Objective: Anorexia nervosa (AN) is associated with serious medical morbidity and has the highest mortality rate of all psychiatric disorders. The National Institutes of Health (NIH) Workshop on ...Overcoming Barriers to Treatment Research in Anorexia Nervosa convened on September 26-27, 2002 to address the dearth of treatment research in this area. The goals of this workshop were to discuss the stages of illness and illness severity, pharmacologic interventions, psychological interventions, and methodologic considerations. Method: The program consisted of a series of brief presentations by moderators, each followed by a discussion of the topic by workshop participants, facilitated by the session chair. Results: This report summarizes the major discussions of these sessions and concludes with a set of recommendations related to the development of treatment research in AN based on these findings. Discussion: It is crucial that treatment research in this area be prioritized.
Objectives: Bipolar disorder is a severe, recurrent, and often highly impairing psychiatric disorder. The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD) is a large‐scale ...multicenter study funded by the National Institute of Mental Health (NIMH) to examine the longitudinal course of the disorder and the effectiveness of current treatments. The current report provides a context for interpreting studies resulting from STEP‐BD by summarizing the baseline demographic and diagnostic characteristics of the first 1000 enrolled.
Methods: The majority of the sample met DSM‐IV criteria for bipolar I disorder (71%). Mean age of patients was 40.6 (±12.7) years and mean duration of bipolar illness was 23.1 (±12.9) years. Among the first 1000 subjects enrolled, 58.6% are females and 92.6% Caucasian. This report compares the STEP‐BD sample with other large cohorts of bipolar patients (treatment and community samples).
Results: Compared with US population and community studies, the first 1000 STEP‐BD patients were less racially diverse, more educated, had lower income, and a higher unemployment rate. Results are discussed in terms of the contributions of STEP‐BD (and other large‐scale treatment studies) in understanding the nature, treatments, and outcomes of bipolar disorder for patients seeking care at academic treatment centers.
Conclusions: The current report provides a context for interpreting future studies resulting from STEP‐BD. The comparison of demographic and clinical characteristics between the samples across clinic‐based studies suggests broad similarities despite the substantial differences in geography, payer mix, and clinical entry point.
1. Despite the considerable advances in the treatments available for mood disorders over the past generation, tricyclic antidepressants (TCAs) remain an important option for the pharmacotherapy of ...depression. 2. The pharmacokinetics of TCAs are characterized by substantial presystemic first-pass metabolism, a large volume of distribution, extensive protein binding, and an elimination half-life averaging about 1 day (up to 3 days for protriptyline). 3. Clearance of tricyclics is dependent primarily on hepatic cytochrome P450 (CYP) oxidative enzymes. Although the activities of some P450 isoenzymes are largely under genetic control, they may be influenced by external factors, such as the concomitant use of other medications or substances. Patient variables, such as ethnicity and age, also affect TCA metabolism. The impact of gender and related reproductive issues is coming under increased scrutiny. 4. Metabolism of TCAs, especially their hydroxylation, results in the formation of active metabolites, which contribute to both the therapeutic and the adverse effects of these compounds. 5. Renal clearance of the polar metabolites of TCAs is reduced by normal aging, accounting for much of the increased risk of toxicity in older patients. 6. Knowledge of factors affecting the metabolism of TCAs can further the development and understanding of newer antidepressant medications.
Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic ...depression in remission.
To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent.
Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017.
Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline.
The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c).
Among 126 participants who were randomized (mean SD age, 55.3 years 14.9 years; 78 women 61.9%), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range IQR, 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016).
Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain.
ClinicalTrials.gov Identifier: NCT01427608.
There is limited information regarding neurocognitive outcomes of right unilateral ultrabrief pulse width electroconvulsive therapy (RUL-UB ECT) combined with pharmacotherapy in older adults with ...major depressive disorder. We report longitudinal neurocognitive outcomes from Phase 2 of the Prolonging Remission in Depressed Elderly (PRIDE) study.
After achieving remission with RUL-UB ECT and venlafaxine, older adults (≥60 years old) were randomized to receive symptom-titrated, algorithm-based longitudinal ECT (STABLE) plus pharmacotherapy (venlafaxine and lithium) or pharmacotherapy-only. A comprehensive neuropsychological battery was administered at baseline and throughout the 6-month treatment period. Statistical significance was defined as a p-value of less than 0.05 (two-sided test).
With the exception of processing speed, there was statistically significant improvement across most neurocognitive measures from baseline to 6-month follow-up. There were no significant differences between the two treatment groups at 6 months on measures of psychomotor processing speed, autobiographical memory consistency, short-term and long-term verbal memory, phonemic fluency, inhibition, and complex visual scanning and cognitive flexibility.
To our knowledge, this is the first report of neurocognitive outcomes over a 6-month period of an acute course of RUL-UB ECT followed by one of 2 strategies to prolong remission in older adults with major depression. Neurocognitive outcome did not differ between STABLE plus pharmacotherapy versus pharmacotherapy alone over the 6-month continuation treatment phase. These findings support the safety of RUL-UB ECT in combination with pharmacotherapy in the prolonging of remission in late-life depression.
The pharmacologic treatment of depression Potter, W Z; Rudorfer, M V; Manji, H
The New England journal of medicine,
08/1991, Letnik:
325, Številka:
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Journal Article
This review was generated from discussions by the Pharmacologic and Somatic Treatments Section of the National Institute of Mental Health Strategic Plan for Mood Disorders Committee on advancing ...novel pharmacologic and somatic treatments for mood disorders. The opening section of the article summarizes in broad strokes, current pharmacologic treatments, and new directions in the field. Thereafter the topics focus on specific research initiatives that could advance the current therapeutics for mood disorders including new basic and clinical research in vivo human imaging procedures, somatic therapeutics, and the vast new area of pharmacogenetics. New scientific and technical opportunities exist today based on advances in basic neuroscience, opportunities in clinical testing, industry interest in advancing central nervous system therapeutics, and on active consumer advocacy groups. The question of how to bring all of these positive forces together to accelerate discovery in mood disorder thera-peutics is the topic of this article.
We examined whether electroconvulsive therapy (ECT) plus medications (“STABLE + PHARM” group) had superior HRQOL compared with medications alone (“PHARM” group) as continuation strategy after ...successful acute right unilateral ECT for major depressive disorder (MDD). We hypothesized that scores from the Medical Outcomes Study Short Form-36 (SF-36) would be higher during continuation treatment in the “STABLE + PHARM” group versus the “PHARM” group. The overall study design was called “Prolonging Remission in Depressed Elderly” (PRIDE). Remitters to the acute course of ECT were re-consented to enter a 6 month RCT of “STABLE + PHARM” versus “PHARM”. Measures of depressive symptoms and cognitive function were completed by blind raters; SF-36 measurements were patient self-report every 4 weeks.
Participants were 120 patients >60 years old. Patients with dementia, schizophrenia, bipolar disorder, or substance abuse were excluded. The “PHARM” group received venlafaxine and lithium. The “STABLE + PHARM” received the same medications, plus 4 weekly outpatient ECT sessions, with additional ECT session as needed. Participants were mostly female (61.7%) with a mean age of 70.5 ± 7.2 years. “STABLE + PHARM” patients received 4.5 ± 2.5 ECT sessions during Phase 2. “STABLE + PHARM” group had 7 point advantage (3.5–10.4, 95% CI) for Physical Component Score of SF-36 (P < 0.0001), and 8.2 point advantage (4.2–12.2, 95% CI) for Mental Component Score (P < 0.0001). Additional ECT resulted in overall net health benefit. Consideration should be given to administration of additional ECT to prevent relapse during the continuation phase of treatment of MDD.
NCT01028508
Supplementing but not supplanting the original series of tricyclic and monoamine oxidase (MAO) inhibitor compounds, a new generation of antidepressant medications has been developed and marketed ...throughout the past decade. Constituting a more diverse group of drugs than the standard agents, the newer drugs in general have more selective acute biochemical actions (reuptake blockade of a single neurotransmitter, inhibition of 1 subtype of MAO), enabling more precise targeting of symptoms and avoiding common antidepressant-associated side effects, especially anticholinergic and cardiovascular effects. Moreover, a number of recent additions to this group, such as bupropion and ademetionine (S-adenosyl-methionine), incorporate novel mechanisms of action, challenging previous concepts of how antidepressants work, and offering opportunities for research into the pathophysiology of mood disorders. Caution in prescribing the newer antidepressants must be applied, however, as recent experience, e.g. with nomifensine, suggests that unforeseen toxicities may not appear until a medication has been in use for several years.
Although the standard tricyclic antidepressants (TCAs) are generally effective in the treatment of depression, they can cause several troublesome adverse effects. Chief among these are their ...anticholinergic actions, which range from annoying dryness of the mouth and constipation to potentially dangerous urinary retention and confusion or delirium in the ill and elderly. Cardiovascular effects of TCAs include orthostatic hypotension, tachycardia and cardiac conduction slowing. Many TCAs are sedating and promote weight gain. Also problematic is the potential lethality of TCAs in overdose. The continual introduction of a host of new antidepressants over the past 15 years has provided an opportunity to improve the benefit-risk ratio for many patients by reducing medication-related toxicity. Selective serotonin reuptake inhibitors (SSRIs) and amfebutamone (bupropion), among others, are examples of effective antidepressants free of tricyclic-like anticholinergic, cardiovascular, sedating and appetite/weight-increasing effects. However, the new-generation drugs also present adverse effects of their own, including gastrointestinal distress, agitation and drug-drug interactions in the case of the SSRIs, and the risk of seizures or psychosis in amfebutamone recipients. Monoamine oxidase (MAO) inhibitors have also been refined; reversible inhibitors of MAO-type A afford protection against the usually feared hypertensive reaction to indirect sympathomimetic substances. The availability of new-generation antidepressants thus increases the likelihood of clinical response with a reduction in unwanted toxicity.
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