Alternative Treatment for Depression

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...

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Other Indications For Antidepressants

Antidepressants may benefit most forms of anxiety disorder, including panic disorder, generalised anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder and social phobia (see p. 393). SSRIs are effective in milder cases of the eating disorder bulimia nervosa, particularly fluoxetine (in higher doses than are required for depression). This effect is independent of that on depression (which may co-exist) and may therefore involve action on transmitter systems other than those involved in modulating depression. Antidepressants appear to be ineffective in anorexia nervosa.

Genetic Epidemiology of Major Depression

Evidence for the genetic contribution to major depression is compelling and comes from a variety of study designs, many of which rely on large population-based twin registries (Bierut et al., 1999 Kendler, Gardner, & Prescott, 1998 Kendler, Heath, Martin, & Eaves, 1986, 1987 Kendler, Karkowski, Corey, & Neale, 1998 Kendler, Neale, Kessler, Heath, & Eaves, In the same way that lifetime prevalence estimates change as a function of varying definition, the estimates of environmental and genetic variance underpinning variation in major depression also vary. Table 11.2 also includes standardized genetic and environmental variance components under the best-fitting models for twin pair resemblance, as a function of the particular diagnostic systems. For all nine definitions, there was no evidence to support the contribution of shared environmental or cultural effects in the etiology of major depression. Instead, family aggregation (i.e., the degree to which siblings and...

Antidepressants In Bipolar Depression

TREATMENT AND PREVENTION OF bipolar depression is a major problem in the long-term treatment of bipolar illness. While about one-third of patients may experience adequate prophylaxis with lithium or val-proate (El-Mallakh 1994), the majority of patients continue to be symptomatic (Ghaemi 2002). For example, although gender distribution of the bipolar diagnosis is equal, women may experience depression at two or three times the rate in men (Goodwin and Jamison 1990). Additionally, depressive symptoms themselves may be more problematic both type I and type II bipolar disorder patients spend one-third to half of their lives, respectively, experiencing depressive symptoms (Judd et al. 2002, 2003). This depressive morbidity is at least three times as common as manic or hypomanic morbidity (Ghaemi et al. 2000 Post et al. 2003a). Early onset of depression appears to be an especially poor prognostic factor. Among 72 children who have experienced a prepubertal, major depressive episode...

Antipsychotics As Antidepressants

The introduction of the second generation of antipsychotics, with relatively less D2 blockade and significant serotonin 5-HT2A receptor blockade, suggested that these agents may be effective in bipolar illness without a significant depressogenic effect. This was insinuated in several short-term, placebo-controlled studies of second-generation anti-psychotics in acute mania (Keck et al. 2003a, 2003b Sachs et al. 2002 Tohen et al. 1999, 2000). In all of these studies, depressive scales were measured. All showed reductions in depressive symptoms in manic or mixed bipolar patients. However, depressive symptoms in mania are not depression, and the issue of whether these agents are antidepressive would have to be investigated in randomized trials of depressed bipolar subjects.

Symptoms Of Major Depression

Each letter stands for a criterion (except for depressed mood) used in diagnosing a major depressive episode. Five or more of the following criteria are needed for at least 2 weeks S sleep changes I (decreased) interest G (excessive) guilt E (decreased) energy C (decreased) concentration A appetite changes P psychomotor agitation or retardation S suicidal ideation APPROACH TO DEPRESSIVE DISORDER Definitions Dysthvniia Fewer, milder, but persistent depressive symptoms with low mood for more than 2 years. Major depression Depressed mood or loss of interest in activities for 2 weeks plus three or four of the other symptoms for a total of five (Table 59-1). Depression is highly prevalent in medical outpatients, thought to be second only to hypertension in general practice. It is estimated that 15 of the general population will experience a major depressive episode at some point in their life. Between 6 and 8 of outpatients in a primary care setting are estimated to...


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,

Diagnosis Of Bipolar Depression

Generally speaking, determining that a patient currently meets criteria for a major depressive episode is straightforward. What is not straightforward, and therefore demands attention, is determining whether the patient's history is consistent with unipolar or bipolar depression. We suggest here a hierarchical model for such a diagnostic assessment, based on the validators of diagnosis used in psychiatric nosology.

Depression and Single Parents

One study that did not clearly fall into the above categories investigated the question of family transmission of depression from mother to child. A sample of 115 white, middle-class mothers (mean age 39.6 years) and their children (mean age 13.1 years) was compared with an African-American, predominantly single-mothers group (mean age 32.9 years) and their children (mean age 8.6 years) for maternal depression and depression in their children (Jones et al., 2000). A critical finding was that maternal depression was predictive of child depressive symptoms. No direct evidence was found for a higher rate of depression in single mothers and their children. The quality of the mother-child relationship was also found to have a nonsignificant effect. The strongest support emerged for transmission of depressive symptoms from mother to child. Eamon and Zuehl (2001) also found that maternal depression in single mothers influenced their children's emotional problems directly and indirectly...

Molecular Modification

Yet another close chemical variation in a therapeutic area where multiple agents already exist. Unenlightened opportunism is often referred to as the me-too approach. An example of this approach can be seen in the development of the tricyclic antidepressants, illustrated in Fig. 3.

Physicochemical Basis of Pain Intervention

Pain management can be approached by intervening at various points of the nociceptive pathway. Transduction is the conversion of the peripheral stimulus at the nociceptor into an electrical signal (35). Agents that have been shown to work at the periphery include nonsteroidal anti-inflammatory agents and capsaicin. Transmission is the afferent ascendance of the electrical signal from the periphery to the neuraxis. Local anesthetics temporarily block transmission. Modulation (i.e., inhibition or facilitation) occurs at the level of the interneurons and supraspinal pathways (36). Opioids, tricyclic antidepressants (TCAs), and GABA agonists are some of the agents effective in manipulating suppression of perceived pain (37).

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...

Treatment Nonresponse

Further detail regarding treatment response will be found in Chapter 7, Antidepressants in Bipolar Depression. In that chapter, evidence is provided to support the associations listed in Table 1-3. Here, we need An interesting clinical question is whether there are variations to antidepressant-induced mania that may not meet classic mania definitions. For instance, antidepressants could induce subthreshold, hypomanic states, often characterized primarily by irritability (Goldberg and Truman 2003), which could then become chronic (El-Mallakh and Karippot 2005). Antidepressants could also potentially lead to subsyn-dromal depressive or manic states (what has been termed roughening Sachs 1996). Manic symptoms induced by antidepressants are often mixed states. Since mixed states are associated with suicidality, the possibility exists that many cases of antidepressant-induced suicidality in children and adults (Khan et al. 2000 Murray et al. 2005 van Praag 2002) may represent the induction...

Interactions At Site Of Absorption

Gut motility may be altered by drugs. Slowing of gastric emptying, e.g. opioid analgesics, tricyclic antidepressants (antimuscarinic effect), may delay and reduce the absorption of other drugs. Purgatives reduce the time spent in the small intestine and give less opportunity for the absorption of poorly soluble substances such as adrenal steroids and digoxin.

Use in Prevention and Therapy

Depression, irritability, and impaired concentration may be the result of mild folate deficiency, and supplementation may be of benefit.9 Folate may be effective as adjunctive therapy with lithium in the treatment of manic-depressive illness. Symptoms of dementia in elderly people may be improved by folic acid sup-plementation.10

Pain Intervention 101 Techniques

Antidepressants must be taken orally for weeks to months before the onset of antinociception. When used in acute pain management, antidepressants readily improve sleep hygiene and promote restorative sleep patterns. Intravenous use of amitriptyline for acute control of mucositis pain has been cited as effective (143). Cardiac rhythm changes and orthostasis can occur with intravenous amitriptyline therefore, use in a monitored setting is encouraged (144).

Depressive Phenomenology

Atypical depressive symptoms seem to be more common in bipolar than in unipolar depression (Agosti and Stewart, 2001 Benazzi 1999, 2001a Ghaemi et al. 2002 Mitchell et al. 2001). In the National Institutes of Mental Health Collaborative Depression Study, a 20-year, prospective cohort study of depressed patients, atypical depressive features were a predictor of bipolar disorder, as opposed to unipolar depression (Akiskal et al. 1995). DSM-IV-TR criteria for atypical features include increased sleep, increased appetite, rejection sensitivity, leaden paralysis, and mood reactivity. The DSM-IV-TR definition of atypical depression is stricter than some clinical definitions, which focus mainly on the sleep and appetite features. An interesting clinical observation is that most bipolar patients have only one of the reversed neurovegetative symptoms that is, many patients experience increased sleep but decreased appetite, or vice versa. If one defines typical depression as decreased sleep and...

Initial Assessment And Resuscitation

The initial clinical review should include a search for known consequences of poisoning, which include impaired consciousness with flaccidity (benzodiazepines, alcohol, trichloroethanol) or with hypertonia (tricyclic antidepressants, antimuscarinic agents), hypotension, shock, cardiac arrhythmia, evidence of convulsions, behavioural disturbances (psychotropic drugs), hypothermia, aspiration pneumonia and cutaneous blisters, burns in the mouth (corrosives). plasma expander such as gelatin or etherified starch. External cardiac compression may be necessary and should be continued until the cardiac output is self-sustaining, which may be a long time when the patient is hypothermic or poisoned with cardio-depressant drugs, e.g. tricyclic antidepressants, (3-adrenoceptor blockers. The airway must be sucked clear of oropharyngeal secretions or regurgitated matter. Cardiac arrhythmia frequently accompanies poisoning, e.g. with tricyclic antidepressants, theophylline, -adrenoceptor blockers....

Parental Chronic Pain and Its Impact on the Children

There is another dimension of chronic pain that may have some implication for children. Because of the high prevalence of the depression and depressive symptoms in the chronic pain population, it is likely that parental depression, in addition to chronic pain, may have added risk for the children. In a review of the literature on the effects of parental depression on children, I showed that children of depressed parents were vulnerable to childhood and later depression as well as wide-ranging psychopathology and behavioral and social disturbances (Roy, 2001). The reasons for this level of vulnerability were not always adequately explained. Some of these issues are further explored in Chapter 8. It is probable that major mood disorders have a genetic basis, thus making the offspring susceptible. Beyond that, parental depression may create problems in child rearing. Parental bonding with young children may be loosened the well parent's attention may also be focused on the patient,...

Case Illustration Mrs Gardner

This stable family situation was put under great strain when Mrs. Gardner developed clinical depression. She received immediate psychiatric assessment, and the diagnosis of unipolar depression was confirmed. Her mood disorder lasted 4 years, during which time the family system was put under enormous strain. One of Mrs. Gardner's symptoms was prolonged isolation in her bedroom for days or even weeks. During these times she cried a lot and starved herself. She lost her job, and the family situation in general and Ann's behavior in particular took a sharp turn for the worse. Several points are worth noting. First, Mrs. Gardner's headaches by themselves had virtually no negative impact on the well-being of the family. Clinical depression, on the other hand, produced very damaging results. Second, the well adult in the system, namely the husband and father, was almost entirely ineffectual in filling any of the gaps created in the family system by the illness of his partner. In fact, he...

A FDA Divisions that Receive INDs for Drugs

Initial INDs for investigational drugs are sent by the sponsor to the appropriate reviewing division of the FDA's Center for Drug Evaluation and Research (CDER). Each of the 15 reviewing divisions is responsible for sustaining medical scientific expertise and regulatory responsibility for drugs within a specific therapeutic area. For example, The Division of Neuropharmacological Drug Products reviews drug products that exert their effects through actions on the central or peripheral nervous systems, such as anxiolytics, antidepressants, and anticonvulsant drugs. The Division of Antiviral Drug Products reviews, for example, antiretroviral drugs, as well as drugs active against the herpes simplex virus. These 15 reviewing divisions are organized into five Offices of Drug Evaluation (ODE), each of which reports to the Office of Review Management within the CDER. The organizational structure of the CDER, as well as the names of the current Directors of each ODE, can be readily viewed on...

Central nervous system findings

Other studies have investigated prolactin responses to fenfluramine, with mixed results. Two studies were unable to demonstrate any difference between the CFS patients' and controls' prolactin responses to this challenge (Bearn and Wessely 1994 Yatham et al. 1995). Nevertheless, a well matched study, comparing both CFS patients without depression and primary depressed patients with controls, demonstrated opposite patterns in the CFS and depressed groups (Cleare et al. 1995). Prolactin responses to fenfluramine were lowest in the depressed group and highest in the CFS group. There was a strong negative correlation between the fenfluramine-mediated response and the levels of cortisol in the system, providing further support for a central role in CFS-related hypocortisolism or reduced cortisol levels. Scanning techniques that investigate both the anatomical structure and the functioning of the brain have been used in CFS studies. Studies investigating structural abnormalities in CFS...

Depression Following Myocardial Infarction Prevalence Clinical Consequences and Patient Management

Depressive symptoms and major depression have been consistently reported as common psychological reactions to myocardial infarction (MI). It has also been argued, on the basis of prospective observational evidence, that depression following MI constitutes an independent, that is, causal, risk for subsequent mortality and morbidity. Two recent meta-analyses have examined this evidence. Unadjusted pooled analyses of both meta-analyses indicate that depression following MI is associated with a 2-fold increased risk of death and recurrent cardiac events. However, with adjustment for potential confounders the associations between depression and these outcomes were attenuated. In addition, two recent randomized trials addressing depression in MI patients (SADHART and ENRICHD) observed a relative reduction in depression with treatment, but found no effects of treatment on mortality, nonfatal rein-

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...

Evidence That Psychosocial Factors Predict CHD Events

Depression is one of the most common chronic conditions encountered in clinical practice and is a also significant problem in cardiac patients, although frequently unrecognized and untreated. Depressive disorders vary from mild depressive symptoms to classic major depression and are characterized by severely depressed mood and often also somatic complaints. Clinical depression, depressive symptoms, and other negative emotions have been associated with an increased risk of AMI in both men and women.12,13,35,36 Similarly, in the NHANES I survey, depression was associated with an independently increased risk of CHD incidence in both men and women, as well as CHD mortality in men.13 However, depression had no effect on CHD mortality in women. In the INTERHEART study,1 24 of patients with recent AMI could be identified as having had at least mild depression during the year before the event, compared to 17.6 among controls, with no gender difference in effect size.

Mechanisms of Psychosocial Impact

The mechanisms by which psychosocial factors increase the risk of cardiovascular disease are complex. In experimental studies, worsened coronary atherosclerosis41 and endothelial dysfunc-tion42 occur in response to social disruption. Decreased heart rate variability, a marker of auto-nomic imbalance, has been related to shift work exposure.43 Several studies have demonstrated links between psychosocial variables and vascular function,44-45 inflammation,46 increased blood clotting and decreased fibrinolysis.47,48 In women without known coronary disease, recurrent major depression was associated with subclinical ather-osclerosis.49 The exact pathophysiological nature of the influence of psychosocial factors remains to be determined, as does the temporal sequence of events.

Management of Psychosocial Risk Factors

In the ENRICHD trial,52 2481 post-MI patients with major or minor depression and or low perceived social support were randomly assigned either to usual medical therapy or to an intervention consisting of up to 6 months of cognitive behavior therapy at a median of 17 days after the index MI, with sertraline added for patients with persistent depressive symptoms. The intervention improved depression and social isolation but not event-free survival. The failure to demonstrate any survival benefit was thought, in part, to have been due to the fact that a large proportion of patients with mild, transient, depression were involved. An ensuing subgroup analysis of those patients enrolled in the ENRICHD with the most severe symptomatology, however, also failed to demonstrate any survival benefit.53 In addition, it was shown that intervention patients whose depression did not improve were at substantial risk for late mortality.

Prolongation Of Action By Vasoconstrictors

Disease, and with co-administered tricyclic antidepressants and potassium-losing diuretics. An alternative vasoconstrictor is felypressin (synthetic vasopressin), which, in the concentrations used, does not affect the heart rate or blood pressure and may be preferable in patients with cardiovascular disease.

Beyond Simple Gene Effects

Gene-environment interactions have been reported in monkeys and in humans. For example, in rhesus macaques, 5-HTTLPR genetic variation interacts with early rearing conditions to affect central 5-HT system homeostasis and emotionality in later life (Barr et al., 2004 Bennett et al., 2002 Lesch et al., 1997). In humans, Caspi and colleagues (2003) reported that the effect of life stress on depression and depression-related symptoms was moderated by the 5-HTTLPR genotype. They followed a cohort of over 1000 participants over a period of 26 years to find that individuals who had experienced multiple life stress events and who carried at least one copy of the 5-HTTLPR short allele had significantly higher rates of depressive symptoms, depression, and suicidality than individuals who were homozygous for the 5-HTTLPR long allele. The neural systems that mediate this interaction are currently unknown.

Drug Therapy In Relation To Psychologicaltreatment

Finally, it must be stressed that all doctors who prescribe psychotropic drugs engage in a 'therapeutic relationship' with their patients. A depressed person whose doctor is empathic, supportive and appears to believe in the efficacy of the drug prescribed is more likely both to take the medication and to adopt a mindset that might actually make him or her feel better than if the doctor seemed aloof and ambivalent about the value of psychotropic drugs. Remembering that placebo response rates of 30-40 are common in doubleblind trials of antidepressants, we should never underestimate the importance of our 'therapeutic relationship' with the patient in enhancing the pharmacological efficacy of the drugs we use. Antidepressants can be broadly divided into four main classes (Table 19.1), tricyclics (TCA, named after their three ring structure), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and novel compounds some of which are related to TCAs or...

Observational Studies

Major depression predicted CM in both bivariate (HR,5.74 95 CI Both major depression (OR, 2.67 95 CI, 1.22-5.85) and depressive symptoms (OR, 3.32 95 CI, 1.69-6.53) were predictive of cardiac events in bivariate analyses only. After adjustment, depression did not predict cardiac events Depressive symptoms predicted CM in bivariate (OR, 7.82 95 CI, 2.42-25.26) and multivariate (OR,6.64 95 CI, 1.76-25.09) analyses. However, major depression only predicted CM in bivariate analyses (OR, Depressive symptoms predicted CM in both bivariate (OR,3.23 95 CI, 1.65-6.33) and multivariate (OR, 3.66 95 CI, 1.68-7.99) analyses Depression predicted cardiac events in those receiving placebo medication after controlling for previous Ml and congestive heart failure (OR 2.45 95 1.14 5.35. However, after additional adjustment for dyspnea, depression did not predict cardiac events (RR, 1.73 95 CI, 0.75-3.98). Major depression only predicted ACM at the 12 month follow-up in Depression predicted ACM and CM...

Summary of the Evidence Concerning Depression and Prognosis

ACM all-cause mortality CI confidence interval CVM cardiovascular mortality ECG electrocardiogram EN RICH D Enhancing Recovery In Coronary Heart Disease HR hazard ratio LVEF left ventricular ejection fraction Ml myocardial infarction MIND-IT Myocardial INfarction and Depression Intervention Trial PVC premature ventricular complexes SADHART Sertraline Antidepressant Heart Attack Randomised Trial * given if mirtazapine was refused or not tolerated ** 249 patients received adjunctive antidepressant medication t SADHART was designed to assess the safety and efficacy of sertraline use in unstable cardiac

Implications for Patient Management

The research on depression following MI has clear implications for patient management. As soon as MI patients are medically stable, as determined by a cardiologist, they should undergo routine screening to identify those that are severely distressed. There are many self-report questionnaires available53 to assess depression, with the Beck Depression Inventory,54 and the Hospital Anxiety and Depression Scale55 being among those most commonly employed. Symptoms of depression should be assessed using a self-report instrument during hospitalization (3 to 7 days post-MI), and 6 weeks or so after discharge (usually when formal cardiac rehabilitation classes begin), to identify those patients who are experiencing significant emotional distress. Appropriate referral to a mental health professional should be considered for those patients demonstrating persistent elevated symptoms of depression, to allow for assessment of clinical depression and appropriate treatment. For those patients who are...

Guide To Further Reading

Anderson IM, Nutt D J et al 2000 Evidence-based guidelines for treating depressive disorders with antidepressants a revision of the 1993 British Association for Psychopharmacology guidelines. Journal of Psychopharmacology 14 3-20 Ballenger J C et al 1998 Consensus statement on panic disorder from the International Consensus Group on Depression and Anxiety. Journal of Clinical Psychiatry 59 47-54 Ballenger J C et al 1998 Consensus statement on social anxiety disorder from the International Consensus Group on Depression and Anxiety. Journal of Clinical Psychiatry 59 54-60 Ballenger J C et al 2000 Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety. Journal of Clinical Psychiatry 61 60-66 Ballenger J C et al 2001 Consensus statement on generalized anxiety disorder. Journal of Clinical Psychiatry 62 53-58 Davies S J C et al 1999 Association of panic disorder and panic attacks with hypertension. American Journal of Medicine...

The social stigma of psychiatric disorder

Endogenously depressed patients are lonely, hopeless and helpless, while the ME patient will only admit to being discouraged. The depressed patient has no future and is anhedonistic but the patient with ME will beg for treatment because this disease is slowing them down, interfering with plans and life. While depressives are phlegmatic and withdrawn, the ME attitude is positive and hopeful.

Very Different Story

The case of the Dales is one of remarkable adaptation in the face of very serious pain and disability. Mrs. Dale, a women in her forties, married with a teenage stepdaughter, was a highly accomplished woman with a degree in music who was injured in a work accident. She had severe leg and knee pain following the accident. She received physiotherapy without any apparent benefit. In fact, her pain condition continued to deteriorate, and she was eventually diagnosed with complex regional pain syndrome. She had serious problems with medications, reacting badly to many narcotic analgesics. During this time she became suicidal and was immediately placed on antidepressants, with beneficial effects. Over a relatively short period of time, she became wheelchair bound and lost some control over her bladder and bowel functions. In short, in a matter of months she became an invalid.

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.

Studies of Neurotransmitter Function

Neurotransmitter function in bipolar and nonbipolar depressions has been investigated using transmitter metabolite levels in body fluids, receptors on peripheral cells, and receptor function using agonist or neuroendocrine challenge techniques. The studies were guided by a series of simple and heuristically useful hypotheses, summarized in Table 2-1. Despite supporting data for each hypothesis, each also had contradictory findings. At a fairly early stage, it was possible to reject hypotheses that major depression, bipolar or otherwise, stemmed from too much or too little of any transmitter (Maas et al. 1991). The second generation of hypotheses held that balances between transmitters, such as norepi-nephrine versus serotonin (Prange et al. 1974) or norepinephrine (NE) versus acetylcholine (Janowsky et al. 1972), were abnormal. The third generation of hypotheses, logically very close to the first generation, held that second messenger function associated with transmitter receptors was...

Mr Friesen A Case of Doing Ones Best

Friesen, a retired senior civil servant, presented with a multitude of pain complaints, the worst of them being his persistent pain from herpes zoster. He also had a long history of emphysema and periodic episodes of clinical depression. The marriage had a checkered history. The couple attributed their marital problems mainly to his long-standing health issues. Previously they had a daughter living with them who suffered from Down syndrome and was entirely dependent on them. The history revealed that the marriage ran into problems soon after their disabled daughter was born. Mrs. Friesen received very little practical or emotional support from her husband in raising the child, who subsequently died in her late teens.

Central nervous system

Adverse effects include sedation and dry mouth. Tricyclic antidepressants antagonise the antihypertensive action and increase the rebound hypertension of abrupt withdrawal. Low dose clonidine (Dixarit, 50-100 microgram d) also has a minor role in migraine prophylaxis, menopausal flushing and choreas.

Clinical Presentation

Poisoning cannot be overlooked in the evaluation of a child with vomiting and abdominal pain. Among the multiple agents most commonly associated with hospital visits are over-the-counter (OTC) analgesic drugs, cold remedies, insecticides, pesticides, personal care products, and fumes. In a child who presents with vomiting and abdominal pain, a cholinergic syndrome is likely. It is characterized by salivation, lacrimation, diarrhea, vomiting, diaphoresis, intestinal cramps, and seizures. Insecticides and nicotine are among the agents that may induce these symptoms. Antihistamines or tricyclic antidepressants produce dry skin, dry mucosae, urinary retention, and decreased bowel sounds (anticholinergic syndrome). Some medications and substances are radiopaque, such as iron tablets, mercury, lithium, tricyclic antidepressants, Play-Doh. and enteric-coated aspirin. Finding the likely agent of poisoning will mostly depend on the history given.

Adrenergic Neuron Blocking Drugs

Adrenergic neuron blocking drugs are selectively taken up into adrenergic nerve endings by the active, energy-requiring, saturable amine (noradrenaline) pump mechanism (uptake-1). They accumulate in the noradrenaline storage vesicles from which they are released in response to nerve impulses, diminishing the release of noradrenaline and so all sympathetic function. They do not adequately control supine blood pressure and are prone to interactions with other drugs affecting adrenergic function, e.g. tricyclic antidepressants and topical nasal decongestants. They are virtually obsolete in hypertension.

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...

Affected Children The Gardner Family

Gardner's case was discussed in Chapter 3. To recap the essentials, this woman in her forties with a very long history of headaches also developed clinical depression. She was very slow to react to antidepressants. In the meantime, her entire family, consisting of husband and two children, John, aged 17, and Ann, aged 12, came apart at the seams. Ann became a great source of concern to both parents. John was old enough to fend for himself and there was no evidence that he had any particular difficulties. He maintained his closeness with his mother and tried to be as helpful as he could around the house. Even in the depth of her depression, Mrs. Gardner continued to show appreciation for John's fortitude and loyalty.

Using a Comprehensive Checklist for a Thorough Suicide Assessment

Lack of interest or pleasure in usually pleasurable activities Alcohol abuse increase during depressive episodes Diminished concentration Global insomnia To receive a diagnosis of major depression or dysthymic disorder, specific criteria must be met. For the purposes of our discussion here, we focus less on the specific diagnostic criteria and more on the general symptoms usually indicative of depression. Overall, the DSM includes three major categories of depressive symptoms, plus one associated depressive symptom pertinent to our discussion According to the DSM, major depressive disorder in adults can be characterized by one of two primary mood symptoms. As noted, one of the mood symptoms is the existence of a sad or depressed mood. However, even if a sad or depressed mood is not present, adult clients may qualify for depression if they are experiencing the second mood symptom a loss of interest or pleasure in usually pleasurable activities. When clients are depressed, they...

Pubertal Status Effects

Since hormonal changes are the cause of the changes in physical growth and development, it is often difficult to disentangle hormonal and status effects on adjustment. For example, as described in the previous section, a study by Angold and colleagues (1998) found that only after reaching Tanner stage III were girls more likely than boys to experience higher rates of depressive disorder. However, subsequent analyses showed that effects of elevated estradiol and testosterone levels eliminated effects due to secondary sexual characteristics (Angold et al., 1999). This study suggests that when pubertal status effects on adjustment are found, they are likely be driven by hormonal changes.

Suicide Quiz Answers and Explanations

When a suicidal patient begins to improve, that's usually a sign that the danger is over. Sometimes, especially in depressed patients, improvement constitutes the time for greatest concern. Depressed patients may make the decision to commit suicide and consequently appear improved. Other depressed patients may use their increasing levels of physical energy to commit suicide. A great deal of regional variation in suicide can be accounted for by weather variables such as temperature and precipitation. Many people think that suicide rates in rainy and cloudy areas must be much higher, but there is no conclusive evidence for this belief. In fact, sunny and dry Nevada has the highest per-capita suicide rate in the United States. Reports are also mixed on whether the moon is associated with suicidal behavior. Even when it appears that weather or lunar variables are associated with suicide, usually other variables are found to account for this apparent link.

The influence of distress on symptoms

This is not to say the symptoms are 'hypochondriacal' or 'all in the head', but psychological distress can cause more physiological activity because individuals are worked-up, upset or worried. Distress can also change the way we look at things so we make more negative interpretations of symptoms that may arise. We have shown that both CFS and depressed patients tend to interpret the meaning of symptoms in a more negative way than do healthy controls (Moss-Morris and Petrie 1997).

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 .

Drug Interactions With Cannabinoids

Most clinical trials have administered cannabinoids alone to treat a particular disorder rather than in combination with other drugs. There appear have been no adverse interactions of any consequence between a wide range of cancer chemotherapies, when cannabinoids have been given to counteract the nausea and vomiting associated with the latter or indeed during specific studies in man (Riggs et al., 1981). The beneficial effects of administering THC with another antiemetic, prochlorperazine, have been referred to above. Considering the central nervous system depressant action of these agents, it would be wise to be cautious when administering them with other, CNS depressants, such as benzodiazepines, barbiturates, antidepressants and alcohol. The interaction between marijuana smoking and the enhanced metabolism of

Inflammation And Brain Serotonin

As indicated in Section 1, psychopathological symptoms include apathy, agitation, delusions, and depressive symptoms. Depressive symptoms are present in half of patients, and another 25 may suffer delusions. Particularly, agitation and depression are seen in somatic illnesses with inflammatory characteristics (e.g., interferon treatment in hepatitis C, myocardial infarction refs. 103-105). In these psychosomatic disorders, brain serotonin may play a crucial role as for example, selective serotonin uptake inhibitors alleviate concomitant psy-chopathology (106). The cause of these symptoms may in part be explained as the result of awareness of the deteriorating state of patient or by suboptimal functions of, for example, the frontal cortex or parts of the limbic system. The limbic system has classically been associated with mood disorders. In addition, emerging psychopathology may be considered as the direct result of inflammation on brain function, presumably mediated by cytokines...

Diagnostic Interviewing

Tured Clinical Interview for Axis I DSM-IV Disorders First, Spitzer, Gibbon, & Williams, 1995). Other schedules are more specific and circumscribed in their goals for example, some structured and semistructured interview schedules evaluate specifically for substance disorders (Psychiatric Research Interview for Substance and Mental Disorders Hasin et al., 1998), anxiety disorders (Anxiety Disorders Interview Schedule T. Brown, Atony, & Barlow, 1995), depressive disorders (Diagnostic Interview for Depressive Personality Gunderson, Phillips, Triebwaser, & Hirschfeld, 1994), and more. Common adult diagnostic interviews are reviewed and described by Vacc and Juhnke (1997), Kronenberger and Meyer (1996), and R. Rogers, (2001).

Client Personal History

At least a minimal social or developmental history information is necessary for accurate diagnosis. Take the assessment of clinical depression as an example. Currently, DSM-IV-TR lists numerous disorders that have depressive symptoms as one of their primary features, including (a) dysthymic disorder, (b) major depression, (c) adjustment disorder with mixed anxiety and depression, (d) adjustment disorder with depressed mood, (e) bipolar I disorder, (f) bipolar II disorder, and (g) cyclothymic disorder. Additionally, there are a number of disorders outside the general mood disorder category that include depressive-like symptoms or that are commonly comorbid with one of the previously listed depressive disorders. These include, but are not limited to (a) posttraumatic stress disorder, (b) generalized anxiety disorder, (c) anorexia nervosa, (d) bulimia nervosa, and (e) conduct disorder. As you may have already concluded from this rather formidable list, the question is not necessarily...

Clinical Use Of Agents

Dal anti-inflammatory agent e.g., aspirin (ASA) or ibuprofen for mild to moderate pain. If the pain persists or increases, then treatment progresses to the second tier, where a narcotic analgesic is added to the regimen. Frequently, this is accomplished by use of a combination product such as ASA plus codeine that combines an opioid with a nonnarcotic analgesic. The third tier is reached when the pain escalates from moderate to severe. At this level the opioid may be used as a single agent, given that opioids do not have a ceiling to their analgesic effect as do the nonnarcotic analgesics such as ASA and APAP (20). Adjuvant drugs, such as tricyclic antidepressants or an-ticonvulsants, may be added to opioid therapy as a means to enhance the efficacy of opioids for pain relief (17, 21).

Pediatric Bipolar Depression

ALTHOUGH AFFECTIVE DISORDERS IN youths are lately receiving much more attention, they continue to be a diagnostic puzzle. It is estimated that 5 of children and adolescents suffer from major depression, 4 from dysthymia, and 1 from bipolar depression (Lewinsohn et al. 1993). Depression in children and adolescents is a serious condition, associated with considerable morbidity and mortality (Kovacs 1996). As discussed in Chapter 1, Diagnosis of Bipolar Depression, bipolar depression as a clinical entity is underdiagnosed in adults and commonly undiagnosed in children. Pediatric depression was not officially recognized until 1975 (Raskin et al. 1978). Since then, it has been conclusively documented both in the psychiatric community and in clinical settings (Angold 1988a, 1988b Fleming and Offord 1990). The decision to utilize adult criteria to diagnose depression in children can be traced to a 1975 conference at the National Institute of Mental Health, and the practice continues in...

Preventing Reinfarction

The active intervention arm received two or three treatment components group cognitive behavior therapy, provision of social support, and, if necessary, antidepressant medication. A comparison group received usual care. Although the intervention appeared to lower levels of depression more than reductions achieved in the usual care condition, there were no differences in survival between the two groups in the 2 years following infarction. More detailed discussion of depression and cardiovascular events is considered in Chapter 32.

Cultural Issues in Treatment Planning A Case Example

Dolores, a 43-year-old American Indian woman, came to counseling because she was suffering from sadness, inability to concentrate, insomnia, and anhedo-nia. These depressive symptoms were associated with two major concerns. First, Dolores was very upset because her husband of 23 years, Gabe, was suffering from a serious gambling addiction but was refusing to go to treatment. Second, Dolores was worried that, because of her diminished functioning and her husband's gambling, she might lose custody of her adopted daughter, Sage.

Background Gender Differences in Cardiac Rehabilitation

A large US study15 with 1084 women and 1397 men with a minor or major depression were treated when indicated with an SSRI or cognitive behavioral therapy. The intervention did not increase event-free survival, but less depression and less social isolation occurred in the intervention group. Depressive disorders have a clear relationship with CHD. There is overwhelming evidence that major depressions are underdiagnosed and untreated in patients with CHD. Approximately one in five patients have a major depression at the time of a cardiac event.20 Depression will also increase the risk of new cardiac events.21 In patients with CHD, the prevalence of major depression is nearly 20 and for minor depression 27 .22

Physiological Studies

For example, N1-P2 augmenting was reported to be related to risk for suicidal behavior, regardless of diagnosis (Buchsbaum et al. 1977), and to be inversely proportional to serotonergic function (Brocke et al. 2000 Hegerl et al. 2001) decreased amplitude and delayed onset of P300 was associated with anhedonia (Dubal et al. 2000). One problem in identifying these results is that some of the bipolar depressed patients may have been experiencing mixed episodes, with manic features accounting for some of the findings that differentiated them from nonbipolar depressed patients.

Peripheral Neuropathy

The pain arising from damage to peripheral nerves can be extremely difficult to control satisfactorily. Patients will commonly describe their pain as a constant burning, tearing or pricking sensation. Diabetic neuropathy is a good example and for some patients the use of tricyclic antidepressants or anticonvulsants is satisfactory. However, for others, these may be ineffective. Conventional analgesics are often of little use.

Is This Pain or Abuse

A major change occurred when their son moved out. Her husband became increasingly menacing. About the same time, she sought psychiatric help for depression and was put on antidepressant medication. She failed to disclose her marital situation to the psychiatrist. The abuse gradually escalated to the point of physical violence. Just about a year before her first visit to the pain clinic, she was hit by her husband around her shoulders. She became very fearful of him as she was totally unsure of how and why she invited his wrath. Rita finally told their son about the hitting, but he just did not believe her. His view of his father was that of a gentle and kind soul who would not hurt a fly. In fact, her husband encouraged her to go to the police. They would see her as a crazy woman and would never believe her. This was her dilemma that no one would believe that her husband was an abusive man.

Clinical Approach

If cognitive decline occurs with prominent mood disturbance, then one consideration is depression or pseudodementia. Distinguish which occurred first often is difficult because many elderly patients with cognitive decline and a declining level of independent functioning suffer from a reactive depression. History provided by involved family members regarding the onset of symptoms or history of prior depression or other psychiatric illness may help establish the diagnosis, and an empiric trial of antidepressants may be considered.

Introduction Analysis Of Urinary Drugs In Clinical And Forensic Toxicology

Clinical and forensic toxicology is concerned with the detection, identification, and measurement of toxic compounds and their metabolites in human body fluids and tissues. Most often the toxic compounds are drugs taken either accidentally or intentionally in quantities sufficient to cause an adverse reaction or death. Analysis and identification of a possible drug or drug combinations, toxicological drug screening and confirmation should encompass as many different classes of drugs as possible. The most important classes being salicylate, paracetamol, antiepileptics, antidepressants, neuroleptics, hypnotics (benzodiazepines, barbiturates, diphenhydramine), digoxin, and theophylline, as well as many illicit drugs, such as opiates, methadone, D-lysergic acid diethylamide (LSD), cocaine, and or its major metabolite benzoylecgonine, cannabinoids and amphetamines. Currently, urinary drug monitoring has established itself as the basis of clinical and forensic toxicology. It is also the...

Sex Differences In Personality Traits Coping And Stressrelated Psychiatric Disorders

Women have higher rates of internalizing disorders, including anxiety and depressive disorders. There also appear to be some sex differences in physiological and behavioral coping with traumatic and chronic adverse life events. For example, women are more likely than men to develop posttraumatic stress disorder (PTSD) following traumatic events (Weiss, Longhurst, & Mazure, 1999 Widom, 1999). Furthermore, experiences of early trauma, such as physical and childhood sexual abuse, have been found to confer a greater susceptibility to developing psychiatric illness and illicit drug abuse on women than on men (MacMillan et al., 2001). The well-known association between adverse life events and increased risk of major depression is significantly higher in women than in men (Maciejewski, Prigerson, & Mazure, 2001). Early life trauma is associated with an increased HPA reactivity to acute and chronic stressors in women (Heim et al., 2000 Nemeroff, 1996). Women with major depression show...

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).

Helplessness and Depression

Seligman (1975) argued that the research on learned helplessness provides a model for clinical depression. For example, there is evidence that helplessness is involved in the relationship between alcohol dependence and depression (Sitharthan, Hough, Sitharthan, & Kavanagh, 2001). More generally, thousands of people each year are diagnosed as depressive. These individuals show insomnia, report feeling tired, often say that life is not worth living, have difficulty performing routine tasks, and may be suicidal. Clinical depression is severe, long lasting, and is not easily traced to a recent environmental experience. Seligman (1975) has suggested that the behavior of helpless dogs may be relevant to the origin and treatment of clinical depression. Depression may arise when a person has a history of inescapable abuse. This could occur when a parent, spouse, or caretaker unreasonably and severely mistreats a child, partner, or elderly person. In other writings, Seligman and his...

Analysis Of Antibiotics

The specimen of choice for chloramphenicol testing is serum, but heparinized and EDTA plasma or cerebrospinal fluid can be analyzed. Typically the trough level is used to evaluate therapeutic effects and the peak level, drawn 1 to 2 hours postdose, is used to monitor toxic levels of chloramphenicol. Often a clotted blood sample is to be collected, but the container should not have gel separation barriers, which leach out some drugs. Likewise, some drugs such as lidocaine, propranolol, and tricyclic antidepressants are disturbed by the plasticizer found in some stoppers (TBEP), so special collection tubes may be required.5

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-

Other Therapeutic Drugs Psychoactive Drugs

Other common psychoactive drugs that require some therapeutic monitoring include tricyclic antidepressants, amitriptyline, desipramine, imipramine, and nortriptyline. Alternative psychoactive drugs are available on the market, but there is a lack of defined concentration-effect relationship for newer psychoactive drugs. Therefore, there is not much value in monitoring blood levels of these drugs.17 For detailed information about these medications, please refer to the table in the appendix.

Mood And Anxiety Disorders

Almost one in five people will experience a significant mood or anxiety disorder at some stage in life. The lifetime prevalence rates of Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) mood and anxiety disorders are shown in Table 11.1. As can be seen, the lifetime prevalence of major depression is almost twice as high for females as for males, and this is a robust finding in the literature (Blazer, Kessler, McGonagle, & Swartz, 1994 Breslau, Schultz, & Peterson, 1995 Kendler & Prescott, 1999 Newman, Bland, & Orn, 1988 Parker & Hadzi-Pavlovic, 2001). Major depressive episode 12.7 21.3 ing nine commonly used definitions of major depression. As is shown in Table 11.2, depending on the definition, the lifetime prevalence rates for major depression ranged from 12 to 33 . The broadest criteria (DSM-III, Research Diagnostic Criteria RDC probable, and DSM-III-R) have the highest prevalence rates of 31 to 33 . Intermediate criteria...

Culturebound Syndromes

The information in Table 13.2 reveals many things about the broad field of mental health diagnostic systems. First, symptoms may be similar across cultures, but causes may be viewed very differently. (Psychotic thinking, anxiety, or depressive symptoms may be consistently described across cultures but attributed to satanic influence, bad behavior, brain disease, trauma, family patterns, learning, etc.) Second, causes of human distress (brain disease, trauma, exposure, grief, attachment loss or disturbance)

What Is the Nature of the Association

Not only do people with various clinical forms of major depression consistently report higher levels of neuroticism (Fanous, Gardner, Prescott, Cancro, & Kendler, 2002 Kendler, Gardner, & Prescott, 2002 Kendler, Kessler, Neale, Heath, & Eaves, 1993 Kendler, Neale, Kessler, Heath, & Eaves, 1993b Roberts & Kendler, 1999 Treloar, Martin, Bucholz, Madden, & Heath, 1999), but the association appears to be causal, because neuroticism or neuroticism-like traits can predict future cases of mood and anxiety disorders. Kendler and colleagues (1993b), in a study of 1733 same-sex female twin pairs, found that neuroticism was strongly related to lifetime prevalence of major depression. Neuroticism also predicted the prospective 1-year prevalence of major depression in those who, at time 1, denied previous depressive episodes, and this was not merely because of overlap with prodromal symptoms of major depression. noses of major depression, dysthymia, obsessive-compulsive disorder...

Alcohol and Substance Use Disorders

Nicotine use and dependence is increasingly recognized as being associated with suicide in bipolar disorder. In a cohort of subjects with unipolar and bipolar disorders followed prospectively after an episode of major depression, smoking was amongst the three most powerful predictors of a future suicide attempt, and was additive with the other two a history of a suicide attempt and severity of depressive symptoms (Oquendo et al. 2004). This association between nicotine use and suicide is present across several major mental illnesses, and may be related to lower brain serotonin function (Malone et al. 2003). The direction of the relationship between smoking and suicide and whether it is causal is unknown. It would be important to understand whether nicotine use

Sources of Covariance among Neuroticism Mood Disorders and Anxiety Disorders

Based on data from the Australian Twin Registry, Jardine and colleagues (1984) examined the covariance between the symptoms of anxiety and depression, using a shortened version of the Delusion Symptoms States Inventory (Bedford & Deary, 1997 Foulds & Bedford, 1975) as well as the Neuroticism scale from the EPQ (Eysenck & Eysenck, 1975). Their results revealed that the phenotypic covariation between the two measures could be best explained by a single genetic factor common to both measures. There was no evidence for genetic factors specific to one measure and having no influence on the other. In a longitudinal design based on 1733 same-sex female twin pairs, Kendler and colleagues (1993b) have estimated that the proportion in the observed correlation between neuroticism and the liability to major depression that could be explained by a shared genetic risk was approximately 70 . In the same study, extraversion was unrelated to lifetime or 1-year prevalence of major depression....

Christel M Middeldorp Danielle C Cath Mireille van den Berg A Leo Beem Richard van Dyck and Dorret I Boomsma

In all studies taking these approaches, neuroticism was related to major depression and anxiety disorders (Bienvenu et al., 2001 Brown, Chorpita, & Barlow, 1998 de Graaf, Bijl, ten Have, Beekman, & Vollebergh, 2004 Johnson, Turner, & Iwata, 2003 Krueger, McGue, & Iacono, 2001 Trull & Sher, 1994). In addition, all studies except one (Johnson et al., 2003) found a relation between low extraversion and one or more of the anxiety disorders, although results were not always consistent on the level of specific diagnoses (Bienvenu et al., 2001 Brown et al., 1998 Trull & Sher, 1994). Results were contradictory regarding the relation between low extraversion and major depression. Brown and colleagues (1998) and Trull and Sher (1994) did find an association, whereas Bienvenu and colleagues (2001) and Johnson and colleagues (2003) did not. Krueger and colleagues (2001) found that internalization a factor on which depression and anxiety disorders loaded correlated negatively...

Psychopharmacologic Interventions Potential Prophylactic Effects

Appropriate maintenance treatment is essential to the well-being of bipolar patients. Although mood stabilization tends to be the immediate goal of psychopharmacologic intervention, clinicians should also consider potential suicidality when treating a bipolar patient. Appropriate maintenance treatment can substantially reduce the risk of suicide (Ba-ethge et al. 2003 Coppen and Farmer 1998 Tondo and Baldessarini 2000, 2001a), but how do we decide what constitutes appropriate maintenance when it comes to suicide prevention Although a variety of mood stabilizers, antidepressants, and antipsychotics have been the focus of research in this realm, the answer is not eminently clear. A third meta-analysis of 32 randomized, controlled trials was recently reported (Cipriani et al. 2005). In these studies, 1,389 patients were randomized to lithium and 2,069 to other agents, including placebo (n 779), antidepressants (n 247), and other mood stabilizers and combination treatments. Lithium...

Klaus Peter Lesch and Turhan Canli

Brain serotonin (5-HT) has been implicated in a number of physiological processes and pathological conditions. These effects are mediated by at least 14 different 5-HT receptors. Although multiple lines of evidence implicate the 5-HT1A receptor in the pathophysiology of anxiety disorders and depression, as well as in the mechanism of action of anxiolytics and antidepressants, its relevance to the therapeutic effectiveness of these drugs has been a matter of considerable debate (Griebel, 1995 Hensler, 2003 Hjorth et al., 2000 Lesch, Zeng, Reif, & Gutknecht, 2003).

Methods for Locating Genes

Linkage, the oldest of these methods, has been used in genetic studies for many years. Some of the very early psychiatric studies applied this technique to finding gene locations for mental illness by using knowledge of Mendelian patterns of transmission. For example, George Winokur, who was chairman of the department of psychiatry at Iowa for many years and an eminent investigator of bipolar disorder, made the observation that manic-depressive illness and red-green color blindness co-occurred in some families. He also noted that father-to-son transmission rarely occurred in bipolar disorder. This led him to propose that bipolar illness might be linked to the X chromosome. Although this observation has not been consistendy replicated, perhaps because the gene is one of small effect in a polygenic multifactorial disorder, it may point to one of the genes involved in bipolar illness. As the search for disease continues, investigators must also worry about another problem environmental...

Bipolar Depression

Similar to that seen for antidepressants in the treatment of unipolar depression (Stark and Hardison 1985). Despite the slow titration schedule, the lamotrigine groups separated from placebo at 3 weeks (1 week after reaching the 50-mg dose), and remained superior for the remaining 4 weeks of the study (Calabrese et al. 1999b).

Genetic Variation In The 5ht Transporter

In their initial study, Lesch and colleagues (1996) also demonstrated that individuals carrying the S allele are slightly more likely to display abnormal levels of anxiety than are L L homozygotes. Since their original report, others have confirmed the association between the 5-HTTLPR S allele and heightened anxiety (Du, Bakish, & Hrdina, 2000 Katsuragi et al., 1999 Mazzanti et al., 1998 Melke et al., 2001), and have also demonstrated that individuals possessing the S allele more readily acquire conditioned fear responses (Garpenstrand, Annas, Ekblom, Oreland, & Fredrikson, 2001) and develop affective illness (Lesch & Mossner, 1998) than do those homozygous for the L allele. Recent studies utilizing pharmacological challenge paradigms of the 5-HT system suggest that these differences in affect, mood, and temperament may reflect 5-HTTLPR-driven variation in 5-HTT expression and subsequent changes in synaptic concentrations of 5-HT (Moreno et al., 2002 Neumeister et al., 2002...

Acute Efficacy in Bipolar I Disorder

In the acute phase, a good amount of evidence suggests that antidepres-sants are more effective than placebo (mostly in the absence of concomitant mood stabilizer) or that certain antidepressants may be more effective than others in RCTs of the acute major depressive episode in bipolar disorder (Amsterdam 1998 Amsterdam et al. 1998 Cohn et al. 1989 Himmelhoch et al. 1982, 1991 Simpson et al. 1991 Thase et al. 1992). Those early studies did not use concomitant mood stabilizers. In the only RCT to assess antidepressant efficacy in lithium-treated patients, imipramine and paroxetine were not overall more effective than placebo when added to lithium for treatment of the acute depressive symptoms in patients with bipolar disorder type I. However, in a secondary analysis of those with low lithium levels (< 0.8), both antidepressants were superior to placebo when added to lithium (Nemeroff et al. 2001). In summary, some antidepressants may be more effective than others in treating bipolar...

Acute Efficacy in Bipolar II Disorder

Some investigators suggest that antidepressants may be effective in type II bipolar depression. In a post hoc pooled analysis of unipolar RCTs, 89 bipolar II subjects were identified in a cohort of 839 fluoxetine- prove efficacy of antidepressants in type II bipolar depression, namely a prospective, double-blind, RCT of sufficient size. No such study has been conducted with standard antidepressants. Therefore, while one might conclude based on the above studies that such efficacy might exist, better research is needed to prove it. The conclusions just discussed may seem to conflict with a recent meta-analysis of RCTs of antidepressants for bipolar depression (Gijsman et al. 2004), which concluded that short-term antidepressants are effective in bipolar depression and that overall switch rates into mania hypoma-nia appear similar for antidepressants (3.8 ) and placebo (4.7 ). Yet there are major problems with the validity of this meta-analysis (Ghaemi and Goodwin 2005)....

Prophylactic Efficacy in Bipolar Disorder

All of the above discussion only relates to acute efficacy. What should one do when the patient is currently depressed If one uses an antidepressant, the next question is what should be done after recovery from the current depression. If the patient responds to an antidepressant, should it be continued or not In other words, do antidepressants prevent new depressive episodes in bipolar disorder The available evidence suggests that, overall, antidepressants do not appear to have long-term preventive benefits in bipolar depression. There have been six double-blind RCTs of prophylaxis of bipolar disorder with antidepressants (Ghaemi et al. 2003). Those studies all compared imipramine with placebo or with lithium. In all cases, imipramine alone or with the addition of lithium were not more effective than lithium alone in the prevention of mood episodes in bipolar disorder. In all cases, there was no added benefit from using imipramine long term. Thus, if one were to conduct a systematic...

Gene Environment Interactions

Given that genes may be expressed through the creation of environmental risks, genetic influences are also hypothesized to influence an individual's susceptibility to such risks (gene-environment interaction). An alternative way of conceptualizing these interaction effects is that the occurrence of the environmental risk factor elicits or activates the genetic predisposition to the pheno-type. In either scenario, an interaction arises when one variable (e.g., a genetic risk factor) has differential effects at varying levels of the other (e.g., an environmental risk factor). We can better illustrate this point by means of a figure. Figure 16.1 presents the results of a family-based design, which utilized data from 1818 adolescent offspring and 1294 parents from the G1219 study (a large community U.K.-based study investigating familial resemblance for emotional and behavioral problems) to examine the effects of parental education and genetic vulnerability on adolescent depressive...

Cognitive and Biological Functioning in Children at Risk for Depression

Major depressive disorder (MDD) is a devastating, sometimes fatal psychological disorder that afflicts nearly one-fifth of the population, making it one of the most prevalent of all psychiatric disorders. MDD is characterized by at least a 2-week period of persistent sad mood or loss of interest or pleasure in daily activities, as well as a number of associated symptoms, such as weight loss or gain, appetite loss, sleep disturbance, psychomotor retardation, fatigue, feelings of worthlessness, and concentration difficulties (American Psychiatric Association, 2000). Clinically significant depression is a pressing societal problem, placing a burden of almost 50 billion per year on the American economy and accounting for over 20 of costs for all mental illness (Stewart, Ricci, Chee, Hahn, & Morganstein, 2003). Moreover, depressive disorders are associated with both an elevated risk of suicide (Hirschfeld & Goodwin, 1988) and an increased risk of mortality from other causes (Murphy,...

Children At Risk For Depression

Research examining depression during childhood and adolescence clearly demonstrates that children can become depressed. Although depressive disorders are less common in early childhood, prevalence rates of depression become comparable to rates in adults by middle adolescence. Consequently, investigators have postulated that mood disorders usually have their first manifestation in middle to late adolescence, making this a particularly vulnerable period for the development of depression (Hankin et al., 1998). Importantly, follow-up studies have shown that depression in childhood and adolescence tends to recur (Kovacs & Paulaukas, 1984), and that continuity exists between childhood and adult mood disorders. Indeed, longitudinal studies have found that children and adolescents with depression tend to have recurrent depressive episodes as adults (e.g., Harrington, Fudge, Rutter, Pickles, & Hill, 1990). Moreover, Pine, Cohen, Gurley, Brook, and Ma (1998) found that depressive...

Neural Bases Of Emotion Regulation And Reward Responsivity In Depression

Although investigators have long speculated about deficits in neural functioning in depression, only relatively recently have advances in neuroimaging allowed researchers to examine neural aspects of depressive disorders. Indeed, depression has now been found to be associated with abnormalities of several cortical and subcortical regions, including the hippocampus, prefrontal cortex, ACC, and amygdala (e.g., Davidson et al., 2002 Mayberg, 2002). Initial research in this area focused largely on differences between currently depressed and nondepressed adults in the volume of these anatomical structures. Drawing on recent findings concerning the involvement of specific structures in emotion regulation, more recent investigations have examined depression-associated differences in patterns of neural activation in response to the processing of emotional stimuli.

Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is an effective treatment for bipolar depression (Zornberg and Pope 1993). Several authors examined whether ECT is more effective in bipolar depression than in unipolar depression. Except for the results reported by Perris and d'Elia (1966), no advantage for bipolar depression over unipolar depression was found. Kukopulos et al. (1980) suggested that ECT, in contrast to tricy-clic antidepressants, does not induce an accelerated course of bipolar illness. However, these authors reported that 39 of their patients developed mania while treated with ECT.

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.

Psychotherapy Treatment Of Nuclear Symptoms And Associated Problems

There are several problems often associated with bipolar disorders that may worsen the quality of life of patients and therefore deserve special attention. Patients may run into problems during their adjustment to a diagnosis common reactions to receiving a diagnosis of a severe, chronic illness are denial, anger, ambivalence, and anxiety (Goodwin and Jamison 1990). It is essential for the clinician to respond appropriately in order to to improve illness awareness, treatment compliance, and avoid self-esteem problems (Colom and Vieta 2002a, 2002b). Another problem that should be carefully addressed by therapists is a patient's feeling of loss and grief after the loss of real or abstract objects, such as a job (which is mentioned by 70 of patients and their partners as the most relevant difficulty in the long term Targum et al. 1981 ), job status (which affects more than 30 of patients Harrow et al. 1990 ), economic status, and loss of love relationships and family support. All of...

Future Directions For Practice And Research

UNTIL RELATIVELY RECENTLY, the development of new pharmacological treatments for depression focused so much on unipolar depression that major depression and unipolar seemed almost to be synonymous. Perhaps bipolar depression had taken a back seat because, until recently, all of the agents developed specifically for the treatment of bipolar disorder were introduced as antimanic agents. When depression did occur in a bipolar patient, it was treated with the same antidepressant agents developed for unipolar depression. Now, with the development of new agents (lamotrigine and perhaps also quetiapine) that may be more effective for bipolar than for unipolar depression, interest in bipolar depression has heightened. Another reason for this new emphasis on bipolar depression is recent longitudinal research indicating that depression represents the bulk of the morbidity associated with bipolar disorder. This component of the illness lasts much longer than the manic component, is harder to...

From Clinical Phenomenology To Diagnostic Validity

The first subject that future research must clarify is the diagnostic validity of our current classification scheme. Considering just depression per se, are the bipolar and unipolar forms different Unfortunately the structure of DSM-IV-TR distinguishes bipolar disorder as a separate illness distinct from all other mood disorders (i.e., from the depressive disorders). Thus, the current DSM system obscures the fact that, originally, the bipolar-unipolar distinction was conceived of as a way to distinguish two forms of a recurrent illness. In other words, the DSM structure gives precedence to polarity over cyclicity or recurrence, thereby obscuring the reality that one rather common variant of unipolar illness is as recurrent or cyclic, much like bipolar illness. Kraepelin's original focus on course and recurrence has been lost to the detriment of research and practice. Just as the wastebasket of disorders subsumed under the DSM-IV-TR diagnosis of unipolar major depressive disorder is...

Directions For Genetic Research

In one study, liability to major depression or generalized anxiety disorder was explained by a genetic model involving a large contribution of additive, nonmendelian genetic inheritance and a smaller contribution of specific environmental effects (the slings and arrows of outrageous fortune) no significant contribution could be found for either mendelian genetic inheritance (i.e., dominant or recessive qualitative patterns, as opposed to additive quantitative patterns) or for shared (i.e., family) environmental effects (Kendler et al. 1993b). This result would suggest that psychosocial research should concentrate on current environmental stressors rather than childhood or family experiences, as has traditionally been the case. Further work is needed to confirm or refute these suggestive findings. To expand on this theme, one of the most consistently observed associations between early psychosocial factors and the development of mental disorders in adults has been the...

Advances In Clinical Psychopharmacology

Without doubt, the greatest practical advance in the treatment of bipolar depression has been the development of lamotrigine as a mood stabilizer with a prominent long-term benefit for depressive symptoms (Calabrese et al. 2003). Despite its small, but real, risk for StevensJohnson syndrome, lamotrigine is also generally well tolerated, thus providing patients an alternative to other mood stabilizers (which have only modest effects against depression and substantially more side effects) and antidepressants (which carry some risk of long-term destabi-lization in addition to more side effects). Nevertheless, many patients still do not respond to or do not tolerate lamotrigine. Unfortunately, the last decade has not seen much progress in knowledge about the efficacy and safety of traditional antidepressants in bipolar depression. As reviewed in a recent meta-analysis (Gijsman et al. 2004), only five placebo-controlled, randomized clinical trials (RCTs) of antidepressants seem to exist,...

Integrating Biological And Psychosocial Aspects Of Mood Disorder

Certainly, an important goal is to integrate psychopharmacological clinical trials with psychotherapeutic aims of treatment and to include combinations of the two treatment modalities as well. This research has valuable practical implications for instance, current data suggest that decisions regarding medication as a component of treatment versus psychotherapy alone (specifically, interpersonal or cognitive-behavioral therapy) should be based more on the nature of the symptoms and especially on whether an illness is recurrent or not, than on speculative etiological bases for the illness. The latter point regarding recurrence is reinforced by Frank et al.'s (1990) landmark study comparing imip-ramine, interpersonal therapy, a combination of the two, and placebo, in which those with three or more episodes responded better to medication or combination treatment than to psychotherapy alone. In other studies of patients with one or two episodes of illness, CBT tended to be as effective as...

Ethics And Public Policy New Questions

Profession needs to be more involved in communicating with and participating in governmental structures to ensure that such funding is available. As the federal budget is tightened in the United States, research funding is increasingly found in the private sector, mainly in the pharmaceutical industry. For investigators participating in pharmaceutical industry-sponsored research, it is necessary not only to appreciate the benefits that accrue for both the industry and society from advances in this research, but also to recognize that the private sector may have financial interests that may not be shared by society at large. The recent debate about antidepressants and risk of suicide (Cipriani et al. 2005) has brought this issue to the forefront. As scientists, future researchers will have to continue to promote the needs of science and society as primary, while also acknowledging that much less research would be possible without the involvement of the pharmaceutical industry....

Druginduced liver damage

Sedatives, antidepressants and antiepilepsy drugs should be avoided or used with extreme caution in patients with advanced liver disease, and particularly those with current or recent hepatic encephalopathy. Enhanced sensitivity of the CNS to such drugs is well documented and adds to the pharmacokinetic changes. Treatment of alcohol withdrawal in patients with established liver disease using chlormethiazole is hazardous, especially given i.v. The temptation to give initial large doses to control agitation must be avoided because this drug, which normally has a high hepatic extraction, can readily accumulate to toxic concentrations. Chlordiazepoxide is preferred. Acute hepatocellular necrosis. This reaction varies from a transient disturbance of liver function tests to acute hepatitis. It can be induced by several drugs including general anaesthetics (halothane), antiepileptics (carbamazepine, phenytoin, sodium valproate, ph nobarbital), antidepressants (MAO...

Stress And Glucocorticoid Effects On Learning And Memory

Studies in humans also support a link between high circulating GC levels and poor learning and memory, although these impairments are not specific to hippo-campal function. However, two studies in nonhuman primates have indicated that GC receptors are expressed in the frontal and prefrontal cortices at levels similar to or greater than the hippocampus 10, 68 , predicting that GC effects on memory may not be greatest in hippocampus-dependent tasks in the primate. Injection of synthetic cortisol in young adults during the peak (highest level) or trough (lowest level) of the diurnal rhythm of endogenous secretion produced an impairment or facilitation of memory, depending on the time of injection 68 . That is, at the highest levels (the combination of both exogenous and endogenous GCs), acutely elevated GCs impaired performance, while at the lowest levels, performance improved. Repeated injections of synthetic cortisol over ten days in healthy, young adult humans have been shown to...

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...

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. People did not follow up on Cade's observation immediately, however, and it was not until the 1960s that Mogens Schou, a Danish psychiatrist, completed systematic studies of the therapeutic effects of lithium in mania. He demonstrated that when treated with lithium, manic patients recovered almost completely from their manic episodes within a few weeks. He went on to explore whether lithium might also be helpful in normalizing mood over the long run by conducting careful longitudinal studies of a relatively large series of bipolar patients. People who had previously been prone to relapse into manic or depressive episodes were found to have a stabilized mood, with...

Defeat Depression

Defeat Depression

Learning About How To Defeat Depression Can Have Amazing Benefits For Your Life And Success! Discover ways to cope with depression and melancholic tendencies! Depression and anxiety particularly have become so prevalent that it’s exceedingly common for individuals to be taking medication for one or even both of these mood disorders.

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