Valerian as a hypnotic for Hispanic patients

Valerian is a botanical used for its sedative effects whose central nervous system activity is ascribed to multiple constituents. Twenty-three established outpatient symptomatic Hispanic volunteers receiving mental health services at a large urban hospital participated in this case study. All complained of insufficient sleep. They were asked to try a popular national brand of valerian ("Nature's Way", 470 mg valerian root) and completed sleep questionnaires at baseline and at the end of Weeks 1 and 2. They were instructed to take 1 capsule each night before retiring and were allowed to increase their dose to a maximum of 3 capsules after Week 1. Twenty patients completed the trial. On an ordinal scale of 1 (no effect), 3 (moderately helpful), and 5 (extremely helpful), 16 patients rated their insomnia as at least "moderately improved" at the end of Week 1. By Week 2, 16 still rated themselves at least "moderately improved," but 15 of them now described their response as either a 4 or a 5. Global improvement at Week 2 was significantly better than at Week 1 (Wilcoxon ranks test p = .005), perhaps reflecting a time-dependent or dose-response relationship. This case study suggests that valerian can be a supplement for improving insomnia in a symptomatic population.     

Sleep-Related Safety Behaviors and Dysfunctional Beliefs Mediate the Efficacy of Online CBT for Insomnia: A Randomized Controlled Trial

Several trials have demonstrated the efficacy of online cognitive behavioral therapy (CBT) for insomnia. However, few studies have examined putative mechanisms of change based on the cognitive model of insomnia. Identification of modifiable mechanisms by which the treatment works may guide efforts to further improve the efficacy of insomnia treatment. The current study therefore has two aims: (1) to replicate the finding that online CBT is effective for insomnia and (2) to test putative mechanism of change (i.e., safety behaviors and dysfunctional beliefs). Accordingly, we conducted a randomized controlled trial in which individuals with insomnia were randomized to either online CBT for insomnia (n = 36) or a waiting-list control group (n = 27). Baseline and posttest assessments included questionnaires assessing insomnia severity, safety behaviors, dysfunctional beliefs, anxiety and depression, and a sleep diary. Three- and six-month assessments were administered to the CBT group only. Results show moderate to large statistically significant effects of the online treatment compared to the waiting list on insomnia severity, sleep measures, sleep safety behaviors, and dysfunctional beliefs. Furthermore, dysfunctional beliefs and safety behaviors mediated the effects of treatment on insomnia severity and sleep efficiency. Together, these findings corroborate the efficacy of online CBT for insomnia, and suggest that these effects were produced by changing maladaptive beliefs, as well as safety behaviors. Treatment protocols for insomnia may specifically be enhanced by more focused attention on the comprehensive fading of sleep safety behaviors, for instance through behavioral experiments.     

Cognitive-behavioral therapy of insomnia: A clinical case series study of patients with co-morbid disorders and using hypnotic medications

Cognitive-behavioral therapy for insomnia (CBTi) has demonstrated considerable efficacy within randomized clinical trials and case-series designs. This case-series study in a community sleep medicine clinic assessed the effectiveness of an eight-session CBTi protocol chronic insomnia patients who were allowed to continue their use of hypnotics (intent-to-treat n = 48), administered by a clinical psychology doctoral student receiving training and supervision in CBTi by a behavioral sleep medicine certified clinician. Outcome measures included daily sleep diaries, self-report measures on insomnia severity, dysfunctional beliefs and attitudes about sleep, daytime sleepiness, as well as medication usage. Patients showed significant improvements in sleep onset latency, wake time after sleep onset, sleep efficiency, insomnia severity, and dysfunctional sleep beliefs from pre- to post-treatment. No changes were seen in daytime sleepiness - patients were not excessively sleepy either before or after treatment. Use of sleep medication declined significantly from 87.5% pre-treatment to 54% post-treatment, despite no active efforts to encourage patients to withdraw. Results demonstrate that a CBTi conducted in a community sleep medicine clinic with patients not required to discontinue sleep-related medications can have similar effects as therapy delivered among those not on medication.     

Best clinical practice with ziprasidone IM: update after 2 years of experience

Acute agitation is a common psychiatric emergency often treated with intramuscular (i.m.) medication when rapid control is necessary or the patient refuses to take an oral agent. Conventional i.m. antipsychotics are associated with side effects, particularly movement disorders, that may alarm patients and render them unreceptive to taking these medications again. Ziprasidone (Geodon) is the first second-generation, or atypical, antipsychotic to become available in an i.m. formulation. Ziprasidone IM was approved by the Food and Drug Administration in 2002 for the treatment of agitation in patients with schizophrenia. In October 2004, a roundtable panel of physicians with extensive experience in the management of acutely agitated patients met to review the first 2 years of experience with this agent. This monograph, a product of that meeting, discusses clinical experience to date with ziprasidone IM and offers recommendations on its use in various settings. In clinical trials, patients treated with ziprasidone IM demonstrated significant and rapid (within 15-30 minutes) reduction in agitation and improvement in psychotic symptoms, agitation, and hostility to an extent greater than or equal to that attained with haloperidol i.m. Tolerability of ziprasidone IM was superior to that of haloperidol IM, with a lower burden of movement disorders. Clinical trials have also shown that ziprasidone IM can be administered with benzodiazepines without adverse consequences. Transition from i.m. to oral ziprasidone has been well tolerated, with maintenance of symptom control. The most common adverse events associated with ziprasidone IM were insomnia, headache, and dizziness in fixed-dose trials and insomnia and hypertension in flexible-dose trials. No consistent pattern of escalating incidence of adverse events with escalating ziprasidone doses has been observed. Changes in QTc interval associated with ziprasidone at peak serum concentrations are modest and comparable to those seen with haloperidol IM. Results of randomized clinical trials of ziprasidone IM have been corroborated in studies in real-world treatment settings involving patients with extreme agitation or a recent history of alcohol or substance abuse. In these circumstances, clinically significant improvement was seen within 30 minutes of ziprasidone IM administration, without regard to the suspected underlying etiology of agitation. Agents with a good safety/tolerability profile, such as ziprasidone IM, may be more cost effective long term than older agents, due to reduced incidence of acute adverse effects (eg, acute dystonia) that often require extended periods of observation. Additional trials of ziprasidone IM in agitated patients in a variety of clinical setting are warranted to generate comparative risk/benefit data with conventional agents and other second-generation antipsychotics.     

Current trends in neuropathic pain treatments with special reference to fibromyalgia

Neuropathic pain and fibromyalgia are prevalent diseases which have major consequences on healthcare resources and the individual. From the clinical point of view neuropathic pains represent a heterogeneous group of aetiologically different diseases ranging from cancer to diabetes. Patients with fibromyalgia also display clinical features common in neuropathic pain suggesting that there might be some overlap. The mechanisms responsible for symptoms and signs in both diseases are still unknown. Recently, there have been numerous reports of various pharmacological treatments of neuropathic pain and fibromyalgia with often disappointing results. Most of the studies were of short duration, had high attrition rates, and displayed other methodological problems. Some compounds had high rates of adverse effects which makes it often difficult for the patients to tolerate the treatment, especially in the long-term. At present, the best options for medication treatment are tricyclic antidepressants in lower dosage than usual in psychiatric disorders and a wide range of anticonvulsants. Opioids are sometimes recommended but have been found to have minor efficacy. Recently, there have been more controlled trials, which are reported here if they had been published between 2002 and 2004. Various compounds have been tested in different studies. Treatment of fibromyalgia, which has many features in common with depressive symptoms, became the focus of interest. New promising studies with dual serotonin-norepinephrine reuptake inhibitors (duloxetine and milnacipram) and a newer antiepileptic drug (pregabalin) are in progress. Future research will have to apply new approaches (e.g., using a mechanism-based classification of neuropathic pain and carrying out studies in populations with the same symptom but not necessarily the same disease) in order to find effective treatments for these common and often debilitating diseases.     

Evaluation of the effectiveness of mindfulness-based cognitive therapy to treat chronic insomnia

IntroductionAs having positive effects on reducing distress and symptoms associated with different mental and physical disorders, many studies have focused on mindfulness-based cognitive therapy.ObjectiveIt is suggested that mindfulness-based cognitive therapy (MBCT) could help reducing insomnia by focusing on certain cognitive factors associated to insomnia.MethodA pre-experimental, pre-test protocol with a post-test and three month follow-up was used to measure the effect of a group intervention of eight sessions and 12 participants.ResultsThe intervention had a positive effect on participants’ subjective evaluation regarding their sleep and the gains were maintained after three months. However, after the intervention, no significant effect was found on the objective measures of sleep. Two factors associated to the maintenance of insomnia, such as dysfunctional beliefs and attitudes about sleep and mental control strategies were improved following treatment and these improvements were maintained during the follow-up.ConclusionThe results of this study suggest that mindfulness-based cognitive therapy might be an interesting addition in the treatment of insomnia, given that it focuses on certain cognitive factors that contribute to the maintenance of insomnia.     

Examining the relation between PTSD and insomnia on aggression

Posttraumatic stress disorder (PTSD) symptoms and poor sleep have been identified as potential causals factor in aggression, violence, and impulsive behavior. Given the high cost of aggression to society and public health, identifying modifiable factors related to aggression, such as insomnia, may guide treatment strategies to help decrease aggression. Participants were 143 Veterans seeking treatment for PTSD at a VA outpatient PTSD clinic. Linear and logistic regression analyses were used to examine the relation between PTSD and insomnia on aggression. Results from bivariate analyses indicated that while both PTSD and insomnia severity were associated with higher aggression scores independently, when PTSD and insomnia were examined together, PTSD severity was the only significant predictor of aggression. Interaction effects yielded nonsignificant results suggesting that poor sleep did not moderate the PTSD and aggression relation. Results suggest that addressing PTSD symptoms as a first treatment target may be more important for decreasing risk for aggression than targeting insomnia. More research is needed to understand whether treating PTSD and insomnia reduces aggression in Veterans.     

AEDs and psychotropic drugs in children with autism and epilepsy

The efficacy of antiepileptic drugs (AEDs) and psychotropic medications in children with autism is limited to the treatment of seizures or to specific behaviors such as irritability, impulsivity, hyperactivity, repetitive behaviors, or aggression. The reliability and value of the available data--to determine the efficacy of these medications in autism--are limited by lack of controlled clinical trials, the small number of subjects, the heterogeneity of the population studied, and the brief duration of most drug trials. Indeed, few controlled clinical trials using AEDs in autism, with or without seizures, have been conducted. Because some AEDs also have a positive effect on mood, the benefits that children with autism sometimes obtain from these medications may not be due to the treatment of the abnormal electrical activity or the seizures per se but to an effect on common neuronal systems responsible for both behavior and epilepsy. The relationship between epilepsy and autism, and specifically the effects that abnormal electrical activity may have on the developing brain, may provide some valuable insights into the type of studies that are needed to help us understand the pathophysiology of autism.     

Insomniacs' reported use of CBT components and relationship to long-term clinical outcome.

Although there is considerable evidence for the efficacy of non-pharmacological treatment of insomnia, many of the larger trials have delivered CBT in multicomponent format. This makes it impossible to identify critical ingredients responsible for improvement. Furthermore, compliance with home implementation is difficult to ascertain in psychological therapies, and even more so when trying to differentiate across a range of elements. In the present report, 90 patients who had completed 12 month follow-up after participation in a clinical effectiveness study of CBT in general medical practice, responded to a questionnaire asking them about their use of the ten components of the programme. Reports of home use were then entered as predictors of clinical response to treatment. Results indicated that reported home use of stimulus control/sleep restriction was the best predictor of clinical improvement in sleep latency and nighttime wakefulness. Cognitive restructuring also contributed significantly to reduction in wakefulness. In spite of being the most highly endorsed component (by 79% of respondents) use of relaxation did not predict improvement on any variable. Similarly, sleep hygiene was unrelated to sleep pattern change and use of imagery training was modestly predictive of poor response in terms of sleep latency. There are methodological limitations to this type of post hoc analysis, nevertheless, these results being derived from a large patient outcome series raise important issues both for research and clinical practice.     

Glucocorticoid receptor antagonists: new tools to investigate disorders characterized by cortisol hypersecretion

Increased cortisol levels have been observed in patients suffering from a number of metabolic and psychiatric disorders. In some of these disorders a causal relationship has been suggested between the increased cortisol secretion and the observed clinical phenomena. Glucocorticoid receptor antagonists which block cortisol effects might have a benefit in both the diagnosis and treatment of these disorders. Selective glucocorticoid receptor antagonists with in vivo potency have not been described thus far, partly due to the similarity between the glucocorticoid and progesterone receptors. In the present studies, we report on three different chemical classes derived from the glucocorticoid/progestagen antagonist RU486. Selected compounds from the classes 11-monoaryl steroids, 11,21-bisaryl steroids and 11-aryl, 16-hydroxy steroids proved to be selective glucocorticoid receptor binders with in vivo antagonistic activity. Most compounds were able to pass the blood-brain barrier. These compounds offer the opportunity to investigate and possibly treat patients with a disturbed hypothalamus-pituitary-adrenal axis without side effects caused by an antiprogestagenic action.     

Predictors of Adherence to a Brief Behavioral Insomnia Intervention: Daily Process Analysis

Behavioral interventions for insomnia are effective in improving sleep, yet adherence is variable, and predictors of adherence have not been consistently replicated. The relationships between daily variations in state factors at the initiation of treatment and adherence have not been investigated. Using 2-week, self-report online logs, this study determined, among 53 college students with probable insomnia, the associations of pretreatment factors and daily factors during treatment on daily variations in adherence to one session of behavioral treatments for insomnia. These treatments included stimulus control therapy (SCT), sleep restriction therapy (SRT), and sleep hygiene (SH). Low self-efficacy was associated with poorer SCT and SH adherence. Participants with a “bed partner or pet” at least some of the time had better SCT adherence. Greater total sleep time and poorer sleep quality were associated with poor SCT and SRT adherence the following night. Greater sleep efficiency was related to greater next night SCT and SRT adherence. Alcohol consumption was related to poorer SRT and SH adherence the following night. Future studies should test the replicability of these findings. Adherence trials may want to test whether discouraging alcohol intake, enhancing treatment-related self-efficacy, and monitoring and providing feedback on sleep, early in treatment, affects adherence.     

Negative effects on family functioning from psychosocial treatments: a recommendation for expanded safety monitoring.

Whereas biomedical products are required to be tested for safety with respect to vulnerable organ systems, psychosocial treatments are not required to be tested for safety with respect to vulnerable social systems such as the family. This article provides some evidence for the need to document the potential negative effects of psychosocial treatments on family-level outcomes. Three randomized controlled trials are reviewed in which independent ratings or self-reports of family functioning were measured. Each of the 3 studies compared the efficacy of a family and a nonfamily treatment. Totally unexpectedly, the nonfamily treatment in each of the 3 trials demonstrated significant declines in family functioning. The authors suggest that psychosocial treatments with vulnerable populations have the potential to produce negative side effects on families. Therefore, it is important to conduct further research to determine whether safety studies should be required for psychosocial treatments.     

Forty years of methylphenidate treatment in Attention-Deficit/ Hyperactivity Disorder

This paper reviews approximately 40 years of stimulant drug treatment of children with behavior and learning problems. These patients generally fall under the rubric of Attention-Deficit/Hyperactivity Disorder (ADHD), with core symptoms of hyperactivity, impulsivity, and inattention being the most studied and most robust of the targets for stimulant treatment. In addition, the drug effects on other targets, such as cognitive and academic function, are included. The largest selection of studies involves methylphenidate. Both qualitative studies and meta-analytic studies from major reviews are examined. Variations in the methodology of the reviews are described and some of the discrepancies in interpretation examined. Despite wide variations in subject selection, types of trials, degree of methodological rigor, and the decade in which the studies took place, the evidence is remarkably consistent The overall results suggest significant clinical impact upon the core features of ADHD. More studies of long-term effects and special populations such as older adolescents and adults will be necessary, though existing evidence strongly supports similar findings as for the younger patients with a diagnosis of ADHD.     

Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older adults 55+ years of age.

Meta-analyses support the effectiveness of behavioral interventions for the treatment of insomnia, although few have systematically evaluated the relative efficacy of different treatment modalities or the relation of old age to sleep outcomes. In this meta-analysis of randomized controlled trials (k = 23), moderate to large effects of behavioral treatments on subjective sleep outcomes were found. Evaluation of the moderating effects of behavioral intervention type (i.e., cognitive-behavioral treatment, relaxation, behavioral only) revealed similar effects for the 3 treatment modalities. Both middle-aged adults and persons older than 55 years of age showed similar robust improvements in sleep quality, sleep latency, and wakening after sleep onset. A research agenda is recommended to examine the mechanisms of action of behavioral treatments on sleep with increased attention to the high prevalence of insomnia in older individuals.     

Role of serotonin and serotonin-selective pharmacotherapy in alcohol dependence

The majority of studies that have examined the usefulness of pharmacotherapies selective for serotonin (5-hydroxytryptamine; 5-HT) as a treatment for alcohol dependence have been standard, double-blind clinical trials that include patients with a variety of clinical presentations. Almost all of the early studies evaluated heavy social drinkers and found only a modest advantage for 5-HT pharmacotherapies in reducing the number of drinks per day. Also, the advantage of these pharmacotherapies was observed primarily when these agents were given at higher daily dosages than suggested prescribing practices for use as an antidepressant. The few studies that evaluated treatment-seeking patients found that 5-HT pharmacotherapies were not instrumental in reducing drinking rates compared with placebo. These results led to a dampening of enthusiasm for use of these agents in treating alcohol dependence. However, more recent investigations have begun to target subgroups with potential abnormalities in 5-HT neurotransmission. The thinking is that these medications should be most useful in alcohol-dependent individuals who have more clearly delineated suggestive signs of 5-HT dysfunction, such as concomitant depression or anxiety. Although few results are available to date, there is growing evidence to suggest that alcohol-dependent subgroups are differentially responsive to 5-HT pharmacotherapies with respect to drinking-related outcomes. This may explain the modest and variable 5-HT pharmacotherapeutic effects that were reported in the earlier studies, which included large heterogeneous patient groups. Further investigations are needed to confirm these initial optimistic results.     

Counseling Outcomes for Youth With Oppositional Behavior: A Meta‐Analysis

This meta‐analysis of clinical trials explored the effectiveness of treatments targeted at changing oppositional behavior. The meta‐analysis included 31 peer‐reviewed treatment studies with school‐age youth ages 6–17 years identified as having oppositional defiant disorder. Results were synthesized using a random effects model for mean difference and mean gain effect size estimates. Findings suggest that counseling/psychotherapy is effective in treating oppositional behavior in school‐age youth at termination, but the long‐term efficacy of such treatment is less stable.     

Incorporating Principles from Acceptance and Commitment Therapy into Cognitive-Behavioral Therapy for Insomnia: A Case Example

Although traditional cognitive behavioral treatments for insomnia have demonstrated efficacy for many individuals with primary and comorbid insomnia, not all individuals benefit from treatment and some experience a subsequent relapse of insomnia. Furthermore, many individuals experience difficulty in implementing the sleep restriction and stimulus control strategies, especially over the long-term. The current article describes ways in which principles from a newer type of behavior therapy, Acceptance and Commitment Therapy (ACT), can be integrated with traditional behavioral treatment strategies for insomnia. A major goal of ACT is to increase willingness to experience unpleasant thoughts, feelings, and physical sensations, and to promote engagement in personally-valued behaviors while non-judgmentally observing these unpleasant experiences. ACT has the potential to enhance the behavioral treatment of insomnia by fostering willingness to experience short-term discomfort (e.g., fatigue) that occurs while implementing sleep restriction and stimulus control strategies. A case example is presented to illustrate how these principles from ACT can be integrated with behavioral techniques in the treatment of insomnia.     

Should We Treat Depression with drugs or psychological interventions? A Reply to Ioannidis

We reply to the Ioannidis's paper "Effectiveness of antidepressants; an evidence based myth constructed from a thousand controlled trials." We disagree that antidepressants have no greater efficacy than placebo. We present the efficacy from hundreds of trials in terms of the percentage of patients with a substantial clinical response (a 50% improvement or more symptomatic reduction). This meta-analysis finds that 42-70% of depressed patients improve with drug and 21%-39% improve with placebo. The response benefit of antidepressant treatment is 33%-11% greater than placebo. Ioannidis argues that it would be vanishingly smaller because systematic biasing in these clinical trials would reduce the drug-placebo difference to zero. Ioannidis' argument that antidepressants have no benefit is eroded by his failures of logic because he does not present any evidence that there are a large number of studies where placebo is substantially more effective than drug. (To reduce to zero, one would also have to show that some of the unpublished studies find placebo better than drug and have substantial systematic or methodological bias). We also present the empirical evidence showing that these methodological concerns generally have the opposite effect of what Ioannidis argues, supporting our contention that the measured efficacy of antidepressants likely underestimates true efficacy. Our most important criticism is Ioannidis’ basic underlying argument about antidepressants that if the existing evidence is imperfect and methods can be criticized, then this proves that antidepressant are not efficacious. He presents no credible evidence that antidepressants have zero effect size. Valid arguments can point out difficulties with the data but do not prove that a given drug had no efficacy. Indeed better evidence might prove it was more efficacious that originally found. We find no empirical or ethical reason why psychiatrists should not try to help depressed patients with drugs and/or with psychotherapeutic/behavioral treatments given evidence of efficacy even though our treatment knowledge has limitations. The immense suffering of patients with major depression leads to ethical, moral, professional and legal obligations to treat patients with the best available tools at our disposal, while diligently and actively monitoring for adverse effects and actively revising treatment components as necessary.     

Informed consent and the use of placebo in poland: Ethical and legal aspects

The concept of informed consent was one of the most fruitful ideas that deeply changed the relationships between physicians and their patients from paternalism to respect for the personal autonomy of subjects needing professional medical care. The great progress in medicine, also involving the pharmaceutical industry, has created an increasing need to perform different clinical and experimental trials. The evolution of clinical research in the last decades has influenced strongly the design of these studies. One of the most important changes in this field has been the use of placebo groups in double-blind controlled studies. The controversies have involved not only the use of placebo when standard or proven treatment was available, but also some specific problems concerning the procedure of obtaining informed consent in such trials. This paper briefly presents the evolution of informed consent in Poland as well as different ethical and legal problems concerning informed consent and the use of placebo controls in clinical trials. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

Non-stimulant treatment of attention-deficit/hyperactivity disorder

Stimulants are a highly efficacious and safe treatment for attention-deficit/hyperactivity disorder (ADHD), with 75% to 90% of patients responding well if two different stimulants (amphetamine and methylphenidate) are used. Nonetheless, a subset of ADHD patients will either fail to respond to stimulants or have side effects that preclude their use (tics, severe loss of appetite, marked insomnia). For such patients, there are a number of non-stimulant agents that serve as second-line treatments. Tricyclic antidepressants (TCAs) are the most studied of these drugs. They are superior to placebo in the treatment of ADHD and may reduce abnormal movements in patients with ADHD/tic disorder. TCAs often produce side effects of sedation, dry mouth, and constipation. Bupropion is superior to placebo in the treatment of ADHD and has a more favorable side-effect profile than the TCAs. A new selective norepinephrine reuptake inhibitor, atomoxetine, has been shown to be efficacious in the treatment of ADHD and has recently received an approvable letter from the Food and Drug Administration. The a-agonists clonidine and guanfacine have also been used as alternative agents in ADHD, though the controlled data are more limited. A recent controlled clinical trial suggests a combination of methylphenidate and clonidine has advantages in the treatment of comorbid ADHD and tics over either medication alone. Clinical guidelines for each of these agents, as well as their use in combination with stimulants in comorbid conditions, will be discussed.