Depression Holistic Treatments

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. Continue reading...

Destroy Depression Summary


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Tricyclic Antidepressants

This class of medications was originally developed for the treatment of depression, for which there are now better choices available. However, several systematic reviews and meta-analyses have concluded that tricyclic antidepressants are effective in relieving pain in a number of chronic pain conditions, in doses that are much lower than would have been used for mood elevation 8, 13-15 . The number needed to treat (NNT)1 is generally in the range of 2.1-2.6 (Table 9.1). TCAs are Table 9.1 Average of number needed to treat among placebo-controlled trials examining tricyclic and SNRI antidepressants for neuropathic pain for benefit (50 reduction of pain), minor and major harm. Reprinted with permission of Pulses Publishing (Lynch and Watson 2006 8 ). Table 9.1 Average of number needed to treat among placebo-controlled trials examining tricyclic and SNRI antidepressants for neuropathic pain for benefit (50 reduction of pain), minor and major harm. Reprinted with permission of Pulses...

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...

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 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...

Other Antidepressants

Analgesics in randomized controlled trials. The two antidepressants available from this group include venlafaxine (Effexor) and duloxetine. Both are effective antidepressants with strong inhibition of 5-HT and NA reuptake. This balanced neurotransmitter profile is similar to that found with the TCAs.

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...

Predictors of Response to Cyclic Antidepressants

Several clinical and demographic factors have been studied as possible predictors of response to treatment of acute depression in the elderly. Age at onset of illness has produced conflicting results. In one study, patients with early-onset depressive disorder who received treatment with nortriptyline and interpersonal therapy achieved remission of the index episode more slowly (Reynolds et al. 1998) in another study, later age at onset was the strongest predictor of slow recovery (Alexopoulos et al. 1996). In the latter study, age and chronicity of episode were also significantly associated with time to recovery. In a study conducted by Flint and Rifat (1997), high baseline anxiety level was associated with delayed response (median of 5 weeks vs. 4 weeks for patients with low anxiety scores), whereas hospitalization for the index episode of depression and attempted suicide predicted shorter time to response. Cognitive dysfunction also may affect treatment response. Kalayam and...

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.


There are many side effects associated with the use of the tricyclic antidepressants (TCAs) (e.g., amitriptyline), that are relevant to the ability to drive, such as blurred vision, slow visual accommodation, disorientation, and eye-hand coordination the most important are the induction of drowsiness,

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.

Affective disorders depression and bipolar disorder

Depressive disorders involve all major bodily functions, mood, and thoughts, affecting the ways in which an individual eats and sleeps, feel about themselves, and think. Without treatment, depressive symptoms can last for weeks, months, or years. Fortunately, however, appropriate treatment can help most individuals suffering from depression. An increasing number of treatment options have become available over the past 20 years for individuals with major depression disorder (MDD), accompanied by a growing body of evidence-based medicine describing their effectiveness, efficacy, and safety that provides clinicians with multiple options to determine the most appropriate treatment for each patient.1 Bipolar affective disorder (BPAD or manic-depressive illness) is a common, recurrent, and severe psychiatric disorder characterized by episodes of mania, depression, or mixed states (simultaneously occurring manic and depressive symptoms). BPAD is frequently unrecognized and goes untreated for...

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

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 ofdisease 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...

Posttraumatic Stress Disorder

DSM-IV-TR classifies PTSD as an anxiety disorder with the major criteria of an extreme precipitating stressor, intrusive recollections, emotional numbing, and hyperarousal. Individuals at risk for PTSD include, but are not limited to, soldiers and victims of motor accidents, sexual abuse, violent crime, accidents, terrorist attacks, or natural disasters such as floods, earthquakes or hurricanes.7 PTSD has acute and chronic forms. In the general population, the lifetime prevalence of PTSD ranges from 1 to 12 and is frequently comorbid with anxiety disorders, major depressive disorder, and substance abuse disorders with a lifetime prevalence of comorbid disease ranging from 5 to 75 . PTSD is often a persistent and chronic disorder and a longitudinal study of adolescents and youth with PTSD showed that more than one-half of individuals with full DSM-IV-TR PTSD criteria at baseline remained symptomatic for more than 3 years and 50 of those individuals with subthreshold PTSD at baseline...

Psychopharmacotherapy for Bipolar Depression

For patients with bipolar depression, treatment may be initiated with mood stabilizers alone, and both lithium and lamotrigine have been shown to be effective antidepressants (Young et al. 2004). Dosing of lithium is as per guidelines in the section Psychopharmacotherapy for Bipolar Disorder later in this chapter, and dosing of lamotrigine follows the same guidelines as for young and middle-aged adults. If monotherapy is ineffective, antidepressants may be added, following the principles spelled out earlier, with an important modification. TCAs are the third-line treatment option in bipolar depression because TCAs may be more prone to induce a switch into mania or hypoma-nia than either 1) the SSRIs or other first-line agents (including venlafaxine, duloxetine, and mirtazapine) or 2) MAOIs, the second-line treatment. Although switch rates for elderly patients per se have not been published, Gijs-man et al. (2004) reviewed six clinical trials in middle-aged adults and found a 10 switch...

N M OBrien and T P OConnor

Histamine toxicity can result in a wide variety of symptoms such as rash, urticaria, inflammation, nausea, vomiting, diarrhoea, abdominal cramping, hypotension, tingling sensations, flushing, palpitations and headache. In general, toxic symptoms are relatively mild and many patients may not attend a doctor. Thus, the exact prevalence worldwide of histamine toxicity is unclear. The prevalence of cheese-related toxicity is also unclear although several incidences have been reported in the literature. For most individuals, ingestion of even large concentrations of biogenic amines, such as histamine, does not elicit toxicity symptoms since they are rapidly converted to aldehydes by monoamine oxidase (MAO) and diamine oxidase (DAO) and then to carboxylic acids by oxidative deamination. These enzymes, present in the gastrointestinal tract, may prevent reduce the absorption of unmetabolised histamine into the bloodstream. However, if MAO and DAO are impaired due to a genetic defect or the...

For Cellbased Interventive Therapies

Chronic neuropathic pain following damage to the peripheral or CNS has been difficult to treat clinically (14). As an illustration of the severity of pain following spinal cord injury (SCI), patients often report pain, rather than immobility, as the major deterrent to good quality of life (15). Pharmacological pain management is based on nonopioid and opioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase 2 (COX-2) inhibitors (16), calcium channel blockers (17), capsaicin (18), nicotine receptor agonists (19), and opioids (20) (e.g., morphine and its derivatives). Adjunct drugs, such as antidepressants and anticonvulsants, often accompany more antinociceptive agents in certain types of pain, like diabetic neuropathy (21). Gabapentin, an anticonvulsant, has become the most common medication for SCI pain (22), probably owing to its calcium channel-blocking functions (23). Combination of medications, such as NSAIDs with opioids, seems to be more...

Changes in Gene Expression

Nonetheless, the notion of bidirectional changes in synaptic excitability achieved in the LTP LTD paradigms of amygdala and hippocampal slices and, preliminarily, in the kindling quenching phenomena, led us to explore the potential frequency-dependence of rTMS in attempts to find optimal therapeutic parameters of this type of brain stimulation in man. Following initial observations of our group, in collaboration with Wassermann and Hallett of the National Institute of Neurological Disorders and Stroke (NINDS), that 20-Hz stimulation of the left frontal cortex of depressed patients appeared able to induce antidepressant effects in some subjects (154), we, and others, conducted more controlled studies demonstrating weak to substantial antidepressant effects of higher-frequency (10- to 20-Hz) stimulation (over the left but not right frontal cortex or occiput) in severely depressed patients (155,156). Whereas Pascual-Leone et al. (156) reported rather dramatic effects on mood with this...

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

Symptom Assessment Close to the Patients Endof Life Multidimensional Issues

Querading (i.e. loss of appetite or fatigue stands for depressive symptoms or dyspnoea) 9 of symptoms. Since these and other symptom-specific phenomena complicate assessment of the patient's symptoms, attempts have been undertaken to identify risk factors for increased or altered symptom expression that result in refractory symptoms. For pain, the main risk factors include incident pain, neuropathic pain, psychosocial suffering, substance abuse, and impaired cognition 10 . A staging system for pain is currently in the multi-centre evaluation phase 11 .

Heidi E Hutton and Glenn J Treisman

The risk behaviors that transmit HIV and complicate HIV treatment are often influenced by psychiatric disorders. Major depression, substance abuse, and chronic mental illness are problems that commonly complicate HIV treatment, but none can generate more distress and dissention among medical providers than personality problems. Caregiver burnout, failure to establish stable medical care relationships, and excessive resource utilization have been associated with certain personality traits and disorders. There has been relatively little research on the role of personality traits in HIV despite their stable, durable, and heritable influence on thoughts, feelings, and behavior. Certain traits, however, appear to increase the likelihood of engaging in HIV risk behaviors, having poorer quality of life and management of HIV, and adhering to treatment regimens. Effective HIV prevention and treatment programs should consider specific personality traits that render some individuals more...

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 Need For Pathway Biomarkers

On October 18, 2006, the FDA's Clinical Pharmacology Subcommittee of the Advisory Committee for Pharmaceutical Science recommended that the FDA revise tamoxifen's drug label to include a warning that postmenopausal women who are CYP2D6 poor metabolizers and are taking tamoxifen to treat breast cancer have an increased risk for breast cancer recurrence. The subcommittee also recommended that the label should include a warning that certain antidepressants may reduce tamoxifen's effectiveness. The subcommittee panel members did not come to a consensus about whether the FDA should recommend CYP2D6 genetic testing for tamoxifen patients, but the majority was in favor of including it as an option in the appropriate section of the drug packaging insert. The panel's recommendations do not require the FDA to make changes to the tamoxifen label however, the FDA usually does follow the advice of subcommittees.

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).

And Amnestic Disorders

This chapter reviews delirium, dementia, and amnestic disorders. Traditionally, these conditions have been classified as organic brain disorders to distinguish them from such diseases as schizophrenia, mania, and major depressive disorder, the so-called functional disorders. With the publication of the DSM-IV, the distinction between functional and organic disorders was eliminated. Significant research into the neurobiological aspects of mental disorders and the utilization of sophisticated neurodiagnostic tests such as positron emission tomo-graphic scanning in individuals with schizophrenia led to the inescapable conclusion that every psychiatric condition has a biological component. Thus, the term functional became obsolete and even misleading.

Newer Sedative and Hypnotic Agents

In recent years, a variety of alternatives to the benzodiazepines have become available to treat both anxiety and insomnia. Buspirone (Buspar) has been shown to reduce anxiety in generalized anxiety disorders, but it does not suppress panic attacks, and is not used as a primary treatment of obsessive-compulsive disorder. Buspirone is not abused by alcoholics and drug addicts, and it does not produce withdrawal symptoms on abrupt discontinuation. Like the antidepressants, buspirone requires several weeks of daily dosing to produce antianxiety effects, which are less dramatic from patients' point of view than are the effects produced by the benzodiazepines (Sussman & Stein, 2002). The antidepressants as a class have been shown to possess antipanic and antianxiety effects opening a new range of uses for these medicines in the treatment of anxiety disorders. The selective serotonin reuptake inhibitors (SSRIs) have emerged as the first-line treatment for many anxiety disorders (Davidson,...

Personality Disorders

Agronin and Maletta (2000) reviewed the literature on personality disorders in late life and found not more than several dozen articles most were cross-sectional prevalence studies in community and treatment populations that used variable diagnostic criteria and inconsistent methodology, thereby allowing few reliable generalizations. Studies that used structured interviews suggested that the prevalence of personality disorders tends to decline with age in community-dwelling subjects. However, personality disorders are as prevalent among elderly patients in geropsychiatric inpatient units as in a young adult comparison sample (Ames and Molinari 1994 Molinari et al. 1994). Studies typically report a higher prevalence of DSM-IV-TR Cluster C personality disorders (avoidant, dependent, and obsessive-compulsive) among older adults than either Cluster A disorders (paranoid, schizoid, and schizotypal) or Cluster B disorders (antisocial, borderline, histrionic, and narcissistic) (Kunik et al....

Medication Induced Delirium

Include such antihypertensives as methyldopa and re-serpine, histamine (H2) receptor antagonists (cimeti-dine), corticosteroids, antidepressants, narcotic (especially opioid) and nonsteroidal analgesics, lithium carbonate, digitalis, baclofen (Lioresal), anticonvulsants, antiarrhythmics, colchicine, bronchodilators, benzodiazepines, sedative-hypnotics, and anticholinergics. Of the narcotic analgesics, meperidine can produce an agitated delirium with tremors, seizures, and myoclonus. These features are attributed to its active metabolite normeperidine, which has potent stimulant and anticholingeric properties and accumulates with repeated intravenous dosing. In general, adverse effects of narcotics are more common in those who have never received such agents before (the narcotically naive) or who have a history of a similar response to narcotics. Principles to remember in cases of drug-induced delirium include the facts that (1) blood levels of possibly offending agents are helpful and...

Neurotransmission and ADD

Depression, a disease that involves feelings of helplessness, despair, and thoughts of suicide, may be caused by or result in decreased levels of the neu-rotransmitter serotonin. Antidepressants blocking the actions of enzymes that degrade serotonin or inhibit its reuptake help alleviate many symptoms of this disease in some people.

Neurodegenerative Diseases

Ahlbom 74 conducted a systematic review of the literature on neurodegenerative diseases and exposure to EMF. The author concluded, For AD the combined data on an association with EMF are weaker than that for ALS. The association between suicide and EMF exposure was also weak. For depressive symptoms an assessment is more complex. For diseases such as Parkinson's, there is not enough information for an assessment.

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

Initial Symptom Management

Neuropathic pain may be treated with some success using adjuvant analgesics, that is, medications not traditionally considered to be pain relievers (228). Adjuvant analgesics, such as tricyclic antidepressants and anticonvulsants, do not have strong antinociceptive analgesic properties in experimental or clinical studies, but have been shown to be helpful in neuropathic pain states (229,230). In addition, the possible effectiveness of opioids for neuropathic pain should not be overlooked, although doses may be considerably higher than typical antinociceptive doses.

Binary Concept Of Pain And Addiction

For example, stress can increase pain (8). A pain patient who takes inappropriate additional doses of his or her opioid medication after stressful situations to treat anxiety must be educated that this is not the correct response to the situation. Behavior therapy to improve coping skills is indicated. Specific pharmacotherapy with medications that are less likely to be misused, such as the Selective Serotonin Reuptate Inhibitor (SSRI) antidepressants or tiagabine hydrochloride (Gabitril ) also may be indicated to treat the anxiety. This is an appropriate biopsychosocial approach to the problem that can lead to a sustainable solution to the patient's problem.

Basic Science Of Addiction

Physical dependence, conversely, is a natural expected physiologic response that can occur with opioids, alcohol, benzodiazepines, corticosteroids, antidepressants, diabetic agents, certain cardiac medications, and many other medications used in clinical medicine. Abrupt cessation or rapid dose reduction resulting in decreasing blood level of the substance and or administration of an antagonist to the substance can produce a withdrawal syndrome that can include, but is not limited to, nausea, vomiting, diaphoresis, diarrhea, abdominal cramps, seizures, or even death (15).

Differential Diagnosis

Individuals with major depressive disorder often complain of lapses in memory and judgment, poor concentration, and seemingly diminished intellectual capacity. Often, these symptoms are mistakenly diagnosed as dementia, especially in elderly individuals. A thorough medical history and mental status examination focusing on such symptoms as hopelessness, crying

The Association Between Dual Diagnosis And Treatment Outcome

In both SUD and psychiatric treatment-seeking populations, dually diagnosed patients typically experience worse outcomes than their singly diagnosed peers (Ritsher et al., 2002 Schaar & Oejehagen, 2001). However, there are specific populations in which the evidence regarding this is mixed, such as the severely and persistently mentally ill (SPMI) (Farris et al., 2003 Gonzalez & Rosenheck, 2002) and ASPD populations (Cacciola, Alterman, Rutherford, & Snider, 1995 Kranzler, Del Boca, & Rounsaville, 1996). The effect of other psychiatric disorders on SUD outcomes may vary by SUD type. For example, co-occurring major depression appears to predict worse alcohol outcomes (Brown et al., 1998 Greenfield et al., 1998), while there is less evidence for its predicting worse cocaine outcomes (McKay et al., 2002 Rohsenow, Monti, Martin, Michalec, & Abrams, 2002). There is also evidence (albeit somewhat inconsistent) that gender may play a role in mediating the effect of co-occurring psychiatric...

Dsmivtr Diagnostic Criteria

The disturbance is not better accounted for by another Axis I disorder (e.g., major depressive disorder, schizophrenia). one-third to one-half of the usual initial dose) are advised and only agents with minimal anticholinergic activity should be employed. Appropriate choices would be the selective serotonin reuptake inhibitors such as paroxetine, fluoxetine, sertraline, citalopram, and escitalopram. Although sertraline, citalopram and escitalopram are least likely to cause drug-drug interactions, even these agents have the potential to increase confusion in Alzheimer's individuals. Agents such as trazodone and mirtazapine have occasionally been employed because of their sedating properties. If tricyclic antidepressants are used, the secondary amines (e.g., desipramine, nortriptyline) are recommended over the tertiary ones (e.g., amitriptyline, doxepin). Careful attention to the possible side effects of these agents, particularly orthostatic hypotension, lowering of the seizure...

Womens Health Premenstrual Syndrome PMS

Premenstrual syndrome (PMS) is a group of symptoms that generally appear 4 to 10 days before menstruation and end, often abruptly, as menstruation begins. The most common symptoms are irritability, nervous tension, depression, mood swings, craving for sugary foods, breast tenderness, water retention, and weight gain.1 The symptoms of PMS can be mild or severe about one in five women have severe symptoms that interfere with daily activities. In many women, an imbalance of too much estrogen and too little progesterone triggers the symptoms of PMS.

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.

Diagnosing Psychiatric Disorders In Patients With Substance Use Disorders

Is independent of substance use or related to intoxication or withdrawal. For example, when examining a patient who has a long history of alcohol dependence and depressive symptoms, it can be difficult to determine whether the depressive symptoms result from the direct pharmacological effects of alcohol, the many losses experienced as a result of the alcohol use, feelings of discouragement about the inability to stop drinking, or an independent mood disorder. Other etiologies, such as metabolic disturbances, head trauma, and personality disorders, must also be considered in the differential diagnosis of depressive symptoms in alcohol-dependent patients (Jaffe & Ciraulo, 1986). Given these considerations, one could ideally establish diagnostic rules to assist in determining whether a psychiatric syndrome is due to substance use or represents a separate and independent disorder. For example, some clinicians may establish a rule that a patient must be abstinent from alcohol and drugs for...

Table 92 Symptoms of Depression

The difference between these normal fluctuations in mood and a diagnosable illness depends on three things the number of symptoms, their severity, and their duration. The criteria that psychiatrists use to diagnose a major depression, as specified in their Diagnostic and Statistical Manual (DSM IV), require that at least five symptoms be present most of the day, nearly every day, for at least two weeks, and that depressed mood or markedly diminished interest or pleasure be among these five symptoms. Further, the symptoms must be an obvious change from the person's usual state. These criteria provide a useful way to place a somewhat arbitrary dividing line between mild but normal blues and pathological blues. who have this type of depression are particularly sensitive to slights and rejections. Unlike the person with melancholia, whose mood does not respond by brightening up when something pleasant occurs, people with atypical depression respond intensely to both positive and negative...

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

Ensuring Utilization of Services

Concepts of normalization should also include normalization of help-seeking behavior, because research suggests that many individuals with significant levels of posttraumatic stress symptoms do not use mental health services, even when they are available. For example, following terrorist attacks, this nonutilization of services appears to be the case with direct survivors (Delisi et al., 2003), family members who lose loved ones (Smith, Kilpatrick, Falsetti, & Best, 2002), emergency workers (e.g., North et al., 2002), and medical staff (e.g., Luce & Firth-Cozens, 2002). Indeed, 3-6 months after the World Trade Center attacks in New York City, only 27 of those reporting severe psychiatric symptoms had obtained mental health treatment (Delisi et al., 2003). This reluctance to use services may characterize many trauma populations. Hoge et al. (2004) found that only 23-40 of those recently returned from combat duty in Iraq or Afghanistan, who met screening criteria for a mental disorder...

Dementia Due to Parkinsons Disease

An expressionless facial countenance. The tremor in Parkinson's disease has a regular rate and is most prominent when the individual is sitting with arms supported and has been described as an intention tremor. Paranoid delusions and visual hallucinations may occur, but auditory hallucinations are rare. Antipsychotics with low incidence of extrapyramidal symptoms such as quetiap-ine, olanzapine, and ziprasidone are recommended. The pharmacological treatment of Parkinson's disease involves the use of a number of types of medication. These include selegiline (Eldepryl), a selective monoamine oxidase inhibitor, levodopa, other dopamine agonists (pramipexole Mirapex , bromocriptine, pergolide mesylate Permax , amantadine), and various anticholinergic agents (e.g., benztropine). Selegiline should not be given to individuals on antidepressant medication as there is a risk that dopaminergic agents may activate psychosis or mania. When discontinuing levodopa after a long course of treatment,...

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,...

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.

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...

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.

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...

Pharmacotherapy Targeting Substance Dependence in Dually Diagnosed Populations

Although pharmacotherapies aimed specifically at decreasing alcohol or drug use (e.g., naltrexone, disulfiram) can be efficacious in improving SUD outcomes in non-dually-diagnosed populations, the literature on the use of these medications in dually diagnosed populations is quite thin. Concerns that disulfiram may cause or exacerbate psychosis (Mueser, Noordsy, Fox, & Wolfe, 2003) have contributed to a reluctance to prescribe it in patients with SPMI (Kingsbury & Salzman, 1990). While there have been no controlled studies of disulfiram in populations with alcohol dependence and SPMI, there have been a few published case reports (Brenner, Karper, & Krystal, 1994) and case series (Kofoed, Kania, Walsh, & Atkinson, 1986 Mueser et al., 2003) describing its tolerability and potential benefit for improving alcohol outcomes and hospital-ization rates for those who remain in treatment. Additionally, there is preliminary evidence that naltrexone may improve drinking outcomes in patients with...

Postmortem Brain Studies

The reciprocal changes in the levels and activity of Gaq 11 in BD occipital cortex also appear to uniquely distinguish this disorder from Alzheimer's disease (79a), schizophrenia (44), alcoholism (44), and major depression (80), in which the activity of Gaq 11 is either increased or decreased in the absence of changes in Gaq 11 and PLC-P1levels. It is also noteworthy that the largest differences in Gas levels and forskolin-stimulated adenylyl cyclase activity were observed in the occipital cortex of BD subjects (10,11). Given the substantial evidence of crossregulation between cAMP and PPI signaling pathways, the possibility that the observed differences in Gaq 11 and PLC-p1 levels may reflect the consequences of relatively greater disturbances in cAMP signaling in this brain region in BD cannot be excluded.

Influence Of Antidepressant Treatments On Neuronal Morphology And Survival

Upregulation of neurogenesis may represent a novel and significant mechanism of antidepressant action, particularly in stress-related illnesses. However, there are several points that must be addressed before the relevance of neurogenesis can be determined. First, do other types of antidepressants increase neurogenesis Do antidepressants block or reverse the negative effects of stress This information will indicate if the enhancement of neurogenesis is a common action of antidepressants or if this effect is specific to certain types of treatments. Second, the controversy about the occurrence of neurogenesis in adult primates must be addressed. Third, the consequences of altered neurogenesis, either increased or decreased, to the function of the hippocampus must be determined. In addition to neurogenesis, the influence of antidepressant treatments on the sprouting of granule cells has been examined. Granule cell sprouting can be studied using a histochemical technique that selectively...

Two Recent Discoveries in Psychiatric Mental Genetics

Schizophrenia is a major mental disorder that occurs in approximately one out of every hundred individuals, a startlingly high prevalence for such a serious illness. It has been known for many years that the disorder runs in families, and a number of family, twin, and adoption studies have indicated that genetic factors are an important component. The 1980s saw several purported advances in the genetics both of schizophrenia and manic-depressive disorder, notably the localization of the former disease to chromosome 5 and the latter disorder to chromosome 11. Unfortunately, those results could not be confirmed, and these (probably) false positives have fueled criticisms of the entire effort to seek any precise genetic contribution to mental disorders. These false positive reports, however, have also engendered a much more sophisticated and critical approach to the methodology of studying complex traits, of which mental disorders are paradigms.

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...

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.

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.

Discontinuation of Benzodiazepine

There are a number of useful publications on the diagnosis and treatment of chronic anxiety (Davidson, 2003 DuPont, Spencer, & DuPont, 2004 Ross, 1994 Spencer, DuPont, & DuPont, 2004). The benzodiazepines can be used to treat either acute or chronic anxiety, as well as the panic attacks that are commonly associated with anxiety disorders. The benzodiazepines can be used either as needed or every day, and they can be used either alone or with other medicines, most often with antidepressants (Davidson, 1997).

Voltagegated Channels

A number of sodium channel blockers act as analgesics. Amitriptyline and other tricyclic antidepressants block these channels, along with other modes of anti-nociceptive activity. Most of the anticonvulsants used to block neuropathic pain are also sodium channel blockers. Potassium channels appear to play an important role in the development of neuronal excitability. There are four families of potassium channels that have different structures, neuropharmacological sensitivities, and functional characteristics the voltage-gated (KV), calcium activated K (Ca) , inward rectifier K (ir) , and the two-pore channels K (2P) K (+) (80). Antinociception has been associated with the opening of some forms of these K (+) channels induced by agonists of multiple G-protein coupled receptors, including alpha(2)-adrenoceptors, opioid, GABA(B), muscarinic, serotonin 5HT-1A, nonsteroidal anti inflammatory drugs (NSAIDs), tricyclic antidepressants, and cannabinoid receptors (80). New research indicates...

Experimental Disease Models

Table 6 Animal models of major depression Reliable prediction of response to antidepressants in rats unpredictable stressors induces long-term changes resembling those found in depressed patients antidepressants has been conducted antidepressants has been conducted Increased immobility in the forced swim test and foot shock response to antidepressants chronic treatment Change in agonistic behavior during the course of antidepressant drug treatment Sensitive to tricyclic antidepressants

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.

First Line Agents Selective Serotonin Reuptake Inhibitors

SSRIs have been studied in elderly depressed patients and have been shown to be effective and generally well tolerated and to have few side effects (New-house 1996). Some side effects, such as mild anorexia, nausea, gastrointestinal upset, jitteriness, and headache, typically diminish within the first few days to weeks of initiation of therapy others, such as sexual dysfunction (including inhibited desire, delayed ejaculation, and anorgasmia) and later-onset weight gain, may not diminish at all. Antidepressants Antidepressants Antidepressants Amitriptyline, imipramine, nortriptyline, desipramine, clomipramine, Antidepressants Amitriptyline, imipramine, sertraline, citalopram, trazodone Benzodiazepines Diazepam, alprazolam, triazolam, midazolam Hypnotics Zolpidem Antihistamines Loratadine, astemizoleb Inducers ( Antidepressants 1A2 Antidepressants 2C9 Fluoxetinea Fluvoxaminea Sertraline Antidepressants 2C19 Fluoxetine Fluvoxaminea Antidepressants Amitriptyline, imipramine, fluvoxamine...

How Are Mood Disorders Treated

The treatment of mood disorders is one of the biggest success stories in modern psychiatry, or for that matter in modern medicine. Effective treatments are available for both mania and depression. Four general classes of treatment are available mood stabilizers, antidepressants, electroconvulsive therapy, and psychotherapy. Mood stabilizers are primarily used to treat bipolar disorder. As the name suggests, they abort the activity of the emotional roller coaster and even out the mood swings so that the emotional temperature fluctuates mildly around the zero point. Because bipolar disorder is a very debilitating illness, mood stabilizers are a godsend to people who previously used to swing between mania and depression. Because being high can be subjectively fun for a person with mania, people with this condition sometimes dislike mood stabilizers because they get rid of the highs. Usually, however, people with mania eventually develop insight about the destructive effects of manic...

Traditional Views Of The Cp

Folate levels are two to three times higher in CSF than in plasma, and transthyretin (TTR) represents 25 of all CSF proteins (18,19). Interestingly, TTR is produced exclusively by the CP. Notably, a link has been described between TTR and depression. Studies in both TTR-null mice and depressed patients suggest a relationship between lowered TTR and increased exploratory behavior and increased Hamilton depression scores.

Complementary and Alternative Approaches

Encouraging lifestyle modifications such as regular exercise may be useful in reducing depressive symptoms, especially in combination with other therapies. Group therapy that used an eclectic approach that combined exercise and preventive health behaviors with psychotherapies (including cognitive and reminiscence therapies) and social skills training was effective in reducing depressive symptoms among a large group of older women living in subsidized housing however, it was more effective among relatively young (55- to 75-year-old) white women than among minority women and individuals older than 75 (Husaini et al. 2004). Educational materials that explain geriatric depression and its effect on family systems (e.g., Miller and Reynolds 2003) are a potentially beneficial adjunct to family, group, or individual therapy. However, few controlled studies of the effectiveness of such self-help materials in treating depression have been done. A recent meta-analytic review (Anderson et al....

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.

Pharmacological treatments of OSA risk factors and morbidities

That particular psychotropic drugs such as the SSRI antidepressants fluoxetine (see also above), sertraline and fluvoxamine may be useful as weight-loss agents was initially suggested by the unexpected observation of weight loss in trials of these agents in patients treated for neuropsychiatry conditions 92 . Subsequently, randomized controlled trials were specifically designed to assess their efficacy as weight-loss agents in obesepatients without neuropsychiatry co-morbidities. Of these agents, fluoxetine has been the most studied, in obese subjects without attendant co-morbidities 93 , in obese subjects with diabetes 94, 95 and in obese subjects with eating disorders 96 . Short-term (8 weeks) studies in the first group showed an approximate weight loss of about 4 kg compared with placebo, though doubts have surfaced about sustained benefit in longer-term studies. Trials of fluoxetine as a weight-loss agent in obese type 2 diabetics have shown mixed results. Fluoxetine has shown to...

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 .

Rates Of Psychiatric Disorders Among People Living With Hiv Infection

The landmark HIV Cost and Services Utilization Study (HCSUS) found that a large, nationally representative probability sample of adults receiving medical care for HIV in the United States in early 1996 (N 2,864 2,017 men, 847 women) reported major depression (36 ), anxiety disorder (16 ), and drug dependence (12 ) (Bing et al., 2001 Galvan et al., 2002), as well as heavy drinking at a rate (8 ) almost twice that found in the general population and high rates of drug use (50 ). The HCSUS study remains the most comprehensive view we have of the prevalence of psychiatric disorders among people living with HIV AIDS, though the study was not designed as a diagnostic assessment of psychiatric disorders among people with HIV AIDS and so rates of psychosis, bipolar disorder, alcohol abuse or dependence, and substance abuse, among others, were not obtained. Disorders of alcohol and other drug (AOD) abuse are differentiated from dependence in the Diagnostic and Statistical Manual of Mental...

Disorders Usually First Diagnosed In Infancy Childhood Or Adolescence

The classification begins with disorders usually first diagnosed in infancy, childhood, or adolescence. The provision for a separate section for so-called childhood disorders is only for convenience. Although most individuals with these disorders present for clinical attention during childhood or adolescence, it is not uncommon for some of these conditions to be diagnosed for the first time in adulthood (e.g., attention-deficit hyper-activity disorder). Moreover, many disorders included in other sections of the DSM-IV-TR have an onset during childhood (e.g., major depressive disorder). Thus, a clinician evaluating a child or adolescent should not only focus on those disorders listed in this section but also consider disorders from throughout the DSM-IV-TR. Similarly, when evaluating an adult, the clinician should also consider the disorders in this section since many of them persist into adulthood (e.g., stuttering, learning disorders, tic disorders).

Substance Induced Mood Disorder

Substance-induced mood disorder is defined in DSM-IV-TR (American Psychiatric Association 2000, p. 409) as a prominent and persistent disturbance in mood that is characterized by depressed mood or markedly diminished interest or pleasure in all, or almost all, activities and or elevated, expansive, or irritable mood along with evidence from the history, physical examination, or laboratory findings that the symptoms developed during, or within a month of, Substance Intoxication or Withdrawal or that medication use is etiologically related to the disturbance in mood . Substance-induced mood disorder may not be diagnosed if depressive symptoms occur exclusively during the course of a delirium. Diagnostic criteria further require that the depression not be better accounted for by a non-substance-induced mood disorder and that the symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Two broad categories of substances...

Substance Induced Mania

Substances known to induce mania include sympathomimetic agents (iproni-azid, procarbazine), psychostimulants (e.g., amphetamines, methylphenidate, cocaine, phencyclidine), tricyclic antidepressants, monoamine oxidase inhibitors, levodopa, yohimbine, bromide, alprazolam, corticosteroids, and many other substances (Table 3 11). In this regard, hypomania or mania that begins during or within 1 month of treatment with one or more of the medications listed here should be considered substance induced.

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).

First Line Agents NonSelective Serotonin Reuptake Inhibitors

Although venlafaxine blocks reuptake of serotonin and nor-epinephrine, its side-effect profile is generally benign and very similar to that of the SSRIs, making it one of the preferred therapeutic agents in the elderly. One study (Trick et al. 2004) found that venlafaxine actually increased the critical flicker fusion threshold in 88 depressed patients (average age 71), whereas the comparator medication, dothiepin (a TCA not available in the United States), reduced the critical flicker fusion threshold. The authors concluded that venlafaxine does not cause cognitive impairment in elderly patients. Advantages. Mirtazapine is an atypical antidepressant with a2-adrenergic antagonist and serotonin type 2 and type 3 receptor blocking activity. It is well tolerated and has few side effects other than sedation, which tends to diminish as the dosage is increased and noradrenergic effects overcome antihis-taminic effects. One controlled study comparing mirtazapine with paroxetine...

Variations in Clinical Presentation

Devanand et al. (2004) studied 211 patients (average age 70) who had received diagnoses of major depression. When they used a cutoff of first episode of major depressive disorder after age 60, they found that late-onset major depressive disorder was less severe (based on the 24-item Ham-D scores) and less frequently associated with melancholia (31 vs. 50 ) than was early-onset major depressive disorder and that fewer than half as many late-onset patients as early-onset patients reported a family history of mood disorder. Age, burden of medical illness (according to the Cumulative Illness Rating Scale), and presence of cardiovascular illness did not differentiate the early- from the late-onset cases. Psychotic features (delusions or hallucinations or both) occur in about 25 of elderly patients with major depression, and in one large epidemiological survey (N 18,980), subjects who reported feelings of worthlessness or guilt were the most likely to have psychotic features (Ohayon and...

Third Line Agents Psychostimulants

Although controlled studies in elderly patients are lacking, a relatively large body of clinical literature supports the use of psychostimulants in elderly depressed patients, particularly those in whom medical illness precludes the use of cyclic antidepressants or MAOIs (Emptage and Semla 1996). Both amphetamines and methylphenidate have been administered, although meth-ylphenidate is generally preferred because of its relatively lower cardiovascular side-effect profile. Dosages range from 5 to 20 mg administered orally twice a day, generally immediately before breakfast and lunch so as not to interfere with appetite or sleep. Cardiovascular side effects are typically limited to very minor increases in blood pressure and heart rate. The most common side effect is mild jitteriness, which may be managed with small doses of benzodiaz-epine anxiolytics, but severe dysphoria and agitation, appetite disturbance, and insomnia requiring discontinuation of treatment may occur rarely. One...

Combined Psychotherapy and Pharmacotherapy

Only a few studies have compared the efficacy of psychotherapy with that of antidepressant medication in treating depression in older adults, and outcomes have been mixed. However, the combination of antidepressant medication with psychotherapy has shown effectiveness for treatment of major depression. This effect has been most clearly documented for interpersonal psychotherapy, less often examined for cognitive-behavioral therapy, and not yet investigated for some other psychotherapeutic approaches (Are n and Cook 2002). Thase and colleagues (1997) conducted a mega-analysis (a meta-analysis of their own original data) of five studies. They administered interpersonal therapy, cognitive-behavioral therapy, and clinical management to elderly patients with major depression, in various combinations with standard pharmacotherapy, and found that psychotherapy alone was as effective as pharmacotherapy or the combination of psychotherapy with pharmacotherapy in patients with mild depression...

Psychopharmacotherapy for Geriatric Depression

Taylor and Doraiswamy (2004) reviewed the randomized, placebo-controlled trials of antidepressants in populations older than 55 and found only 18 trials With this limited evidence base in mind, in the following section, we review the advantages and disadvantages of currently available antidepressants in the treatment of nonpsychotic depression, including major depression, dys-thymia, and minor depression. Because the presence of psychosis (hallucinations, delusions, severe thought disorder, or behavioral regression) appears to significantly reduce the rate of response to antidepressant therapy, even when concomitant antipsychotic medications are prescribed, psychotic depression is discussed under a separate heading later in this chapter ( Psychopharmaco-therapy for Psychotic Depression ). The most well-studied and widely used psychopharmacotherapy for non-psychotic depression in the elderly is the reuptake-inhibiting antidepressants which include the tricyclic antidepressants (TCAs),...

Psychotherapy for Geriatric Depression

The best-studied psychotherapeutic interventions with older adults are behavior therapy, cognitive-behavioral therapy, and problem-solving therapy (Arean and Cook 2002 Gatz et al. 1998). All share a common theoretical framework that emphasizes the importance of learning adaptive responses. These interventions have been examined in well-controlled studies in relatively diverse populations by several independent investigators, and clear benefits have been shown relative to no-intervention and wait-list control subjects. In major depression, benefits for those who respond to such therapies have been shown to persist for at least 1 2 years. Most studies have found little difference in efficacy between these procedures. Cognitive-behavioral therapy has been Reduce the efficacy of antidepressant medication or psychotherapy Create disability, contributing to both chronicity and reduced treatment efficacy Increase the need for simplified medication dosing schedules (e.g., once daily)...

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...

Clinical Presentation

As is true for all dementing illnesses, the clinical presentation of Alzheimer's disease depends on the stage of illness and may be obscured or complicated by symptoms related to concomitant physical and psychiatric illness, including depressive or anxiety disorders, psychosis, and delirium. Table 5-9 summarizes the clinical and laboratory findings typically observed in uncomplicated cases as the disease progresses (Group for the Advancement of Psychiatry 1988). Functional symptoms nearly indistinguishable from those of concomitant psychiatric illness are part of the presentation of Alzheimer's disease, even in the early stages, and patients may present to general psychiatric clinical settings. Gormley and Rizwan (1998) reported that one-third of Alzheimer's disease patients had delusions, and 11 had hallucinations within the month before evaluation, and this prevalence was not affected by severity of dementia or of depressive symptoms. Farber and colleagues (2000) found that 63 of...

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

The Scale of the Problem

In this study, urine was tested by immunoassay for the following drugs alcohol, amphetamines, methyl amphetamines (including ecstasy), cannabis, cocaine, opiates, methadone, lysergic acid diethylamide, benzodiazepines, and tricyclic antidepressants. The incidence of medicinal drugs likely to affect driving had not significantly changed from the 1985-1987 study (67). However, illicit drug taking in drivers had increased sixfold in percentage terms, and there was a comparable increase among passengers. In addition, an in-

Symptom Rating Scales and Depression Screening

Although depression rating scales were originally designed for research purposes, use of such scales in clinical practice can enhance the uniformity and reliability of assessment. Symptom rating scales are not sufficient to establish a diagnosis of depression, but they can help to identify individuals whose depressive symptoms exceed the norm and they can provide a means of tracking treat- The BDI (Beck et al. 1961) is another self-rated scale that has been widely used with older adults. The BDI is particularly useful for assessing psychological features of depression, including dysphoric mood, pessimism, self-criticism, and guilt. This instrument is recommended for tracking symptom severity in older persons with relatively clear-cut depression that is not complicated by psychosis or prominent somatization. It also may help to distinguish normal or complicated bereavement from major depression because bereaved individuals would not be expected to obtain high scores on items evaluating...

Obsessive Compulsive Disorder

OCD is a chronic and often disabling disorder that affects 2-3 of the US population. OCD has been labeled a 'hidden epidemic' and is ranked 20th in the Global Burden of Disease studies among all diseases as a cause of disability-adjusted life years lost in developed countries. OCD is often associated with substantial quality of life impairment especially in individuals with more severe symptoms. The disease usually begins in adolescence or early adulthood with 31 of first episodes occurring at 10-15 years of age and 75 by the age of 30. The essential features of OCD are recurrent obsessions or compulsions that are severe enough to be time consuming (i.e., take more than 1 h per day) and or cause significant levels of distress or interference with normal daily activities. OCD can have comorbidity with major depression and social phobia, as well as other mental disorders such as eating disorders and schizophrenia.9

The Social Context of Science

Depression is a disorder that affects nearly 19 million Americans, and billions of dollars have been spent on research. Much of this funding has helped researchers understand changes in brain chemistry and to design effective drug therapies to treat depression. However, we know that major risk factors for depression in the United States include gender (depression is twice as common among women as among men), societal status (risk of depression is greater among ethnic minorities), and geographic location (city dwellers are more likely to become depressed than rural residents). These risk factors suggest that, in addition to biology, environmental conditions probably play some role in the origin of depression. Despite these observations, until recently there has been relatively little research on techniques of preventing depression, even among these high-risk groups. A review of the medical literature reveals six times as many research papers on using...

Evening Primrose Oenothera biennis and Borage Borago officinalis

Evening primrose has become a popular herb for premenstrual syndrome, although whether it really helps is uncertain because the results of research have been inconsistent. Borage has a reputation for treating depression, inflammation, fevers, and coughs, but these effects have never been tested. Both plants are sources of the fatty acid, gamma-linolenic acid, but it is not certain what effect gamma-linolenic acid has on seizures. Some research suggests that these herbs may reduce seizures some suggests that they may increase them. More research is needed to resolve this issue, so it may be best for patients to avoid evening primrose and borage until more is known about their effects.

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.

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.

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.

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

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...

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).

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....

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...

Post Herpetic Neuralgia

Treatments include drugs used in the management of neurogenic pain including antidepressants, anticonvulsant drugs and opioids. Topical agents have been used but the outcomes are variable and there is little evidence of efficacy with the exception of topical Lidocaine (Lidoderm) although it should be said that the benefit is only modest -23 . Surgery (cutting the nerve) appears to be unhelpful and can make the situation worse. Early use of antiviral agents does not seem to make a great difference in the subsequent occurrence of PHN. There is now evidence that

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...

Repetitive Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) uses a rapidly changing magnetic field (produced by electrical coils placed near the scalp) to induce electrical current in brain tissue. It has been studied as an adjunct to antide-pressants and as a solo treatment for depressive disorders and is regarded by some investigators as a potential alternative to ECT. Results from open studies have been mixed, and a meta-analysis by Martin et al. (2003) concluded that current trials are of low quality and provide insufficient evidence to support the use of rTMS in the treatment of depression (p. 480). Studies published since that review offer little to challenge that assessment. A doubleblind, controlled study found a modest, clinically nonrelevant decrease in HAM-D scores in both rTMS and sham patients over 2 weeks of treatment (p. 1323), but over the subsequent 12-week follow-up, the rTMS group continued to improve significantly compared with the placebo group. The authors concluded that...

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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