Anxiety disorders affect one in 10
The Canadian Network for Mood and Anxiety Treatments describes anxiety as the body’s way of telling us that we feel vulnerable and unprepared. It is anxiety that makes sure we are vigilant and equipped to accomplish the tasks or situations facing us, like exams, an icy road or a challenging social or work situation. Without anxiety, our response to those types of stressful situations could be inadequate and lead to undesirable consequences.
We need a certain amount of anxiety to function effectively. It is when anxiety becomes prolonged and disrupts out daily lives that it becomes pathological.
Anxiety disorders are the most common mental health problems. Anxiety affects twice as many women as men and occurs in about ten per cent of the population, including children. Anxiety disorders are illnesses yet they are often perceived as mental weakness or character flaws.
The website of the Canadian Mental Health Association states that the disorders affect the behaviour, thoughts, emotions and physical health of the people who experience them. Research shows that they are caused by biological and circumstantial factors, just like other illnesses such as heart disease and diabetes. Individuals can experience more that one type of anxiety disorder and can be accompanied by depression, eating disorders and substance abuse.
Sildenafil citrate Australia
Anxiety disorders include Generalized Anxiety Disorder, or GAD, Obsessive Compulsive Disorder, Post Traumatic Stress Disorder, Panic Disorder and specific phobias. These diagnosable illnesses are treatable. Left untreated, the individual experiencing the illness can be distressed and cause distress to those around them. The disorders can be disruptive and severely limit normal activities.
The two main treatment approaches are cognitive behavioural therapy and drug therapy. Anti-depressant and anti-anxiety medications are generally prescribed because most anxiety disorders have some biological component. Cognitive behavioural techniques include helping people to turn their anxious thoughts into thoughts that are less anxious and more rational.
Because of the stigma associated with mental illness generally and anxiety disorders specifically, many anxiety disorders go untreated and continue to disrupt the lives of the individuals who experience them.
Off-Label Use of Atypicals May Do More Harm Than Good
Off-label use of atypical antipsychotics may do more harm than good, a new meta-analysis suggests.
A combined analysis of more than 150 efficacy trials showed significant increases in behavioral symptom scores for dementia in the elderly after they were treated with aripiprazole, olanzapine, or risperidone; benefits for nonelderly patients with generalized anxiety disorder (GAD) after they received quetiapine; and benefits for patients with obsessive-compulsive disorder (OCD) after receiving risperidone augmentation.
However, analysis of more than 200 adverse outcome studies showed that treatment-related adverse events, including death, were common in these patient groups.
“Besides the small but statistically significant effect found for dementia, the other improvements were a bit smaller than we expected, with moderate effects for GAD and OCD,” lead author Alicia Ruelaz Maher, MD, psychiatrist at the Akasha Center for Integrative Medicine in Santa Monica, California, and assistant clinical professor in psychiatry at the University of California, Los Angeles, School of Medicine, told Medscape Medical News.
“As for the other conditions that these medications commonly treat, we just did not find enough of an effect. And despite olanzapine being known to cause weight gain, I was surprised to find it was not effective in causing weight gain in eating disorders,” said Dr. Maher, who is also a clinical adjunct at the RAND Health Southern California Evidence-Based Practice Center in Santa Monica.
She noted that the study is the “largest study of its kind on this subject,” and prompted clinicians to reconsider the way they prescribe atypical antipsychotics.
“I think the biggest takeaway is that instead of just prescribing blindly, we now have evidence to guide us. There are certainly times when the cost-benefit analysis would go towards using medication, but I would hope that the side effects are kept in mind.”
The study appears in the September 28 issue of JAMA.
Doubling of Off-Label Use
“Atypical antipsychotic medications are approved for marketing and labeling by the US Food and Drug Administration (FDA) for treating schizophrenia, bipolar disorder, and depression under drug-specific circumstances,” write the researchers.
However, these medications “are commonly used” off-label to treat dementia, anxiety, OCD, eating disorders, substance abuse, and posttraumatic stress disorder.
“We’ve been noticing that off-label use is increasing. In fact, over the past several years it has doubled,” said Dr. Maher.
“Some clinicians feel that if a medication is effective in treating 1 condition, it might also be effective in treating others. And that often works, especially in psychiatry. However, there are also plenty of instances where off-label use was determined to be useless or even harmful.”
To evaluate the benefits and safety of these medications for off-label use, the investigators examined data from 162 trials with efficacy outcomes conducted through May 2011.
“Controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with placebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions were included,” report the researchers.
“Clozapine was excluded due its almost exclusive use for schizophrenia,” they add.
Minimal Efficacy
A total of 231 large observational studies were also examined that assessed adverse events and included at least 1000 patients each.
The efficacy review included 14 placebo-controlled trials that evaluated elderly patients with dementia who had symptoms such as psychosis, mood alterations, and aggression.
Overall results showed that aripiprazole, olanzapine, and risperidone showed small but significant effect changes, ranging from 0.12 to 0.20. Quetiapine showed an effect change of 0.11, but this was not deemed significant.
There was a difference of 3.41 points in the pooled Neuropsychiatric Inventory total score for dementia behavior symptoms between treatment with antipsychotics and with placebo. However, this was below the 4-point improvement threshold “considered to be the minimum clinically observable change,” report the researchers.
In combined analysis of trials evaluating GAD, a “favorable response” was defined as showing at least 50% improvement on the Hamilton Anxiety Rating Scale. Overall results showed that quetiapine was associated with a 26% greater likelihood of a favorable response at 8 weeks than placebo.
Augmentation with risperidone after not responding to other treatments was associated with a 3.9-fold greater likelihood than placebo of a favorable response (showing at least a 25% improvement on the Yale-Brown Obsessive Compulsive Scale) for patients with OCD.
The study authors note that “evidence does not support” using olanzapine to treat eating disorders, or using any antipsychotic medications to treat substance abuse. Furthermore, they add, “[t]he level of evidence is mixed regarding personality disorders and is moderate for an association of risperidone with improving [posttraumatic stress disorder].”
Rethinking Off-Label Use
Adverse events in elderly patients included an increased risk for death (pooled odds ratio, 1.54) and urinary tract symptoms overall, stroke for risperidone, and extrapyramidal symptoms for olanzapine and risperidone compared with placebo.
In the nonelderly, treatment-related adverse effects from antipsychotics included weight gain (especially with olanzapine), extrapyramidal symptoms, fatigue, sedation, and akathisia for aripiprazole.
“This systematic review demonstrates evidence for the efficacy of atypical antipsychotic medications for only a few of the off-label conditions that are currently being treated,” write the researchers.
“This evidence should prove useful for clinicians considering off-label prescribing…and should contribute to optimal treatment decision-making for individual patients with specific clinical symptoms and unique risk profiles.”
Dr. Maher added that she hopes this leads to clinicians examining each patient’s individual needs.
“For example, if a patient already has kidney problems, then urinary tract symptoms might be a bigger issue than in someone who doesn’t. It’s just really about looking at the individual.”
However, she also noted that although moderate levels of evidence were found for some of these conditions, further research might bring about changes in the results.
“We need to use this information and be wary of prescribing when it isn’t warranted; but also we need to keep looking at this issue in future studies.”
A Complicated Decision
“While meta-analysis studies are always useful, one doesn’t make treatment decisions based on just 1 [study],” Anthony Rothschild, MD, Irving and Betty Brudnick endowed chair and professor of psychiatry at the University of Massachusetts Medical School in Worcester, and director of the Center for Psychopharmacologic Research and Treatment, told Medscape Medical News.
Caveats of chronic exogenous corticosterone treatments in adolescent rats and effects on anxiety-like and depressive behaviour and HPA function
Administration of exogenous corticosterone is an effective preclinical model of depression, but its use has involved primarily adult rodents. Using two different procedures of administration drawn from the literature, we explored the possibility of exogenous corticosterone models in adolescence, a time of heightened risk for mood disorders in humans.
Methods: In experiment 1, rats were injected with 40 mg/kg corticosterone or vehicle from postnatal days 30 to 45 and compared with no injection controls on behavior in the elevated plus maze (EPM) and the forced swim test (FST).
Experiment 2 consisted of three treatments administered to rats from postnatal days 30 to 45 or as adults (days 70 to 85): either corticosterone (400 μg/ml) administered in the drinking water along with 2.5% ethanol, 2.5% ethanol or water only. In addition to testing on EPM, blood samples after the FST were obtained to measure plasma corticosterone.
Analysis of variance (ANOVA) and alpha level of P <0.05 were used to determine statistical significance.
Results: In experiment 1, corticosterone treatment of adolescent rats increased anxiety in the EPM and decreased immobility in the FST compared to no injection control rats. However, vehicle injected rats were similar to corticosterone injected rats, suggesting that adolescent rats may be highly vulnerable to stress of injection.
In experiment 2, the intake of treated water, and thus doses delivered, differed for adolescents and adults, but there were no effects of treatment on behavior in the EPM or FST. Rats that had ingested corticosterone had reduced corticosterone release after the FST.
Ethanol vehicle also affected corticosterone release compared to those ingesting water only, but differently for adolescents than for adults.
Conclusions: The results indicate that several challenges must be overcome before the exogenous corticosterone model can be used effectively in adolescents.
