Depression No More

Destroy Depression

Destroy Depression is written by James Gordon, a former sufferer of depression from the United Kingdom who was unhappy with the treatment he was being given by medical personnell to fight his illness. Apparently, he stopped All of his medication one day and began to search for answers on how to cure himself of depression in a 100% natural way. He spent every waking hour researching all he could on the subject, making notes and changing things along the way until he had totally cured his depression. Three years later, he put all of his findings into an eBook and the Destroy Depression System was born. The Destroy Depression System is a comprehensive system that will guide you to overcome your depression and to prevent it from injuring you mentally and physically. Read more here...

Destroy Depression Summary


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The writer presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this book are precise.

This ebook does what it says, and you can read all the claims at his official website. I highly recommend getting this book.

Tricyclic antidepressants

TCAs were introduced in the 1950s and became the gold standard treatment for depression before the launch of the first SSRI, fluoxetine, in 1987.42 All current antidepressants rely upon the principle of enhancing monoamine neurotransmission interfering with the presynaptic transporter that reimports the neurotransmitter from the synaptic cleft once released from presynaptic nerve terminals. The classic tricyclic compounds were much less specific, representing a shotgun approach to several neurotransmitter receptors and transporters. Now they are increasingly used as a third-line therapy as the side-effect profile of second-generation SSRI antidepressants is far superior. The leading TCAs are imipramine (23), clomipramine (24), and amitriptyline (25), along with a number of other marketed products.

Major Depressive Disorder And Mood Disorders With Depressive Features Due To Hiv And Aids

Depressive illness is a major cause of distress in patients with HIV and AIDS, and has a severe impact on the quality of life and on medication adherence. Depression is a debilitating condition its symptoms include sadness, pessimism, anhedonia, guilt, and sui-cidality in addition to neurovegetative changes such as impaired sleep and appetite. These latter signs can often be confused with the primary illness, as HIV and AIDS often produce fatigue, anorexia, and wasting syndromes, making the diagnosis of depression challenging in this patient group. Additionally, somatic symptoms of depression may be confused with opportunistic infections, further complicating the differential diagnosis and increasing utilization of physicians' time and services. Major depressive disorder is frequently underdiagnosed and undertreated (Evans et al., 1996-97) in persons with HIV and AIDS. Depression in HIV can be either primary or secondary in nature. When depression develops during the course of HIV...

Major Depressive Disorder

Major depression is one of the most common mood disorders in HIV-seropositive individuals, and it was the earliest reported mood disturbance of HIV. Rates of depression in HIV have varied widely across studies due to differing sample populations, which are difficult to compare as they share little else in common other than their HIV serostatus. The landmark HIV Cost and Services Utilization Study (HCSUS) identified high rates of drug use (50 ), major depression (36 ), anxiety disorder (16 ), and heavy drinking (12 ) among a large representative sample of adults receiving care for HIV in early 1996 (Bing et al., 2001 Galvan et al., 2002). The HCSUS study remains the most well-designed and comprehensive study of the prevalence of psychiatric disorders in an HIV-infected population, although other studies provide snapshots of the high rates of comorbid psychiatric disease in this population (Winiarski et al., 2005). Depression is the most common reason for psychiatric referral among...

Classification and subclassification of major depression disorder and bipolar affective disorder Major depressive disorder The symptom criteria for major depression in DSM-IV-TR and ICD-10 guidelines are very similar (Table 2), although the coding systems are somewhat different.6'7 One difference is that the ICD-10 has a separate, optional subdiagnosis for depression with and without somatic symptoms. The latter is not present in the DSM-IV system. Both sets of guidelines have depressive disorder subdiagnoses for the following Table 2 Abridged DSM-IV criteria for major depressive episode C. The symptoms are not due to a physical organic factor or illness. The symptoms are not better explained by bereavement (although this can be complicated by major depression) Bipolar disorder This describes a spectrum of disorders in which episodes of depression and mania occur, interspersed with periods of normal mood. It is also known as bipolar depression or manic depression. BPAD is characterized by cycles of mania and depression, which cause a person with...

Suicidality in children and adolescents being treated with antidepressant medications

In 2004, the FDA directed manufacturers of all antidepressant drugs to revise the labeling for their products to include a boxed warning and expanded warning statements that alert healthcare providers to an increased risk of suicidality (suicidal thinking and behavior) in children and adolescents being treated with these agents, and to include additional information about the results of pediatric studies.36 The FDA also informed manufacturers that it had determined that a Patient Medication Guide (MedGuide) to be given to patients receiving the drugs to advise them of the risk and precautions that can be taken, is appropriate for these drug products. These labeling changes are consistent with the recommendations made to the agency at a joint meeting of the Psychopharmacologic Drugs Advisory Committee and the Pediatric Drugs Advisory Committee in September 2004.36 The drugs that are the focus of this new labeling language are all those included in the general class of antidepressants...

Antidepressants 603521 Monoamine oxidase inhibitors

The first generations of MAOI antidepressants were hydrazine derivatives, e.g., phenelzine and isocarboxazide, which are probably converted into hydrazine to produce long-lasting inhibition of MAO. Tranylcypromine is essentially a cyclized amphetamine without the covalent bond. Selegiline (15), a propargylamine MAOI, contains a reactive acetylenic bond that interacts irreversibly with the flavin cofactor of MAO resulting in prolonged MAOI activity. Selegiline is still used in clinical practice today, mainly in Parkinson's disease. However, a new patch delivery formulation of selegiline that is proposed to overcome the adverse events associated with MAOIs is in Phase III studies for major depression. Rasagiline (16) is currently marketed for Parkinson's disease in Europe.

Herbs That May Interact with Antidepressant Medications

Tricyclic antidepressants are an older class of antidepressant medications. These drugs, which include amitriptyline (Elavil) and nortriptyline (Pamelor), may be used to treat depression or pain in people with MS. When using these antidepressants, one should avoid St. John's wort, belladonna, henbane, jimson weed, mandrake, and scopolia. St. John's wort also should be avoided when taking the antidepressants known as SSRIs, which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil).

Major Depression

Nunes and Levin (2004) performed a meta-analysis of antidepressant medication efficacy for the treatment of co-occurring depression and SUD. The results indicated that in this patient population, the efficacy of antidepressants is comparable to that seen in patients with depression alone. Studies that required at least 1 week of abstinence before treating the depression yielded larger effect sizes and lower placebo response, suggesting that requiring even at least 1 week of abstinence before initiating medication treatment can successfully screen out transient depressive symptoms. Also, studies that exhibited better depression outcomes as a result of antidepressants also showed decreased quantity of substance use. However, rates of sustained abstinence or SUD remission were low across studies, highlighting the importance of treatment directed at the SUD as well when treating these patients.

Social Cost and Market

Various projections indicate that sales of drugs to treat neurological diseases alone will approach 20 billion by 2007 reflecting an absence of effective treatments for AD and the use of generic L-dopa as first-line treatment for Parkinson's disease. Drugs for the treatment of psychiatric disorders represent a much larger market with sales of the selective 5HT reuptake inhibitor (SSRI) class of antidepressants currently in the 10 billion range. Together the current market for CNS drugs is in excess of 70 billion. Should effective drugs be identified for the treatment of AD, this will account for an additional 6-8 billion in sales given the incidence of these diseases and their long-term nature. At the decade beginning in 2001, the global CNS drug market (including pain) was approximately 50 billion1 with estimates of 105 billion in 2005, 200 billion in 2010, and one estimate2 approaching 1.2 trillion.

Addictionsubstance abuse

Addictions that may be added to these disorders include nymphomania, compulsive shopping, and overeating, all of which, in excess, lead to behaviors that are both illogical and harmful. Returning to the anhedonia context of addiction behaviors, the inability to gain pleasure from normally pleasurable experiences, it is debatable whether the milder forms of addiction are not in fact manifestations of depression. In this context, it is noteworthy that current medications for the treatment of obesity, the impulse dyscontrol related to food consumption, are antidepressants.

The Benefits of Exercise

Along with a healthy diet, exercise is the cornerstone of good health. Physical activity produces a multitude of benefits for your overall health and well-being. Being active helps prevent heart disease and stroke by lowering cholesterol levels and making the heart pump more efficiently. It reduces the risk of dying prematurely, especially of heart disease. Physical activity helps control your weight and prevent obesity, which is a risk factor for high blood pressure and diabetes. Regular exercise also can improve your mood, reduce stress, and relieve depression, not to mention build muscular strength and tone, increase your flexibility, Anabolic steroids are especially risky because they have a number of unwanted side effects. Steroids can cause acne, raise blood pressure, damage the liver, reduce sperm counts, decrease the size of the testicles, increase the size of the breasts, cause erectile dysfunction, and speed up the development of baldness. Anabolic steroids also can cause...

Clinical Trial Issues

Trials for novel antipsychotic drugs usually employ the randomized double blind placebo-controlled design and focus on a reduction in acute psychotic symptoms and the prevention of relapse as primary outcomes.52 Trials usually average 50-60 participants, but large studies have been reported with sample sizes ranging from 200 up to 2000 subjects. Typical trial length is 6 weeks or less, but trials lasting for more than 6 months have provided valuable information on long-term treatment. Several issues are apparent in generalizing the results obtained from clinical trials to the general population of schizophrenics, and to clinical practice. Most large clinical trials for novel antipsychotic medications are carried out in a population of acute exacerbated schizophrenic patients, or in patients that are resistant to available treatments. The trials typically exclude individuals with comorbid psychiatric disorders or those that require continued use of antidepressants or mood stabilizers....

Global depression market

Although depression is a global phenomenon, the global market for antidepressants is unevenly distributed. In 2004, the US antidepressant market accounted for 71 of the global market compared to 24 in Europe and 5 in the rest of the world (mainly Japan). While depression is a mature market, there are several key drivers for its further growth including (1) improvements in the efficacy (2) speed of onset (3) safety tolerability of NCEs and (4) a reduction in remission rates and relapse recurrence. Effective treatment for moderate-to-severe depression includes a combination of somatic therapies (pharmacotherapy or electroconvulsive therapy (ECT)). ECT has been rejuvenated for the treatment for the most severe, melancholic depressions, particularly in the elderly (who are more prone to adverse effects of drugs) and in patients who do not respond to antidepressants.

Disease Basis 60321 Causes of Depression

The etiology of depression and BPAD is unknown. Depression is polygenic in nature with both genetic and epigenetic components, making the use of genetically engineered rodents as models for drug discovery precarious.12'13 Moreover, emerging understanding of the biochemical mechanisms is compromised by the fact that most of the drugs used to treat depression and bipolar disorders (e.g., lithium and antidepressants in general) have complex and ill-defined pleiotypic mechanisms of action.12

Norepinephrine transporter polymorphisms

At least 13 polymorphisms of NET have been identified,20 the functional significance of which is unknown. Alterations in the concentration of NE in the CNS have been hypothesized to cause, or contribute to, the development of psychiatric illnesses such as major depression and BPAD. Many studies have reported altered levels of NE and its metabolites NMN and dihydroxyphenylglycol (DHPG) in the CSF, plasma, and urine of depressed patients as compared with normal controls. These variances could reflect different underlying phenotypes of depressive disorders with varying effects on NE activity. The melancholic subtype of depression (with positive vegetative features, agitation, and increased hypothalamic-pituitary-adrenal (HPA) axis activity) is most often associated with increased NE. Alternatively, so-called atypical depression is associated with decreased NE and HPA axis hypoactivation. In one study, urinary NE and its metabolites were found to be significantly higher in unipolar and...

Genetic and Environmental Origins of Depression and Bipolar Disorder

In the case of major depressive illness genetic factors account for about 30 of the variance and environmental factors play a major role in inducing the illness.22'23 The first direct evidence of the importance of genetic variation in drug response was shown in depressed patients with a short form of the SERT promoter, who had a worse response to SSRIs than those with the long isoform.21 Other genes have been associated with antidepressant treatment and undoubtedly the field of pharmacogenomics and its application to the pathophysiological mechanisms of affective disorders will continue to grow together with the technological advances resulting in the human genome mapping of psychiatric mood disorders.22

Drug Interactions

Antianxiety drugs See Alcohol Anticholinergic drugs Additive anticholinergic side effects and or l antipsychotic effect Antidepressants, tricyclic Additive anticholinergic side effects Barbiturate anesthetics T Chance of tremor, involuntary muscle activity, and hypotension Barbiturates See Alcohol also, barbiturates may l effect due to T breakdown by liver CNS depressants See Alcohol also, l effect of phenothiazines due to T breakdown by liver Hydantoins T Risk of hydantoin toxicity Tricyclic antidepressants T Serum levels of tricyclic antidepressant

Epidemiological Status

It has been estimated that over a lifetime, the global prevalence of depression is 21.7 for females and 12.7 for males who suffer from depression at some point. The APA has estimated that 5-9 of women and 2-3 of men in the US suffer from depression at any given time.9 A Norwegian study showed that 24 of women suffer major depression at some point in their lives and 13.3 suffer from dysthymia, while 10 of males suffer from major depression at some point and 6 suffer from dysthymia.23 Depression in children and adolescents is a cause of substantial morbidity and mortality in this population, being a common disorder that affects 2 of children and up to 6 of adolescents. Although antidepressants are frequently used in the treatment of this disorder, there has been recent controversy about the efficacy and safety of these medications in this population. This led to the US Food and Drug Administration (FDA) publishing a list of recommendations from the Psychopharmacologic Drugs and...

Symptoms of Depression and Bipolar Disorder

It is clear that not all individuals with depression or undergoing manic episodes experience every symptom, with severity varying between individuals and over time. With ever increasing numbers of treatment options available for patients with major depression and BPAD, and a growing body of evidence describing their efficacy and safety, clinicians often find it difficult to determine the best and most appropriate evidence-based treatment for each patient. Therefore, European and US consensus guidelines using statistical methods to synthesize and evaluate data from a number of studies (meta-analyses) have been published with recommendations for the treatment of major depression and bipolar disorder.2-4 These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing, management when initial treatment fails, continuation treatment, maintenance treatment to...

Common Features Of Cognitive Vulnerability Models A Framework Encapsulating Relationships

It seems that individuals become more supersensitive or defenseless to the impact of negative events, and therefore cope less well, once a psychological disorder such as a depressive episode (Hammen, 1991) has been acquired. Such an observation invites comparisons to the weakened state of people who are medically ill. Taken collectively, this line of reasoning suggests that even when individuals have equivalent vulnerability-stress combinations, they can still differ in their trajectories of disorder owing to differences in protective and exacerbating factors.

The role of the placebo response and future clinical trial design

Less than 50 of the active treatment arms showed a significant difference from placebo and the magnitude of the change in the placebo group had a greater influence on the drug-placebo difference than the change in the drug group. The proportion of trials in which antidepressants were shown to give a significantly better HAM-D score than placebo (P

New Methods of Conducting and Evaluating Clinical Trails

One particular initiative designed to evaluate psychiatric medicines is the New Clinical Drug Evaluation Unit Program (NCDEU) funded by the NIMH, which comprises over 1000 clinicians and industry and regulatory personnel. The NCDEU recently addressed the question of whether clinical trials of antidepressants reflect drug potential, and several groups involved in the initiative focused on different aspects of trial design, e.g., heightened placebo effect from such factors as a high dropout rate, poor site selection or poor protocol design, and their effect on masking the potential of active drugs. The NCDEU team reviewed 37 clinical trials, all of which had used the HAM-D. The HAM-D 'depressed mood' items according to DSM-IV-TR ICD-10ACC are defined by the following core criteria37 Also included in this evaluation were the CGS-I severity and CGS-I improvement scores to measure improvement from baseline at the end of week 6 and week 8 of the acute NCE treatment phase. In 13 (35 ) of the...

Adam W Carrico Michael H Antoni Lawrence Young and Jack M Gorman

Because of the many the stressors inherent in HIV infection, psychosocial and biomedical issues must be addressed for successful disease management (Schnei-derman et al., 1994). The anticipation and impact of HIV antibody test notification emergence of the first symptoms of disease changes in vocational plans, lifestyle behaviors, and interpersonal relationships and the burdens of complex medication regimens are all highly stressful. These multiple challenges can create a state of chronic stress that may overwhelm an individual's coping resources and significantly impair emotional adjustment to ongoing demands of the illness (Leserman et al., 2000). Accordingly, HIV-positive individuals are at increased risk for developing an affective or adjustment disorder across the disease spectrum (Bing et al., 2001). Although reductions in mood disturbance have been observed following the introduction of highly active anti-retroviral therapy (HAART Rabkin et al., 2000), the risk of developing...

Studies in MS and Other Conditions

Symptoms of MS that have been investigated in some aromatherapy research are anxiety, depression, pain, and insomnia. For anxiety, studies of variable quality indicate that beneficial effects may be obtained with the use of lavender oil, Roman chamomile oil, and neroli (orange) oil. However, no large, well-designed clinical studies have examined this antianxiety effect. Preliminary information suggests that a lower dose of antidepressant medication may be needed by depressed men when the medication is used in combination with aromatherapy using a citrus fragrance. Lavender in bath water does not appear to relieve childbirth-associated pain. Positive and negative results have been obtained in other studies of aromatherapy and pain. Several fragrances, especially lavender, have been evaluated in sleep studies in animals and humans. Some positive results have been reported, but these studies are of variable quality.

Selective norepinephrine reuptake inhibitors

SNRIs are a class of antidepressants characterized by a mixed action on both major monoamines of depression NE and serotonin. In essence, SNRIs are improved TCAs with less off-target activity, e.g., muscarinic, histaminic and -adrenergic receptors, and MAOI. The combination of inhibition of 5HT and NE uptake confers a profile of effectiveness comparable to TCAs and is reported to be higher than SSRIs, especially in severe depression. SNRIs are purported to be better tolerated than TCAs and more similar to SSRIs without the associated sexual dysfunction seen with the latter. Venlafaxine (38) and milnacipran (4) have been approved so far, and several others are in development. They are active on depressive symptoms, as well as on certain comorbid symptoms (anxiety, sleep disorders) frequently associated with depression. SNRIs appear to have an improved rate of response and a significant rate of remission, decreasing the risk of relapse and recurrence in the medium and long term and...

Catechol Omethyltransferase inhibitors

Expected to have higher levels of transynaptic catecholamines due to a reduced COMT degradation of NE and DA. COMT inhibitors (entacapone (40) and tolcapone (41)) could therefore be beneficial as adjuncts to L-dopa not only in Parkinson's disease but also in the coincident depressive illness associated with rapid cycling.

Treatment of bipolar disorder

Lithium can be a very effective treatment for the depression that occurs in bipolar disorder. Antidepressants, including SSRIs, may also be prescribed. Antidepressant medications used to treat the depressive symptoms of bipolar disorder, when taken without a mood-stabilizing medication, can increase the risk of switching into mania or hypomania, or developing rapid cycling, in people with bipolar disorder. Therefore, mood-stabilizing medications are generally required, alone or in combination with antidepressants, to protect patients with bipolar disorder from this switch. Lithium and valproate are the most commonly used mood-stabilizing drugs today.

Special Issues in Assessment of PTSD

High rates of comorbidity are common in PTSD across diverse samples (e.g., males, females, veterans, sexual assault victims, crime victims, the general population), traumatic events (e.g., military, combat, rape, physical assault, childhood sexual abuse, violence), and patient and nonpatient status (help-seeking patients vs. community-based groups Keane & Kaloupek, 1997 Kessler et al., 1994 Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995). The most commonly diagnosed comorbid disorders are substance use disorders, mood disorders (e.g., major depressive disorder and dysthymia), and anxiety disorders (e.g., panic and phobias). Unlike other forms of depression seen in the absence of PTSD, when combined with PTSD depression often seems unremitting and in many cases appears as a double depression (i.e., major depressive episodes combined with longstanding dysthymia). In many cases, substance abuse may be secondary to PTSD and represent an effort to self-medicate symptoms. The...

CAMP response elementbinding protein CREB

Antidepressants usually take weeks to exert significant therapeutic effects. This lag phase is suggested to be due to neural plasticity, which may be mediated by the coupling of receptors to their respective intracellular signal transduction pathways. Phosphorylated CREB, a downstream target of the cAMP signaling pathway, is a molecular state marker for the response to antidepressant treatment in patients with MDD. The transcriptional activity of CREB is upregulated by antidepressant treatment. Therefore, it has been hypothesized that antidepressant treatment exerts its therapeutic effect by this mechanism.74 NCEs under clinical development in this area and other CNS disorders include ND1251, MEM 1917, and HT-0712 IPL-455903 (92).

Stress Management And Psychiatric Interventions

In a subsequent trial of CBSM, this intervention was tailored to assist HIV-positive persons in managing the emergence of symptoms. HIV-positive MSM who had mild symptoms (category B of the 1993 CDC definition) were randomly assigned to either a 10-week group-based CBSM intervention or a modified wait-list control group. Men in the wait-list control group completed a 10-week waiting period before they were reassessed and invited to participate in a 1-day CBSM seminar. Results indicated that CBSM decreased depressive symptoms, anxiety, and mood disturbance over the 10-week intervention period (Lut-gendorf et al., 1997, 1998). Decreases in depressive symptoms and enhanced social support over the 10-week intervention period partially explained concurrent reductions in HSV-2 IgG antibody titers (Lut-gendorf et al., 1997 Cruess et al., 2000c). Subsequently, a buffering effect of CBSM on EBV IgG antibody titers was observed up to 1 year following CBSM (Carrico et al., 2005a). Similar to...

Stress Induced Hyperthermia

Stress-induced hyperthermia is an autonomic response that occurs prior to and during stress and or stress-related events.66 The first paradigms used group housed mice and evaluated the change in rectal temperature twice at 10min intervals. The procedure produced reliable elevations in animal core temperatures with anxiolytics reducing the stress-induced hyperthermia response. Later studies showed that similarly robust effects could be produced using singly housed mice, allowing for an average of 10 fewer mice per study. Diazepam and chlordiazepoxide had anxiolytic activity in this model,67 although subunit selective GABAA compounds like Zolpidem exhibited only marginal activity.67 5HT1A receptor agonists (e.g., flesinoxan) have a dose-related inhibition of the hyperthermia response, while partial agonists like buspirone produce a lesser effect.66 In general, antidepressants (e.g., imipramine, chlomipramine, and

Primary Nursing Diagnosis

Patients with bulimia generally do not need hospitalization unless they experience severe electrolyte imbalance, dehydration, or rectal bleeding. The bulimia is usually managed with individual behavioral and group therapy, family education and therapy, medication, and nutritional counseling. Work with the interdisciplinary team to coordinate efforts and refer the patient to the physician to evaluate the need for antidepressants and anti-anxiety medication.

Monoamine Transport Inhibitors

The tricyclic antidepressants (TCAs) were originally designed to improve upon the efficacy and side effect profile of the phenothiazine class of antipsychotics. Their pharmacological spectrum was quite well understood in that these compounds interact with multiple brain neurotransmitter systems. The TCAs inhibit reuptake of monoamine neurotransmitters (dopamine (DA), 5HT, and NE) increasing their levels and function in the brain. TCAs include imipramine, desipramine, nortriptyline, amitriptyline, clomipramine, and doxepin (Figure 5). These compounds also interact with a variety of biological targets like muscarinic receptors, complicating their pharmacology and contributing to side effects such as orthostasis, dry mouth, and constipation. Clomipramine is the most effective TCA for panic disorder, OCD, and SAD87 but more selective reuptake inhibitors have displaced the use of the tricyclics due to their improved side effect profile.

Design in a Best Case Scenario

In most research, the strongest test of the causal hypotheses of a cognitive vulnerability model is provided by a true experimental design. The unique importance of experimental designs is that independent variables are directly manipulated, and extraneous factors, including individual differences that are present prior to the study, are controlled. For example, in clinical trials or therapy-outcome studies, different treatment conditions (e.g., cognitive therapy versus pharmacotherapy) represent the manipulated independent variable(s), and participants with some disorder (e.g., all with major depressive disorder) are randomly assigned to the different treatment groups or conditions. The effects of the randomly assigned independent variables (e.g., treatment conditions) are then assessed on measures of the dependent variables (e.g., scores on depression inventories). In true experimental designs, the experimental control over sources of error permits a relatively strong basis for...

Torsades de Pointes

-Correct underlying cause and consider discontinuing drugs that cause Torsades de Pointes (dofetilide, ibutilide, sotalol, amiodarone, quinidine, procainamide, disopyramide, moricizine, bepridil, phenothiazines, tricyclic and tetracyclic antidepressants, vasopressin, imidazoles, pentamidine) correct hypokalemia and hypomagnesemia.

Background and Introduction

The female sex hormone estrogen plays an essential role in reproduction and is important for the overall maintenance of physiologic homeostasis in a woman's body.1'2 During menopause, which occurs in women at an average age of 51, the amount of estrogen produced by the ovaries decreases and this estrogen deficiency causes menstrual periods to become less frequent and then stop.3-5 The loss of estrogen is responsible for many of the uncomfortable symptoms associated with menopause, including hot flashes, mood swings or depression, sleep disorders, vaginal dryness, and urinary dysfunction.6 Osteoporosis or bone loss is another consequence of reduced estrogen levels after menopause.7-11 In women, bone density increases until ages 30-35,12 but slowly declines after menopause.13 Postmenopausal women are also at increased risk for coronary heart disease (CHD)14,15 and Alzheimer's disease,16-18 as a result of estrogen deficiency. The realization that the symptoms reported by postmenopausal...

Description Of Empirical Research

Nary study (Telch, Agras, & Linehan, 2000) and a larger-scale randomized controlled trial (Telch et al., 2001), DBT for binge eating was found to significantly reduce binge eating episodes. Lynch and colleagues propose a similar conceptualization of depression in older adults. Their adaptation of DBT teaches DBT skills and problem-solving strategies to decrease the behaviors maintaining depression in this population and increase more flexible and functional behaviors. In a randomized controlled pilot study of depressed older adults (Lynch et al., 2003), those who received DBT combined with antidepressant medication demonstrated greater reductions on several key measures of depression than individuals who received antidepressant medication alone.

Research Issues and Problems

The former is a structured interview guide with rating scales relevant to the specific diagnostic categories, whereas the latter provides criteria whereby investigators can select relatively homogeneous groups of subjects who meet specified criteria of diagnosis. Although the Research Diagnostic Criteria were used to obtain more precise diagnostic designations, as noted earlier, such diagnostic criteria tended to be quite selective and to leave a significant number of patients undiag-nosed. In the NIMH Treatment of Depression Collaborative Research Program, uniform inclusion criteria, including a diagnosis of Major Depressive Disorder based on the Research Diagnostic Criteria and a score of 14 or greater on a modified seventeen-item Hamilton Rating Scale for Depression were used ''and uniform exclusion criteria were used across sites'' (Elkin, 1994, p. 116). Data were also obtained on a number of patient clinical, demographic, and personality variables that might be related to...

Specificity Of Negative Cognitive Styles To Hopelessness Depression

The hopelessness theory (Abramson et al., 1989) proposes that negative cognitive styles confer vulnerability to HD, specifically, rather than to other subtypes of depression. Supporting this hypothesis, studies have found that negative cognitive styles, both alone and interacting with negative life events, are more strongly related to depressive symptoms hypothesized to be part of the HD symptom cluster (see Table 2.2) than to symptoms not part of the HD symptom cluster (Alloy & Clements, 1998 Alloy et al., 1997 Hankin, Abramson, & Siler, 2001 Joiner et al., 2001 Metalsky & Joiner, 1997) or to symptoms of other forms of psychopathology (Alloy & Clements, 1998). In addition, preliminary analyses based on the first 2 years of prospective follow-up in the CVD project indicated that cognitive risk predicted first onsets and recurrences of HD (as described earlier), but not DSM melancholic depression.

Cognitivebehavioral Interventions

Bryant et al. 49 , treating motor vehicle and industrial accident victims who met criteria for ASD, compared five sessions of non-directive supportive counseling (providing support and education and teaching problem solving skills) with brief cognitive-behavioral treatment (trauma education, progressive muscle relaxation, imaginal exposure, cognitive restructuring, and graded in vivo exposure to avoided situations). At the conclusion of treatment, 8 of the participants in the cognitive-behavioral treatment group and 83 of those in the supportive counseling group met criteria for PTSD. Six months after the trauma, these criteria were met by 17 in the former group and 67 in the latter. There was also a significant reduction in depressive symptoms in the former group compared to the latter.

Rumination As A Mediator And Moderator Of Cognitive Vulnerability To Depression

According to the response styles theory of depression (Nolen-Hoeksema, 1991), individuals who tend to ruminate in response to dysphoria will be at increased risk for experiencing more severe and prolonged depressions than will individuals who tend to distract themselves from their dysphoria. Rumination refers to behaviors and thoughts that focus one's attention on one's depressive symptoms and on the implications of these symptoms (Nolen-Hoeksema, 1991, p. 569), whereas distraction refers to active attempts to ignore depressive symptoms by focusing on pleasant or neutral activities. Several studies have found support for this theory, demonstrating that rumination is associated with a greater likelihood of major depression and longer and more severe episodes of depression (e.g., Just & Alloy, 1997 Morrow & Nolen-Hoeksema, 1990 Nolen-Hoeksema, 2000 Nolen-Hoeksema & Morrow, 1991 Nolen-Hoeksema, Morrow, & Fred-rickson, 1993 Nolen-Hoeksema, Parker, & Larson, 1994 Spasojevic & Alloy, 2001)....

Sleep Wake Cycle and Hypnotics

Pharmacotherapeutic measures are indicated only when causal therapy has failed. Causes of insomnia include emotional problems (grief, anxiety, stress ), physical complaints (cough, pain), or the ingestion of stimulant substances (caffeine-containing beverages, sympa-thomimetics, theophylline, or certain antidepressants). As illustrated for emotional stress (B2), these factors cause an imbalance in favor of excitatory influences. As a result, the interval between going to bed and falling asleep becomes longer, total sleep duration decreases, and sleep may be interrupted by several waking periods.

Cognitive Vulnerabilitystress Interaction And Prospective Development Of Depression

Prospective incidence rate of DSM-III-R major depressive disorder (left) and hopelessness depression (right) as a function of cognitive risk group status and Time 1 stress-reactive rumination. LR Low Risk HR High Risk Lo-SRR Low Stress-Reactive Rumination Hi-SRR High Stress-Reactive Rumination. FIG. 2.1. Prospective incidence rate of DSM-III-R major depressive disorder (left) and hopelessness depression (right) as a function of cognitive risk group status and Time 1 stress-reactive rumination. LR Low Risk HR High Risk Lo-SRR Low Stress-Reactive Rumination Hi-SRR High Stress-Reactive Rumination. Robinson, Garber, & Hilsman, 1995) in predicting depressive symptoms. However, there have been a handful of published studies that have found no support for this hypothesis (Cole & Turner, 1993 Joiner & Wagner, 1995 Tiggemann, Winefield, Winefield, & Goldney, 1991). To date, little evaluation of the vulnerability-stress hypothesis has been conducted with the CVD project data....

Discharge And Home Healthcare Guidelines

Review use of any pain medication prescribed, as well as non-pharmacologic comfort measures for episiotomy, lacerations, and hemorrhoid care. Instruct the patient to report any increase in perineal or uterine pain, foul odor, fever or flulike symptoms, or vaginal bleeding that is heavier than a menstrual period. Sadness or mood swings that persist beyond 4 weeks should be reported to the physician.

Psychological effects

A woman who is sexually assaulted loses control over her life during the period of the assault. Her integrity and her life are threatened. She may experience intense anxiety, anger, or fear. After the assault, a rape-trauma syndrome often occurs. The immediate response may last for hours or days and is characterized by generalized pain, headache, chronic pelvic pain, eating and sleep disturbances, vaginal symptoms, depression, anxiety, and mood swings.

Chlorpromazine hydrochloride

Uses Acute and chronic psychoses, including schizophrenia manic phase of manic-depressive illness. Acute intermittent porphyria. Preanes-thetic, adjunct to treat tetanus, intractable hiccoughs, severe behavioral problems in children, neuroses, and N&V. Treatment of choreiform movements in Huntington's disease. Special Concerns Use during pregnancy only if benefits outweigh risks. PO dosage for psychoses and N&V has not been established in children less than 6 months of age.

Neuropsychological Evaluation

In contrast to the overreporting of symptoms among depressed patients, HIV-seropositive patients with bona fide cognitive impairment may be less aware of their cognitive difficulties (Moore et al., 1997, Rourke et al., 1999b). HIV-seropositive patients with frontal-executive disturbance have few subjective memory complaints, but neuropsychological testing has revealed that in addition to conceptual problem-solving deficits, these patients also have memory deficits. Clinicians need to be aware that these patients will be less accurate in their self-appraisals of cognitive functioning, thus complaints from a collateral source (i.e., significant other, social worker, family member) warrant a neuropsychological evaluation referral.

Gender Differences in Psychopathology

Eysenck (1995) suggested that the dispositional trait underlying schizophrenia is an important ingredient of creativity and noted that the incidence of schizophrenia is higher in men than women. The Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) (American Psychiatric Association, 1994) stated, however, that although men tend to be institutionalized at a greater rate, community-based studies have suggested an equal gender ratio between the men and women who have schizophrenia. As I mention in the chapter on neurotransmitters (chapter 8), enhanced creativity appears to be associated with affective disorders. According to the dSm-IV, bipolar disorders are also equally distributed between men and women. Major depressive disorders, however, are reported more frequently with women. Although the higher incidence of depression in women might be related to an ascertainment-reporting bias (e.g., men are less likely to go for professional help), the incidence of mood...

Clomipramine hydrochloride

Action Kinetics Significant anti-cholinergic and sedative effects as well as moderate orthostatic hypotension. Significant serotonin uptake blocking activity and moderate blocking activity for norepinephrine. tv2 19-37 hr. Effective plasma levels 80-100 ng mL. Time to reach steady state 7-14 days. Metabolized to the active desmethylclomip-ramine.

Desipramine hydrochloride

Action Kinetics Slight anticholi-nergic and sedative effects and slight ability to cause orthostatic hypotension. Effective plasma levels 125-300 ng mL. ti 2 12-24 hr. Time to reach steady state 2-11 days. Response usually seen within the first week.

Multivariate Behavior Genetic Studies of Mood and Anxiety Disorder Symptoms

Study by Kendler et al. (1996 see earlier), who reported that genetic and environmental influences on various subtypes of depressive illness appeared to have different etiologies. Research with adults suggests that genes may act in a nonspecific way to confer risk for a variety of mood and anxiety syndromes, and the particular syndrome manifested depends either on the degree of genetic risk (e.g., as indexed by number of ill relatives) or on individual-specific, nonshared environmental influences. On the other hand, a few studies (reviewed later) suggest that the mood and anxiety syndromes are etiologically heterogeneous, and different sets of genes and or environmental risk factors influence different patterns of symptoms within a diagnostic grouping. In this way, behavior genetic research can contribute to the development of an etiologically based classification of psychopathological syndromes. Following, we review multivariate behavior genetic studies that have contributed to our...

Treatment of insomnia

Despite widespread use of standard hypnotics and sedating antidepressants for chronic insomnia, their role for this indication still needs to be defined by further research 8 . In particular, clinicians must be cautious with antidepressants, which disturb sleep architecture and have various side effects 54, 55 .

Longterm Health Consequences

Among the major problems affecting the victims are psychological difficulties resulting from isolated life in temporary housing. This isolation and the loss of community sometimes have led to tragedies such as suicides and so-called solitary death (unattended death in temporary housing). More than 250 cases of solitary death have been reported among victims of the earthquake. This has become a major social concern among the population in Kobe and a reason to blame the local government. Lack of local health personnel was cited as one of the contributing factors for this tragedy. According to our study on schoolchildren, psychological effects have been marked among girls of a younger age who lost families and friends. Neurotic symptoms decreased after 6 months but depressive symptoms and physical complaints continued even after 12 months 7,8 . A few articles from the Kobe area report a relatively low prevalence of post-traumatic stress disorder (PTSD) among victims compared with data in...

Depression and Suicide Risk

Individuals who are considered a suicide risk in the acute phase require support, containment, and possibly antidepressant medication or hospitaliza-tion. The risk of providing suicidal individuals with exposure is that it may enhance their attention toward the negative aspects of their experience. There is considerable evidence that depressed people have poor retrieval of specific positive memories (Williams, 1996), so depressed individuals may have difficulty reinterpreting their traumatic memories following exposure. in contrast, they may focus on pessimistic views of their trauma and engage in ruminative thoughts that can compound suicidal ideation. These possibilities indicate that depression and suicide should first be managed in seriously suicidal people acute stress reactions can be addressed after these immediate problems are contained.

In Search and Discovery of Potential New Therapeutic Indications

The search for additional indications for modafinil naturally focused on diseases associated with wake deficits and somnolence. The effects of the drug in an animal model of sleep-disordered breathing suggested that modafinil might be effective in reducing sleepiness associated with sleep apnea,50 and this was subsequently demonstrated in the clinic.51-53 Other disorders where somnolence or sedation was concomitant with the disease, e.g., Parkinson's disease,54-56 myotonic dystrophy,57-60 fibromyalgia,61 amyotrophic lateral sclerosis,62 multiple sclerosis,63 cerebral lymphoma,64 or resulting from the side-effects of other medications such as antidepressants,65 antipsychotics,66 dopaminergic D2 agonists,67,68 opioids,69 or valproic acid,70 have also proven to be amenable to treatment with modafinil. Based on the activity of modafinil in the forced swim test in animals, considered as predictive of some antidepressant activity in humans, several preliminary clinical studies demonstrated...

Cerebral Cortex And Swimming

Mesolimbic Mesocortical Pathway

Dopamine (DA) is the major cate-cholamine neurotransmitter of the mammalian CNS, comprising at least 50 of the total CNS catecholamine content. There are four major dopaminergic pathways in the brain. The mesolimbic pathway originates in the ventral tegmental region of the midbrain, near the substantial nigra, and projects to several higher centers of the limbic system, including the amygdala, the frontal and cingulate cortex, the nucleus acumbens, the olfactory tubercle, and the septum. These areas mediate mood changes and cognitive function, and are believed to be the sites where drugs such as cocaine and amphetamines produce their stimulant effects. Other CNS drugs such as antidepressants, which block MAO, and antischizophrenia neu-roleptic drugs, which block DA receptors, may act in these regions. The nigrostriatal pathway projects from the substantia nigra to the corpus striatum, and specifically to the putamen and caudate nuclei, which are implicated in the control of fine motor...

Harold W Goforth Mary Ann Cohen and James Murrough

Mood disorders have complex synergistic and catalytic interactions with HIV infection. They are significant factors in nonadherence to risk reduction and to medical care. Mood disorders associated with HIV include illness- and treatment-related depression and mania, responses to diagnoses of HIV, and comorbid primary mood disorders such as major depressive disorder and bipolar disorder. While persons with HIV and AIDS may have potentially no or multiple psychiatric disorders, alterations in mood are frequent concomitants of HIV infection. They have a profound impact on quality oflife, level ofdistress and suffering, as well as direct and indirect effects on morbidity, treatment adherence, and mortality. In this chapter we will describe the significance of each of the mood disorders and their impact on the lives ofpersons with HIV and AIDS and on their families and caregivers. More detailed discussions of the epidemiology and prevalence of mood disorders are found in Chapter 4....

Impact Phase And Early Actions

Primary aims of these units were to provide pertinent information, relief from the traumatic experience and or crisis intervention to the victims upon their request. The goal of intervention was not simply the prevention of post-traumatic stress disorder (PTSD), but also the management of acute stress reactions, grief, depression, and a host of other maladaptive psychological and behavioral responses according to the individual needs of the victims. Psychological care included mainly listening to the victims while they were referring to their personal experiences and ventilating their emotional overcharge, in addition to prescription of anxiolytic and or antidepressant medication whenever needed. Also, particular emphasis was given to fostering resilience by providing coping skills training at an elementary level and education about the expected stress response, traumatic reminders and normal versus abnormal functioning. Anxiety

Adjustment Disorder with Depressive Features

Treisman and colleagues (1998) have cautioned against dismissing depressive symptoms in a person with HIV as a variant of a normal reaction to a progressive and fatal illness. While many patients diagnosed with HIV enter a transient period of demoralization and sadness related to normal bereavement and loss, most gradually recover and are able to continue life in a meaningful fashion. Leserman and colleagues (2002) documented the impact of psychosocial factors such as stressful life events, depressive symptoms, and lack of social support on HIV illness progression, but these studies have not been limited to the diagnosis of adjustment disorder. Therefore, while providing valuable inferential information on the role of adjustment disorder, they are limited to subjects with more profound depressive illness as well as chronic time spans extending beyond the 3-month diagnostic limit (Evans et al., 1997 Leserman et al., 1999, 2000, 2002).

Parent Child Bonding and Attachment

Studies that examine the cognitive component of the link between interactions such as these and depression, however, are much less common than those assessing the link between parent-child interactions and the development of depression per se.3 McCranie and Bass (1984) reported that among women nursing students, an overcontrolling mother was associated with greater dependency needs, whereas for students who reported both a mother and a father who were overcontrolling, a greater tendency toward self-criticism was found. Likewise, in a study among medical students, Brewin, Firth-Cozens, Furnham, and McManus (1992) reported that higher levels of self-criticism were related to reports of inadequate parenting. This was especially true for individuals who consistently reported high levels of self-criticism. Similar results have been found by Blatt, Wein, Chevron, and Quinlan (1979). Because both self-criticism and dependency are thought to be possible cognitive vulnerability factors, and...

Health Status Questionnaire

The Health Status Questionnaire 2.0 (HSQ 2.0), an assessment from Pearson Assessments, is an outcomes measurement tool that yields a profile of scores on eight health attributes, an index of health status change, and an indication of risk for the presence of a depressive disorder. This instrument is designed to be easily administered via self-report, personal interview, or telephone interview. Designed as a general outcomes measure to be used in all settings that provide primary or mental health care services, it captures aspects of both physical and emotional health.

Physiological Effects

Severe, immediate effects appear to be rare, but they do occur altered mental status, convulsions, hypo- or hyperthermia, severe changes in blood pressure, tachycardia, coagulopathy, acute renal failure, hepatotoxicity, rhabdo-myolysis, and death have all occurred (Demirkiran, Jankovic, & Dean, 1996 Khalant, 2001). There are numerous case reports of a single dose of MDMA precipitating severe psychiatric illness. MDMA probably induces a range of depressive symptoms and anxiety in some individuals for that reason, people with affective illness should be specifically cautioned about the dangers of using MDMA (Cohen, 1998 McCann, Ridenour, Shaham, & Ricaurte, 1994 McDowell, 1998).

Selective serotonin reuptake inhibitors SSRIs

While the primary mode of action of TCAs was thought to be inhibition of NE reuptake, a reassessment of the actions of the diverse antihistamines on the reuptake of various biogenic amines, especially 5HT, led to the hypothesis that an increase in brain noradrenergic function caused the energizing and motor stimulating effects of the TCAs, but that an increase in 5HT function was responsible for their mood-elevating effects.42 Structural analogs of diphenhydramine were sought as novel antidepressants. The phenoxyphenylpropylamine pharmacophore was used to identify fluoxetine (1), the first SSRI.33 The phenomenal success of fluoxetine (1) as an antidepressant led to the identification of other SSRIs, e.g., paroxetine (2), citalopram (34), fluvoxamine (3), and sertraline (35).

Differential Diagnosis

(up to 25 of patients meet criteria for a current depressive disorder and up to 70 have elevated scores on depression rating scales), and cognitive dysfunction (up to 82 impairment on some measures) (Crone and Gabriel, 2003). Compared to patients with HIV alone, patients with comorbid HIV and hepatitis C are more likely to have disturbances in executive function and dementia (Ryan et al., 2004). The pattern of cognitive impairment associated with hepatitis C is similar to that of HIV. Patients with mild liver disease tend to have impairment in attention and concentration, and patients with more severe liver fibrosis have problems with learning, psychomotor speed, and cognitive flexibility. Patients with end-stage liver disease and cirrhosis experience superimposed delirium ( hepatic encephalopathy ). Combination pegylated interferon alpha 2a and ribavirin treatment for hepatitis C is well known to be a cause ofdysphoria, suicidal ideation, anxiety, sleep disturbance, fatigue, mania,...

Animal Models of Depression

Animal models of depression26-28 and BPAD have proved to be of considerable value in elucidating basic pathophysiological mechanisms and in developing novel treatments. However, the challenges faced by psychopharma-cologists in modeling human affective disorders in experimental animals are fraught with difficulties. As new targets emerge through hypothesis-driven research or serendipity, the challenge is to link the mechanism to a clinical complex and heterogeneous disorder. Consequently, much of the animal research today is framed around physiological and neurobiological phenomena that may bear little resemblance to the disease state. However, Matthews etal.29 argue that the poverty of reliable clinical science feedback needs to be addressed first, which would aid future model development. Table 6 outlines the pros and cons of the classical models of depression (e.g., Porsolt forced swim test (FST), tail suspension test, olfactory bulbectomy, learned helplessness, chronic mild...

Alkene oxide substrates

Drug Metabolism

A number of neurotropic agents contain a conjugated alkene group incorporated in an iminostilbene (19, Figure 9 X NR) or dibenzosuberene (19, Figure 9 X CHR or C CHR) ring system. Examples include the anticonvulsant carbamazepine and the antidepressants protriptyline and cyclobenzaprine. As a rule, these drugs are oxidized by cytochrome P450 to the corresponding epoxide (20, Figure 9), but hydration to the dihydrodiol (21) is usually low for reasons of unfavorable positioning in the catalytic site (for a review see5).

Ipt The Matrix For

Our initial treatment approach was standard IPT, a proven efficacious treatment for depression that includes abnormal grief as a possible problem area. Complicated grief resembles major depression in symptoms of dysphoric affect, guilty ruminations, suicidality, and social withdrawal so it seemed reasonable that IPT would be an efficacious treatment. Surprisingly, though, we found that standard IPT did not appear to sufficiently reduce CG symptoms in many patients. Consistent with this observation, CG appears to be only minimally responsive to antidepressant medication. Lack of efficacy of standard treatments for depression fit with a growing body of data indicating that CG is a separate condition, distinct from major depression (Prentice & Brown, 1989 Prigerson, Frank, et al., 1995). One difference in CG is the presence of symptoms resembling PTSD (Jacobs, Mazure, & Prigerson, 2000). CGT thus includes techniques to target the separation and traumatic distress symptoms related...

Overview and Comparison of Drug Classes

Historically the treatment of ADHD relied on agents affecting monoaminergic neurotransmission, and largely consisted of the stimulants, antidepressants, and antihypertensive agents (Table 1).1'65 The primary pharmacological treatment for ADHD continues to be the use of stimulants, particularly methylphenidate and amphetamines. Methylphenidate has long been the leading treatment for ADHD however it has a short duration of action and a midday dose is required. In schoolchildren, this necessitates dosing during the school day and contributes to poor compliance and social stigma. The importance of avoiding this midday dose is underscored by the success of Concerta (J & J), a novel formulation of methylphenidate designed to provide both rapid and sustained release, and Adderall XR (Shire), a QD formulation of mixed amphetamine salts.

Treatment Of Psychiatric Disorders In The Context Of

Specific considerations should be given to patients with HIV and severe, chronic mental illness. Approximately 2.6 of persons in the United States meet the criteria (based on duration, disability, and diagnosis) for severe mental illness (SMI) in a given year (Kessler et al., 1996). Most individuals with SMI have schizophrenia, bipolar disorder, and major depressive disorder

Recovery after a Stroke

After a stroke, many people experience feelings of depression (see page 345). They may feel frustrated or isolated, especially if they have not been able to return to their usual routine or if they are having problems communicating with others. Symptoms of depression include sleeplessness, indifference, and withdrawal. For most of these people, the depression is temporary. It may be helpful for the person to join a support group to share experiences and information with others who are in a similar situation. Talking with a psychiatrist or another mental health professional may help the person cope with and overcome his or her depression. To treat prolonged depression, a doctor may prescribe antidepressant medications such as tricyclic antidepressants, serotonin reuptake inhibitors, monoamine oxidase inhibitors, or bupropion.

Severe Mental Illness And Hiv Risk

Bipolar disorder (previously called manic-depressive illness) is an illness that impacts the affective domain of one's mental health and accounts for many patients with severe mental illness. Often presenting with psychosis, this condition may be misdiagnosed as schizophrenia when severe. In the classic descriptions of manic-depressive illness, patients spend extended periods of time depressed, usually weeks to months at a time, followed by shorter periods when they are in an elevated, euphoric, and energized state, referred to as mania. Most often, patients cycle from one type of mood to the other, these cycles often interspersed with periods of normal moods but occasionally with intermediate mixed states that have features of both depressive and elevated mood states simultaneously or in rapid succession. The emotions and emotional changes in patients with bipolar disorder run their lives and can have a strong effect on their attitude toward treatment from minute to minute (Treisman...

The First Step The Discovery of Adrafinil

Using a battery of classical behavioral tests in mice, the stimulant potential of adrafinil was confirmed, based on a dose-dependent increase in locomotor activity, antagonism of barbital-induced narcosis, and a decrease in the duration in the forced swim test.5 Interestingly, adrafinil did not display any of the other effects normally observed with amphetamine and nonamphetamine (methylphenidate-like) stimulants it failed to induce changes in core temperature did not produce stereotyped or climbing behavior and did not increase lethality in aggregated mice. Adrafinil was also devoid of other effects usually seen with classical antidepressants. It thus had no interaction with reserpine-, oxotremorine-, or apomorphine-induced hypothermia (although it slightly potentiated yohimbine-induced toxicity) lacked peripheral sympathetic effects (lack of mydriasis, salivation, piloerection, or antagonism of reserpine-induced ptosis) and lacked peripheral anticholinergic effects (lack of...

Pharmacological Treatment of Chronic Cocaine Addiction

Clinical researchers have tried to identify drugs to reduce cocaine craving and prevent relapse. Numerous drugs looked promising in initial open-label trials but did not prove efficacious in subsequent placebo-controlled studies. These pharmacological treatments have included dopaminergic agonists (e.g., monamine oxidase inhibitors, amantadine, mazindol, methylphenidate, pemoline, bromocriptine, L-dopa, and pergolide), neurotransmitter precursors (L-tyrosine, L-tryptophan, and multivitamins with B complex), carbamazepine, and antide-pressants, including desipramine and fluoxetine. In a meta-analysis examining 45 clinical trials examining mostly antidepressants, carbamazepine, and dopa-mine agonists, no significant impact of drug treatment was found, regardless of the type of drug or dose used (Lima, Soares, Reisser, & Farrell, 2002).

The Cognitive Vulnerabilitystress Models Of Unipolar Depression

In Beck's (1967) model of depression, negative self-schemata organized around themes of failure, inadequacy, loss, and worthlessness serve as vulnerabilities for the onset and exacerbation of depression that are activated by the occurrence of stressful events relevant to the content of the self-schemata. Such negative self-schemata are often represented as a set of dysfunctional attitudes in which the individuals believe that their happiness and self-worth depend on being perfect or on others' approval. Consistent with cognitive science operationalizations of the schema construct (e.g., Alba & Hasher, 1983 Taylor & Crocker, 1981), Beck (1967) hypothesized that depressive self-schemata influence the perception, interpretation, and recall of personally relevant experiences, thereby leading to a negatively biased construal of one's personal world. When activated by the occurrence of negative events, depressive self-schemata lead to the onset or exacerbation of depressive symptoms through...

Depressed inpatients outpatients

A convenience sample of 39 inpatients and 19 outpatients from the San Diego VA diagnosed with current Major Depressive Episode. Participants were 78 male with an average age of 46 (range 20-70). While the study demonstrated strong sensitivity of the QWB-SA to depression severity, the results reported here are for baseline only. Data is reported on inpatients and outpatients separately, with no data on separate QWB-SA component scores. 1. Pyne, J.M., Sieber, W.J., David, K., Kaplan, R.M., Rapaport, M.H., and Williams, D.K. (2003). Use of the Quality of Well-Being - Self-Administered version (QWB-SA) in assessing health-related quality of life in depressed patients. Journal of Affective Disorders, 76, 237-247. 1. Pyne, J.M., Sieber, W.J., David, K., Kaplan, R.M., Rapaport, M.H., and Williams, D.K. (2003). Use of the Quality of Well-Being - Self-Administered version (QWB-SA) in assessing health-related quality of life in depressed patients. Journal of Affective Disorders, 76, 237-247.

Methodological Challenges Of Vulnerability Research In Bipolar Spectrum Disorders

Events or cognitive styles in childhood or early adolescence. No study to date has done this. Third, as a consequence of many mood swings and interepisodic symptoms, many bipolar individuals lead chaotic lives. This, in turn, increases the likelihood that they actually contribute to the occurrence of stressors in their lives through poor judgment, poor coping skills, and other symptoms (Alloy, Abramson, Raniere, et al., 1999 Hammen, 1991 Johnson & Roberts, 1995). To deal with this problem, some investigators of life events and bipolar disorders have included only those events that are independent of the participants' behavior, and we note these studies in our review. Given these methodological challenges for vulnerability research, much work remains to be done in investigating the role of cognitive styles and life events as vulnerabilities for bipolar spectrum disorders.

Case Example Illustrating Common Obstacles

Sam was a 34-year-old unemployed European American male with a college education. He had a long history of alcohol and drug abuse, starting with his first drink at the age of 8. In addition, Sam had an extensive history of being physically and sexually assaulted. At the time he sought treatment, he had already been abstinent from alcohol and drugs for 6 months, due to a previous traumatic incident. Thus, at his initial assessment, Sam met criteria for PTSD, major depressive disorder, and polysubstance dependence in early full remission. The index event that brought him into treatment this time was a more recent assault, which included a sexual assault. The CPT treatment then began, and during the first session, the therapist explained the symptoms of PTSD, gave a rationale for treatment, described the course of the therapy, and explained the first homework assignment, which was to write an Impact Statement about the meaning of the index assault.

A Putative number of transmembrane domains

Transporters act as reuptake sites for neurotransmitters, and the pathophysiology of major depressive disorders is believed to involve serotoninergic systems, including SERTs. SERTs, for example, are reduced in depression, and various genetic studies implicate these transporters in the disease.388 Long-term exposure to reuptake inhibitors causes downregulation, as one might expect. However, this effect is reversible in 48 h. There is also a remodeling that appears to be necessary for therapeutic utility, as antidepressants such as SSRIs take from 2 weeks to 4 weeks to achieve their full effects.

Retrospective Studies

An improvement over retrospective chart reviews is represented by retrospective studies that actually conducted interviews with or administered questionnaires to bipolar individuals regarding their past experiences of life events. Only some of these studies assessed the independence of the events from bipolar individuals' behavior and differentiated manic from depressive episodes. Glassner, Haldipur, and Dessauersmith (1979) retrospectively interviewed 25 bipolar patients and their relatives about the patients' life events preceding their first and most recent episodes of disorder. They found that 75 of first episode and 56 of subsequent episode patients reported a stressful event prior to onset. Utilizing the same methodology with 46 bipolar patients and their relatives, Glassner and Haldipur (1983) reported that 64 of late onset (onset after age 20) versus 23 of early onset bipolar patients reported a stressful event preceding their initial episode. Bidzinska (1984) reported that...

As Sources Of Distress

The treatment of fatigue is an important area for psychiatrists treating patients with HIV, as it can directly improve quality of life, alleviate distress, and improve functioning. Breitbart and colleagues (2001) and others have described effective and safe treatments with either methylphenidate or pemoline. The role of antidepressants, androgenic steroids, and modafinil in treating fatigue has also been examined (Rabkin et al., 2004a, 2004b). Further discussion of HIV-associated fatigue can be found in Chapter 16.

Unmet Needs for Treating Bipolar Disorder

More than 2 million adults in the United States are living with BPAD. Less than half of these patients achieve a response to existing therapy that allows them to lead active lives, while many continue to suffer frequent recurrences of mania and depression. Lithium has been the treatment of choice for BPAD, as it can be effective in smoothing out the mood swings common to this disorder. Its use must be carefully monitored, as the range between an effective dose and a toxic one is limited. Valproate is approved for first-line treatment of acute mania. Other anticonvulsants used for BPAD include lamotrigine and gabapentin together with second-generation antipsychotics.

Cognitive Styles Associated with Bipolar Spectrum Disorders

Three studies have examined the cognitive patterns of currently manic or hypomanic individuals and obtained results consistent with the importance of distinguishing between explicit and implicit assessments of cognitions. Bentall and Thompson (1990) compared students who scored high versus low on a hypomania scale on an emotional Stroop test in which the participants named the ink colors of depression-related and euphoria-related words written in different colored inks. Consistent with prior findings on the emotional Stroop task with unipolar depressed patients (Ingram et al., 1998), Bentall and Thompson found that hypomanic students took longer to color name the depression-related words, but not the euphoria-related words. These findings were replicated by French, Richards, and Scholfield (1996), even after controlling for the effects of anxiety on Stroop task performance. Lyon, Startup, and Bentall (1999) administered Bentall and Thompson's (1990) emotional Stroop test, Winters and...

Current Treatment of Irritable Bowel Syndrome

The goal of IBS treatment is to provide rapid, sustained, global relief of the multiple symptoms of IBS with a single, effective, well-tolerated agent. However, because of the complexity and overlap of the neural circuitry of the gut and CNS and potential occurrence of multiple pathophysiological disturbances, it has proved difficult to identify a single optimal therapeutic target. The choice of therapy has traditionally been based on the primary bowel symptom. Because of the multiplicity of symptoms associated with IBS, patients often need to use a variety of agents to achieve relief. Traditional treatment approaches rely on a combination of dietary changes, bulking agents, laxatives, antispasmodics, antidiarrheal agents, and antidepressants. These therapies, in general, target individual symptoms and therefore do not address the multiple-symptom complex.142 Clear-cut evidence for their use in patients with IBS is lacking. An evidence-based review of IBS therapies concluded that,...

Unmet Medical Needs

In addition to their limited efficacy, many of the traditional prescription and OTC medications used for patients with IBS can aggravate IBS symptoms.19 The extent of the problem with traditional medications was indicated by an on-line survey of 668 subjects with physician-diagnosed IBS, 504 (75 ) of whom had IBS-C.189 Participants reported an average of 3.3 + 2.7 adverse effects from their IBS medications.189 The likelihood of experiencing a severe adverse event was greater with prescription drugs (antidepressants, 16 antispasmodics, 11 laxatives, 9 ) than with OTC agents (laxatives, 8 fiber supplements, 6 ).189 For 74 of participants, adverse events were the main reason for discontinuing treatment. Respondents also reported missing work or school and refrained from taking part in social or athletic activities due to the adverse effects of IBS medications.189

Figure 64 Chemical structures of iproniazid and other MAO inhibitors

If one considers the first wave of antidepressant drug development as starting with classic pharmaceutical research and resulting in the tricyclic antidepressants, and the second wave starting with clinical observations and yielding SSRIs such as fluoxetine, then the current or third wave would start with pathophysiological, pharmacogenomic, or etiological models and will hopefully yield a new generation of therapies that extend beyond monoamine therapeutics. Representative new approaches are listed below433'434

Prevalence of Cardiovascular Diseases

Globally, CVD represents the second greatest disease burden in men and third largest disease burden in women. The percentage of disability-adjusted life years (DALY) lost was nearly 7 for men compared to human immunodeficiency virus acquired immune deficiency syndrome (HIV AIDS) which represented nearly 7.5 of the DALY lost worldwide. For women, the primary contributors to DALY lost were unipolar depressive disorders and HIV AIDS which represented 8.4 and 7.2 , respectively while CHD represented only 5.3 .8,9 Cardiovascular disease accounts for nearly 10 of the DALY lost in developing countries and nearly 18 in industrialized countries. The DALY is an indicator of the total burden of the disease and reflects the healthy years of life lost to a specific disease.

Endogenous Mental Disease Acute Psychotic Episodes

Excited delirium may also occur in the absence of stimulant drugs such as cocaine, methamphetamine or alcohol in individuals with endogenous mental disease. Clinically, these are usually referred to as acute psychotic episodes, and tend to occur in individuals with schizophrenia, schizoaffective disorders or delusional disorders. Acute psychotic episodes happen both in and out of mental facilities. They may occur because of the patient's discontinuance of medications or development of tolerance to the medications. If the episode occurs outside a mental health facility, the police are usually called on to deal with the individual if inside the facility, it is nursing or support personnel. Sudden death can be caused by either the physiological effects of catechola-mine and hypokalemia following the struggle or a combination of these effects and the effects of the medications the patient is or was on. Many patients, nowadays, are on medications, some of which have a cardiotoxic...

Cognitive Vulnerability Stress Prediction of Bipolar Mood Episodes

Hammen, Ellicott, Gitlin, and Jamison (1989) tested Beck's (1987) event congruence, vulnerability-stress hypothesis in 22 unipolar and 25 bipolar patients. Specifically, the patients were categorized into sociotropic and autonomous subtypes and then followed for 6 months with independent assessments of symptoms and life events. Based on Beck's (1987) theory, it was predicted that patients who experienced a preponderance of negative life events that were congruent with their personality style (interpersonal events for sociotropic patients and achievement events for autonomous patients) would be more likely to experience an onset or exacerbation of symptoms. Hammen et al. obtained support for the event congruence hypothesis only in the unipolar patients. However, there were trends consistent with the hypothesis for the bipolar patients as well and Hammen et al. suggested that a longer period of follow-up might be needed to obtain the effect in bipolar patients. Indeed, in a later study,...

Proportion of Negative Events

Residualized change in Halberstadt Mania Inventory (HMI) scores at Time 2 as a function of attributional style for positive events and the proportion of negative life events (total negative events total events) experienced. High ASQ-PC refers to a more internal, stable, global attributional style for positive events and Low ASQ-PC is a less internal, stable, global attributional style for positive events. Adapted from Cognitive Styles and Life Events in Subsyndromal Unipolar and Bipolar Mood Disorders Stability and Prospective Prediction of Depressive and Hypomanic Mood Swings, by L. B. Alloy, N. Reilly-Harrington, D. M. Fresco, W. G. Whitehouse, and J. S. Zechmeister, 1999, Journal of Cognitive Psychotherapy An International Quarterly, 13, p. 35. Adapted with permission from Springer Publishing Co.

Prevention Strategies

An adequate suicide history includes an assessment of present suicidal ideas and plans by asking direct and open-ended questions. Since past suicide attempts are, along with hopelessness, the strongest predictors of future completed suicide, the clinician must always ask about previous attempts and elicit a family history of suicide. Timely treatment of the psychiatric disorders associated with heightened suicide risk could prevent suicide in individuals at risk. Antidepressants should be prescribed to depressed and anxious suicidal patients, but it is important to remember that anhe-donia and psychomotor retardation lift first when these are prescribed, and hopelessness, dysphoria, and suicidal behavior take longer to improve (Mann, 2005). Psychotherapy can reduce a sense of alienation, provide symptomatic relief, increase networking, and promote conflict resolution. Psychotherapy modalities that can help suicidal patients include interpersonal, cognitive-behavioral, psychodynamic,...

Pharmacotherapy For Dually Diagnosed Patients

During the past decade, the literature regarding when to prescribe pharmacotherapy for dually diagnosed patients has changed considerably. Previous consensus in the field reflected reluctance to prescribe psychotropic medications in these populations. However, this consensus was based on earlier, methodologically flawed studies. For example, older studies examining the use of antidepressants in alcoholics often did not use standardized methods to assess the depressed population, had inadequate dosing or duration of antidepressants, and sometimes measured mood or drinking outcomes, but not both (Ciraulo & Jaffe, 1981). More recent studies have demonstrated that phar-macotherapy can improve outcomes for the psychiatric disorder and sometimes for the SUD as well (Greenfield et al., 1998 Schubiner et al., 2002). Still, it is important also to incorporate psychosocial treatments directed at improving substance use outcomes when treating dually diagnosed patients. The literature on...

Shortcomings of current therapy

Dextroamphetamine is a category D drug methamphetamine, modafinil, and mazindol are category C drugs and methylphenidate has no adequate animal studies and manufacturer suggests use if benefits outweigh risks. Pemoline is the only category B stimulant, and it carries a small, although significant, risk of hepatotoxicity. When the potential for teratogenicity is unknown, the benefits to the patient have to be weighed against the potential risks to the fetus for many patients, it is suggested that stimulant use be discontinued or reduced during attempts at conception and for the duration of the pregnancy 115 . For the treatment of cataplexy, GHB is a pregnancy category B drug, while the antidepressants, such as venlafaxine, atomoxetine, and fluoxetine are category C drugs. As with stimulant use during pregnancy, the benefits to the patient have to be weighed against potential risks to the fetus.

Attention DeficitHyperactivity Disorder

Although not as well-studied as stimulants, nonstimulant medications that lack abuse potential are possible alternatives in the treatment of ADHD. In adult populations, only bupropion (Wilens et al., 2002), desipramine (Wilens et al., 1996), and atomoxetine (Michelson et al., 2003) have undergone double-blind, placebo-controlled study and demonstrated effectiveness in the treatment of hyperactivity and inattention. However, none of these trials included patients with active SUDs. To our knowledge, the only published trials of antidepressants as treatment for ADHD in populations with a current co-occurring SUD are a single-blind trial of bupropion for adult ADHD and cocaine abuse (Levin, Evans, McDowell, Brooks, & Nunes, 2002), and an open-label study of venlafaxine in patients with ADHD and alcohol use disorder (Upadhyaya, Brady, Sethuraman, Sonne, & Malcolm, 2001). Both showed improvements in hyperactivity and inattention, as well as improved substance use outcomes. However, these...

Drugs Prescribed For Gun Shot Wounds

Common drugs of abuse encountered in death cases include ethyl alcohol, barbiturates, pain killers, stimulants such as cocaine and methamphetamine, heroin, morphine, LSD, marijuana, and antidepressants. These drugs can readily be discovered through routine postmortem drug screens by testing blood, urine, or other tissues. Chemicals such as carbon monoxide and cyanide may be involved. Blood and urine are not usually tested for these chemicals however, the circumstances of death may lead the examiner to suspect these chemicals as a cause of death (such as carbon monoxide in fire). Special samples such as hair may be needed to test for cases of heavy metal poisoning, such as arsenic.

Fields Of Expertise Within Toxicology

In addition to the necessity of continuous energy generation, the heart must maintain rhythmic function throughout its lifetime. Substances such as cocaine and cyclopropane that decrease the reuptake of norepinephrine after its release from noradrenergic neurons are prone to cause fatal arrhythmias. Additionally drugs that modify plasma membrane ion channel function can also cause arrhythmias. More recently cardiotoxicity from drugs that prolong the QT-interval has been reported. Such drugs include several antimicrobial agents, antidepressants, and anti-migraine agents. This broadly based toxicological effect has clear implications for the drug discovery process 20 .

Sequential Parallel and Integrated Treatment Models

In sequential treatment, the more acute condition is treated first, followed by the less acute co-occurring disorder. The same staff may treat both disorders, or the less acute disorder may be treated after transfer to a different program or facility. For example, a manic patient with a cocaine use disorder needs mood stabilization before initiating substance abuse treatment. Conversely, a patient with major depression and alcohol withdrawal delirium is not in a position to discuss treatment adherence to antidepressant medication. Instead, this issue is best addressed when the patient is more stable. Although sequential treatment has the advantage of providing an increased level of attention to the more acute disorder, a typical disadvantage of this model is that patients are often

Social Anxiety Disorder

The ECNP consensus meeting on SAD72 recommended the conventional double-blind, placebo-controlled, randomized group comparison study to demonstrate efficacy in SAD. Since the latter can be either generalized or nongeneralized, studies investigating efficacy in this disease concentrate on generalized SAD with symptoms of at least four distinct social situations. As in other anxiety disorders, there is a larger drug versus placebo effect seen in patients in the severe to moderate SAD subgroups, as based on scores of 50-70 in the Liebowitz social anxiety scale (LSAS). A potential confounding issue in SAD trials is the presence or absence of comorbid disease. For example, patients suffering from major depressive disorder over the previous 3-6 months should be excluded from the SAD trial if the study will include a potential antidepressant so the results can be deemed relevant for the general population with SAD rather than those with comorbid MDD. The LSAS is the current gold standard...

Treatment Considerations

S., Zhang, C., Cohen, P., & Whiteman, M. (2002). Drug use and the risk of major depressive disorder, alcohol dependence, and substance use disorders. Arch Gen Psychiatry, 59, 1039-1044. Darke, S., & Ross, J. (2000). The use of antidepressants among injecting drug users in Sydney, Australia. Addiction, 95, 407-417.

Other Sedatives and Hypnotics

The use of sedating antidepressants such as Desyrel (trazodone) and Elavil (amitriptyline) to treat insomnia at dose levels lower than are effective for the treatment of depression, such as the use of sedating antihistamines for this indication, is clinically problematic, since these agents may be both less effective and more likely to produce undesirable side effects (especially in producing daytime sedation) than the use of benzodiazepines in this indication (Mendelson et al., 2001).

Subconscious Incubation

EEG studies of autistic patients also suggest that some of these people might be in chronically high states of physiological arousal (Hutt, Hutt, Lee, & Ounsted, 1965). In contrast, studies of physiological arousal in depression, as determined by EEG power analysis, have revealed that depressed patients have reduced arousal that is altered with treatment (Knott, Mahoney, & Evans, 2000 Nieber & Schlegel, 1992). If, as I suggested previously, lower levels of physiological arousal allow people to increase the extent of their concept representations and increase their cognitive flexibility, then it would follow that people with depression might have a propensity to be creative and patients with autistic spectrum disorder would tend to have limited creativity. Functional imaging studies of patients with depression can provide some insight into the mechanisms by which depression might provide the basis for creative inspiration. Many such studies have shown that depression is associated with...

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