Treatment of major depressive disorder--method and selection of the treatment

There are many ways of treatment for depression. Among them the most popular and effective treatment is pharmacotherapy. In the acute phase, pharmacotherapy with antidepressants, certain forms of psychotherapy, the combination of pharmacotherapy plus psychotherapy, and electroconvulsive treatment have clearly proven to be efficacious in most types of unipolar depressive disorders. The common augmenting agents probably are lithium, thyroid hormone, dopaminergic agents, and mood stabilizers. Certain treatments may be more effective in specific subtypes; for example, light therapy is useful for seasonal affective disorder. During the 16-24 weeks following remission, patients with antidepressant medications in the acute phase should be maintained on these agents to prevent relapse. For patient pharmacotherapy or psychotherapy has not been effective, the use of ECT may be useful. Following the continuation phase, maintenance-phase treatment should be considered for patients who have many depressive episodes to prevent recurrences of major depressive disorder.     

Therapy of affective disorders

The key to the proper treatment of affective disorder is a correct diagnosis of the subtype of depressive illness. Thus, primary treatment recommendations include the TCAs for a depressive episode; ECT for a depressive episode with psychotic features; and MAOIs for dysthymic disorder and atypical depressive episodes. Nonresponding patients are treated with either lithium augmentation of TCA therapy, an MAOI, or ECT. Second-generation antidepressants are not usually indicated as initial treatments. They are recommended in situations in which their adverse-effect profiles offer significant advantages over TCAs in an individual patient. Second-generation antidepressants have not been extensively studied in patients who do not respond to TCAs. Maintenance antidepressant may be necessary to prevent recurrent depressive episodes. Lithium remains the mainstay of acute treatment of mania and for prophylaxis of subsequent affective episodes. In lithium-refractory or lithium-intolerant patients, carbamazepine is recommended. Valproic acid and verapamil have been useful, primarily in patients who do not respond to lithium and carbamazepine.     

ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression: The ELEKT-D study protocol

Major depressive disorder (MDD) is the most common mental illness and the leading cause of disability worldwide. Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. Ketamine has emerged as the first rapid-acting antidepressant and shows robust short-term efficacy in clinical trials, but there are concerns about its long-term safety and efficacy. While response rates are similar between ECT and ketamine in clinical trials, these treatments have never been compared head-to-head in a sufficiently large, well-powered randomized study. Here we describe the study protocol for ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression (ELEKT-D), a non-inferiority, comparative effectiveness trial. Patients with TRD seeking clinical treatment are randomized (1:1) to receive ECT (thrice weekly) or intravenous ketamine (twice weekly) for 3–5 weeks. The primary outcome is the proportion of responders in each group at the end of study visit, as measured by a patient-reported outcome measure (Quick Inventory of Depressive Symptomatology-Self Report). The study is powered such that the non-inferiority margin allows for ketamine to retain 90% of the ECT treatment effect, with a projected sample size of 400 patients (200 per group). Secondary outcomes include remission rates, depression severity, cognitive functioning, quality of life, adverse events, and tolerability. The results of the ELEKT-D study will have important implications for patient choice, clinical practice, and health insurance policies.     

Depression in the elderly. Characteristics and clinical management

Major depression and clinically significant depressive symptoms occur commonly in the community-dwelling, medically ill, and institutionalized elderly. Both major depression and depressive symptoms need thorough evaluation and treatment because of the significant morbidity and mortality associated with these syndromes. Depression may be difficult to diagnose, especially in the medically ill elderly, because of the masking of depressive symptoms by somatic complaints or the presumption that symptoms are attributable to concurrent medical illness. Therefore, the clinician must be alert to the possibility of depression in the elderly patient. Although no specific diagnostic test is available, rating scales can be useful in screening for depression in the elderly patient. It is necessary to rule out medical illness or medications as contributing factors to depression. Psychotherapy and psychopharmacology, alone or in combination, are effective treatments for most elderly patients with depression. ECT is a safe and effective treatment for major depression in this population. Depression in the elderly is potentially a chronic and relapsing illness with significant associated medical and social morbidity. Because of their frequent contact with the elderly, nurses play a particularly important role in the diagnosis and treatment of depression. They need to recognize typical and atypical symptoms of depression and must be familiar with the potential side effects of antidepressant treatment. Close monitoring for these potential side effects can minimize disability. By working as a team with physicians, psychologists, and others, nurses have a necessary role in the care of the elderly depressed patient.     

Other treatments for depressive patients

Electroconvulsive therapy(ECT) is one of the most important methods in treating depressive patients especially who can not be improved with medication. Meta analysis shows that ECT is superior to pharmacotherapy as acute treatment for depression. ECT was invented in 1938, and it took some improvement afterwards such as development of modified ECT and introduction of brief-pulse stimulation for the purpose of reducing adverse effects. However, adverse effects such as cognitive impairment are not completely solved, and some patients do not respond to ECT. Transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are under investigation to get over the shortcomings of ECT.     

Parkinson's disease and depression

Up to 40% of cases of Parkinson's disease are associated with the occurrence of depression. The symptoms of the patients' depressive state may be factors such as significant weight change, insomnia or hypersomnia, psychomotor retardation, fatigue or loss of energy, feelings of worthlessness or inappropriate guilt, decreased concentration and indecisiveness, and recurrent thoughts of death or suicidal ideation. Given these conditions, drugs prove ineffective in many cases. Electroconvulsive therapy (ECT) has been reported to be beneficial in cases of drug-resistant depression. ECT has also been applied to Parkinsonian patients with depression and found to be effective with both depression and the Parkinsonian symptom. Transcranial magnetic stimulation(TMS) has recently been investigated for application in cases of depression and has become known as a valuable tool for depression therapy. TMS is easily implemented even in outpatient therapy. TMS will make a great contribution to the therapy of depression with Parkinson's disease.     

ECT in the treatment of recurrent psychotic depression.

Two cases of recurrent psychotic depression are reported in which ECT (electroconvulsive therapy) was administered with good results for previous episodes of depression, but treatment of the current episode with combined drug therapy (antidepressant and antipsychotic drugs) in one case and antidepressant chemotherapy in the other resulted in failure to improve. The patients were transferred to another facility, and improved when ECT was administered. Pertinent literature on ECT and drug treatment of depression is reviewed, and the conditions for which ECT is probably the treatment of choice are enumerated.     

Antipsychotic use at adult ambulatory care visits by patients with mental health disorders in the United States, 1996-2003: national estimates and associated factors

OBJECTIVES: This retrospective analysis was conducted to derive national estimates of typical, atypical, and combination (typical-atypical) antipsychotic use and to examine factors associated with their use at adult (age >-18 years) ambulatory care visits by patients with mental health disorders in the United States. METHODS: Data on adult visits with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for a mental health disorder were extracted from the office-based National Ambulatory Medical Care Survey and the outpatient facilitybased National Hospital Ambulatory Medical Care Survey from 1996 through 2003. The visits were categorized according to whether use of a typical, atypical, or combination antipsychotic was mentioned (either prescribed, supplied, administered, ordered, or continued at the visits). Total weighted visit estimates, weighted visit percentages, and 95% CIs were calculated across the 3 types of visit groups. Bivariate analysis was performed on the association between selected characteristics and the 3 visit groups. Multivariate logistic regression was performed on factors associated with atypical versus typical antipsychotic use. RESULTS: During the 8-year period, there were an estimated 47.7 million adult ambulatory care visits involving a mental health disorder and mention of an antipsychotic (weighted percent: 0.83%; 95% CI, 0.73-0.93). From 1996/1997 to 2002/2003, visits involving atypical and combination antipsychotics increased by 195% and 149%, respectively, and visits involving typical antipsychotics decreased by 71%. Men, blacks, and those with public insurance made more visits in which combination antipsychotics rather than typical or atypical antipsychotics were mentioned. Relative to typical or combination antipsychotic visits, more atypical antipsychotic visits involved antide-pressants (weighted percent: 61.23% atypical, 37.29% typical, and 38.32% combination). Fewer atypical antipsychotic visits compared with typical or combination antipsychotic visits involved psychotic disorders (weighted percent: 32.94%, 51.23%, and 69.93%, respectively) and medications for extrapyramidal symptoms (weighted percent: 6.69%, 29.95%, and 36.64%). In multivariate analyses controlling for sex, race, diagnosis of schizophrenia, region, diagnosis of anxiety, and recent years, atypical versus typical antipsychotic use was significantly less likely at visits by those aged 41 to 64 years compared with those aged 18 to 40 years (adjusted odds ratio [OR] = 0.63; 95% CI, 0.47-0.84; P = 0.002); significantly less likely at visits by those with public compared with private insurance (Medicare OR = 0.59 [95% CI, 0.40-0.88], P = 0.010; Medicaid OR = 0.44 [95% CI, 0.28-0.69], P < 0.001); and significantly more likely at visits associated with depression compared with those not associated with depression (OR = 1.92; 95% CI, 1.26-2.93; P = 0.003) and those associated with bipolar disorder compared with those not associated with bipolar disorder (OR = 2.10; 95% CI, 1.32-3.36; P = 0.002). CONCLUSIONS: This retrospective analysis found more atypical than typical or combination antipsychotic use at US ambulatory care visits by adults with mental health disorders other than schizophrenia or psychoses in the period studied. Atypical versus typical antipsychotic use was significantly less likely at visits by adults aged 41 to 64 years and those with public insurance, but significantly more likely at visits by those with depression or bipolar disorder.     

Treating a psychotic syndrome in 2007

It is well established that we have to consider 3 patterns of psychotic symptoms: positive (hallucinations, delusion...), negative (affective flatness, autism...) symptoms and disorganization (ambivalence, incoherence...). In the past, ECT (electroconvulsivotherapy) was the first effective treatment in psychiatry. Conventionnal neuroleptics have been determinant in the significant evolution of care to psychotic patients. ECT use is now better defined in terms of practise and indications. Assessment of new antipsychotic medications is mainly focused on efficacy on positive symptoms. Atypical antipsychotics brought improvement in treating psychotic syndromes: they are better tolerated and more effective on the whole spectrum of psychotic syndromes including emotional symptoms than conventional neuroleptics. Atypical antipsychotics have raised questions about metabolic and cardiac risks. Compliance remains a cause of failure of many antipsychotic treatments. Treating a psychotic syndrome requires complementary strategies to medications: conditions of assistance and rehabilitation, choice of psychotherapy. Research program are currently orientated towards: - identification of prepsychotic symptoms and endophenotypes which can be treatment targets; - assessment of putative therapeutical means such a brain stimulation.     

Pharmacologic treatment of depression

The pharmacological treatment of depression is focussed on antidepressants. Different substance groups with different biochemical mechanisms and side effects have antidepressant effects. Based on these different substances the pharmacological treatment of depression has become more and more differentiated. The combination of antidepressants and other drugs (lithium, carbamazepine, benzodiazepines, stimulants, antipsychotics, hormones) offers additional possibilities. The combination with other biological treatments of depression enlarges the spectrum of treatments. The inclusion of non-biological therapies makes the therapeutic possibilities with proven antidepressant efficacy rich and powerful.     

ECT in an Adolescent with Down Syndrome and Treatment-Refractory Major Depressive Disorder

The efficacy of electroconvulsive therapy (ECT) as a treatment for patients with major depressive disorder who are intolerant of or refractory to antidepressant medications is well known. This treatment may be overlooked in children and adolescents, and in those with developmental disabilities. The case report of a 15-year-old male with Down syndrome and treatment-refractory major depressive disorder who received ECT is presented. Four bilateral ECT treatments resulted in a substantial improvement of the patient's depressive symptoms. In this case, ECT was a safe and effective treatment for an adolescent with Down syndrome. Although no generalization can be based on a single case report, when appropriate, ECT should be considered as a treatment for this patient population.     

Rational use of antidepressants

The key to the proper treatment of affective illness is a correct diagnosis of the subtype of depressive illness. Thus, primary treatment recommendations include the tricyclic antidepressants for a major depressive episode, electroconvulsive therapy for a major depressive episode with psychotic features, and monoamine oxidase inhibitors for dysthymic disorder and atypical depressive episodes. Nonresponding patients are treated with either lithium augmentation of TCA therapy or ECT. Second-generation antidepressants are recommended in situations where their adverse effect profiles offer significant advantages over TCAs in an individual patient. Maintenance antidepressant treatment may be necessary to prevent recurrent depressive episodes.     

Pharmacological management of agitation in emergency settings

Objective: To review, firstly, published studies comparing classic antipsychotics, benzodiazepines, and/or combination of both; and secondly, available data on the use of atypical antipsychotic medications in controlling agitation and aggressive behaviour seen in psychiatric patients in emergency. Method: In the first review, studies comparing antipsychotics, benzodiazepines, and combination of both; and in the second review, efficacy trials of atypical antipsychotics that include an active and/or inactive comparator for the treatment of acute agitation were identified and reviewed. Data from clinical trials meeting the inclusion criteria were summarised by recording improvement rates, definition of improvement, and timing of defined improvement for individual studies. Results: In the first review, 11 trials were identified meeting the inclusion criteria, eight with a blind design. The total number of subjects was 701. These studies taken together suggest that combination treatment may be superior to the either agent alone with higher improvement rates and lower incidence of extrapyramidal side effects. In the review of atypical antipsychotic agents as acute antiagitation compounds, five studies were identified, three with a blind design. The total number of subjects was 711, of which 15% (104) was assigned to the placebo arm. This review found atypical antipsychotics to be as effective as the classic ones and more advantageous in many aspects. Conclusion: Atypical antipsychotics such as risperidone, ziprasidone, and olanzapine with or without benzodiazepines should be considered first in the treatment of acute agitation. If these agents are not available the combination of a classic antipsychotic and a benzodiazepine would be a reasonable alternative. An oral treatment should always be offered first for building up an alliance with the patient and suggesting an internal rather than external locus of control.     

Electroconvulsive therapy improves severe pain associated with fibromyalgia

The pathophysiology of fibromyalgia remains unknown. Several reports have recently suggested the novel concept that fibromyalgia is due to the central nervous system becoming hyper-responsive to a peripheral stimulus. The effect of electroconvulsive therapy (ECT) as pain remedication in cases of fibromyalgia without major depressive disorder was studied in a prospective trial lasting three months. All of the patients taking part in the study fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. Technetium-99m ethyl cysteinate dimer single photon emission computed tomography was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. Pain assessment in the patients was undertaken by use of the visual analog scale (VAS) and by evaluation of tender points (TPs). Beck's depression inventory (BDI) was further used to assess depressive mood change in the patients. Our study clearly demonstrated that pain was significantly less severe after ECT, as indicated by the VAS scale for pain and the evaluation of TPs. A further notable observation was that thalamic blood flow was also improved. We conclude that a course of ECT produced notable improvements in both intractable severe pain associated with fibromyalgia and also in terms of thalamic blood flow.     

AANA Journal course: update for nurse anesthetists--anesthetic management during electroconvulsive therapy: effects on seizure duration and antidepressant efficacy.

Electroconvulsive therapy (ECT) is an effective treatment for some types of depression and psychotic disorders. Although ECT is considered effective and relatively safe, the treatment team must know how to deal with adverse effects. The American Psychiatric Association recognizes no absolute contraindication except brain tumor with increased intracranial pressure. However, patients who have other medical problems are at risk of complications. Optimizing the safety and efficacy of treatment is a goal when providing ECT. Muscle relaxants, barbiturate anesthesia, anticholinergic agents, and oxygenation are used to reduce the risk of complications. The use of ECT requires a knowledge of the effect of anesthetic agents on seizure activity. This article reviews ECT, anesthesia for ECT, and the effect of propofol and methohexital on seizure duration and seizure efficacy.     

Latest therapies for bipolar disorder. Looking beyond lithium

Effective treatments of bipolar disorder now extend to a panoply of choices that include various anticonvulsants and antipsychotics. Although lithium still has an important role, particularly in "classic" mania and suicide prevention, the other FDA-approved agents are better tolerated and more efficacious for mixed states and rapid cycling. It is not uncommon to use combination therapy for this challenging disorder. The FDA has approved olanzapine, risperidone, and quetiapine in combination with either lithium or divalproex for acute mania and the combination medication of olanzapine and fluoxetine for acute bipolar depression. Maintenance treatments that have received FDA approval include olanzapine and lamotrigine. Off-label use of adjunctive medications may be required to target residual symptoms.     

Therapeutic options in treatment-resistant depression

The phenomenon of treatment-resistant depression (TRD), described as the occurrence of an inadequate response after an adequate treatment with antidepressant agents (in terms of dose, duration, and adherence), is very common in clinical practice. It has been broadly defined in the context of unipolar major depression, but alternative definitions for bipolar depression have also been suggested. In both cases, there is a remarkable lack of consensus amongst professionals concerning its operative definition. A relatively wide variety of treatment options for unipolar TRD are available, whilst the evidence is very scanty for bipolar TRD. TRD is associated to poor clinical, functional, and social outcomes. Several novel therapeutic options are currently being investigated as promising alternatives, targeting the neurotransmitter system outside of the standard monoamine hypothesis. Augmentation or combination with lithium or atypical antipsychotics appears as a valid option for both conditions, and the same occurs with electroconvulsive therapy. Other non-pharmacological strategies such as deep brain stimulation may be promising alternatives for the future. The use of cognitive behaviour therapy is recommended for unipolar TRD, but there is no evidence supporting its use in bipolar TRD.     

ANTIDEPRESSANTS IN THE ELDERLY

Antidepressants are effective in the treatment of depression but their use in the elderly merits special attention. In general, the tertiary amine tricyclic antidepressants (TCAs) tend to produce significant side-effects in the elderly. In contrast, nortriptyline, desipramine and lofepramine are better tolerated than other TCAs. The newer antidepressants including the selective serotonin reuptake inhibitors are useful alternatives in the treatment of depression in the elderly. As pharmacokinetic studies show that higher steady-state plasma levels of tertiary amine antidepressants may be found in the elderly than in the younger population, a lower dosage is recommended. However, the need for a lower dose in the elderly is less certain for the secondary amine TCAs. The optimum duration of continuation and maintenance antidepressant therapy requires further study. For delusional depression, there is evidence to support the superiority of ECT and combination antipsychotic/antidepressant treatment over antidepressant alone. The ultimate choice of antidepressant will be a balance of efficacy, safety, acceptability and cost.     

Treatment with lithium, alone or in combination with olanzapine, relieves oxidative stress but increases atherogenic lipids in bipolar disorder

The changes in antioxidant-oxidant balance play important roles in the pathophysiology of neuropsychiatric conditions. Bipolar disorder (BD) is a psychiatric condition with recurrent mood disturbances. This study evaluates the effects of treatment with lithium, alone or in combination with antipsychotic olanzapine, on oxidant-antioxidant status and atherogenic character in patients with BD. The blood samples from 15 patients were tested before the treatment (pre-treatment phase) and at the ends of two consecutive treatment periods: period I, treatment with lithium and an antipsychotic drug, olanzapine (first 6 months) and period II, treatment with only lithium (6 months following period I). We measured serum atherogenic lipids (total cholesterol, triglycerides, and LDL-cholesterol), plasma lipid peroxides (thiobarbituric acid-reactive substances), antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) in neutrophils and lymphocytes, and total antioxidant status in plasma. Compared with pre-treatment phase, the lipid parameters were increased with each treatment; especially, LDL-cholesterol was significantly increased only with lithium treatment. These findings alert to be cautious about use of lithium in patients with atherogenic conditions. Moreover, plasma lipid peroxides were decreased significantly after the combination therapy and further decreased with lithium treatment. Antioxidant enzyme activities in lymphocytes were decreased after both types of treatment. Importantly, plasma total antioxidant status was increased only with lithium treatment. Thus, treatment with lithium alone decreases already up-set oxidant status in BD. In conclusion, the combination therapy with olanzapine is better in terms of atherogenic profile, while lithium alone produces better antioxidant status in patients with BD.