probability of a favorable long-term response to Pramipexole and the potential side effects for our patient. We also highlight the need for future studies designed to test the efficacy of Pramipexole in geriatric patients with TRD.
文摘AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that the benefits of intraand cross-class switch do not significantly differ. Data on combination strategy are controversial regarding TCA-SSRI combination(positive results in old studies, negative in more recent study) and bupropion-SSRI combination(three open series studies but not three controlled trails support the useful of this combination) and positive regard mirtazapine(or its analogue mianserine) combination with ADs of different classes. As regards the augmentation strategy, available evidences supported the efficacy of TCA augmentation with lithium salts and thyroid hormone(T3), but are conflicting regard the SSRI augmentation with these two drugs(1 positive trial out of 4 for lithium and 3 out of 5 for thyroid hormone). Double-blind controlled studies showed the efficacy of AD augmentation with aripiprazole(5 positive trials out 5), quetiapine(3 positive trials out 3) and, at less extent, of fluoxetine augmentation with olanzapine(3 positive trials out 6), so these drugs received the FDA indication for the acute treatment of TRD. Results on AD augmentation with risperidone are conflicting(2 short term positive trials, 1 short-term and 1 long-term negative trials). Case series and open-label trials showed that AD augmentation with pramipexole or ropinirole, two dopamine agonists, could be an effective treatment for TRD(response rate to pramipexole 48%-74%, to ropinirole 40%-44%) although one recent double-blind placebo-controlled study does not support the superiority of pramipexole over placebo. Evidences do not justify the use of psychostimulants, omega-3 fatty acids, S-adenosil-Lmetionine, methylfolate, pindolol, lamotrigine, and sex hormone as AD augmentation for TRD. Combining the available evidences with our experience we suggest treating non-responders to one SSRI bupropion or mirtazapine trial by switching to venlafaxine, and nonresponders to one venlafaxine trial by switching to a TCA or, if TCA are not tolerated, combining mirtazapine with SSRI or venlafaxine. In non-responders to two or more ADs(including at least one TCA if tolerated) current AD regimen could be augmented with lithium salts(mainly in patients with bipolar depression or suicidality), SGAs(mostly aripiprazole) or DA-agonists(mostly pramipexole). In patients with severe TRD, i.e., non-responders to combination and augmentation strategies as well as to electroconvulsive therapy if workable, we suggest to try a combination plus augmentation strategy.CONCLUSION: Our study identifies alternative effective treatment strategies for TRD. Further studies are needed to compare the efficacy of different strategies in more homogeneous subpopulations.
基金sponsored by Project of the First Affiliated Hospital of Shihezi University Medical College in 2010, No. YL2010-S024
文摘The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression （TRD） and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment.
基金Supported by Transformational funding support from the National Health Services,Nottinghamshire Healthcare NHS TrustLena Palaniyappan received benefit in kind to speak at a conference organised by Magstim Limited
文摘As the global population gets older, depression in the elderly is emerging as an important health issue. A major challenge in treating geriatric depression is the lack of robust efficacy for many treatments that are of significant benefit to depressed working age adults. Repetitive transcranial magnetic stimulation(r TMS) is a novel physical treatment approach used mostly in working age adults with depression. Many TMS trials and clinics continue to exclude the elderly from treatment citing lack of evidence in this age group. In this review, we appraise the evidence regarding the safety and efficacy of rT MS in the elderly. A consistent observation supporting a high degree of tolerability and safety among the elderly patients emerged across the Randomised Controlled Trials and the uncontrolled trials. Further, there is no reliable evidence negating the utility of rT MS in the elderly with depression. We also identified several factors other than age that moderate the observed variations in the efficacy of rT MS in the elderly. These factors include but not limited to:(1) brain atrophy;(2) intensity and number of pulses(dose-response relationship); and(3) clinical profile of patients. On the basis of the current evidence, the practice of excluding elderly patients from TMS clinics and trials cannot be supported.
文摘Background Depressive disorder is a well-known chronic, recurrent and disabling mental disease with high direct and indirect costs to society in both western and eastern cultures. Approximately 40% of depressed patients show only partial or no response to initial or even multiple antidepressant medications and are usually called treatment-resistant depression （TRD） patients. The present work was to measure the features of sensory gating （SG） P50 in TRD patients with the intent of understanding the characteristics of this disease. Methods In 50 TRD patients, 39 non-treatment-resistant depression （NTRD） patients and 51 healthy controls （HC）, auditory evoked potential P50 was measured using the conditioning/testing paradigm presented with auditory double clicks stimuli, and 36 TRD patients had repeated measurements after an 8-week venlafaxine treatment course. Results All the depressive disorder patients, including the TRD and NTRD groups, showed an increased testing stimulus wave （$2-P50） amplitude compared to controls （P 〈0.01 and P 〈0.05）, but there was no significant difference between the TRD and NTRD groups （P 〉0.05）. There were significant differences in the ratio of testing stimulus （S2） and conditioning stimulus （S1） （S2/S1） and in the value of 100 × （1-S2/S1） among the three groups. Compared to the baseline, TRD patients had no significant changes of features and different expression of P50 after acute treatment （P 〉0.05）. Meanwhile, a statistically significant positive correlation of S2/S1 with the scores of the 17-item Hamilton Rating Scale for Depression （HAMD-17） （P 〈0.01）, and a significantly negative correlation of S1-S2, 100 × （1-S2/S1） with the scores of HAMD-17 （P 〈0.01） were observed in the TRD patients＇ baseline measurement, but there was no correlation after venlafaxine treatment （P 〉0.05）. Conclusions Both the TRD and NTRD patients had obvious SG deficits, with a more severe deficit in TRD patients. Although, with a correlated relationship to the severity of depressive symptoms, SG P50 deficit might be suggested as a trait marker for TRD, and a combination of S2/S1 ratio, S1-S2 and 100 × （1-S2/S1）, was recommended for electrophysiological measurement in TRD patients.
文摘Comorbid anxiety with depression predicts poor outcomes with a higher percentage of treatment resistance than either disorder occurring alone. Overlap of anxiety and depression complicates diagnosis and renders treatment challenging. A vital step in treatment of such comorbidity is careful and comprehensive diagnostic assessment. We attempt to explain various psychosocial and pharmacological approaches for treatment of comorbid anxiety and depression. For the psychosocial component, we focus only on generalized anxiety disorder based on the following theoretical models:(1) "the avoidance model";(2) "the intolerance of uncertainty model";(3) "the meta-cognitive model";(4) "the emotion dysregulation model"; and(5) "the acceptance based model". For depression, the following theoretical models are explicated:(1) "the cognitive model";(2) "the behavioral activation model"; and(3) "the interpersonal model". Integration of these approaches is suggested. The treatment of comorbid anxiety and depression necessitates specific psychopharmacological adjustments as compared to treating either condition alone. Serotonin reuptake inhibitors are considered first-line treatment in uncomplicated depression comorbid with a spectrum of anxiety disorders. Short-acting benzodiazepines(BZDs) are an important "bridging strategy" to address an acute anxiety component. In patients with comorbid substance abuse, avoidance of BZDs is recommended and we advise using an atypical antipsychotic in lieu of BZDs. For mixed anxiety and depression comorbid with bipolar disorder, we recommend augmentation of an antidepressant with either lamotrigine or an atypical agent. Combination and augmentation therapies in the treatment of comorbid conditions vis-à-vis monotherapy may be necessary for positive outcomes. Combination therapy with tricyclic antidepressants, gabapentin and selective serotonin/norepinephrine reuptake inhibitors(e.g., duloxetine) are specifically useful for comorbid chronic pain syndromes. Aripiprazole, quetiapine, risperidone and other novel atypical agents may be effective as augmentations. For treatment-resistant patients, we recommend a "stacking approach" not dissimilar from treatment of hypertension In conclusion, we delineate a comprehensive approach comprising integration of various psychosocial approaches and incremental pharmacological interventions entailing bridging strategies, augmentation therapies and ultimately stacking approaches towards effectively treating comorbid anxiety and depression.
文摘Both type 2 diabetes and depression are common and are projected to increase.There is increasing evidence for a bidirectional relationship between the two.Diabetes is a risk factor for depression;contrariwise,individuals with depression are at greater risk of developing diabetes.They are a burden for both the individual and the society.Co-existent depression worsens diabetic control because of obesity,insulin resistance and the adverse metabolic effects of anti-diabetes medicines.In addition,compliance to lifestyle measures required for diabetes is also compromised such as following a specific diet,taking proper medications on time,getting metabolic parameters assessed and maintaining a sleep cycle.Depression occurs in many grades;mild depression is more common in diabetes than frank or full-blown depression leading to suicide.Unfortunately,there are not enough trained and accessible mental health professionals such as psychologists or psychiatrists to deal with the increasing burden of depression in diabetes.Therefore,alternate models for management of mild to moderate depression are required.There is evidence that a team-approach by employing health care assistants can lower the risk of cardiac risk factors.INtegrating DEPrEssioN and Diabetes treatmENT study was carried out to determine whether the team-approach using non-health care professionals could be effective in managing mild to moderate depression and to study its effects on metabolic parameters among subjects with type 2 diabetes mellitus.The international study,carried out in four independent centers in India assessed the impact of a trained but not qualified non-psychiatrist in coordinating and forming a fulcrum between the patient,the family and the consultant endocrinologist/diabetologist.The interventions were fine-tuned to be culturally appropriate by qualitative interviews before they began.It was shown that the outcomes of both depression and diabetes could be improved by the employment of a clinical care coordinator.It is possible to scale up the studies to wider geographical areas and health-care organizations.
文摘Corrosion of metal components constitutes a major challenge in many engineering systems, with appropriate design, proper material selection, and heat treatment as commonly used control strategies. In this study, the corrosion behaviour of heat-treated (annealed, normalised, hardened, and tempered) NST 37-2 steel in three concentrations (1.0, 1.5 and 2.0 M) of hydrochloric acid solution was investigated using weight loss and electrode-potential methods. Results showed that corrosion rate increased with increase in acid concentration. The decreasing order of corrosion resistance was Tempered > Annealed > Normalised > Hardened > Untreated. The surface pictures of the heat-treated and untreated samples showed uniform and pitting corrosion with the latter becoming more pronounced as concentration increased.
文摘This brief review discusses the behavioral consequences of two pharmacologically selected lines of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats were selected on the basis of differential hypothermic and behavioral responses to the anticholinesterase, diisopropylfluorophosphate (DFP). FSL rats are more sensitive to the hypothermic effects of cholinergic, serotonergic, and dopaminergic agonists but less sensitive to the locomotor or stereotypic effects of dopamine agonists. FSL rats exhibit greater immobility in the forced swim test and reduced social interaction compared with FRL rats, but do not differ in saccharin intake, behavior in the elevated plus maze, or responses for rewarding brain self-stimulation. The exaggerated immobility and reduced social interaction are counteracted by chronic treatment with antidepressants. Because FSL rats were more sensitive to 5-HT1A receptor agonists, high (HDS) and low (LDS) 8-OH-DPATsensitive lines were selectively bred for differential hypothermic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). HDS rats were also more sensitive to the hypothermic effects of oxotremorine, a cholinergic agonist, but selection for this response did not diverge with later selection. HDS rats exhibited greater immobility in the forced swim test than LDS rats and this correlated response could be seen early in selection (generation 3). HDS rats also showed reduced social interaction compared to LDS rats, but did not differ in behavior in the elevated plus maze. These findings confirm that selection for hypothermic responses to pharmacological agents do have behavioral consequences, notably the production of depressive-like phenotypes, which can be counteracted by chronic antidepressant treatment. Because increased 5-HT1A receptor sensitivity was common to both selected lines (FSL and HDS), neurobiological processes dependent on this receptor could contribute to the abnormal behaviors that manifest in these rat lines and thus suggesting a mechanism underlying depressive behaviors in humans. However, available human data are inconsistent with this hypothesis and suggest that other mechanisms underlie these behavioral abnormalities in HDS and FSL rats. These mechanisms as well as additional behavioral testing in these rat lines will be discussed.
