Brugada‐like cardiac disease in myotonic dystrophy type 2: report of two unrelated patients

Background: Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystem disorder caused by CCTG repeat expansions within intron 1 of the ZNF9 gene on chromosome 3q. Cardiac conduction disturbances, supraventricular arrhythmias, and cardiomyopathy are described in DM2 but Brugada‐like features have not yet been reported. Brugada syndrome (BS) is a genetically heterogeneous cardiac conduction disorder which is characterized by a significant ST‐segment elevation upon ECG evaluations and bears an increased risk for sudden cardiac death. Case reports: We report two unrelated patients with genetically confirmed DM2 who developed clinical relevant cardiac arrhythmias with syncopal events from 35 (patient 1) and 47 years (patient 2). Brugada‐like ECG findings were present in both patients. Family history was negative for BS, but the mothers of both index patients were also affected by DM2 and had different ventricular rhythm disturbances. SCN5A gene sequencing revealed an unknown genetic variant c.4140 C > A, p.N1380K, in patient 1, while no mutation was detected in patient 2. Discussion: Our observations may suggest that Brugada‐like cardiac arrhythmias can occur in DM2, as this seems also to be the case in DM1. The chance association of two independent inherited disorders has to be considered and cannot be excluded in one of our patients. However, on statistical grounds, this possibility cannot explain all observed cases of DM with Brugada‐like cardiac disease.     

The impact of antidepressant discontinuation versus antidepressant continuation on 1-year risk for relapse of bipolar depression: a retrospective chart review

BACKGROUND: Current treatment guidelines recommend discontinuation of an antidepressant within 3 to 6 months after remission of depression in patients with bipolar illness. Yet few studies directly compare the impact of antidepressant discontinuation versus antidepressant continuation on the risk for depressive relapse in patients with bipolar disorder who have been successfully treated for a depressive episode. METHOD: In a retrospective chart review, patients with DSM-IV bipolar disorder who were treated for an index episode of depression by adding antidepressant medication to ongoing mood stabilizer medications were identified. The risk of depressive relapse in 25 subjects who stopped antidepressant medications after improvement was compared with the risk of depressive relapse in 19 subjects who continued antidepressants after improvement. RESULTS: Termination of antidepressant medication significantly increased the risk of a depressive relapse. Antidepressant continuation was not significantly associated with an increased risk of mania. CONCLUSION: While this study may have been limited by the retrospective nature of the chart review, nonrandomized assignment of treatment, and reliance on unstructured progress notes, it suggests that antidepressant discontinuation may increase the risk of depressive relapse in some patients with bipolar disorder. Further research is needed to clarify whether maintenance antidepressant treatment may be warranted in some patients with bipolar disorder, especially in those with frequent recurrent depressive episodes.     

Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up

OBJECTIVE: While guidelines for treating patients with bipolar depression recommend discontinuing antidepressants within 6 months after remission, few studies have assessed the implications of this strategy on the risk for depressive relapse. This study examined the effect of antidepressant discontinuation or continuation on depressive relapse risk among bipolar subjects successfully treated for an acute depressive episode. METHOD: Eighty-four subjects with bipolar disorder who achieved remission from a depressive episode with the addition of an antidepressant to an ongoing mood stabilizer regimen were followed prospectively for 1 year. The risk of depressive relapse among 43 subjects who stopped antidepressant treatment within 6 months after remission ("discontinuation group") was compared with the risk among 41 subjects who continued taking antidepressants beyond 6 months ("continuation group"). RESULTS: A Cox proportional hazards regression analysis indicated that shorter antidepressant exposure time following successful treatment was associated with a significantly shorter time to depressive relapse. Furthermore, patients who discontinued antidepressant treatment within the first 6 months after remission experienced a significantly shorter period of euthymia before depressive relapse over the length of 1-year follow-up. One year after successful antidepressant response, 70% of the antidepressant discontinuation group experienced a depressive relapse compared with 36% of the continuation group. By the 1-year follow-up evaluation, 15 (18%) of the 84 subjects had experienced a manic relapse; only six of these subjects were taking an antidepressant at the time of manic relapse. CONCLUSIONS: The risk of depressive relapse in patients with bipolar illness was significantly associated with discontinuing antidepressants soon after remission. The risk of manic relapse was not significantly associated with continuing use of antidepressant medication and, overall, was substantially less than the risk of depressive relapse. Maintenance of antidepressant treatment in combination with a mood stabilizer may be warranted in some patients with bipolar disorder.     

The outcome of antidepressant use in the medically ill

To examine the feasibility of using antidepressant medication to treat major depressive syndromes in the hospitalized medically ill, we reviewed a series of psychiatric consultations meeting the following criteria: the consultant diagnosed a major depressive syndrome, treatment with an antidepressant was advised, the consultee initiated the antidepressant, and hospitalization had been prompted by a major medical illness. The final sample of 50 consultations, representing less than 5% of the case reviewed, was assessed by retrospective study of entries in the medical record. Judgments regarding response were thus a function of routine clinical observation and care. Drugs were not randomly assigned; rather, the choices represented ongoing clinical usage patterns. Two major points emerge from the data of the study. First, 32% of the trials were terminated due to side effects judged to be unacceptable by the physicians or consultants. Delirium accounted for half of such side effects; cardiotoxicity, however, was not evident. Second, only 40% of patients with medical illnesses, including malignant neoplasm, insulin-dependent diabetes, and epilepsy, responded to treatment. The trials of antidepressants in medical-surgical inpatients did not achieve the pattern of therapeutic responses routinely characterizing comparable interventions in psychiatric patients with primary affective disorder.     

抗抑郁药联合治疗之前应考虑各种单药优化治疗方案(英文)

许多慢性抑郁症患者或反复发作的抑郁症患者对现有的各种抗抑郁药物治疗反应不理想。医生在治疗这些患者时,可能在原来抗抑郁药物的基础上增加其他药物,包括用第二种或第三种抗抑郁药物辅助治疗。虽然在高收入国家这是精神科医生和初级保健医生广泛使用的方法,但是证明这种抗抑郁药联合治疗方法有效的证据不多。只有当不同种类的抗抑郁药物的单药优化治疗方案无效后,才可谨慎使用联合治疗的方法。     

The bipolar spectrum and the antidepressant view of the world

Whereas much progress has been made in the diagnosis and treatment of schizophrenia and depression in recent years, bipolar disorder continues to be frequently misunderstood, leading to its inconsistent diagnosis and treatment. In this article, we seek to identify the causes of this problem and suggest possible solutions, based on a critical review of studies concerning the nosology of bipolar disorder and the effects of antidepressant agents. Bipolar disorder appears to be underdiagnosed as well as frequently misdiagnosed as unipolar major depressive disorder. Underdiagnosis can stem from patients' impaired insight into mania and failure to involve family members in the diagnostic process and also from clinicians' inadequate understanding of manic symptoms. Underdiagnosis may also reflect disagreement about the breadth of the bipolar spectrum. We therefore propose a heuristic definition of "bipolar spectrum disorder," a diagnosis that gives greater weight to family history and antidepressant-induced manic symptoms. This diagnosis would include all forms of bipolar illness that are not type I or II . The evidence also suggests that antidepressants are probably overused and mood stabilizers underused. We consequently recommend aggressive use of mood stabilizers and less emphasis on antidepressants. In summary, the state of diagnosis and treatment in bipolar disorder is suboptimal. More diagnostic attention to the criteria for mania is necessary. In addition, the current pattern of antidepressant use in bipolar disorder does not appear to be evidence-based.     

Mediating roles of adherence attitude and patient education on antidepressant use in patients with depression

PURPOSE. The purpose of this study was to examine the roles of adherence attitude to antidepressants and patient education as mediators in mediating patients' attitudes toward antidepressant use. DESIGN AND METHODS. A sample of 201 outpatients, 50 years of age or older, with major depressive disorder, completed a drug use questionnaire, attitudes toward and patient education about antidepressants questionnaire, and Adherence Attitude Inventory. FINDINGS. Attitudes toward antidepressants were positively associated to antidepressant use, an association explained by the mediating variable, patient education about antidepressants. Adherence attitudes to antidepressants were a mediator that accounted to a significant degree for the causal relationship between attitudes toward antidepressants and antidepressant use. PRACTICE IMPLICATIONS. Adequate patient education and an understanding of patients' adherence attitude to antidepressant use are needed in nursing practice to reduce patients' uncertainty about treatment and increase successful treatment.     

重性抑郁障碍患者出院后的服药依从性及其影响因素

目的 对出院重性抑郁患者的服药依从性进行评价并分析其影响因素.方法 选取2012年8月～2013年8月在唐山市第五医院住院符合DSM-Ⅳ重性抑郁障碍诊断的144例患者.在出院时对其进行一般情况、对自己服用抗抑郁药基本知识掌握情况、对抗抑郁药物的态度、对医生交流风格的评价等,在患者出院后第4、8、16周使用Morisky问卷对患者的依从性进行评价.探讨上述各因素对服药依从性的预测作用.结果 144例患者16周后的完全依从率为36.1％.完全依从组与部分依从组在年龄、婚姻状况、家属对患者服药的态度、是否知道药物的不良反应、是否知道抗抑郁药的作用机制、抗抑郁药物态度、医生交流风格评价等因素的差异有统计学意义（P＜0.05）,将是否为完全依从作为因变量,将以上项目作为自变量进行Logistic回归,结果显示抗抑郁药态度及是否知道抗抑郁药的作用机制2个变量进入方程,回归系数分别为2.323,1.205.结论 出院后重性抑郁症患者的服药依从性较低,对抗抑郁药的态度和抗抑郁药知识是服药依从性的影响因素.     

Late-life depression and mortality: influence of gender and antidepressant use

BACKGROUND: Depression may increase the risk of mortality among certain subgroups of older people, but the part played by antidepressants in this association has not been thoroughly explored. AIMS: To identify the characteristics of older populations who are most at risk of dying, as a function of depressive symptoms, gender and antidepressant use. METHOD: Adjusted Cox proportional hazards models were used to determine the association between depression and/or antidepressant use and 4-year survival of 7,363 community-dwelling elderly people. Major depressive disorder was evaluated using a standardised psychiatric examination based on DSM-IV criteria and depressive symptoms were assessed using the Center for Epidemiological Studies-Depression scale. RESULTS: Depressed men using antidepressants had the greatest risk of dying, with increasing depression severity corresponding to a higher hazard risk. Among women, only severe depression in the absence of treatment was significantly associated with mortality. CONCLUSIONS: The association between depression and mortality is gender-dependent and varies according to symptom load and antidepressant use.     

A 20-year longitudinal observational study of somatic antidepressant treatment effectiveness

OBJECTIVE: This observational study examined the effectiveness of somatic antidepressant treatments as administered in the community. METHOD: The study group consisted of 285 subjects with an intake diagnosis of major depressive disorder who had entered the National Institute of Mental Health Collaborative Depression Study as early as 1978, had at least one additional affective episode, and had been followed for up to 20 years, as recently as 1999. The characteristics that distinguished subjects receiving various levels of somatic antidepressant treatment were accounted for in what was called a propensity for treatment intensity model. The effectiveness of somatic antidepressant treatment during major affective episodes was then examined. RESULTS: Those who received higher levels of antidepressant treatment tended to have more prior episodes, more severe depressive symptoms, and more intensive somatic therapy during prior episodes and prior well intervals than those who received lower levels. Treatment effectiveness analyses that were stratified by propensity for treatment intensity demonstrated that those who received higher levels of antidepressant treatment were significantly more likely to recover from affective episodes. In contrast, those treated with lower levels were no more likely to recover than those who did not receive somatic treatment. CONCLUSIONS: Despite the indications of more severe depressive illness, those who received higher levels of somatic antidepressant treatment were more likely to recover from recurrent affective episodes. Results from this observational study extend the generalizability of reports from randomized clinical trials of antidepressants to a wider, more representative group of individuals who suffer from major depression.     

Results of a phase II study of the antidepressant effect of rolipram

The antidepressant effect of rolipram, believed to be based on a new mechanism of action, was investigated in an open phase II study in 10 depressive patients, most of whom had been refractory to previous antidepressant therapy. Five patients displayed a good to very good improvement of their depressive condition. Four patients failed to show any substantial improvement, and therapy had to be withdrawn in one case due to deterioration of the condition. In most cases, the antidepressant effect of the trial preparation became noticeable after 2-4 days of treatment only. Basing on the presented cases, the tolerance can be described as excellent compared to other antidepressants. Although, on the whole the trial yielded very encouraging results, only double-blind trials can determine the true antidepressant efficacy of rolipram.     

Factors associated with antidepressant use in depressed and non-depressed community-dwelling elderly: the three-city study

OBJECTIVES: The aim of this study was to identify factors associated with antidepressant use in non-depressed and depressed elderly persons, assuming that they varied according to clinical status. METHODS: We studied 7,868 French community-dwelling subjects aged 65 years and over. The Center for Epidemiological Studies-Depression scale and the Mini International Neuropsychiatric Interview were used to define three groups: non-depressed, high depressive symptoms and current major depressive disorder. Separate analyses were performed to identify the factors which were associated with antidepressant use in each group. RESULTS: Antidepressant use (55% selective serotonin re-uptake inhibitors, 25% tricyclic antidepressants, 20% other types) increased from 4.9% in non-depressed subjects to 17.3% in subjects with high depressive symptoms (HDS) and 33.6% of in those with current major depressive disorder (MDD). The factors associated with antidepressant use varied according to depression status. In particular, men with current MDD were more often treated with antidepressants than women whereas, in both the HDS and the non-depressed groups, antidepressant use was, as has been observed elsewhere, more frequent in women. Gender also had a strong modifying effect on the relationship between antidepressant use and history of major depression. Finally, the direction of the association between antidepressant use and cognitive performance varied according to depression status. CONCLUSIONS: This study showed that the direction and strength of the association between antidepressant use and demographic and health-related factors varied according to the severity of depression symptoms. Further studies are needed to clarify the relationship between gender and cognition and antidepressant use.     

Isokinetic muscle performance in major depressive disorder: alterations by antidepressant therapy.

The aims of this study were (i) to examine whether patients with major depressive disorder (MDD) differ from healthy control subjects with respect to isokinetic muscle performance (IMP) as measured by a dynamometer; (ii) to investigate the effect of subchronic treatment on the IMP in depressed patients. Thirty-eight patients with MDD, and 41 sex- and age-matched healthy controls participated in this study. The severity of depression and anxiety levels was evaluated by the Hamilton Depression and Anxiety Scales. Quadriceps and hamstring IMPs were determined by using an isokinetic dynamometer before and after subchronic antidepressant treatment. The patients had lower IMP levels than healthy controls. After treatment for three months with selective serotonin reuptake inhibitors, the IMP levels increased significantly. These findings suggest that (i) MDD may be characterized by reduced IMP levels; and (ii) treatment with antidepressants may increase the IMP levels, being a state marker for depression. It was concluded that (i) isokinetic muscle performance may be used as a state marker for monitoring antidepressant drug effects on MDD; (ii) isokinetic exercise increasing IMP may be used in the treatment of depression.     

Isokinetic muscle performance in major depressive disorder: alterations by antidepressant therapy.

The aims of this study were (i) to examine whether patients with major depressive disorder (MDD) differ from healthy control subjects with respect to isokinetic muscle performance (IMP) as measured by a dynamometer; (ii) to investigate the effect of subchronic treatment on the IMP in depressed patients. Thirty-eight patients with MDD, and 41 sex- and age-matched healthy controls participated in this study. The severity of depression and anxiety levels were evaluated by the Hamilton Depression and Anxiety Scales. Quadriceps and hamstring IMPs were determined by using an isokinetic dynamometer before and after subchronic antidepressant treatment. The patients had lower IMP levels than healthy controls. After treatment for three months with selective serotonin reuptake inhibitors, the IMP levels increased significantly. These findings suggest that (i) MDD may be characterized by reduced IMP levels; and (ii) treatment with antidepressants may increase the IMP levels, as a state marker for depression. It was concluded that (i) isokinetic muscle performance may be used as a state marker for monitoring antidepressant drug effects on MDD; (ii) isokinetic exercise increasing IMP may be used in the treatment of depression.     

Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms

OBJECTIVE: With a multitude of antidepressants available, predictors of response to different classes of antidepressants are of considerable interest. The purpose of the present study was to determine whether norepinephrine transporter gene (NET) and serotonin transporter gene (5-HTT) polymorphisms are associated with the antidepressant response to milnacipran, a dual serotonin/norepinephrine reuptake inhibitor. METHOD: Ninety-six Japanese patients with major depressive disorder were treated with milnacipran, 50-100 mg/day, for 6 weeks. Severity of depression was assessed with the Montgomery-Asberg Depression Rating Scale. Assessments were carried out at baseline and at 1, 2, 4, and 6 weeks of treatment. The method of polymerase chain reaction was used to determine allelic variants. RESULTS: Eighty patients completed the study. The presence of the T allele of the NET T-182C polymorphism was associated with a superior antidepressant response, whereas the A/A genotype of the NET G1287A polymorphism was associated with a slower onset of therapeutic response. In contrast, no influence of 5-HTT polymorphisms on the antidepressant response to milnacipran was detected. CONCLUSIONS: The results suggest that NET but not 5-HTT polymorphisms in part determine the antidepressant response to milnacipran.     

ECG changes in epilepsy patients

Objectives - To investigate the frequency of ECG abnormalities suggestive of myocardial ischaemia in patients with severe drug resistant epilepsy and without any indication of previous cardiac disease, assuming that these changes may be of significance for the group of epileptic patients with sudden unexpected death. Material and methods - Twelve patients with medically intractable epilepsy were investigated with simultaneous long ECG and EEG recordings while attending either epilepsy surgery investigational procedures or the investigational programme for diagnostic purposes, and one while having an episode of status epilepticus. Results - The ECG recording failed in 1 patient. This patient had chest pain and minor yet morphologically conspicuous changes in the ECG, suggestive of myocardial infarction. He died in heart arrest. Eight epilepsy patients had episodes of ST segment depression in the ECG, many of which coincided with video-and EEG documented epileptic seizures. Two patients experiencing simple partial seizures and 1 patient experiencing absence seizures had no ST segment depressions in the ECG. One patient had an episode of status epilepticus secondary to brain damage and no ST segment deviation was seen during the ECG recording which continued until 3 h before the patient died. Conclusion - Patients with severe drug resistant epilepsy have episodes of ST segment changes, some of which are closely related to epileptic seizures. Further studies are needed to confirm the present results and to investigate the nature of these changes and document the effect of prophylactic treatment with cardioactive drugs to reduce the risk of sudden death.