Treatment for Panic Attack

Panic Away End Anxiety and Panic Attacks

Barry Joseph McDonagh is a very popular author of Panic Away eBook. He is more than just a program developer based on his long research and education. As a result of his personal experience and research, Joe Barry decided to take a new approach to dealing with panic attacks. The core of the program is the 21 7 Technique, which is made up of the 21 Second Countdown and the 7 Minute Exercise. This is then followed by C.A.L.M. Recovery, which helps to integrate this technique into your life. Panic Away aims to restore you back to your former care free self through eliminating panic attacks and reduce general anxiety fast. That first key step to an anxiety free life, revealed in Panic Away, is shared and sinks in your brain in such a powerful way with the videos of Jane dealing with panic, that I give Panic Away my highest recommendation. Read more...

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I usually find books written on this category hard to understand and full of jargon. But the author was capable of presenting advanced techniques in an extremely easy to understand language.

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Drug Therapy Of Depression And Anxiety Disorders

Major affective and anxiety disorders represent the most common psychiatric illnesses and are those encountered most often by primary-care clinicians. Major depression may represent a spectrum of disorders, varying in severity from mild and self-limited conditions to extraordinarily severe, psychotic, incapacitating, and deadly diseases. The antipsychotic, antianxiety, antimanic, and antidepressant drugs affect cortical, limbic, hypothalamic, and brainstem mechanisms that are of fundamental importance in the regulation of arousal, consciousness, affect, and autonomic functions. Physiological and pharmacological modifications of these brain regions may have important behavioral consequences and useful clinical effects regardless of the underlying cause of any mental disorder. The lack of diagnostic or even syndromal specificity of most psychotropic drugs tends to reduce the chances of finding a discrete mechanistic correlate for a specific disease based simply on the actions of...

Characterization Of Depressive And Anxiety Disorders

The primary clinical manifestations of major depression are significant depression of mood and impairment of function. Some features of depressive disorders overlap those of the anxiety disorders, including panic-agoraphobia syndrome, severe phobias, generalized anxiety disorder, social anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder. Extremes of mood also may be associated with psychosis, as manifested by disordered or delusional thinking and perceptions that often are congruent with the predominant mood. Conversely, secondary changes in mood may be associated with psychotic disorders. This overlap of disorders can lead to errors in diagnosis and suboptimal treatment. Mood and anxiety disorders are the most common mental illnesses, each affecting up to 10 of the general population at some time in their lives. Anxiety disorders may be acute and transient, or more commonly, recurrent or persistent. Symptoms may include mood changes (fear, panic, or...

Pharmacotherapy Of Anxiety

Anxiety is a symptom of many psychiatric disorders and an almost inevitable component of many medical and surgical conditions. Symptoms of anxiety commonly are associated with depression and especially with dysthymic disorder (chronic depression of moderate severity), panic disorder, agoraphobia and other specific phobias, obsessive-compulsive disorder, eating disorders, and many personality disorders. Sometimes, no treatable primary illness is found, or if one is found and treated, it may be desirable to deal directly with the anxiety at the same time. In such situations, antianxiety medications are frequently and appropriately used. Currently, the benzodiazepines and the SSRIs are the most commonly employed pharma-cotherapies for common clinical anxiety disorders (see Chapter 16). Benzodiazepines sometimes are given to patients presenting with anxiety mixed with symptoms of depression, although their efficacy in altering the core features of severe major depression has not been...

Depression Anxiety and Sleep Disturbances

Summary This journal article discusses issues in the treatment of depression, anxiety, and sleep disturbances in patients with dementia. The author reviews evidence suggesting that both pharmacologic and nonpharmacologic therapies are effective for the treatment of depression, and that treatment for depression in dementia should focus not only on symptomatic relief but also on functional improvement. He notes that little attention has been given to the treatment of anxiety in patients with dementia, and advises that benzodiazepines should be used with caution in such patients because of the risk of worsening their cognitive function. He also discusses considerations in the effective management of sleep disturbance in patients with dementia, including the use of nonpharmacologic approaches such as activity programs, environmental interventions, and educational interventions.

Obsessive Compulsive Anxiety Disorders in Childhood

Childhood-onset obsessive-compulsive disorder Pediat-ric-onset obsessive-compulsive disorder Obsessive-Compulsive Disorder (OCD) is currently classified as an anxiety disorder ( Anxiety Disorders) in Compulsions are repetitive physical or mental acts an individual feels driven to perform in a characteristic, stereotyped way, usually to relieve the anxiety or discomfort associated with depression. Typical symptoms of OCD include contamination obsessions and cleaning compulsions (i.e., fear of germs and compulsive hand washing), forbidden thoughts (i.e., obsessions about harm coming to self or others, sexual, or religious obsessions), hoarding, and symmetry (i.e., the need to have things symmetrical, ordered, arranged) (Bloch et al. 2008). These obsessions and or compulsions must be severe enough to cause significant distress or impairment or be time-consuming (take up more than 1 h a day). Typically, patients with OCD have insight that their obsessions and compulsions are excessive and...

Panic Disorder Definition

This disorder is characterized by recurrent unexpected panic attacks followed by at least 1 month of persistent concerns about additional attacks (i.e., anticipatory anxiety), worry about the implications or consequences of the panic attack or significant changes in behavior (e.g., avoidance) related to the attacks. Panic attacks are not better accounted for by a comorbid mental disorder and are not normally due to the direct physiological effects ofa substance or general medical condition. Depending on whether criteria are also met for agoraphobia, panic disorder with or without agoraphobia is diagnosed.

Social Anxiety Disorder

Several studies have established the efficacy of sertraline in the treatment of social anxiety disorder (also known as social phobia). In one of the earliest studies, sertraline treatment (at flexible doses of 50-100 mg day) showed a statistically significant improvement compared with placebo, as measured by the Liebowitz Social Anxiety Scale (LSAS) (Katzelnick et al. 1995). A large double-blind, placebo-controlled study followed more than 200 Canadian outpatients with generalized social phobia for 20 weeks, measuring response on CGI-I scores and mean reductions on the social phobia subscale of the Marks Fear Questionnaire and the Brief Social Phobia scale (Van Ameringen et al. 2001). Fifty-three percent of patients treated with sertraline, compared with only 29 of patients receiving placebo, were either much or very much improved by the study's end, as measured by CGI-I scores. Statistically significant changes favoring sertraline were seen on the other two study measures as well....

Anxiety And Stressrelated Disorders

Anxiety disorders have recently been found to be correlated more closely than depression with chronic painful conditions in a large US sample of chronic pain patients.26 In particular, people who are fearful of anxiety-related sensations, who interpret somatic symptoms as harmful and who avoid situations where these feelings are likely to arise, have greater disability.27 The term anxiety sensitivity'' has been used to describe this condition in these individuals.28 The diagnoses included under this rubric comprise generalized anxiety disorder (GAD), panic disorder, phobias, posttraumatic stress disorder, adjustment disorders, and obsessive compulsive disorder.

Generalized anxiety disorder

The symptoms of this disorder include excessive anxiety and worry, occurring frequently for a period of at least six months with difficulty in controlling this. Additionally, the person concerned has at least three additional symptoms including restlessness, becoming tired easily, difficulty in concentrating, irritability, muscle tension, or disturbed sleep.29 Early work suggested that female patients with chronic pain and who were not seeking compensation had a higher frequency of GAD than expected,30 although women with anxiety were not found to have a poorer prognosis compared with men in a recent investigation.31 Higher degrees of anxiety were related to greater intensity of pain in this study.31 This same study showed that patients with this symptom have a poorer prognosis and this has been shown by others.32 It has been suggested that patients with chronic pain may use worry to reduce the physical sensations associated with pain, and thus fulfil the diagnostic criteria for...

The anxiety disorders

Recent studies have begun to confirm the widely held hypothesis that caffeine can be a contributing factor in the maintenance, and perhaps even genesis, of some anxiety disorders. Included are post-traumatic stress disorder (PTSD),223 phobia,304,305 obsessive-compulsive disorder,306 and panic dis-order.307-309 One study showed, for example, that excessive caffeine consumption is a common factor in the PTSD reactions seen in combat troops. Based on their results, the investigators recommended decaffeinated beverages for all troops entering combat situations.223 There is also an emerging body of research that implicates caffeine in the genesis of panic attacks,309,310 and the drug has long been used as a panicogenic agent to elicit anxious reactions for clinical purposes.307308 One study recently showed that caffeine can cause the dysregulation of multiple neuronal systems that results in panic attacks.308 Moreover, this panic response to excessive amounts of caffeine was found to have...

HT2C Effects on Factors Influencing Learning Processes 2451 Anxiety

The 5-HT2 receptor family seems to be particularly involved in anxiety because several drugs effective for the treatment of anxiety disorders interact with this type of receptor (Mora et al. 1997 Peroutka 1995). Mora et al. (1997) tested mCPP, ritanserin and propen-1-yl phenol hemifumarate (SR-463496A), a selective 5-HT2A 2C receptor antagonist (Rinaldi-Carmona et al. 1992) on two types of fear. The authors used a paradigm in which the same rat in one experimental session was exposed to two types of fear, in an elevated T-maze with the perpendicular arm closed and the other with arms open. By placing the animal in the closed arm, the training of inhibitory passive avoidance is evaluated by measurement of the time that the animal takes to leave the closed arm during three consecutive trials. This inhibitory avoidance task is assumed to represent conditioned fear. The same animal is placed in the open arm in a one-way escape task, which is assumed to represent unconditioned fear (Graeff...

BuspironeIs Anxioselectivity Possible

The question arises whether anxiolytic activity must always be accompanied by concomitant skeletal muscle relaxant and anticonvulsant activity as well as strong sedation. Can an anxioselective drug exist that will not interact significantly and additively with CNS depressant compounds, particularly alcohol More significantly, both from a medical and sociologic viewpoint, will it be possible to treat anxiety and stress without the added complication of potent sedative effects, dependency, and abuse Evaluation of a series of cyclic imides as potential psychotropic agents yielded three candidates with tranquilizing action and very low sedative effects. The compound chosen for detailed pharmacologic evaluation, MJ9022-1, buspirone (BS), was marketed in 1986 as the first member of a new class of azaspirodecanediones. Early screening led to the erroneous belief that the compound might have antipsychotic properties. However, when further testing revealed that the compound had a taming effect...

Spielberger State Trait Anxiety Inventory

The Spielberger State-Trait Anxiety Inventory (STAI)28 is the most widely used measure of anxiety, a construct that is not used as extensively as depression is with chronic pain patients, but nevertheless a very important one with pain patients. The STAI is a 40-item inventory that assesses trait anxiety, a characterological, stable dimension of anxiety that is relatively consistent over time, as well as state anxiety, transitory feelings of anxiety usually in response to specific situations. Patients are asked to rate statements on a four-point scale regarding how they feel right now (state anxiety) and how they feel generally (trait anxiety).

Benzodiazepines and Anxiolytics

Benzodiazepines have been employed acutely to mitigate pain arising from muscle spasm (e.g., after spinal cord injury). The presumption is that patients with marked anxiety are prone to heightened muscle tension, which may exacerbate musculoskeletal pain. Other uses for benzodiazepines have included treatment of restless legs syndrome, tension headache, and neuropathy (Bartusch et al. 1996 Bouckoms and Litman 1985 Dellemijn and Fields 1994). Clonazepam, a long-acting benzodiazepine, might be effective in patients with neuropathic pain in which allodynia (painful sensations elicited by normally nonnoxious stimuli, such as a bedsheet pulled up along the legs) appears to be a prominent feature (Bouckoms and Litman 1985). Buspirone is an anxiolytic agent that differs from benzodiazepines, mediating an antianxiety effect through the 5-HTja receptor. One study reported that patients with neuropathic pain tended not to respond favorably to bus-pirone treatment (Kishore-Kumar et al. 1989)....

Benzodiazepines As Anxiolytic Agents

The treatment of anxiety and sleep disorders is dominated by the BZDs. These drugs induce sleep (act as hypnotics) in high doses and lead to sedation and reduced anxiety (anxiolytic) at lower doses. They function by an enhancement of the GABA-mediated inhibition of the CNS and act in an allosteric manner on the GABA receptor. The discovery of the

Genetics Of Anxiety And Related Disorders 21 Anxietyrelated traits in mood disorders

A large body of evidence from family, twin, and adoptee studies has been accumulated that a complex genetic component is involved in anxiety-related traits and in the liability to anxiety spectrum disorders. While genetic research has typically focused either on normal personality characteristics or on psychiatric disorders, with few investigations evaluating the genetic and environmental relationship between the two, it is of critical importance to answer the questions whether a certain quantitative trait etiopathogenetically influences the disorder or whether the trait is a syndromal dimension of the disorder. Nevertheless, some studies have implicated anxiety-related personality traits, such as neuroticism or negative emotionality, in the comorbidity of mood disorders (Kendler et al. 1993a Livesley et al. 1998). Separation of anxiety spectrum disorders from mood disorders including depression and bipolar disorder in current consensual diagnostic systems remarkably enhanced interest...

Serotonin 1a Receptor And Antidepressant Anxiolytic Response

While multiple lines of evidence implicate the serotonin 1A receptor (5HT1A) in the pathophysiology of anxiety and depression as well as in the mechanism of action of anxiolytics antidepressants, its relevance to the therapeutic effectiveness of these drugs has been a matter of considerable debate (Griebel 1995 Hensler 2003 Hjorth et al. 2000 Lesch et al. 2003). The 5HT1A receptor is encoded by an intronless gene (HTR1A) located on human chromosome 5q12.3. Several rare missense polymorphisms, including the Gly22Ser variant which results in altered agonist-elicited downregulation, have been found within the protein coding of HTR1A. Moreover, Lemonde and coworkers (Lemonde et al. 2003) reported a functional C-1019G single nucleotide polymorphism (SNP) in the transcriptional control region of HTR1A (HTR1A-1019) and demonstrated in in vitro experiments that the G variant displays differential binding efficiency of the repressors enhancer-type transcriptional regulator NUDR DEAF-1. NUDR...


There is much speculation as to how anxiety can influence pain. For example, pain can heighten anxiety, which in turn can result in muscle strain and spasm. If the strain and spasm are severe enough, localized ischemia and muscle cell damage can arise, resulting in the release of pain-producing substances that then precipitate further pain. Heightened responses of lower back muscles, as shown by electromyography (EMG), were observed among patients discussing personal anxiety-provoking stressors (Flor et al. 1985). Similarly, heightened tension in frontal muscles, associated with personal distress, was noted among patients with tension headaches. This anxiety-pain relationship makes intuitive sense but has not been consistently borne out in evaluations using EMG. One reason for this is that although EMG can reflect activity in superficial muscles, it may not measure the recordings of deeper muscles, where pain may actually originate. Also, a time lag is expected between the experience...

Anxiety Disorders

The HPA axis has also been studied in patients with anxiety disorders, particularly panic disorder, with and without comorbid major depression. Both the cortisol response to dexamethasone and the response to CRH have been examined in pure panic disorder without comorbid depression. The earliest study with dexamethasone demonstrated a 15 nonsuppression rate in panic disorder (Curtis et al. 1982). A number of other studies have since been conducted, and the overall incidence of cortisol nonsuppression is 17 in panic disorder (13 studies), while the incidence for major depression is 50 (Heninger 1990). Grunhaus et al. (1987) compared patients with major depression to those with major depression with panic disorder and found a similar rate of cortisol nonsuppression following dexamethasone administration (approximately 50 ) in the two populations, suggesting that the presence of comorbid panic disorder had little impact beyond that of depression on dexamethasone nonsuppression. In CRH...

Panic Disorder

None of the tricyclic or tetracyclic drugs are approved for use in panic disorder. Yet imipramine was the first drug described for use in this disorder (Klein 1964). In fact, observation of the effects of imipramine helped to establish the diagnostic utility of panic disorder. The efficacy of both tertiary and secondary tricyclics has been demonstrated in controlled trials (Jobson et al. 1978 Munjack et al. 1988 Zitrin et al. 1980). In treating this disorder, the drug is initiated at a low dose to avoid exacerbation of panic symptoms.


Conflicting data exist concerning the efficacy of buspirone augmentation. Many open trials have suggested efficacy as an augmentation strategy (302-305) however, placebo-controlled trials have not fully supported the clinical reports. In a study of 102 outpatients with MDD who did not have an adequate response to 6 weeks of treatment with fluoxetine or citalopram, buspirone (doses of 10-30 mg b.i.d.) or placebo was added after a 2-week placebo wash-in period (306). Although buspirone was superior to placebo on the MADRS after 1 week, no difference was found at 6 weeks, except in patients with baseline MADRS scores greater than 30. In another study of 119 patients who failed to respond to paroxetine or placebo after a minimum of 4 weeks, buspirone or placebo was added for an additional 4 weeks (307). Although the combinations were well tolerated, there was no difference between groups, with both showing substantial improvement on the Clinical Global Impression Scale (50.9 buspirone,...


Anxiety is a very common concomitant condition in patients with chronic pain, presenting as panic, PTSD, obsessive compulsive disorder (OCD), etc. Although anxiolytics do not possess intrinsic analgesic activity, anxiety is often accompanied by somatic complaints of chest pain, GI upset, or neurologic symptoms such as dysesthesias, headache, which may be relieved by anxiolysis. Benzodiazepines are also a mainstay in the treatment of restless legs syndrome (RLS). Although most RLS studies were conducted with clonazepam, current recommendations focus on shorter acting benzodiazepines such as triazolam (Silber et al. 2004).

Behavioral tests of pain phenotype

In addition to new models, work is being conducted to improve the range of behavioral tests employed in vivo (Figure 1.3). For example, spontaneous exploratory activity assessed in the open field paradigm is classically used as a measure of anxiety-related behavior in rodents.28 This test has been used as a measure of locomotor activity in pain models29 and more recently, additional measures of thigmotactic behavior indicate the presence of altered exploratory behavior in rodent models of pain without the presence of locomotor deficits. This behavior is sensitive to clinically employed analgesics, such as gabapentin and morphine,19,27 suggesting the thigmotaxis to be correlated to a nonstimulus-evoked pain-like behavior in rodents be it spontaneous pain or pain comorbidities.

Origins and Development of Pain Management

Sion and anxiety) not only emerge as a consequence of pain but also can contribute to pain, thereby exacerbating and maintaining it. Psychological factors can likewise interfere with treatment adherence and efficacy. Patients' frustration caused by ongoing pain, the effects on functioning, and the impact on families and relationships can contribute significantly to psychiatric morbidity. As a result of these factors, leaders in pain management training declared traditional medical models of pain to be too shortsighted and required a modification in traditional training conceptualizations (Loeser 2001).

Imaging Of The Brain In Neuropathic Pain

Neural correlates of allodynia have been examined in various conditions, including patients with neuropathic pain, central pain, or experimentally provoked allodynia. However, the existing data are controversial with some suggesting that allodynia is processed differently than nociceptive pain and others suggesting they share a common neural basis. Areas shown to be involved in allodynia include the parietal association cortex,194 medial thalamus, putamen, and prefrontal cortex.195 The ACC, which is almost always activated during acute pain in normal subjects and is involved in the affective (cognitive-evaluative) component of pain, has been differentially associated with processing of allodynia.196197, 198,199 This suggests that A-p-mediated pain may have a unique cortical representation in some situations which may aid further understanding of the phenomenon that is tactile allodynia. The amygdala, which plays an important role in fear-conditioning and affective disorders, such as...

Collecting Pig Choroid Plexus

From there, we started parallel autoradiographic studies to establish what came to be the 5-HT2C receptor, as will be discussed later in section 1.4 in this chapter. The project in fact followed a research plan carried out in parallel in two different buildings Autoradiographic experiments were done at building 360 (JMP lab), while membrane assays were carried out at building 386 (DH lab). During the autumn of 1983 and the whole year 1984, it become quite usual to Angel to walk daily from one place to the other, bearing tissue samples, autoradiograms and counter prints in his hands, and frequently, a certain level of anxiety in his mind, since we were using old-generation liquid scintillation counters, with rather modest throughput, when we were preparing hundreds of samples. This meant that they had to be loaded and unloaded one by one, by hand with two or three loading sessions per day, weekends included every sample was labeled by hand in case of counter failure and to allow...

Moderators Of The Depressionimmune Link

Finally, co-morbidity in depression has emerged as a major concern in biologic research in psychiatry with recent epidemiological data showing, for example, that as many as 50 of depressed patients are co-morbid for an anxiety disorder such as panic (Stein & Uhde, 1988 Murphy, Oliver, Sobol, Monson, & Leighton, 1986). Moreover, the prevalence of alcohol and tobacco dependence is high in depressed subjects (Breslau, Peterson, Schultz, Chilcoat, & Andreski, 1998 Schuckit, 1986), but few studies have examined the contribution of alcohol intake or cigarette smoking on alterations of immune function in depressed subjects despite the well-recognized effects of these substances on immune parameters. The following will consider the effects of comorbidity for anxiety and or substance dependence in the relation between depression and immunity. Six symptom clusters, defined by factor analysis of items from the HDRS, were identified anxiety somatization, weight loss, cognitive...

Alprazolam Definition

Alprazolam is a high-potency, short-acting anxiolytic benzodiazepine medication used in the treatment of anxiety, panic, and phobic disorders. It has some antispas-modic and anticonvulsant effects. It is not antidepressant. It is sometimes used in conjunction with antipsychotic medication in acute psychotic episodes. Unwanted effects include sedation, headaches, paradoxical excitement, confusion, cognitive and psychomotor impairment, and confusion in the elderly. Long-term use may induce dependence with withdrawal reactions. Recreational use and abuse can occur alprazolam is a scheduled substance.

Implications of pharmacologically altered AEA signaling

There are an overwhelming number of implications for AEA and other endocannabinoids in various physiologically and pathophysiologically relevant human states including pain (Hohmann and Suplita, 2006), appetite (Kirkham and Tucci, 2006), reproduction (Wang et al., 2006), mood and anxiety (Witkin et al., 2005), the cardiovascular system (Ashton and Smith, 2007), alcoholism (Rodriguez de Fonseca et al., 2005), spasticity (Pertwee, 2002), neurodegeneration (Battista et al., 2006), and inflammation (Ashton, 2007). In fact, these cited references are merely examples of the numerous reviews recently written on each representative topic.

Impact of pain on quality of life

Estimates of the economic burden associated with pain fail to do justice to the extent of suffering and reduced quality of life experienced by patients and warrants pain relief being regarded as a universal human right.18 Chronic pain, along with musculoskeletal disorders, has been shown to be associated with some of the poorest quality-of-life states.60,61,62,63 In patients referred to a Danish multidisciplinary pain center, the severity of impairment was equal to or lower than patients with cardiopulmonary diseases and major depression, and their Psychological General Well-being Scale scores were lower than those with hypertension and gastrointestinal problems, while they also displayed high levels of anxiety and depression, as measured by the Hospital Anxiety and Depression Scale.63 In a study of over 600 patients attending a chronic pain clinic in Sydney, Australia, there were greatly reduced SF-36 domain scores between clinic patients and Australian norm values, as shown in Table...

Transporters as Targets for Drug Discovery

Whitlock et al. describe progress in the discovery of SSRIs, noradrenaline reuptake inhibitors (NRIs), and SNRIs from 2000 to the present day. Whilst Chen et al. focus on recent developments in the search for triple SERT, NET and DAT reuptake inhibitors. The interest in these areas stems not only from the potential for improved antidepressant efficacy and side effect profiles, as has been proposed for the triple reuptake inhibitors 38 , but the recognition that by tweaking the transporter profile potential therapies for other diseases associated with neurotransmitter imbalance can be developed. For example, although duloxetine 6 (Fig. 1), a dual SNRI, was initially launched in 2004 for the treatment of major depressive disorder (MDD) 39 , since 2004 additional approvals have been granted for pain associated with diabetic neuropathy 40 and fibromyalgia 41 , for stress urinary incontinence 42 and generalised anxiety disorder 43 . NRIs have been licensed for the treatment of attention...

Receptor Looking for a Therapeutic

The clinical relevance of 5-HT2C receptor editing has been linked in association studies to suicidality (Niswender et al. 2001), schizophrenia (Sodhi et al. 2001), anxiety (Hackler et al. 2006), depression (Iwamoto et al. 2005), and spatial memory (Du et al. 2007). However, these data need confirmation, as is common in the field. 5-HT2C receptors have been shown to modulate mesolimbic dopaminergic function, where they exert a tonic inhibitory influence over dopamine neurotransmission (Di Giovanni et al. 1999 Bubar and Cunningham 2007) and, therefore, the interest in this receptor as a therapeutic target for treating abuse (Bubar and Cunningham 2006). The 5-HT2C receptor is also believed to mediate, in part, the effects of antidepressants, e.g., mirtazapine or agomela-tine (Cremers et al. 2007), possibly by stimulating neurogenesis, as well as that of atypical antipsychotics (Herrick-Davis et al. 2000). 5-HT2C receptors are expressed in the amygdala, and functional magnetic resonance...

Pharmacogenetics In Clinical Research And Drug Development

From the Regulatory side, the FDA in North America (http www.fda.-gov cder guidance 5900dft.doc) and other regulatory bodies, including the MHLW in Japan, have published draft guidelines (for example the FDA's VDGS Voluntary Data Submission Guidelines) to provide guidance to pharmaceutical companies on how pharmacogenetic data will be used as part of regulatory decisions and to encourage the inclusion of pharmacogenetic data as part of drug development. It should be noted that such pharmacogenetic data may be used to support more efficient and successful clinical development strategies, without necessarily resulting in label restrictions based on genotype. Rather, data can be applied to ensure that novel, more effective medicines reach the patient as quickly as possible (Roses 2004). An example of this for psychiatry is the use of pharmacogenetics to dissect out placebo response, or perhaps more correctly, non-specific drug response, a major confounder in clinical studies not only for...

Psychiatric Examination

Often times, psychiatric illnesses are associated with health behaviors and pyschophysiologic changes that promote medical illness. Attributing a patient's pain to solely a psychiatric cause is not a diagnosis of exclusion. More importantly, undertreated psychiatric disease may exacerbate pain states (Hudson et al. 1985). Thus, to assess the psychiatric status of the chronic pain patient, a physician should perform a Mini-Mental status exam and discuss any existing depression or anxiety symptoms (Wittink et al. 2004).

Pharmacological Properties

Although Parkinson's disease (PD) is classified as a movement disorder, it should also be considered as a neuro-behavioral'' disorder. The diagnosis of PD is based on the presence of clinical criteria having to do purely with movements and the absence of exclusionary or atypical features, laboratory tests being of little or no value. Nevertheless, the most devastating aspects of PD are more often behavioral. Other nonmotor problems, such as sympathetic dysfunction and sleep disorders have only attracted clinical and research attention in the last few years. For perspective two studies, one a large retrospective review in Australia, and the other, a county wide prospective study with formal testing in Norway, both concluded that by the time of death, 80 of PD patients are demented. In addition, at any point in time, somewhere between 30 and 50 are depressed 40 suffer from anxiety 40 with apathy 30 of drug treated patients with visual hallucinations 5-10 of drug treated patients with...

Nuclear Hormones Focus On Steroids

In view of the GABAA enhancing potential of 3ff.-reduced neuroactive steroids, these steroids have been suggested to possess sleep-modulating or -promoting (Mendels and Chernik 1973), anticonvulsant (Frye and Scalise 2000), anxiolytic (Crawley et al. 1986), and neuroprotective (Rupprecht 2003) properties. Finally, it has been postulated that neuroactive steroids may also contribute to psychiatric symptoms sometimes observed during pregnancy and in the postpartum period (Pearson Murphy et al. 2001).

Current Concepts and State of Knowledge

Anxiety has been defined as an emotional state aroused by the perception of threat, which is subjectively experienced as unpleasant. In its full expression, behavioral, autonom-ic endocrine, affective, and cognitive perceptual changes are manifested. Although usually adaptive, leading to harm avoidance, anxiety may turn out to be disruptive, giving rise to different pathologies. In modern psychiatric classifications, such as the Diagnostic and Statistical Manual, 4th edition, revised (DSM-IV-RT) of the American Psychiatric Association, anxiety is considered pathological when excessive, disproportional to the eliciting event, causing significant distress, disrupting interpersonal relationships, and impairing social and occupational functioning. According to the symptomatology and time course of development, anxiety disorders are classified into different nosological categories, such as generalized anxiety disorder (GAD) and panic disorder (PD). The first question one should face while...

Biologic Actions of Oleamide

To date, a specific oleamide receptor'' has not been identified. However, there are examples where oleamide was shown to have effects on well-established receptor systems, most likely through allosteric interactions with the receptor proteins themselves. These systems include the GABAA (Laposky et al., 2001 Lees et al., 1998 Verdon et al., 2000), serotonin2A (Boger et al., 1998a Huidobro-Toro and Harris, 1996 Thomas et al., 1997, 1998), sero-tonin2C (Huidobro-Toro and Harris, 1996), and serotonin7 (Alberts et al., 2001 Hedlund et al., 1999, 2003 Thomas et al., 1997, 1998) receptors. In general, the effects of oleamide on these systems are remarkably sensitive to specific structural features of oleamide whereby, subtle changes in acyl chain length, presence position and stereochemistry of the double bond or alterations in the amide terminus all diminished the oleamide effects. The fact that oleamide modulates 5-HT receptor activity suggests that, in addition to sleep regulation, it...

Structured clinical interview

The clinical interview also affords the opportunity to evaluate the patient's beliefs and cognitions about their pain. However, the primary utility of the clinical interview is to formulate a diagnosis in conjunction with the standardized questionnaires. Particular diagnostic categories carefully evaluated for include levels of depression and anxiety, PTSD, and somatization disorders. This facilitates the design of a comprehensive treatment plan, devised together with the patient as well as the rest of the multidisciplinary team.

Central excitatory systems

The long-term increase in pain sensitivity frequently seen following injury or peripheral nerve damage is thought to be due to both alterations in transmission within the spinal cord and to changes in descending controls that run back to the spinal cord from the brainstem. Within this circuit, nocic-eptive information is also relayed to higher centers in the brain via projection neurones. The neuroanatomy of these ascending pain pathways is highly complex, and supraspinal contacts include centers involved with the sensory-discriminative aspects of pain such as the intensity, location and duration of the stimulus as well as centers involved in the affective-cognitive aspects including anxiety, emotion and memory 61 . Importantly, these are the same areas of the brain that modulate descending serotonergic and noradren-ergic inputs from the brainstem that regulate nocic-eptive processing at spinal levels. Thus, a network of spinal and brain circuits can change spinal sensitivity to...

Central inhibitory systems

There are other important sites of opioid actions located in the 5HT and noradrenergic nuclei of the brainstem and midbrain, including the raphe nuclei (RVM), the periaqueductal gray matter (PAG) and the locus coeruleus. These areas of the brain are important in sleep, anxiety and fear and explain how these functions interact with and are altered by pain. Opioid receptors in these zones, when activated, alter the level of activity in descending pathways from these zones to the spinal cord that in turn reduces activity of spinal cord neurones. The relative roles of the 5HT receptors in the spinal cord are unknown but the spinal target for noradrenaline (NA) released from descending pathways is a2 receptors which have similar actions and distribution to the opioid receptors. Sedation and hypotension with a2 agonists presently limit their use as analgesics but they are useful veterinary drugs.

Historical Perspective of Pharmacology

A recent example of an integrated pharmacological approach to drug discovery is that of the novel anxiolytic AC-5216 (Kita et al., 2004). This compound was synthesized as a potent (Ki 0.3 nM), orally active agonist for the peripheral BZ receptor. Also known as the mitochondrial BZ receptor or translocator protein, this site is involved in the synthesis of endogenous neurosteroids that enhance GABAergic neurotransmission. Whole animal testing revealed that AC-5216 had anti-anxiety effects in mice in the Vogel-conflict test (0.1-3 mg kg p.o.), the light dark box (0.003-0.01 mg kg p.o.), and social interaction tests (0.01-0.3 mg kg p.o.). These actions were blocked by the peripheral BZ mitochondrial BZ receptor antagonist, PK 11195 (3 mg kg i.p.). Further behavioral tests revealed that AC-5216 was also active in the Porsolt forced swim test (3-30 mg kg p.o.), a measure of antidepressant activity. Unlike the classical BZ, diazepam, AC-5216 did not produce muscle relaxation, nor did it...

Alterations in Physiological Function Circardian Rhythms Sleep Pain Perception and Appetite

Painful physical symptoms are also common complaints in depression (194). This may in part be related to the shared 5-HT and NE pathways in depression and pain (195) since 5-HT and NE modulate pain through the descending pain pathways. Serotonergic projections descend through the rostral ventral medulla and the pontine raphe into the spinal cord where they modulate pain. Norepinephrine neurons also project through the dorsolateral pons, locus coeruleus, medial and lateral parabrachial nuclei, and associated areas into the spinal cord to modulate pain. The effects of 5-HT and NE are synergistic in this system. Thus, dual reuptake inhibitors are effective in relieving the physical symptoms associated with depression (196). Recent functional imaging studies indicate that the presence of anxiety may accentuate pain perception (197).

Challenges for Animal Models of Autism

Tasks that could examine these behavioral symptoms in rodents have been already developed and are summarized in Table 1. However, an animal model of autism based solely on behavioral assays would be incomplete. Animal model should also address a combination of the neuro-pathological, biochemical and genetic factors implicated in autism. Another challenge lies in the fact that many clinical hallmarks of autism are difficult or almost impossible to replicate in rodents, e.g., theory of mind (ability to intuit the feelings and intentions of others) or speech deficits. It is also important to realize that assumed core psychopathological phenomena observed in autism are present as common clinical features in schizophrenia, depression, obsessive-compulsive disorder and other medical and psychiatric illnesses. What is specific for autism is a pattern of socio-behavioral aberrations and their appearance before the age of three, and animal models should try to address this fact.

Genetically Induced Models

A second approach uses monogenic aberrations, such as loss of Fmrl or methyl-CpG-binding protein-2 (Mecp2) function, that underlie syndromes associated with autistic-like behavior. The Fmrl-null mice display increased levels of social anxiety, reduced social interaction, hyperactivity, and deficits in spatial and reversal learning. Interestingly, exposure to an enriched environment can reverse some behavioral deficits in this model. The Mecp2-null mice show deficits in social behavior, hypoactivity, impaired learning and memory, and increased anxiety. A third approach uses gene mutations relevant to loci for autism susceptibility, identified by association or linkage studies. For example, Relnrl + mice show lower rates of separation distress calls, impairments in reversal learning, increased anxiety, decreased pre-pulse inhibition, and a progressive loss of Purkinje cells. Similarly, Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in...

Adverse Effects Of 02selective Agonists

The major adverse effects of j-receptor agonists occur as a result of excessive activation of b receptors tremor, to which tolerance develops and which can be minimized by starting oral therapy with a low dose of drug and progressively increasing the dose as tolerance to the tremor develops feelings of restlessness, apprehension, and anxiety, which may limit therapy and tachycardia, primarily via j1 receptors but also possibly via cardiac j2 receptors, or to reflex effects that stem from j2 receptor mediated peripheral vasodilation. During a severe asthma attack, heart rate actually may decrease during therapy with a j agonist, presumably because of improvement in pulmonary function with consequent reduction in endogenous cardiac sympathetic stimulation. In patients without cardiac disease, j agonists rarely cause significant arrhythmias or myocardial ischemia however, patients with underlying coronary artery disease or preexisting arrhythmias are at greater risk. The risk of adverse...

HT2CRMediated Contributions to Affective Behaviors

Mice constitutively lacking 5-HT2CRs show multiple measures of diminished anxiety-related behaviors in many exploratory tasks. Constitutive 5-HT2CR - Y mice spent more time in the central region of an open field, crossed into the open arm of an elevated zero maze more frequently (and spent more time in this open arm), spent more time exploring a novel object placed in the home cage, and spent more time in a mirrored chamber compared with wild-type littermates (Heisler et al. 2007a). Taken together, these results suggest that constitutive loss of 5-HT2CRs is mildly anxiolytic. Furthermore, mice demonstrating this anxiolytic phenotype were noted to activate fewer cells in the BNSt (when staining for the early gene product c-fos) compared with wild-type littermates. immunocytochemistry) following footshock when compared with wild-type littermates (Bonasera et al. 2005). These studies suggest that 5-HT2CRs on populations of BNSt projection neurons are required to appropriately activate...

Drugs as Inhibitors of Monoamine Transporters

The most important CNS drugs that target the norepinephrine and serotonin neurotransmitter transporters (NET and SERT) are the tricyclic antidepressants and their modern counterparts. The discovery that imipramine potently inhibited NET in sympathetic nerves 10 and the finding that this also applied in the brain 11 led to the first understanding of the mechanism of action of the tricyclic antidepressants. Following the discovery of the serotonin uptake system in brain it soon became apparent that the classical tricyclic drugs imipramine and amitriptyline were also potent inhibitors of SERT. This reinforced the monoamine hypothesis of depression as a monoamine deficiency state, and stimulated much further research in the pharmaceutical industry to discover new inhibitors of monoamine uptake. An effort to improve the selectivity of antidepressants was made in the 1970's by scientists at the CIBA-GEIGY Company in Switzerland (now Novartis), who developed the selective norepinephrine...

Some Unanswered Questions

Although the monoamine uptake inhibitors have proved very successful in the treatment of depression and anxiety states many questions remain unanswered. How can drugs that are selective norepinephrine reuptake inhibitors be equally effective as those that selectively target serotonin reuptake In reality none of the antidepressants is completely selective for NET or SERT. In some cases the formation of active metabolites alters the drug selectivity profile. Thus the non-selective compound imipramine and the partially NET-selective compound lofepramine are extensively metabolized to desipramine, a highly potent and selective NE reuptake inhibitor. Similarly whereas amitriptyline has little selectivity for NET or SERT, the metabolite nortriptyline is a selective NET inhibitor. Alternatively some have suggested that the SSRI's act indirectly to modulate noradrenergic function 21,22 .

Psychological Effects From Patients Seeking Treatment For Chronic Pain

It may come as no surprise that among the most well-documented effects that come with chronic pain is emotional distress or mood disturbance. In their very useful review paper, Banks and Kerns11 reported that depression is disproportionately prevalent in sufferers of chronic pain compared to other chronic medical conditions, that depression is most likely to be a result and not cause of chronic pain, and that 30.0-54.0 percent of patients seeking treatment for chronic pain suffer with a diagnosable depressive disorder. There is also evidence that patients with chronic pain have high prevalence rates of anxiety disorders, including panic disorder and generalized anxiety disorder, and substance use disorders, although the prevalence figures appear varied across studies.12 Rates of current anxiety disorders may range from 16.5 to 28.8 percent and current substance use disorders from 15 to 28 percent.12 In comparison with the clinical data, a recent nationally representative sample of the...

Assessment Methods For Emotional Distress

For years, the standard assessment method for anxiety in relation to chronic pain included use of instruments such as the Spielberger State-Trait Anxiety Inventory (STAI).53 We questioned the utility of the STAI in a study demonstrating that instruments assessing more pain-specific fear and anxiety responses appear more useful, and are stronger predictors than general measures, like the STAI, of patient functioning.54 General measures of anxiety tend to be highly correlated with measure of depression and, thus, do not provide additional information in most clinical assessments. They also do not take into account the source of the distress and, thus, are not as helpful in the design or selection of treatment methods as they could be. As an alternative for measuring pain-related fear and avoidance, clinicians or researchers might use the Pain Anxiety Symptoms Scale (PASS).33,34 The distinction between the PASS and other measures related to fear of pain, such as the Fear Avoidance...

Processes In Chronic Painrelated Disability And Suffering

Withdrawing socially, and using assistive devices can be behavior patterns that serve only as attempts to limit contact with pain, and do not serve purposes the pain sufferer would otherwise rate as most important and meaningful in their life. In essence, dealing with pain can move an individual, unwittingly, away from what they care about most. Part of this process can be referred to as a values failure or a failure of values-based action.71 We have found that patients with chronic pain rate their success at living according to their values in areas of family, intimate relations, friends, work, health, and growth or learning, as significantly lower than the level of importance with which they hold their values in these domains.72 We have also found that the losses that come with the failures of values to guide action contribute to significant anxiety, depression, and disability in patients with chronic pain. Additional analyses in this same study demonstrated that both acceptance of...

Risk factors for occurrence

Anxiety Psychosocial factors that traditionally have been reported to be associated with low back pain are anxiety, depression, emotional instability, and alcohol or drug abuse 16 . A recent systematic review of observational studies of psychosocial factors for the occurrence of back pain found insufficient evidence for an effect of psychosocial factors in private life, such as family support, presence of a close friend or neighbor, social contact, social participation, instrumental support and emotional support 17 . A prospective cohort study provided evidence that psychologic distress at 23 years of age more than doubled the risk of low back pain onset 10 years later, while other factors (e.g. social class, childhood emotional status, Body Mass Index, job satisfaction) did not increase the risk 18 . Another systematic review found a clear link between psychologic variables and low back pain 19 . Psychologic variables that are associated with low back pain are stress, distress or...

Herpes simplex virus type

HSV encephalitis is treated with intravenous acyclovir, 15-30 mg kg three times daily for 10 days. Because cerebral edema is a frequent cause of death, intubation and hyperventilation to bring the partial pressure of carbon dioxide to 25mmol l may be critical. Dexamethasone should also be given intravenously at an initial dose of 10 mg, followed by 4-8 mg every 4-5 h for the next 3 days. Total fluid intake should be reduced to one-half to two-thirds of maintenance, and the patient's head should be elevated to 30 . Mannitol can be given in repeated doses of 0.25-2 g kg, and serum osmolality should be monitored and kept below 310m0sm l. The effectiveness of mannitol decreases with repeated use, and rebound increases in intracranial pressure may occur. Anticonvulsant medications are used if seizures develop there are no data to support seizure prophylaxis in this situation.

Posttraumatic stress disorder

As well as genetic heterogeneity, incomplete penetrance, pleiotropy, and interaction multiple genes complicate genetic studies of PTSD and its treatment. One strategy to get around these problems is to perform genetic analysis of traits associated with PTSD, rather than PTSD itself, an approach that has yielded promising results for other diseases with complex genetics. Hypothalamic-pituitary-adrenal axis dysfunction, physiologic markers of increased arousal, and increased acoustic startle response are PTSD-associated traits accessible to genetic analysis. However, the power of these traits to distinguish PTSD from non-PTSD patients need to be determined before they can be employed in genetic studies. Only a few association studies have been reported. Comings et al. (1996) reported that the A1 allele of the dopamine D2 receptor gene (DRD2) was significantly more common among PTSD patients as compared to veteran controls. Differences in rates of substance abuse, which appear also be...

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Other conditions in which ephedra is contraindicated are anxiety disorders, angle-closure glaucoma, prostate adenoma with residual urine volume, pheochromocytoma, and thyrotoxicosis (Gruenwald et al. 1998). Known medications that may interact adversely with ephedrine include heart glycosides, halothane, guanethidine, MAO inhibitors, secale alkaloids, and oxytocin. Addiction and Dependence

Selective Serotonin Reuptake Inhibitors

Of all three groups of antidepressants, the SSRI group (see Table 5.2) has the poorest profile for pain relief (APS, 2006). When compared with placebo, these medications did not have any significant advantage for pain relief. Given the lack of efficacy for pain relief in these medications and the profile of side effects, sexual dysfunction, anxiety, sleep disorder, and headache, the SSRIs are not medications that should be given unless there is a specific indication for use. The recommended use for this group of medications is for patients who have concurrent depression, anxiety, or insomnia (APS, 2008).

Dose versus Treatment Chronicity

The patient reported that the more dramatic symptoms resolved after treatment was discontinued. However, he never fully recovered his ability to retain complex details without using notes and continues to have difficulty remembering the names of clients, appointments, and distinctions between various projects at work. The success of his company has suffered as a result. Formal neuropsychological testing performed 3 years after treatment cessation revealed low average to average performance on tests of information-processing speed, and severe impairments of verbal memory and fine motor skills. These findings are in marked contrast to his estimated pre-illness superior intellectual level. Personality assessment revealed mild anxiety and depression. The potential for irreversible neurologic toxicity from prolonged cytokine treatment may become more problematic as increasing numbers of patients are cured or have very long-term remissions from their disease.

Citalopram Definition

Citalopram is a selective serotonin reuptake inhibitor (SSRI). It is commonly used in the treatment of depression and some of the more severe anxiety disorders (e.g., obsessive-compulsive disorder, panic disorder, social anxiety disorder). As with other SSRIs, the most troublesome side effect of citalopram is sexual dysfunction (dysorgas-mia and erectile dysfunction) mild side effects include drowsiness, headache, and nausea. Escitalopram, the S-enantiomer of racemic citalopram, is also marketed as an antidepressant.

Controlling Bias in Research and Practice

The obvious challenge is to create a system in which data, and not bias, drive treatment recommendations. With such evidence, the clinician will be able to offer the patient expert advice as to the form of intervention best suited for the presenting complaint. By careful, unbiased education, patient attitudes may be changed so that they can be steered toward whatever form of intervention has been demonstrated to be most effective. The right of a patient with disabling symptoms of anxiety to demand immediate relief in the form of an anxiolytic medication must be respected, not challenged. At the same time, the clinician must take pains to educate the patient that this relief is likely to be short term and evanescent once the medication is discontinued. Such patients should be given impartial information as to the availability of potentially more effective treatments leading to longer lasting relief. This information should include a discussion of whether nonpharmacological treatment...

Associated with ethanol exposure

As mentioned above, ethanol withdrawal syndrome is a life-threatening condition and is also a hallmark for physical dependence to ethanol.122 Other symptoms of eth-anol withdrawal syndromes in humans include tachycardia, sweating, tremor, hypertension, anxiety, agitation, auditory and visual hallucinations, and confusion.121122 Therefore, ethanol withdrawal symptoms are disabling enough to lead many subjects to resume alcohol consumption at the early stages of withdrawal.2112137138

Clomipramine Definition

Clomipramine, the 3-chloro derivative of imipramine, is a tricyclic antidepressant with a tertiary amine chemical structure. It is a potent, but not selective, serotonin reuptake inhibitor its primary active metabolite, desmethyl-clomipramine, inhibits reuptake of norepinephrine. Although originally introduced for the treatment of depression, clomipramine is now used more frequently for the treatment of obsessive-compulsive disorder. Even for this indication, it is usually employed only after nonre-sponse to a selective serotonin reuptake inhibitor (SSRI) while clomipramine may have slightly greater efficacy than the SSRIs, it also has a less-favorable side-effect profile. Side effects include marked sedation, cardiovascular effects, and anticholinergic effects (e.g., constipation, dry mouth, blurred vision, urinary retention). Clomipramine is dose dependently associated with a higher risk of seizures than other tricyclics like other tricyclics, it has a high potential for lethality...

Cognitive Theory Expectation Theory

The cognitive theory states that patient expectations are critical in the placebo response. The administration of a placebo creates an expectation of a certain response, and the expectation of this response creates a biological effect. The mechanisms whereby expectancies might produce biological effects are many. They include (1) a reduction in anxiety which could aid immune system functioning, (2) changes in cognition or coping mechanisms, or (3) changes in behavior that would improve health outcomes (Stewart-Williams and Podd 2004). Patient expectations can be quite specific, and studies have shown that expectations of pain relief in particular body parts lead to the expected effect in that body part alone (Benedetti et al. 1999, Montgomery and Kirsch 1996).

Use of Cholinesterase Inhibitors in Other Dementia Related Illnesses

In the past few years, dementia with Lewy Bodies has become increasingly recognized and may now be the second most common cause of progressive dementia, after Alzheimer's disease. In a multicenter, international study, McKeith and colleagues studied 120 patients with dementia with Lewy Bodies in a randomized, double-blind, placebo-controlled fashion. At the end of the 20-week trial, the researchers noted improvement in areas of behavior including anxiety, hallucinations, attention, and memory in patients who were on a high dose of rivastigmine (6-12 mg day) 76,77 . A small, open-label study by Shea et al. showed that donepezil may have efficacy in cognition and behavioral disturbance in patients with dementia with Lewy Bodies 78 . Case reports have also described possible efficacy of cholinesterase inhibitors in improving neuropsychiatric symptoms associated with dementia with Lewy Bodies, in particular hallucinations and agitation 79,80 . No drug is currently FDA approved for the...

Psychological Component

The essential components of the psychological variables related to pain are summarized in Table 12.2. It is important that clinicians assess the effect of pain on the patient's psychological functioning. Psychological functioning includes concentration, motivation or energy, and emotions such as depression or anxiety. It is imperative to recognize that transient sub-syndromal emotional and cognitive reactions to life events, e.g., sadness, anger, and fear, as well as the emotional distress accompanying psychiatric disorders (discussed below) are germane to the psychological component of chronic pain assessment. Because these items are interrelated, there will be considerable overlap and bidirectional influences between pain and one's moods, cognitive appraisals, and coping strategies. control over pain and related stressors, are robust predictors of pain and disability and significantly impede one's adaptation in the face of chronic painful conditions (Keefe et al. 2005, Sullivan et...

Types Of Cam Therapies

Chronic pain is one of the primary reasons that patients try CAM therapies. Patients look for ways to relieve not only the daily pain but the anxiety and uncertainty that the pain produces. Many of the techniques are minimally invasive, such as acupuncture, or noninvasive, such as the energy therapies of Reiki or therapeutic touch (TT). Because many patients are attracted to this type of therapy, incorporating it into the plan of care can help track outcomes and determine benefit. Because the use of these therapeutics is controversial and research is limited, it is helpful to monitor the benefit of these therapies when they are added to a plan of care.

Management Of Insomnia

Adequate sleep improves the quality of daytime wakefulness, and hypnotics should be used judiciously to avoid its impairment. A number of pharmacological agents are available for the treatment of insomnia. The perfect hypnotic would allow sleep to occur with normal sleep architecture rather than produce a pharmacologically altered sleep pattern. It would not cause next-day effects, either of rebound anxiety or of continued sedation. It would not interact with other medications. It could be used chronically without causing dependence or rebound insomnia on discontinuation. Regular moderate exercise meets these criteria but often is not effective by itself, and many patients may not be able to exercise. However, even small amounts of exercise often are effective in promoting sleep. Controversy in the management of insomnia revolves around two issues pharmacological versus nonpharmacological treatment and the use of short-acting versus long-acting hypnotics. The side effects of hypnotic...

Insomnia Accompanying Major Psychiatric Illnesses

Adequate control of anxiety in patients with anxiety disorders often produces adequate resolution of the accompanying insomnia. Sedative use in the anxiety disorders is decreasing because of a growing appreciation of the effectiveness of other agents, such as adrenergic receptor antagonists (see Chapter 10) for performance anxiety and serotonin reuptake inhibitors for obsessive-compulsive disorder and perhaps generalized anxiety disorder. The profound insomnia of patients with acute psychosis owing to schizophrenia or mania usually responds to dopamine-receptor antagonists (see Chapter 18) benzodiazepines, often used adjunctively in this situation to reduce agitation, will result in improved sleep.

Behavioral Problems in Nursing Home Residents Safe Ways To Manage Dementia

Pharmacological, that can help control these behaviors. Non-pharmacological treatment options include environmental changes, bright-light treatment, and restraints and behavior modification. Pharmacological options involve the use of neuroleptics, benzodiazepines, and other agents such as beta-blocker therapy, carbamazepine, lithium, trazodone hydrochloride, and buspirone hydrochloride. According to the authors, patients should be assessed to differentiate delirium from dementia, and possible precipitants of disturbed behavior should be investigated. The authors suggest that ultimately, long-term success with patients with dementia may depend in part on realistic expectations. 21 references.

Experimental Pain Studies And Depression

These differences in pain thresholds and tolerances suggest patients with depression may experience a differential analgesic response to opioid medications compared to patients without depression. In a randomized, cross-over, double-blind, placebo-controlled study, 60 patients with chronic low back pain were stratified into three groups based on the severity of depressive, anxiety, and neurotic symptoms.9 Subjects in each of the three groups were administered 4-6 mg of morphine intravenously and pain severity was assessed over three hours. The total analgesic response was significantly greater in the low psychopathology group compared to the high psychopathology group. Additionally, the analgesic placebo response was significantly greater in the high psy-chopathology group compared to the low group. While the mechanisms mediating the association between chronic pain, depression, and analgesia remain to be fully elucidated, alterations in emotional processing could be important...

Substance Abuse and Dependence

Although chronic pain patients may be vulnerable to developing new substance use disorders in the course of treatment (Dersh et al. 2002, Brown et al. 1996, Dunbar and Katz 1996), investigations assessing the presence of opioid dependence in chronic pain patients have reported contradictory conclusions. Some contend that this is an extraordinarily rare event (Zenz et al. 1992) whereas other investigators have found high rates of opioid dependence in chronic pain populations (Ives et al. 2006, Wu et al. 2006). Risk factors for opioid dependence include a prior history of substance abuse prior physical sexual abuse major depression, anxiety disorders, and personality disorders (Dersh et al. 2002, Ives et al., Fishbain et al. 1998). Opioids have been a predominant focus however, several other agents used in pain treatment are likewise prone to abuse and dependence including the muscle relaxant carisoprodol ketamine ergot alkaloids and barbiturates employed in migraine treatment and...

Hints Of Phenotypes For Variant Sert Alleles From Genetic Studies In Mouse And

Although functional coding variants have yet to be identified in hSERTs, functional variants in promoter and intronic regions have been investigated for their relationship to clinical syndromes. As noted above, the s alleles of the 5HTTLPR have been found to associate with reduced transcriptional activity of the SERT promoter and with neuroticism and anxiety traits (Lesch et al., 1996). However, the degree to which the 5-HTTLPR influences SERT expression is at present controversial, with both supportive (Little et al., 1998 Heinz et al., 2000) and contradictory (Willeit et al., 2001) evidence. Recently, Du and co-workers (Du et al., 2000) were able to replicate the finding of Lesch of an association between 5-HTTLPR s alleles and neuroticism, but only in a male population, the gender of the original Lesch studies. These findings suggest that gender-specific expression of phenotypes may need to be considered in evaluation of SERT variants and that neuroti-cism and anxiety continue to...

Pharmacology and adverse effects including suicide

Side effects associated with use of these medications are related to enhanced serotonergic transmission. Frequently encountered side effects include nausea, vomiting, tremor, anxiety, agitation, sweating, sleep disturbance, diarrhea, and sexual dysfunction. Paroxetine has affinity for muscarinic receptors which account for mild anticholinergic effects, predominantly dry mouth, constipation, and blurred vision. Long-term use of paroxetine has been associated with weight gain.108

Adjuvant Roles of Other Psychopharmacologic Agents Benzodiazepines

To mitigate pain arising from muscle spasm, e.g., after spinal cord injury. This effect may be due to an indirect effect related to their psychotropic properties, i.e., alleviation of anxiety. The presumption is that reducing patient anxiety attenuates muscle tension and associated musculoskeletal pain.

Causes and Treatment of Behavioral Changes

Summary This article describes Alzheimer's disease as an increasingly common management concern for primary care physicians. Although little can be done for the primary symptoms of the dementing process, the secondary behavioral complications of this illness may be amenable to behavioral or pharmacologic manipulation. Agitation may be responsive to environmental or psychosocial intervention. Treatment with low doses of antidepressants can improve depressive symptoms. Mild anxiety is best treated with emotional support from the family and caregiver. Benzodiazepines can be used with caution. Insomnia can be reduced by encouraging a routine that prevents daytime napping and keeping the patient busy during the day. Pharmacotherapy for disturbed sleep often causes more harm than good and should be avoided if possible. 3 references. (AA-M).

Histamine Antagonists

Used alone, antihistamines appear to have an analgesic ceiling effect. Histamine antagonists can augment opiate receptor binding of opioid analgesics (Rumore and Schlichting 1986) and therefore are often employed as co-administered adjuvant agents. The failure to observe substantial analgesia from the use of these agents alone, however, has largely restricted the use of histamine antagonists for persons with chronic pain who have other indications. These agents may be particularly useful in patients given their sedative, anti-emetic, antipruritic, and anxiolytic properties. They are generally well tolerated, with few respiratory or gastrointestinal side effects.

Sympathomimetics Stimulants

Although the literature is limited by number of subjects, duration, and trial design, there is some evidence to support the use of methylphenidate (5-15 mg two to four times daily), donepezil (5-10 mg daily), and modafinil (200-400 mg daily) for the pharmacologic management of opioid-induced sedation and fatigue (Larijani et al. 2004, Reissig and Rybarczyk 2005). Potential adverse effects can include overstimulation (e.g., anxiety, insomnia, and even paranoia), appetite suppression, exacerbation of motor abnormalities (e.g., tics, dyskinetic movements), and confusion. Contraindications for stimulant use include glaucoma, poorly controlled hypertension, arrhythmias, and cardiovascular disorders, anorexia, seizure disorders, and hyperthyroidism. Methylphenidate is a schedule II medication under federal regulatory control caution is advised in patients with current or preexisting substance use disorders, especially prior stimulant abuse (e.g., cocaine).

Burning Mouth Syndrome

Summary This article discusses burning mouth syndrome (BMS), a condition that is characterized by a burning sensation in the tongue or other oral sites, usually in the absence of clinical and laboratory findings. Affected patients often present with multiple oral complaints, including burning, dryness, and taste alterations. Burning mouth complaints are reported more often in women, especially after menopause. Typically, patients awaken without pain but note increasing symptoms through the day and into the evening. Conditions that have been reported in association with BMS include chronic anxiety or depression, various nutritional deficiencies, type 2 diabetes, and changes in salivary function. However, these conditions have not been consistently linked with the syndrome, and their treatment has had little impact on BMS symptoms. Recent studies have pointed to dysfunction of several cranial nerves associated with taste sensation as a possible cause of BMS. Given in low dosages,...

Crf1 receptors and pathophysiology of ibs symptoms

Other support for CRF signaling pathways in the pathophysiology of IBS came from a report that the peripheral injection of a-helical CRF9-41 prevented electrical stimulation-induced enhanced sigmoid colonic motility, visceral perception, and anxiety in IBS patients compared to healthy controls, without altering the HPA axis.121 CRF antagonists almost normalized the altered EEG activities in IBS patients under basal and in response to CRD.122 Consistent with preclinical studies, anatomical and biochemical studies of colonic biopsies from IBS patients support a possible role of mast cells as effectors in visceral nociception.123 Comorbidity with anxiety and depression CRFj antagonists blocked stress-related

Brain Targeted Surgical Interventions

In the brain, a hypophysectomy can be performed for intractable pain in association with hormonally responsive cancers. The transsphenoidal approach is used for resection or ablation with radiofrequency or alcohol. Both metastatic breast and prostate cancer pain have been treated with very good results. Cingulotomy is usually performed for psychiatric illness, particularly obsessive compulsive disorder and depression, but is also used to treat chronic pain syndromes. Lesioning the cingulate gyrus, part of the limbic system, disrupts the perception of pain. The pain is still felt by the patient, but it does not

RNA Editing of HTR2C in Mental Disorders Cellular and Animal Studies

Characteristics among mice strains, such as level of anxiety and stress reactivity. Recently, functional consequence of altered RNA editing in vivo was directly tested. Kawahara et al. created the knock-in mice of fully edited (VGV) and nonedited (INI) HTR2C (Kawahara et al. 2008). While the INI mice were reported to grow normally, the VGV mice showed severe growth retardation by the activation of the sympathetic nervous system and increased energy expenditure.

Recent developments in drug discovery metabolite identification

Castro-Perez and co-workers also described the use of a five-channel MUX interface to a qToF mass spectrometer for parallel LC MS high resolution analysis for in vitro and in vivo metabolite identification.39 They reported a four-fold throughput increase. However, inter-channel cross-talk and a three-fold reduction in sensitivity relative to a single sprayer system were comparable to results reported by Yang et al. in quantitative bioanalytical applications.40 In general, implementing this technology in a metabolite identification laboratory for routine support of drug discovery is challenging. Nagele and Fandino reported the use of a conventional single electrospray qToF mass spectrometer combined with column switching using a two-position ten-port valve for the simultaneous determination of the metabolic stability and metabolite identification for buspirone.41 The metabolic stability determinations were performed with a short (2.1 x 50 mm, 1.8 pm particle size) C18 column....


Alprazolam, (Xanax), is rapidly absorbed from the GI tract. Protein binding is lower ( 70 ) than with most benzodiazepines because of its lower lipophilicity. a-Hydroxylation of the methyl group to the methyl alcohol (a reaction analogous to benzylic hy-droxylation) followed by conjugation is rapid consequently, the duration of action is short. The drug is a highly potent anxiolytic on a milligram basis.

Tricyclic Antidepressants

The bulk of the evidence pertaining to the use of antidepressants in pain states has been directed at the utility of TCAs (Table 5-6). Neuropathic and idiopathic pains may respond better to TCA use than do nociceptive pains. However, these agents may be effective in nociceptive pain states when there is a comorbid depression or anxiety that complicates the disorder. The efficacy of TCAs appears to be related to the reuptake inhibition of NE and 5-HT. TCAs with a broad spectrum of activity may be more effective in pain reduction than those with neu-rotransmitter-specific effects. Thus, amitriptyline and imipramine appear to be more effective than desipramine or clomipramine (Max et al. 1992).

Genetic Manipulations

A complementary approach involves targeted disruptions of gene expression in specific brain regions only during critical periods of postnatal brain development. An example is provided by mice engineered to lack the serotonin1A receptor (5-HT1AR) protein. These mice exhibit increased anxiety-like behavior on a variety of tests. Selective expression of 5-HT1AR in the hippocampus and cortex, but not the raphe nuclei, restores to normal the behavior of 5-HT1AR knockout mice (Gross et al. 2002). Additional evidence suggests that tissue-specific 5-HT1AR expression during postnatal development, but not in adulthood, is necessary to achieve the behavioral rescue effect. This model indicates that developmental changes in 5-HT1AR gene expression within specific brain regions are involved in the emergence of anxiety-like behavior in adulthood.

The Role of Glucocorticoids in Physiology

Besides involvement in the negative feedback loop of the HPA-axis, glucocorticoids in the brain also influence behavior, learning, and memory (McEwen and Sapolsky, 1995 McGaugh et al., 1996 Sapolsky, 1996). Cognitive processes, electrophysiological properties of hippocampal neurons, and anxiety clearly involve glucocorticoid action, and both the GR and the MR may contribute to these effects. Especially in the hippocampus, it could be shown that under basal conditions the MR is completely occupied and mediates tonic effects of glucocorticoids, whereas under conditions of elevated hormone levels the GR increasingly binds hormone, resulting in a dynamic response of the neurons (Joels and deKloet, 1994). Interestingly, different populations of hippocampal neurons show divergent requirements for glucocorticoids. In the pyramidal neurons of the CA regions, chronically elevated glucorticoid levels lead to damage of the cells (Magarinos et al., 1996). Accordingly, memory impairment in elderly...

Drug Addiction And Drug Abuse Drug Dependence

Although many physicians are concerned about creating addicts, relatively few individuals begin their drug addiction problems by misuse of prescription drugs. Confusion exists because the correct use of prescribed medications for pain, anxiety, and even hypertension commonly produces tolerance and physical dependence. These are normal physiological adaptations to repeated use of drugs from many different categories. Tolerance and physical dependence are explained in more detail later, but it must be emphasized that they do not imply abuse or addiction. This distinction is important because patients with pain sometimes are deprived of adequate opioid medication simply because they have shown evidence of tolerance or they exhibit withdrawal symptoms if the analgesic medication is stopped abruptly.

Psychoneuroendocrinology Introduction

An association between hormones and psychiatric disorders has been long recognized, but it is only in the past few decades that we have reached an understanding of the mechanisms underlying this association. A full account of the myriad ways in which the various endocrine systems influence neurobehavioral function would be beyond the scope of a single chapter. We will therefore focus on examples of promising research directions in this area namely, how the stress and reproductive hormone axes contribute to the pathoetiology of psychiatric conditions, in particular mood and anxiety disorders. Major depression is considered to be a maladaptive, exaggerated response to stress, and although it is accompanied by abnormalities in multiple endocrine systems, it is the hypothalamic-pituitary-adrenal (HPA) axis that is the main component of the physiological stress response that plays the key role. Stressful life events, particularly those related to loss, have a strong causal relationship...

Behavioral Experiments The Example Of Exposure And Response Prevention

Behavioral experiments are an integral part of mainstream cognitive therapy27 and seen as a significant vehicle for producing cognitive and behavioral change. Behavioral experiments are developed to test individual's beliefs about the consequences (emotional, behavioral, and cognitive) of either engaging or not engaging in particular behaviors. Behavioral experiments can be used to help with many of the problems that are experienced by patients with chronic pain. The clearest example of the use of behavioral experimentation has emerged in the therapeutic application of the fear-avoidance model.28,29 III This model proposes that a proportion of chronic pain patients are inactive because they fear that movement will produce physical damage to their bodies, i.e. their behavior is negatively reinforced by the avoidance and reduction of anxiety. Treatment comprises analyses of the patient's avoidance behavior and the development of a hierarchy of feared situations. Patients' predictions...

Sociodemographic factors

The mechanisms of gender differences in FMS are not fully understood. An interaction between biologic, psychological and sociocultural factors has been postulated 41 . Between puberty and menopause, adult women usually show lower responses of the hypothalamic-pituitary-adrenal axis (HPA) and autonomic responses than men of the same age 42 . Female gender is a risk factor for psychologic distress and some mental disorders (affective and anxiety disorder, PTSD) which are associated with FMS. Functional somatic syndromes

Pharmacologic Management of Myofascial Pain and Dysfunction

Summary This article on the pharmacologic management of myofascial pain and dysfunction is from an issue of Oral and Maxillofacial Clinics on the medical management of temporomandibular disorders (TMD). The authors discuss the most frequently used classes of drugs, providing information about their mechanism of action, indications and contraindications, methods of use, and possible adverse side effects. Specific drugs discussed include anti-inflammatory medications, including nonsteroidal anti-inflammatory drugs, and corticosteroids muscle relaxants (other than benzodiazepines) antianxiety medications antidepressant medication opiate narcotic analgesics and local anesthetics. A final section covers the placebo effect. The author emphasizes the importance of understanding the patient in terms of compliance and tolerance of side effects in order to achieve successful management with pharmacologic therapy. 2 figures. 6 tables. 25 references. (AA-M).

Safety of CCK antagonists

If strong opioids are being used, particularly at higher doses, then there may be anxiety at adding a drug that magnifies the analgesic effect that opioid gives in case it also increases other opioid-related side effects, and particularly if it depresses respiration. A study in a primate model and human clinical studies reassure that addition of a CCK antagonist to a strong opioid may increase pain relief but does not cause respiratory depression.

Ethyl Loflazepate Definition

Ethyl loflazepate is a benzodiazepine that has anxiolytic, anticonvulsant, sedative, and skeletal muscle-relaxant properties. Its elimination half-life is 51-103 h. It also produces an active metabolite that is stronger than the parent compound. The symptoms of an overdose of ethyl loflazepate include sleepiness, agitation, and ataxia. Hypotonia may also occur in severe cases. These symptoms occur much more frequently and severely in

Methods In Studying The Regulation And Trafficking Of Transmembrane Transporters

Normal behavior and general health depend on the proper functioning of neurotrans-mitter transporters (Jaber et al., 1997 Beckman and Quick, 2000). Studies show that neurotransmitter transporters play a role in regulating the time course of neurotransmitter levels in the synaptic cleft (Isaacson et al., 1993 Giros et al., 1996 Diamond and Jahr, 1997). Distinct behavioral effects caused by altered transporter function are demonstrated by the actions of cocaine, amphetamine, and alcohol (Amara and Sonders, 1998) by diseases such as depression, obsessive-compulsive disorder, schizophrenia, and epilepsy (Beckman and Quick, 2000) and by the binding of therapeutic drugs to transporters for the treatment of drug abuse and psychiatric disease (Iverson, 2000). These behavioral effects are probably caused by the ineffective regulation of transporters in vivo.

Why Do Pain Patients Seek

Astin2 identified chronic pain as a predictor of CAM use. Other predictors included poorer health status, more education, anxiety, back problems, urinary tract problems, interest in spirituality and personal growth psychology, and having had a change in philosophy of life. Interestingly, dissatisfaction with conventional medicine did not predict the use of CAM. In fact, only about 4 percent of individuals report relying exclusively on CAM.2,3

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Hop (Humulus lupulus) is a flowering vine that grows in Europe, Western Asia, and North America, and is reported to have anxiolytic sedative effects (figure 6.8) (Kowalchik and Hylton 1987). It is an ingredient of beer, but is also consumed as a tea. The female flowers are placed in a pillow to treat insomnia by their fragrance. It has not been well studied, but the responsible agent is believed to be 2-methyl-3-butene-2-ol, because it produces sedation when injected intraperitoneally in mice (Hansel et al. 1980). In humans, one study found no CNS depressant effects when administered orally (Hansel and Wagener 1967). However, the effects produced by inhalation (thus avoiding digestion and absorption issues), have not been studied.

Acidbase Balance And Electrolytes

The phase of primary respiratory alkalosis rarely is recognized in children with salicylate tox-icity. They usually present in a state of mixed respiratory and renal acidosis, characterized by a decrease in blood pH, a low plasma bicarbonate concentration, and normal or nearly normal plasma Pco2. Direct salicylate-induced depression of respiration prevents adequate respiratory hyperventilation to match the increased peripheral production of CO2. Consequently, plasma Pco2 increases and blood pH decreases. Because the concentration of bicarbonate in plasma already is low due to increased renal bicarbonate excretion, the acid-base status at this stage essentially is an uncompensated respiratory acidosis. Superimposed, however, is a true metabolic acidosis caused by accumulation of acids as a result of three processes. First, toxic concentrations of sal-icylates displace 2-3 mEq L of plasma bicarbonate. Second, vasomotor depression caused by toxic doses of salicylates impairs renal...

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To have anxiolytic effects in humans, but no formal studies have been done. In mice, lemon balm has sedative effects in familiar (staircase test) and unfamiliar (two-compartment test) environments, and to have analgesic activity (writhing test) (Soulimani et al. 1991). It also increased the sedative activity of a barbiturate (pentobarbital). Although these effects are promising, further work would be needed to identify active constituents and confirm whether effects occur in humans. Geranium There are several members of the Geranium family (Geraniaceae), some of which have been anecdotally reported to have anxiolytic or sedative effects. However, there is a paucity of research to support the use of this herb as a CNS depressant (Manolov et al. 1977 Tasev et al. 1969). Summary and Conclusions There are several herbs with CNS depressant effects that have been used mostly for anxiolytic and sedative effects historically. This has been supported by neuropharmacological, animal, and human...

Synaptosomal Serotonin Uptake and Its Selective Inhibitors SSRI

Serotonin (5-hydroxytryptamine, 5-HT) occurs in the intestinal wall, where it regulates motility and secretion in blood platelets, where it modulates platelet aggregation and vascular blood flow and in the CNS, where it acts as a neurotrans-mitter in areas of the midbrain. At least seven different receptors for serotonin have been characterized, which mediate a wide variety of different physiological effects. Depression and anxiety are thought to be the result of actions on 5-HT1A receptors in the brain limbic system. Following release from neurons by a depolarizing action potential at central synapses, the activity of 5-HT is terminated by neuronal reuptake. This is performed by a synaptic membrane amine transporter protein, specific for 5-HT, which also co-transports sodium and chloride ions to repolarize the neuronal membrane. Sertraline belongs to the group of selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed group of anti-depressants which have...

Metabolism And Inactivation

Symptoms of hypoglycaemia resulting from increased sympathetic activity include hunger, pallor, sweating, palpitations, anxiety and tremulousness. Other symptoms include headache, visual disturbances such as blurred or double vision, slurred speech, paraesthesia of the mouth, alterations in behaviour, and impaired mental or intellectual ability (Anonymous, 1985). Some patients, especially the elderly or those with long-standing diabetes, may not experience the typical early warning symptoms of a hypoglycaemic attack.

How To Win Your War Against Anxiety Disorders

How To Win Your War Against Anxiety Disorders

Tips And Tricks For Relieving Anxiety... Fast Everyone feels anxious sometimes. Whether work is getting to us or we're simply having hard time managing all that we have to do, we can feel overwhelmed and worried that we might not be able to manage it all. When these feelings hit, we don't have to suffer. By taking some simple steps, you can begin to create a calmer attitude, one that not only helps you feel better, but one that allows you the chance to make better decisions about what you need to do next.

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