Depression No More

Destroy Depression

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

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The Frequency Of Depressive Disorder

Table 1.4 Annual and lifetime prevalence of major depressive episode from studies Table 1.4 Annual and lifetime prevalence of major depressive episode from studies Table 1.5 Prevalence rates for depressive disorders recent large-scale surveys Table 1.5 Prevalence rates for depressive disorders recent large-scale surveys Age 15-54 1-year prevalence University of Michigan version of CIDI DSM-IV major depressive disorder 1-year prevalence ICD-10 depressive episode Automated presentation of CIDI 1-week prevalence CIS-R ICD-10 depressive disorder 1-week prevalence CIS-R ICD-10 depressive disorder Some community psychiatric studies using SCAN have now been published (WHO, 1992). Two are British and are located in Camberwell (inner south London) and Derry (Londonderry), Northern Ireland, respectively (Bebbington et al., 1997 McConnell et al., 2002). The 1-year prevalence rates of ICD-10 depressive episode were 6 and 7 , respectively. The rate in Derry would be expected to be higher than in...

Imaging bloodflow change in depressive disorder

Detected in the 'resting' brains of depressed patients.(2 25) Many resting-state studies have shown a reduction of regional brain functional activity, most frequently reported in the prefrontal cortex, compared with normal controls. However, the exact location of prefrontal change (dorsolateral, ventrolateral, orbitofrontal, and medial frontal areas) has been variably emphasized by different authors.(2 25 and 26) Psychological challenge paradigms have been applied in a few studies in depressed cohorts to test whether specific brain regions, subserving select cognitive processes, are impaired in depressed patients. For example, the Tower of London planning task has been used to investigate a 'planning network' in depressed patients 27) Patients in this study showed reduced activity throughout the network with complete loss of functional activity in the anterior cingulate cortex a cortical region involved in attentional processing and highly connected with other prefrontal areas. Using...

The Genetic Epidemiology Of Major Depression

The study of genetic epidemiology is of interest because it seeks to attribute a relative weight to the effects of genes, the shared and non-shared environment, and gene-environment interactions. Sullivan and colleagues (2002) have recently reviewed the literature on the genetic epidemiology of major depression, using specific inclusion criteria. On the basis of the five family studies that met their criteria, they concluded that the odds ratio of being affected with major depression in the first-degree relatives of probands compared with those of unaffected comparison subjects was around 2.8. Twin studies are capable of providing estimates for the relative strength of genetic effects and the effects of the shared and non-shared environments. Sullivan and colleagues (2002) reviewed five studies covering 21 000 individuals that met their criteria. Although the studies showed appreciable variation in the heritability of major depression, all reported significant heritability estimates,...

Major depression with or without melancholia

Obvious in major depression than in mild depression. Diagnosis of major depression according to DSM-IV requires at least five of the nine symptoms in Table 1, and ICD-10 requires six of the ten symptoms in Table. Negative beliefs such as 'loss of self-esteem' or 'inappropriate guilt' are the core symptoms of major depression. Inappropriate guilt is experienced as punishment for past misdeeds (prior to the current episode of depression). The prevailing element of negative beliefs is a sense of loss which is associated with lower self-esteem experienced retrospectively.(9) The symptom which discriminates best between anxiety states and major depressive disorder is guilt. (1

Depressive disorders Diagnostic issues

A key issue for the epidemiology of depressive disorders is defining the boundaries of major depression and dysthymia. Depressive symptoms in the community are common, and defining both the symptom count and the duration at which depressive symptoms count as part of a clinical disorder is arbitrary. Recently, Kendler and Gardner*7) examined the boundaries of major depression as defined by DSM-IV in a population-based twin sample of women. They found that, if a twin had four or fewer depressive symptoms, syndromes composed of symptoms involving no or minimal impairment, and episodes lasting less than 14 days, then the individual's co-twin was still at an increased risk of major depression. Kendler and Gardner concluded that they could find no empirical support for the DSM-IV requirement of duration for 2 weeks, five symptoms, or clinically significant impairment. These authors suggested that major depression, as articulated by DSM-IV, may be a diagnostic convention imposed on a...

Medication and physical treatments Acute treatments for depression Antidepressants general issues

The first modern antidepressants, tricyclics and monoamine oxidase inhibitors, became available in the late 1950s, coinciding with the introduction of randomized controlled trials in psychiatry, which were therefore widely used for these drugs. A progressive tightening of requirements by drug licensing authorities since has ensured that efficacy evidence is good for most antidepressants in use. Overall efficacy of most antidepressants appears to be similar as does speed of response at effective dose, although newer drugs with lower side-effects may permit more rapid build-up of dose. The evidence also indicates limitations in the magnitude of efficacy. Differences in proportions of subjects responding well on antidepressant and on placebo are of the order of 30 per cent. Few reviews have used the concept of effect size, but they suggest effect sizes of 0.4 to 0.8. (1. This is partly due to the good response often seen in placebo groups in controlled trials. This group controls for all...

Clinical use of antidepressants

For most antidepressants, side-effects are most apparent in the early weeks and some tolerance develops so that build-up of dose over 2 to 3 weeks is advisable. Newer drugs, better tolerated, allow more rapid dose escalation. For fluoxetine, the exceptionally long half-life of the active metabolite means that blood levels build up for some weeks, even on a standard dose. Dose division during the day can be based on pharmacology. Half-lives of most antidepressants are such that, combined with delay in therapeutic effects, one dose per day is adequate, but for most, two doses per day is better three doses are useful where daytime sedation is an advantage. For fluoxetine only a single dose is appropriate. Moclobemide, as a competitive monoamine oxidase inhibitor which is easily displaced and metabolized, should be given in three doses daily. For sedative antidepressants, administration of two-thirds of the dose at night is beneficial and enables avoidance of hypnotics, although it may...

Management of depressive disorders

Depression usually responds to a combined approach of antidepressant medication and cognitive therapy. Selective serotonin re-uptake inhibitors (SSRIs paroxetine, fluoxetine, sertraline) are replacing tricyclic antidepressants (dothiepin, amitriptyline, imipramine) as the first choice drugs in the treatment of depression. They are better tolerated, safer in overdose, and cause fewer side effects in the presence of physical illness. Other newer antidepressants, such as venlafaxine and mirtazapine, increase the availability of both serotonin and noradrenaline, and can be effective if there is an inadequate clinical response to one of the SSRI drugs. Monoamine oxidase inhibitors (phenelzine, tranylcypromine) are also effective in depressive illness. They are used by some psychiatrists as the preferred drug when depression is accompanied by anxiety, phobic symptoms, weight gain, hypersomnia, and fatigue. For many years they have been underused because of fears of their interaction with...

Efficacy of serotonergic versus adrenergic antidepressants

Whilst anecdotal reports have suggested that clinical benefit can be obtained with a range of antidepressant medications, consistent effectiveness has only been demonstrated for the SRIs. Several studies have directly compared clomipramine with other antidepressants and a consistent pattern emerges antidepressant drugs that are less potent SRIs than clomipramine are generally ineffective in OCD.(7.,8 and 918)

The use of antidepressants for pain relief

Antidepressant drugs are often used for the treatment of pain in patients who are not depressed. Randomized controlled trials (19 indicate that antidepressants, in doses within the usual therapeutic range, provide more effective analgesia than placebo preparations in the treatment of diabetic neuropathy, postherpetic neuralgia, and atypical facial pain, as well as chronic non-malignant pain. Antidepressants are more effective than acetylsalicylic acid and benzodiazepines. Different tricyclic antidepressants appear to be equally effective and are more effective than selective serotonin reuptake inhibitors. The analgesic effect occurs in patients who are not depressed and is independent of any antidepressant effect.

Acute treatment of major depression

The first acute study of IPT was a four-cell, 16-week randomized trial comparing IPT, amitriptyline (AMI), combined IPT and AMI, and a nonscheduled control treatment for81 outpatients with major depression (DiMascio et al., 1979 Weissman et al., 1979). Amitripty-line more rapidly alleviated symptoms, but, at treatment completion, there was no significant difference between IPT and AMI in symptom reduction. Each reduced symptoms more efficaciously than the control condition, and combined AMI-IPT was more efficacious than either active monotherapy. Patients with psychotic depression did poorly on IPT alone. One-year follow-up found that many patients remained improved after the brief IPT intervention. Moreover, IPT patients had developed significantly better psychosocial functioning at 1 year, whether or not they received medication. This effect on social function was not found for AMI alone, nor was it evident for IPT immediately after the 16-week trial (Weissman et al., 1981). The...

Geriatric depressed patients

IPT was initially used as an addition to a pharmacotherapy trial of geriatric patients with major depression to enhance compliance and to provide some treatment for the placebo control group (Rothblum et al., 1982 Sholomskas et al., 1983). Investigators noted that grief and role transition specific to life changes were the prime interpersonal treatment foci. These researchers suggested modifying IPT to include more flexible duration of sessions, more use of practical advice and support (for example, arranging transportation, calling physicians), and the recognition that major role changes (for example, divorce at age 75) may be impractical and detrimental. The 6-week trial compared standard IPT to nortriptyline in 30 geriatric, depressed patients. The results showed some advantages for IPT, largely due to higher attrition from side effects in the medication group (Sloane et al., 1985). Reynolds et al. (1999) conducted a 3-year maintenance study for geriatric patients with recurrent...

Depressive mood disorders

Convulsive therapy achieved its widest use and greatest efficacy in the relief of mood disorders, both depression and mania. Depressive mood disorders, dominated by sadness, hopelessness, fear of the future, and persistent thoughts that life is no longer worth living, are evinced in several forms melancholia, delusions, pseudodementia, and catatonia. Melancholia, or melancholic depression, is manifested by vegetative symptoms of inability to sleep, interrupted feeding, and weight It is useful to identify the various forms of depression, because some call for specific treatments. Melancholic patients and those with pseudodementia often respond to antidepressant medications, but psychotic depressed patients require high doses of both antidepressant and antipsychotic medications. Catatonic depressed patients respond best to sedative drugs such as the barbiturates or the benzodiazepines. But all patients with any of these disorders respond to ECT. Although it may not be the first...

Costeffectiveness of antidepressants

Since the advent of tricyclic antidepressants, the treatment of depression has been dominated by pharmacotherapy. This seems set to continue following the introduction of new drugs, particularly the selective serotonin reuptake inhibitors. These pharmaceutical products are widely accepted to have at least equivalent efficacy as tricyclic antidepressants, yet have a lower risk of toxicity and adverse side-effects, ( J.,12.) leading to potentially greater compliance and consequent reductions in the use of health and other services. Against this, the newer drugs carry considerably higher acquisition costs. There is consequently an important cost-effectiveness question to be considered are the higher acquisition costs worth paying in terms of the reduced toxicity, adverse side-effects, and need for service inputs A variety of study designs and methods have been used to address this cost-effectiveness question, specifically (a) prospective studies, (b) retrospective studies, and (c)...

Atypical antidepressants

Bupropion is a relatively selective dopamine-uptake blocker that is effective in treating depression ( Table 1). Its efficacy and side-effect profile are similar to those of Trazodone and nefazodone, which are chemically related compounds with an affinity for several receptors and uptake transporters, also treat depression ( TableJ). Although trazodone lacks anticholinergic side-effects, it is highly sedative.

Reasons For Discrepancies In Rates Of Depressive Symptoms

Probably the most salient reason for the wide range of figures quoted for rates of depression revolves around how depression is diagnosed. Conventional diagnostic tools, such as DSM-IV criteria,8 can be difficult to apply to patients with PD, because it specifically excludes symptoms resulting from a general medical condition or a direct physiologic effect of a substance, such as a medication. In persons with PD, this presents obvious problems, particularly when trying to decide about the DSM-IV somatic symptoms such as changes in psychomotor activity, sleep, appetite, weight, and energy level. If one follows the exclusive directions of DSM-IV, many patients will end up without a primary mood disorder diagnosis in spite of appearing to meet criteria for major depression. In these cases, one is forced to use other diagnostic entities such as mood disorder secondary to general medical condition.

Clinical management of panic disorder A Tricyclic antidepressants

For these tricyclic antidepressants typically takes three to four weeks. 2. Approximately one fourth of patients cannot tolerate the side effects of tricyclic antidepressants, which include constipation, dry mouth, blurred vision, urinary retention, sedation, weight gain, and orthostatic hypotension. Tricyclic antidepressants

Tricyclic Antidepressants

Seven TCA drugs are available in the United States for treatment of major depression. They are generally categorized as tertiary or secondary amines. Tertiary amines include imipramine (Tofranil), amitriptyline (Elavil), trimipramine (Surmontil), and doxepin (Sin-equan). Desipramine (Norpramin), nortriptyline (Pam-elor), and protriptyline (Vivactil) are secondary amines.

Recurrent depression Recurrent major depression

After a single episode of major depression around 85 per cent of patients experience recurrent episodes. (17) While the first episode of major depression is often provoked by a negative life event such as loss of job, retirement, marital separation. or divorce, subsequent episodes are often unprecipitated (positive life events can also provoke depression). Depressive episodes typically increase in frequency and duration as they return. (.18) This phenomenon has been explained by 'kindling', a process in which repeated stimulation causes an escalating response.(19) Usually, the intervals between episodes of unipolar depression are symptom free, but some patients experience dysthymia between episodes. Such cases have been called 'double depression'. (29

Depressive episode Clinical features

When patients with depression in later life are compared with younger depressed patients few clinical features distinguish them. Gurland (1) found hypochondriacal complaints to be the only symptom that was more common in older depressed people. Musetti et al.(2) were also unable to identify any special clinical features which differentiated younger from older outpatient-attenders. Brodaty et al.(3) found that elderly depressive patients were more agitated and had more depressive delusions. However, when the groups were matched according to whether they met criteria for the specific subtype of 'melancholia' almost all differences disappeared. Elderly people tend to minimize their feelings of sadness and instead become hypochondriacal (morbidly preoccupied with a fear of illness). (1) In late life, newly arising neurotic symptoms (severe anxiety, phobias, obsessional-compulsive phenomena, or hysteria) are seldom primary diagnoses but are usually secondary to depressive illness. Any act...

Conjoint IPT for depressed patients with marital disputes IPTCM

It is well established that marital conflict, separation, and divorce can precipitate or complicate depressive episodes (Rounsaville et al., 1979). Some clinicians have feared that individual psychotherapy for depressed patients in marital disputes can lead to premature rupture of marriages (Gurman & Kniskern, 1978). To test and address these concerns, Kler-man and Weissman developed an IPT manual for conjoint therapy of depressed patients with marital disputes (Klerman & Weissman, 1993). Both spouses participate in all sessions, and treatment focuses on the current marital dispute. Eighteen patients with major depression linked to the onset or exacerbation of marital disputes were randomly assigned to 16 weeks of either individual IPT or IPT-CM. Patients in both treatments showed similar improvement in depressive symptoms, but patients receiving IPT-CM reported significantly better marital adjustment, marital affection, and sexual relations than did individual IPT patients (Foley et...

Cytokine Balance and Antidepressants

More recently, a number of studies focused on the pro and anti-inflammatory cytokine balance in major depressive disorders. A dysregulation within the cytokine balance could induce depressive symptoms due to lower levels of anti-inflammatory cytokines and higher levels of proinflammatory cytokines. Anti-inflammatory cytokines or cytokine receptors are known to evoke an antiinflammatory state both on their own (IL-10, TGFP) receptors and also by the blockade of the binding of proinflammatory stimuli to their cell surface receptors (IL-1ra, soluble TNF receptors II). Growing evidence supports the idea of an anti-inflammatory action of antidepressants, which could explain their efficiency on depressive symptoms. In some clinical studies, it has been reported that antidepressants may attenuate the effects of proinflammatory cytokines by increasing the production of anti-inflammatory cytokines such as IL-10 and IL-1ra. Most antidepressant treatments could significantly reduce the IFNy...

Tricyclic and tetracyclic antidepressants

Neurovegetative Symptoms Depression

Maprotiline, a tetracylic compound, and the large group of tricylic antidepressants ( Table, 1) effectively treat the neurovegetative signs of depression. Potential sites of action are at the level of receptors (desensitization of presynaptic a 2-receptors, subsensitivity of b-adrenergic receptors), reuptake transporters (block of monoamine reuptake), and intracellular second-messenger systems. Table 1 Treatment indices and side-effect profiles of common antidepressants The cyclic compounds do not have significantly different efficacy in treating depression but do show a variety of side-effect profiles. Adverse effects are closely related to their chemical structure and their affinity for postsynaptic receptors. Amitriptyline, clomipramine, and doxepin have a high affinity for muscarinic cholinergic receptors and cause more anticholinergic side-effects (dryness of mouth, blurred vision, constipation, urinary retention) than the other cyclic compounds. Sedation and orthostatic...

Antidepressants and Female Sexual Dysfunction

Although numerous medications can have an adverse impact on sexual function, few classes of medications have been demonstrated to have more impact on sexual function than antidepressants. Although many of the various classes of antidepressant agents can affect sexual function, the selective serotonin reuptake inhibitors (SSRIs), such as paroxetine, sertraline, or fluoxetine, have been shown to adversely affect libido, arousal, as well as the ability to reach orgasm.27 Under a physician's care, options may include switching agents, dose reduction, or drug holiday. Bupropion (Wellbutrin) may be an effective alternative.28 In addition, studies have suggested that the use of sildenafil with selective SSRI medications may effectively combat the FSD associated with the SSRI. It is also important to recognize that FSD may present with many of the same symptoms as depression, such as poor energy and lack of interest. We have seen numerous patients who were misdiagnosed as having depression,...

Depressive disorders one two or three principal types

The extended debate as to whether the depressive disorders are best conceptualized as comprising one or more distinct disorders warrants overview. The 'unitarian' view posits one depressive disorder, varying essentially by severity. The strict 'binarian' view argues for two separate types. This latter challenge is fundamental, taking us to the heart of any consideration of the diagnosis and classification of the depressive disorders. To the unitarians (despite evidence of quite varying aetiological factors), depression essentially varies only by degree, allowing treatment decisions (e.g. electroconvulsive therapy (ECT), antidepressant drugs, psychotherapy, or cognitive-behavioural therapy) to be decided on the basis of severity or frequency of episode. The opposing argument for conceding subtypes has been well put by Kendell, (18) who drew on important historical analogies distinguishing between cardiac and renal forms of 'dropsy' allowed prediction of those who would respond to...

Treatment Of Major Depression

It is often surprising for the student to learn that mood-elevating agents do not act as stimulants of the central nervous system (CNS). With the exception of varying degrees of sedation, the antidepressants have little effect on behavior early in treatment. During this period patients will, however, have side effects specific to the class and agent being used. Only after 2 to 3 weeks of dosing will a therapeutic benefit on depression emerge. At this point the patient begins to demonstrate elevation in mood and self-esteem. In addition, many of the vegetative signs of the illness (e.g., insomnia, anorexia) abate, and the patient regains an interest in daily activities. Failure to continue the medication, however, will result in an immediate relapse into the depressive state. Therefore, maintenance therapy must be continued for at least 6 months.

Serotonergic drugs including tricyclic antidepressants

Tricyclic antidepressants, such as clomipramine, amitriptyline, and imipramine, have powerful or moderate effects on serotonin neurones, and have been demonstrated to have some beneficial effects in certain disorders with childhood or adolescent onset. These include enuresis, separation anxiety disorder, school phobia, and obsessive-compulsive disorder. Studies using these drugs to treat depression have yielded equivocal results. Desipramine, a tricyclic antidepressant without clear serotonergic effects, has been tested in attention disorders. The new serotonergic drugs, such as fluoxetine, sertraline, and fluvoxamine, are supported by limited child and adolescent data in selective mutism, obsessive-compulsive disorder, and other syndromes listed under anxiety disorders in the DSM-IV.

Major depression

Few disorders illustrate the interaction between genetics and environment more clearly than major depression. In Kendler's study of twins (21) he followed 2164 members of female-female twin pairs. Recent stressful events were the single most powerful risk factor for an episode of major depression. Genetic factors were substantial, but not overwhelming. He followed this cohort of subjects for 17.3 months. During that time 14 per cent of them had major depressive episodes. He found that the four most powerful predictors of a major depression in the month of the occurrence were death of a close relative, serious marital problems, assault, and In other words, those with the highest genetic risk had only a 1.1 per cent probability of having a depressive episode without a life stressor, but the risk rose to 14.6 per cent if they were exposed to a severe life event. On the other hand, those subjects with the lowest genetic risk had only a 0.5 per cent probability of depression onset per...


Antidepressant drugs, such as the tricyclic antidepres-sants and the selective serotonin reuptake inhibitors (SSRIs), are very important for the treatment of psychotic depression (see Chapter 34). They have been shown to be effective when used in the treatment of several anxiety disorders, including general anxiety, obsessive-compulsive disorder, and several phobias, including agoraphobia. Because the SSRIs are less toxic than the tricyclic antidepressants, their use in the treatment of anxiety is safer and less likely to produce serious side effects.

Depressive disorders

Sadness and grieving for loss of health and well being are normal responses in cancer patients. (3) A continuum is seen, beginning with these normal responses, and increasing intensity reaching the level of subsyndromal symptoms, adjustment disorder with depressed mood, and major depression and mood disorder related to medical condition. These are the most common depressive disorders encountered in patients seen at our counselling centre. A special diagnostic problem exists in cancer. Vegetative symptoms of depression are the same as many physical symptoms seen in patients with cancer, especially fatigue, slowed psychomotor activity, insomnia, absent libido, anorexia, and weight loss. The clinician must focus on the psychological symptoms of depression to make a diagnosis persistent depressed, dysphoric mood, feeling of worthlessness, guilt, anhedonia, and preoccupation with hopelessness and death ( Tab.l. , 2). The factors for suicidal risk in patients with cancer are several. They...

The burden of mental illness

Using the DALY as the basic statistic, the World Development Report(2) concludes that mental health problems make up 8.1 per cent of the total GBD. Of that 8.1 per cent, the largest contributors are depressive disorders, self-inflicted injuries. Alzheimer's disease and other dementia, and alcohol dependence, followed by epilepsy, psychoses, drug dependence, and post-traumatic stress disorder. Depressive and anxiety disorders account for between one-quarter and one-third of all primary-health-care visits worldwide.(3,,4) When appropriately diagnosed and treated, suffering is alleviated, disability prevented, and function restored when ignored, major losses persist.(5) By the year 2025, three-quarters of all elderly persons with dementia (about 80 million) will live in low-income societies. Mental retardation and epilepsy rates are three to five times higher in low-income societies compared with industrialized countries. In some Asian and African countries, up to 90 per cent of patients...

Competing Classifications

Unfortunately, much of the pressure for change has continued to originate from clinical and political demands. Revisions have sometimes had the appearance of tinkering in order to capture some imagined essence of the disorders included (Birley, 1990). What looks like fine-tuning can nevertheless make considerable differences to whether individual cases meet criteria or not, and thus disproportionately affects the putative frequency of disorders. We should jettison classifications only on grounds of inadequate scientific utility and as seldom as possible, since too rapid revision defeats the objective of comparison. Like all such classifications, DSM and ICD are created by committees. The natural tendency to horse-trading between experts selected precisely because they are powerful and opinionated leads to an over-elaborate structure, an excess of allowable classes and subclasses, and complicated defining criteria. Thus, in DSM-IV-R (APA, 1994), there are potentially 14 categories to...

Leaky Classes And Comorbidity

Thus, Kessler (2000) has defended the status of generalized anxiety disorder (GAD) as an independent condition, despite its high comorbidity, arguing that it does, for example, precede major depression, and also outlasts it. However, this would be expected if GAD represented a low threshold disorder that could transmute into a higher threshold disorder with the addition of a few symptoms. GAD and depression certainly share a common genetic diathesis (Mineka et al., 1998). The superimposition of major depression on a long-lasting minor depressive disturbance (dysthymia) has been called double depression (Keller et al., 1997). The comorbidity of anxiety and depression may arise because anxiety states can transform into depressive disorders with the addition of relatively few symptoms (Parker et al., 1997). Depression anxiety is equally apparent in adolescents (Seligman & Ollendick, 1998), as is the link between dysthymia and major depression (Birmaher et al., 1996). The idea that there...

Depression And The Threshold Problem

In response to the threshold problem, there has been a burgeoning literature recently relating to subthreshold, subclinical, minor, and brief recurrent affective disorder (Schotte & Cooper, 1999). The tendency to extend the threshold downwards is apparent in the establishment of the category of dysthymia, referred to above, a depressive condition characterized only by its mildness (that is, a lack of symptoms) and its chronicity. The category has, nevertheless, become a study it its own right it has clear links with major depression, presumably because it is relatively easy for someone who already has some depressive symptoms to acquire some more and meet criteria for the more severe disorder. It is also associated with psychosocial distress, both recent and distant. Some authors have gone so far as to suggest that it reflects abnormalities of neuroendocrine and neurotransmitter function (Griffiths et al., 2000). It can be concluded from this discussion that the epidemiological...

Ethnic Considerations

Likewise, a genetic factor in African-Americans makes them less responsive to beta-blocking agents used in cardiac and antihypertensive medications. Asians have a genetic factor that causes undesirable side effects when given the typical dose of benzodiazepines (diazepam Valium ) alprazolam Xanax , tricyclic antidepressants, atropine, and propranol Inderal . Therefore, a lower dose must be given.

Questionnaires And Interviews

Brugha and his colleagues (2001) conducted a two-phase study of the general population of Leicestershire, UK. In the second phase, 172 subjects selected for an increased probability of exhibiting cases of psychiatric disorder were interviewed with both CIDI and SCAN, in random order. The coefficients of concordance for the various ICD-10 diagnoses varied between poor and fair. The authors calculated that using CIDI would give prevalences about 50 greater than those obtained from SCAN. The index of agreement for any depressive episode was poor (0.14). As expected, the discrepancies arose particularly from cases around the threshold for recognition.

The difficulties in keeping up to date

All doctors, and other health care professionals, have a considerable need for accurate and up-to-date information that often go unrecognized and unmet. (D In psychiatry, many new treatments have been introduced over the last decade, including new antidepressants, antipsychotics, and antidementia drugs. There have also been developments in non-pharmacological treatments, such as psychotherapy and models of service organization, as well as advances in diagnosis, prognosis (including assessment of risk) and aetiology. As these clinical advances are made, it is important that doctors are informed about them in a manner that is timely, accurate, and unbiased. Ideally perhaps, every psychiatrist would have access to the original scientific articles. However, this is not often feasible. Time in clinical practice is very limited and many clinicians do not have the skills needed for an adequate systematic search, and a critical appraisal and interpretation of the findings of research studies....

Are the results relevant for your patient

To determine the relevance of the study to real-life patients, it is important to examine the inclusion and exclusion criteria of the trial. The main inclusion criteria are discussed above. Patients excluded from the trial were women who were pregnant or of child-bearing age but unwilling to use an effective contraceptive method. Exclusion criteria also included major medical conditions, bipolar disorder, psychosis, panic disorder, concurrent major depressive disorders, generalized anxiety disorder, history of alcohol or other drug dependency within the previous 12 months, serious suicidal risk, previous non-response to two or more adequate antidepressant trials, and use of psychotropic drugs within 2 weeks of enrolment. The use of the study results will have to take these inclusion and exclusion criteria into account, and the clinician needs to judge the relevance of the results for the individual patient.

Pharmacological Therapy

Neuropsychiatric issues are often a major cause of morbidity and mortality, as suicide is not infrequent (see chapter by Sano). Depression should be aggressively treated. Selective serotonin-reuptake inhibitors and tricyclic antidepressants may be useful for depression, in addition to mood-stabilizing medications such as anticon-vulsants. The second-generation neuroleptics, especially clozapine and quetiapine, may improve both mood disorders and chorea. Classical neuroleptics should be avoided in order to avoid potential induction of tardive movement disorders.

Other Sociodemographic Variables That Influence Rates Of Depression

In most Western societies, women are even now less likely to be employed than men. Employment generally has beneficial effects on psychological health it brings interest, income, fulfilment, social contacts, and status, and provides structure and a sense of control (Jahoda, 1982 Krause & Geyer-Pestello, 1985). The availability of these benefits is likely to differ both among women, and between men and women. The advantages of employment are weaker in married women (Roberts & O'Keefe, 1981 Roberts et al., 1982 Warr & Parry, 1982), more so if they have children (McGee et al., 1983 Parry, 1986), most so when the children are of pre-school age (Haw, 1995). Full-time employment is particularly demanding (Cleary & Mechanic, 1983 Elliott & Huppert, 1991). The most likely explanation for these findings is role conflict and overload. Thus, part of the excess of depressive disorders in women may be related both to their reduced involvement in employment and to the particular strains they are...

The hypothalamicgrowth hormone axis

Although the HPA and HPT axes have been more closely scrutinized in patients with psychiatric disorders, there is virtual universal agreement that the blunted growth-hormone response to a variety of provocative stimuli (particularly clonidine, an a 2-adrenergic agonist) in depressed patients is the most consistent finding in affective disorders research.(29) The mechanism underlying this phenomenon remains obscure, but it is of particular interest that, at least in some studies, it appears to persist upon recovery from depression, suggesting that it is a trait marker for depression vulnerability. There are reports of similar findings with other growth hormone-provocative stimuli, such as the use of apomorphine, desipramine, or levodopa. In addition, the blunted growth-hormone response to clonidine in depressed patients is particularly robust in those who have recently attempted suicide. Clearly, further work in this area is warranted, especially in the context of several reports of...

The hypothalamicpituitarygonadal axis

In view of the remarkable gender differences in the prevalence rate of depression, the relatively high rates of postpartum depression, as well as the reduction in libido that is so characteristic of depression, it is plausible to posit a reduction in HPG axis activity in depressed patients. Therefore it is somewhat surprising that so little research has been conducted on HPG axis activity in depression and other psychiatric disorders. Indeed, a comprehensive database on this extraordinarily important area is simply not available, but the field has recently been reviewed. (3D A series of older studies documented no differences in basal gonadotrophin levels in depressed patients when compared to controls. The gonadotrophin-releasing hormone ( GnRH) stimulation test has only been administered to a relatively small number of depressed patients although the results revealed a blunted or normal response, no firm conclusions can be drawn from this limited data set. Indeed, such studies...

The hypothalamicprolactin axis

This pituitary hormone, which acts on the mammary gland, plays a critical role in lactation. Unlike the other axes described, this axis is unique in having a non-peptide release-inhibiting factor, dopamine. In addition, although there is relatively strong evidence for the existence of a prolactin-releasing factor, its isolation and characterization has not yet been realized. One of the difficulties in completing this task is the presence of TRH, which is a potent prolactin-releasing factor, and may in fact function physiologically in this regard. Interestingly, although the TSH response to TRH in depressed patients is often blunted, the prolactin response is not. Although the results are not unequivocal, most studies have not observed alterations of prolactin secretion in depressed patients. (34) In contrast to this small database is a remarkably large database on the use of provocative tests of prolactin secretion in patients with psychiatric disorders. To summarize briefly, they...

Biological Explanations For The Sex Ratio In Depression

Direct evidence linking hormone status to depressive disorder has some face validity oestradiol and progesterone seem to modulate the neurotransmitter and neuroendocrine systems, including those involving monamines, and there are transitions in women's lives characterized by hormonal shifts that may also be associated with mood disturbance (childbirth and the menopause). The evidence in this area is extremely complicated (Bebbington, 1996). Moreover, there is a more plausible neuroendocrine hypothesis for depression involving glucocorticoids. This offers an explanation for a range of other neurohumoral phenomena, and a mechanism whereby extrinsic stress may result in the features of depressive disorder (Checkley, 1998 Dinan, 1994). It links overactivation of the hypothalamico-pituitary-adrenal (HPA) axis and the associated hypercortisolism with the changes in the central monaminergic pathways thought to underlie depression and the actions of antidepressants. These changes will...

Serotonin Transporter

With those of the tricyclic antidepressants. SSRIs act by interfering with the activity of the serotonin transporter (SERT) (49). A number of polymorphisms have been reported in the SERT gene (50-52), and genetic variations in the SERT promoter have been linked to altered functions, such as the association between the short (S) allele (44 bp deletion) of the SERT-PR site and poor response to fluvoxamine and paroxetine in patients treated for major depression (53,54).

The Childhood Antecedents Of Later Depression

There are clear associations between certain childhood experiences, circumstances, and characteristics, and later depression. This is despite the rarity of childhood depressive disorder. What links there are must therefore usually be indirect the causal connection appears to operate over a gap of years. This suggests some enduring change that mediates the later propensity to depression. Such changes might include psychological, temperamental, and biological predispositions, and an increased sensitivity to adult stress is a plausible mechanism. For example, the tendency of women to become depressed in response to domestic violence in adulthood is increased if they had also experienced abuse in childhood (Roberts etal., 1998). A variety of childhood traumas are associated with later depressive episodes (De Marco, 2000). Childhood abuse, whether physical, emotional, or sexual, is associated with later psychopathology (Bifulco et al., 1991 Fergusson et al., 1996 Mullen et al., 1996). This...

Imaging 5hydroxytryptamine receptors

One recent success is the radioligand (11)C WAY 100635 for imaging 5-HT1A receptors in the human brain.(22) As many different antidepressant treatments alter 5-HT1A receptor function in rodents, this ligand will be useful investigating 5-HT 1A receptor populations in depressed patients before and after treatment especially. (11)C M-methylspiperone, (18)F altanserin, (18)F ethylspiperone, (18)F setoperone or (18)F altanserin, and the SPET tracer (123)I ketanserin have been used to measure 5-HT2 receptor number a receptor implicated in depressive illness, suicidal behaviour, and psychosis. Many of these 5-hT 2 ligands have been hampered by either the lack of selectivity, or the relatively low ratio of specific to non-specific signal obtained in the human brain, (23 although a few reports have appeared reporting reduced 5-HT2 receptor number in drug-free depressed patients. Further studies are needed using more selective ligands with higher signal to noise ratios, such as (11)C MDL...

The Epidemiology Of Treatment For Depression

There are various ways in which the delivery of treatment for depression can be assessed (Bebbington et al., 1996). One is to assume that identified depressive disorders need treatment of one sort or another, and to establish how often they actually received it. This is technically a measure of utilization. Another approach is to establish directly whether treatment was actually needed before quantifying how often it was delivered. Need can be defined either by experts, or by the individual in question (when it is called want, demand, or subjective need). Investigations of general population samples are the obvious source of such information. The obvious questions are as follows. Did this person have a need for professional treatment Did he or she seek psychiatric help at either primary or secondary care level Was he or she then prescribed treatment Did he or she take the treatment prescribed Studies of any kind are rare, but give a clear picture of under-treatment. The Australian...

Chapter References

The genetic aetiology of childhood depressive symptoms a developmental perspective. Development and Psychopathology, 8, 751-60. 9. Rice, J.P., Endicott, J., Knesevich, M.A., and Rochberg, N. (1987). The estimation of diagnostic sensitivity using stability data an application to major depressive disorder. Journal of Psychiatric Research, 21, 337-45.

Neurochemical Models Of Depression

Brain neurochemistry was one of the first suspects in the search for the biological basis of depression. The original monoamine hypothesis of depression derived from the findings that monoamine depletion by the drug reserpine caused depression, while antidepressants inhibited monoamine reuptake. Subsequent reports that there were reduced monoamine breakdown products in the CSF led to the theory that there is a deficiency of noradrenaline, dopamine, 5-HT, or all three at monoaminergic synapses. From this original hypothesis, several proposed biological models of depression are worth discussing.

A population perspective

In terms of the final of the four questions about events listed earlier, 'neurotic' conditions that form the bulk of depressive disorders, even in patient series, need to be considered in terms of a population perspective. Figure.,2 summarizes the findings of six population studies of women aged between 18 and 65 carried out in a comparable manner, using the same semistructured interview-based measures as in the Islington survey, including the Present State Examination. The bottom half of

Torsades De Pointes Ventricular Tachycardia

-Correct underlying cause and consider discontinuing quinidine, procain-amide, disopyramide, moricizine, lidocaine, amiodarone, sotalol, cisapride, Ibutilide, phenothiazine, haloperidol, tricyclic and tetracyclic antidepressants, ketoconazole, itraconazole, bepridil, hypokalemia, and hypomagnesemia.

Secular changes in incidence

This refers to the rise and fall of diseases in populations, with the possibility of making projections into the future. For example, there is some evidence that schizophrenia has been dropping in incidence and becoming more benign in its clinical course, (8) it is possible that depressive disorder has become more frequent in persons born since the Second World War(9l0) (the suicide rate of young persons has indisputably increased in many industrialized countries), it is likely that eating disorders have increased in frequency in some industrialized countries, and it is certain that the use of heroin and the AIDS epidemic with its neuropsychiatric sequelae are new arrivals and will be a continuing burden.

Nineteenth century psychiatry

Kraepelin's important differentiation of manic-depressive illness from dementia praecox (schizophrenia) did not begin to be defined until 1896. Asylums contained patients suffering from many varieties of psychiatric illness who had nothing in common with one another except their inability to comply with the standards of behaviour demanded by society.

Sexuality and repression

Freud remained convinced that sexual satisfaction was the key to happiness, and that what was wrong with the neurotic was failure to achieve a normal sex life. This central conviction had two roots. In his autobiographical study, Freud acknowledges his debt to the ideas of G.T. Fechner, a professor of physics and then philosophy at Leipzig University. During the course of a manic-depressive illness, Fechner introduced the idea of a universal 'pleasure principle', which Freud adopted. Freud also took from Fechner the notion of a 'principle of constancy', the idea that the main function of the mental apparatus was to bring about the discharge of instinctual tension in order to maintain stability. Freud thought that one dominating principle governing human behaviour was the need to reach a state of tensionless tranquillity (he called it the Nirvana principle). Freud treated powerful emotions as disturbances to be abolished rather than as pleasures to be sought. He seems to have been...

Psychoanalysis and psychosis

Although Freud had practically no experience of psychotic patients, and specifically stated that psychotic patients were not suitable subjects for psychoanalysis, this did not deter him from writing about their presumed psychopathology in psychoanalytic terms. For example, he wrote a penetrating account of severe depressive illness in Mourning and Melancholia(7) and a less convincing interpretation of paranoia in Psycho-Analytic Notes on an Autobiographical Account of a Case of Paranoial) and A Case of Paranoia Running Counter to the Psycho-Analytic Theory of the Disease.(9) Psychoanalytic ideas were eagerly discussed in psychiatric hospitals because they offered a new interpretation of mental illness in terms of psychopathology even when there was no prospect of cure. Psychoanalysis was gradually establishing itself throughout Europe.

Intracellular signalling models

There is evidence that antidepressants are able to modify intracellular signalling, as for example, by enhancing the cyclic AMP pathway activation occurring after serotonergic receptor stimulation. It has been hypothesised that G proteins, important signal transducers in the phosphoinositol system, are overactive in depression they are also potentially important in the mechanism of action of lithium. Several growth factors and neurotrophins are altered in depression, and may be important in neuronal changes seen in depression. Antidepressants also have effects on the expression of these factors. A new cellular model of depression is evolving in which there are felt to be impairments in signalling pathways that regulate neuroplasticity and cell survival (Manji et al., 2001).

Neuropsychiatry symptoms

The relationship between AD and depression is complex. Depression is a risk factor for AD, depression can be confused with dementia (pseudodementia), depression occurs as part of dementia, and cognitive impairments are found in depression. Depression occurring as a symptom of dementia will be considered here. Assessing the mood of a person with dementia is difficult for obvious reasons. However, psychomotor retardation, apathy, crying, poor appetite, disturbed sleep, and expressions of unhappiness all occur frequently. The rates of depression found in cohorts of patients with AD vary widely, reflecting changes in prevalence at different levels of severity and difficulties in the classification of symptoms suggestive of depression in those with cognitive loss. A major depressive episode is found in approximately 10 per cent of patients, minor depressive episode in 25 per cent, some features of depression in 50 per cent, and an assessment of depression by a carer in up to 85 per...

Clinical features

Table J summarizes nine studies which report clinical details of 190 autopsy-confirmed DLB cases.(6) Dementia is usually, but not always, the presenting feature a minority of patients present with parkinsonism alone, some with psychiatric disorder in the absence of dementia, and others with orthostatic hypotension, falls, or transient disturbances of consciousness. Fluctuation in cognitive performance and functional ability, which is based in variations in attention and level of consciousness, is the most characteristic feature of DLB It is usually evident on a day-to-day basis, and often apparent within much shorter periods. The marked amplitude between best and worst performance distinguishes it from the minor day-to-day variations that commonly occur in dementia of any aetiology. Repeated visual hallucinations are present in about two-thirds of patients. They take the form of vivid, colourful, and sometimes fragmented figures of people and animals, which are usually described in...

Adaptations in the Signaling Systems Involved in Opioid Tolerance Dependence

But what is the mechanism by which PKA enhances opioid tolerance Chronic administration of opiates has been observed to upregulate the cAMP pathway and to activate PKA in locus coeruleus cells. Stimuli that upregulate the cAMP pathway after chronic administration (e.g., stress or opiates) increase the excitability of locus coeruleus neurons, whereas stimuli that downregulate the cAMP pathway (e.g., antidepressants) exert the opposite effect. In these cells PKA activates a nonspecific cation current that modulates pacemaker activities of these cells (86). PKA has also been shown to modulate the G Gj protein selectivity of the D-adrenergic receptor (87,88). Thus, activation of PKA during chronic opioid exposure might also result in AC stimulation by switching the opioid receptor from Gi to Gs coupling, leading to an increase of the intracellular cAMP level.

What is the evidence that early life experiences influence the development of negative cognitive structures

Certainly, the children of depressed parents are at increased risk of psychiatric problems, particularly major depression in adolescence and adulthood (Cohn et al., 1986 Field, 1984 Tronick & Gianino, 1986). Furthermore, depressed adults do tend to report having been parented in problematic ways in childhood (e.g., Brewin et al., 1992 Koestner et al., 1991 Zemore & Rinholm, 1989). However, these findings could be due to a number of factors. What is more important to demonstrate, from the perspective of the cognitive model, is that early experiences influence the formation of cognitive systems that make an individual vulnerable to depression. Unfortunately, this mediation hypothesis has not been studied sufficiently to draw a conclusion. In one study using an undergraduate sample, very limited support was found for a mediating relationship of cognitive variables between reports of maladaptive parenting and subsequent depression (Whisman & McGarvey, 1995). Moreover, among depressed...

Drugs Acting On The Central Nervous System

In general, elderly people are more sensitive to medications that affect central nervous system function. Drugs of particular relevance in this regard are benzodiazepines, major tranquillisers and antidepressants, which are all frequently used by elderly patients. In a study of medicine use in general practice, psychotropic drugs were prescribed more commonly than any other group and accounted for up to one-fifth of all prescriptions (Skegg et al., 1977). The proportion of patients receiving such medicines increased steadily with age 21.4 of men and 29.9 of women over 75 years of age were receiving a sedative or hypnotic. Adverse reactions due to psychotropic drugs are known to be a frequent cause of hospital admission in the elderly (Williamson and Chopin, 1980 Hallas et al., 1992).

Mood disorders and psychosis

Clinically, one has the impression that depression after a head injury is more difficult to treat. This is consistent with the observation that depression, in those who have not suffered a head injury, is more difficult to treat if the patient is found to have evidence of brain damage. However, some studies in head-injured depressed patients have found good response rates. The selection of an antidepressant is no different from that used to treat depression in the absence of brain injury, provided that the principles given in Box3 are taken into account.

Alcoholinduced mood disorders

Alcohol is a central nervous system depressant. Taken regularly in high doses it may provoke feelings of sadness. Episodes of withdrawal or relative withdrawal can lead to excitability and nervousness, including anxiety. The more a person drinks, the more likely it is that these symptoms will occur. Finally in the stage of alcohol dependence, up to 80 per cent of people report depressive symptoms at some time in their life. About one-third of male patients and up to 50 per cent of female patients have experienced longer periods of severe depression.( ) These high prevalence rates are noteworthy, since more than 20 per cent of alcoholics have attempted suicide once or more and about 15 per cent die in their attempt. Besides depressive features, alcohol-induced mood disorders may also comprise manic symptoms or mixed features. However, the diagnosis should only be used when the symptoms cause clinically significant impairment or distress in social, occupational, or other areas of...

Alcoholinduced anxiety disorders

This diagnosis should only be used when anxiety symptoms are thought to be related to the direct physiological effects of alcohol. The symptomatology may involve anxiety, panic attacks, and phobias. Both alcohol-induced anxiety disorders and mood disorders can develop during intoxication, withdrawal, or up to 4 weeks after cessation of alcohol consumption. During intoxication or withdrawal, the diagnosis should only be given when the symptomatology clearly exceeds what would be expected from anxiety or depressive symptoms during a regular intoxication or withdrawal episode.

Emotional Functioning In Depression

How does depression affect the generation of emotional states From depressed patients' prototypical reports of emotion, it appears that MDD involves disturbances in both appetitive (positive) and defensive (negative) motivational systems. That is, depressed individuals typically report experiencing low levels of positive feeling states such as joy or amusement, and high levels of negative feeling states such as sadness, anxiety, and shame (Clark et al., 1994). Given this pattern of reporting, it is reasonable to hypothesize that depression should serve to decrease responsiveness to positive incentives and increase responsiveness to negative incentives. Interestingly, empirical research examining emotional reactivity in MDD provides only partial support for this hypothesis, suggesting instead that depression serves to diminish emotional reactivity to both positive and negative stimuli.

Treatment of coexisting disorders Affective disorder

Depression is common in patients who are dependent on alcohol. The drinking may have alienated friends, family, or employer, with resulting feelings of hopelessness, guilt, and lack of direction. Alcohol can reduce appetite, energy, and sexual drive. The drinker wakes in the small hours of the night feeling anxious owing to the rebound wakefulness of alcohol withdrawal. Those signs and symptoms suggesting depressive illness commonly clear with abstinence and help in tackling or tolerating personal problems and improving relationships. Sometimes (more often in women than in men) a depressive episode precedes the alcohol dependence. Alcohol was taken in part as self-medication. Sometimes depressive symptoms continue despite abstinence. In these cases, antidepressants should be offered in the usual way. (6 64 Relapsing alcoholism, secondary to depressive illness, is an indication for long-term antidepressants. Lithium is not a treatment for alcohol dependence itself, but is effective if...

Anxiety and panic disorder

Three studies suggest that the serotonin agonist buspirone can help reduce both drinking and anxiety. (65) Tricyclic antidepressants and selective serotonin-reuptake inhibitors (SSRIs) have been shown to be effective in randomized controlled trials of panic disorders, but alcohol dependence has been an exclusion criterion in these trials. Newly abstaining alcohol-dependent patients seem particularly susceptible to the unwanted effects of serotonergic medication (see above).

Guidelines for management of misuse of nonprescribed benzodiazepines

Assessment should attempt to confirm evidence for benzodiazepine dependence. Assessment over a number of visits should involve obtaining urine specimens to determine objectively the regularity (or intermittent nature) of benzodiazepine consumption. Part of the initial assessment process should identify underlying psychiatric disorders that may have been the trigger for a doctor initiating a prescription or for the patient obtaining drugs for the purpose of self-medication. High levels of psychiatric morbidity have been found among samples of patients with severe benzodiazepine dependence. (18) The commonest conditions are probably anxiety disorders for which anxiolytics have been prescribed injudiciously however, in some instances major depressive disorders may be treated or self-medicated with benzodiazepines. Thorough assessment should explore for evidence of major depression and if identified, consideration should be given to the use of antidepressant medication combined with...

Acute psychological problems associated with MDMA use

Increased anxiety(2,26) and panic(2,28 have been described, with the three cases of the latter study complicated by prolonged agorophobia which responded to serotonergic antidepressant drugs. Major depressive disorder(29) and prolonged depersonalization with panic and suicide following ingestion (30) have also been described. Numerous cases of MDMA-related psychoses have also been reported(3 ,32,) as well as flashbacks(3 34) and even craving for chocolate 35 It has been suggested( 2,22) that such idiosyncratic disturbances are more likely to occur in those already predisposed to psychiatric disorders. It is possible that people predisposed to mood disorders may experience their first episode of psychological disturbance earlier than they would have done had they not taken MDMA. Controlled long-term cohort studies of users, with baseline measures of risk factors, are needed to assess this.

Adult smoking disadvantage and dependence

The most striking feature of the evolution of smoking in developed Western countries over the past 20 years has been the increasing association of cigarettes with markers of disadvantage, whether it be socioeconomic position, or a range of factors indicating stressful living circumstances. (47) High rates of smoking are seen in the unemployed, lone parents, people who are divorced or separated, the homeless (United Kingdom Office of Population Censuses and Surveys), heavy drinkers, (47) drug users (United Kingdom Office of Population Censuses and Surveys), and prisoners. (48) Cigarette smoking is strongly associated with psychiatric illness, whether it be schizophrenia 49,50 depressive illness 51 or a variety of other neurotic disorders. ty The association of cigarettes with lowered levels of psychological well being is not confined to those with a formal psychiatric diagnosis, but extends also into the general population of smokers. (5 53) Between 1973 and 1994 rates of smoking among...

Nonnicotine pharmacological treatments

Many other drugs to aid smoking cessation have been tested, but most have so far failed to yield evidence of efficacy (including most anxiolytics and antidepressants that have been tested), while in others such as clonidine signs of promise have been offset by an unacceptable side-effect profile. Recently, the drug bupropion, an atypical antidepressant with some noradrenergic and dopaminergic activity, became the first non-nicotine medicine licensed for smoking cessation in the United States, Canada, and Mexico. The mechanism of action appears not to be related to the drug's antidepressant effect but rather to pathways common to addiction. Clinical trials, among non-depressed smokers, have shown clear advantage over placebo,(60) and there is evidence that bupropion and the nicotine skin patch have additive effects in enhancing outcomes. (61)

Continuities And Discontinuities In Depression Continuities in the short term

Many studies of clinical samples have reported that young people with a depressive disorder have a high risk of recurrence or persistence (Asarnow et al., 1988 Emslie et al., 1997b Goodyer et al., 1991 1997b Kovacs et al., 1984a McCauley et al., 1993). For example, Kovacs and colleagues (Kovacs et al., 1984a) undertook a systematic follow-up of child patients with a major depressive disorder, a dysthymic disorder, an adjustment disorder with depressed mood, and some other psychiatric disorder. The development of subsequent episodes of depression was virtually confined to children with major depressive disorders and dysthymic disorders. Thus, within the first year at risk, 26 of children who had recovered from major depression had had another episode by 2 years this figure had risen to 40 and by 5 years the effected cohort ran a 72 risk of another episode On long-term follow-up, major depression and dysthymia were associated with similar rates of most outcomes (Kovacs et al., 1994)....

Continuities in the long term

It seems, then, that both depressive symptoms and depressive disorder show significant continuity over time. Do these continuities extend into adulthood The available data suggest that they do. Harrington et al. (1990) followed up 63 depressed children and adolescents on average 18 years after their initial contact. The depressed group had a substantially greater risk of depression after the age of 17 years than a control group who had been matched on a large number of variables, including non-depressive symptoms and measures of social impairment. This increased risk was maintained well into adulthood and was associated with significantly increased rates of attending psychiatric services and of using medication, as compared to the controls. Depressed children were no more likely than the control children to suffer non-depressive disorders in adulthood, suggesting that the risk of adult depression was specific and unrelated to comorbidity with other psychiatric problems. Raoetal....

Processes Involved In Continuity Direct persistence of the initial depression

The review thus far suggests that depression in young people is associated with a variety of adverse outcomes, particularly further episodes of depression and suicidal behaviour. What processes could underpin these strong continuities over time The first point is that the strength and specificity of the continuities clearly support the idea that in some cases there may be direct persistence of the initial depression. At first sight, the finding that most cases of major depression among the young remit within a year (see below) would seem to suggest that direct persistence is uncommon. However, a detailed, 12-year prospective study of adults who had presented with major depression found that while only 15 had major depressive disorder (MDD)-level symptoms during the follow-up, 43 had subthreshold depression (Judd et al., 1998). The same may apply to depression in young people major depression and dysthymia often overlap and one can lead to the other (Kovacs et al., 1994). The...

Differential diagnosis Other psychiatric disorders Other psychoses

It could be argued that distinguishing schizophrenia from schizoaffective disorder, schizophreniform disorder, delusional disorder, etc. is a largely academic exercise. Until recently, treatment in psychiatry was entirely symptom or syndrome based. Thus manic symptoms respond to antimanic agents including lithium, psychotic symptoms respond to neuroleptics, and depressive symptoms respond to antidepressants.(1. ,. 8) Other 'mood-stabilizing' agents are also of value especially when combined with neuroleptics. However, it is possible that with increasing clinical experience and research using the new generation of 'atypical' antipsychotic agents such as clozapine, risperidone, and olanzapine, more specific indications will emerge. A recent report of efficacy of olanzapine in schizoaffective disorder in comparison to haloperidol is a case in point. (19 However, a tendency to reduce all psychotic disorders to 'serious mental illness' is unfortunate. It encourages a sloppy approach to...

The disease and disability burden of schizophrenia

According to World Bank and WHO estimates, (75 no less than 25 per cent of the total 'burden of disease' in the established market economies is at present attributable to neuropsychiatric conditions. Measured as proportion of the disability-adjusted life-years ( DALYs) lost, schizophrenia, bipolar affective disorder, and major depression together account for 10.8 per cent of the total, i.e. they inflict on most communities losses that are comparable to those due to cancer (15 per cent) and higher than the losses due to ischaemic heart disease (9 per cent).

Biological vulnerability

Physiology (Casat & Powell, 1988), melatonin (Shafii et al., 1996), thyroid-hormone levels (Dorn et al., 1996 Kutcher et al., 1991), sleep (Emslie et al., 1987), and brain imaging (Steingard et al., 1996). Several studies have shown that, in comparison with non-depressed patients, depressed young people are less likely to show suppression of cortisol secretion when the exogenous corticosteroid dexamethasone is administered (Casat & Powell, 1988) and more likely to have sleep abnormalities (Appelboom-Fondu et al., 1988 Cashman et al., 1986 Emslie et al., 1987 Kutcher et al., 1992 Lahmeyer et al., 1983 Riemann & Schmidt, 1993). There has been very little longitudinal research on most of these measures. There is, however, some evidence that cortisol levels predict subsequent depression. Goodyer and colleagues (Goodyer et al., 1998) found that higher cortisol DHEA levels at night predicted both the persistence of major depression and subsequent disappointing life events. They hypothesized...

Familygenetic vulnerability

There is evidence that affective disorders in adults have a genetic component. Genetic influences seem strongest for bipolar disorders (McGuffin & Katz, 1986), but unipolar major depressions also show significant heritability (Kendler et al., 1993), as do seasonal affective disorders (Madden et al., 1996). There have thus far been no large systematic twin or adoption studies of depressive disorder in young people. There is, however, evidence from twin studies of modest genetic influences on depressive symptoms in late childhood and adolescence (Eaves et al., 1997 Thapar & McGuffin, 1994), though this has not been replicated in adoption studies (Eley et al., 1998). Twin studies also suggest that some of the stability in depressive symptoms arises from genetic factors (O'Connor et al., 1998).

Depression in schizophrenia

In the WHO International Pilot Study of Schizophrenia, (33) the proportion of patients with initial schizophrenic symptomatology who developed non-schizophrenic (mostly affective) episodes in the course of time increased from 3 per cent in the first 2 years to 17 per cent at the end of the 5-year follow-up. In contrast, subsequent episodes with schizophrenic features occurred in fewer than 10 per cent of the patients with an initial diagnosis of major depression. Depression is the most common non-schizophrenic syndrome intercurrent with schizophrenia also in those patients who retain the essentially schizophrenic character of their illnesses. The proportion who develop clear-cut episodes of major depression ranges from 15 per cent during a 5-year follow-up (50) to 24 per cent during a 12-year follow-up.(20) This is a much higher period prevalence rate than in the general population, which suggests that depression is part of the clinical spectrum of schizophrenia. Based on such data, a...

Formulating treatmentmanagement plans

Depression during the maintenance phase can have as many causes as depression in other contexts, but despite initial pessimism, there is now good evidence that such mood states do respond to traditional (tricyclic) antidepressants ( 0 ) and they should be vigorously treated.

Biological Markers in Croatian War Veterans with Combat Related Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a severe psychiatric illness associated with disturbances in diverse neurobiological systems. The evaluation of a variety of biomarkers might facilitate a goal of modern medicine, a proper treatment for an individual patient at a given stage of disease. This is especially important in PTSD, a disorder with a complex clinical picture, diverse symptoms, and frequent comorbidities. Biological markers (platelet serotonin, platelet monoamine oxidase, plasma lipid levels, plasma dopamine beta hydroxylase, plasma cortisol and serum levels of thyroid hormones) were determined, and clinical symptoms were evaluated, in 93 male war veterans with chronic combat related PTSD, using the Clinician Administrated PTSD Scale, Positive and Negative Syndrome Scale, and the Hamilton Rating scales for Depression and Anxiety. Platelet serotonin concentration and plasma dopamine beta hydroxylase activity were similar in PTSD subjects and healthy controls....

Continuation treatment

If mood disorders or cyclic episodes occur, treatment with antidepressants, mood stabilizers (lithium or valproate), or an anticonvulsant drug (carbamazepine) may be indicated. Care must be taken to distinguish between a post-neuroleptic depression and the development of a (schizo)affective disorder.

Combinations of risk factors

It seems, then, that the risk of further episodes of depression is predicted by many factors. It is likely that it is the combination of several of these risk factors that poses the greatest risk. Thus, for instance, Beardslee et al. (1996) examined risk factors for affective disorder within a random sample of 139 adolescents. Single risk factors such as parental major depression, parental non-affective diagnosis, or a previous child psychiatric diagnosis increased the risk of subsequent affective disorder from 7 to 18 . However, when all three risk factors were present, the risk jumped to 50 major depression in women suggest that genetic influences may alter the sensitivity of individuals to the depression-inducing effect of adverse life events (Kendler et al., 1995). In other cases, it seems as if people act in ways that increase their likelihood of adversity, a pattern which in turn increases their risk of depression. One of the best-known examples of this phenomenon comes from the...

Recovery from an episode of depression

It is important to distinguish between long-term continuities discontinuities in the course of depressive disorders and the prognosis for the index attack. Indeed, the available data suggest that the majority of children with major depression will recover within 2 years. For example, Kovacs et al. (1984b) reported that the cumulative probability of recovery from major depression by 1 year after onset was 74 and by 2 years, 92 . The median time to recovery was about 28 weeks. This study included many subjects who had previous emotional-behavioural problems and some form of treatment, and might therefore have been biased towards the most severe cases. However, very similar results were reported by Keller et al. (1988) in a retrospective study of recovery from first episode of major depression in young people who had mostly not received treatment (Keller et al., 1991), and by Warner et al. (1992) in a study of the children of depressed parents. In a community survey, Garrison et al....

General aspects of the treatment of delusions

Since many illnesses are associated with delusions we have to tailor the psychopharmacological approach to suit each particular condition. In delusional disorder, the schizophrenias, and schizoaffective disorder, neuroleptics are the mainstay, with antidepressants, mood stabilizers, and electroconvulsive therapy sometimes playing subsidiary roles.

Depressive and manic states

What are depression and mania Ideally, one would first describe 'normal' or average mood. While this can be difficult, an operational definition might be that 'normal' or average mood is the state of not feeling particularly euphoric or sad, except under the right circumstances. For example, if something good happens, one would feel happy for a while, and if something bad were to happen, one would feel sad or down for a while. Most people can relate to this definition. Superficially, depression and hypomania can be viewed as extremes of these normal fluctuations in mood. But clinical depression (or mania) are more than extremes of normal mood. They represent syndromes in which, in addition to mood, there are disturbances in thought, psychomotor state, behaviour, motivation, physiology, and psychosocial function. Depressive states are sometimes easier to comprehend owing to similarities with non-pathological depression and mourning. Mood is bleak, pessimistic, and despairing. A deep...

Midtwentieth century Adolf Meyer and the evolution of American psychiatry

During the first half of the twentieth century, the views of Adolf Meyer( 5.) gradually assumed a dominant position in American psychiatry. Meyer believed that psychopathology emerged from interactions between an individual's biological and psychological characteristics and his or her social environment. While allowing for biological and genetic factors, the Meyerians understood them as part of an individual's vulnerability to specific psychological and social influences. This perspective was symbolized by the rubric 'manic-depressive reaction' in the first official American Psychiatric Association diagnostic manual published in 1952 (DSM-I). Meyer's approach differs from the standard disease model, in which clinical phenomena in a given patient are understood (and, therefore, potentially predictable) in terms of a given disease with a specific natural history and pathophysiology. When the Meyerian focus, considerably influenced by psychoanalysis, turned to manic-depressive illness,...

Moving from depression to diagnosis

A common misperception among some clinicians and patients is to think of 'depression' as being equivalent to unipolar depression, which is then treated with antidepressants. There are a number of reasons for this phenomenon the first is that patients often lack insight into their manic symptoms not knowing that they are ill, they deny their manic symptoms to clinicians. Second, depressive symptoms tend to last longer than manic symptoms, sometimes are more frequent, and often are more psychically painful thus, patients tend to seek assistance when depressed rather than when manic. Third, the many new antidepressants that have become available over the past 10 years have been extensively marketed to physicians at the same time that 'depression awareness' programmes have educated the public about the availability of safe and effective treatments. Simultaneously, few new treatments for bipolar disorder have become available, and there has been scant professional and public education...

Clinical Implications Implications for initial management

The time course of major depression in young people is highly regular across studies (see above). Once triggered, 50 of all episodes last around 7 months and 80 last 1 year. Only 10 or less last 2 years or longer. It is important, therefore, that clinicians enquire carefully about the duration of depressive symptoms. Patients who present shortly after the onset of symptoms have a good chance of recovering within the next few months. In such cases, a sensible initial approach might consist of a relatively brief intervention, especially as there is evidence that the response rate to inactive interventions or placebo is around 30-40 (Harrington et al., 1998a Hazell et al., 1995). By contrast, those who present for treatment after, say, 6 months may be less likely to recover spontaneously within the next 4 weeks. In such cases, there is a stronger case for initiating an intensive form of treatment straight away.

Recurrent bipolar episodes

Only about 10 per cent of patients with 'manic-depressive' disorder have mania. Kraepelin, who followed hundreds of patients with manic-depressive illness, observed very few with only recurrent manic episodes. 4 Recurrent manic episodes are more often interspersed with depressive episodes. Mixed states may emerge with the simultaneous presence of depression and manic symptoms (see discussion of acU e ,miX d ,. Pi.Sod. S, below). About 85 per cent of patients with an acute episode of mania will run a chronic episodic course. (l7

Rapid cycling disorder

In DSM-IV rapid cycling disorder is a specifier in ICD-10 it is mentioned only in an annex for disorders under consideration. In DSM-IV it can be applied to both bipolar type I and bipolar type II disorders. There should have been at least four episodes fulfilling the criteria of major depression, mania, hypomania, or mixed mood disorder in the previous 12 months. The episodes are demarcated by either partial or full remission for at least 2 months or a switch to an episode of opposite kind.

Need for continuation and maintenance treatments

While behavioural difficulties such as conduct disorders show strong continuity over time, emotional problems among the young tend to be short-lived. The studies described here suggest that this view is mistaken, at least so far as clinical cases of depressive disorders are concerned. They are associated with considerable impairment of psychosocial functioning, and in severe cases vulnerability extends into adult life. It is apparent, then, that both assessment and treatment need to be viewed as extending over a prolonged period of time. Young people with severe depressive disorders are likely to have another episode, and so it is important that we develop effective prophylactic treatments. But for how long should these treatments continue Research with depressed adults distinguishes between the need for continuation treatments and maintenance treatments. The idea behind continuation treatments is that although treatment may suppress the acute symptoms of depression, studies of the...

Need for vigorous treatment of the first episode

The finding that the first episode of depression can lead to scarring is important because it suggests that much greater attention should be paid to the recognition and treatment of the first episode of depression. Since late adolescence is a common period for the onset of adult depressive disorders (Smith & Weissman, 1992), the implication is that child and adolescent psychiatry could have an important part to play in the prevention of depression in adulthood. Indeed, there are plenty of developmental examples of the ways in which early disorders that are not managed appropriately can lead to permanent changes in both the biology of individuals and their psychosocial functioning (Wolkind & Rutter, 1985).

Classification of affective mood disorders Formal classification

For the depressive disorders, both ICD-10 and DSM-IV have multiple conditions and specifiers. The ICD-10 system allows mild and moderate depressive episodes (with or without a 'somatic syndrome' conceptualized as reflecting 'melancholic' features), and severe depressive episode (with or without psychotic symptoms). There are separate codes for a similar set of 'recurrent' disorders, while several 'persistent' mood disorders (including cyclothymia and dysthymia) and residual conditions are listed. DSM-IV has two principal 'stem' disorders (major depressive episode and dysthymia), with the first having a number of optional specifiers including 'with' melancholic, catatonic, psychotic, or atypical features, as well as including disorders showing longitudinal patterns of rapid cycling or a seasonal pattern. Both systems have categories for affective disorders secondary to organic disease, while DSM-IV includes mood disorders due to a general medical condition or substance use, or...

Use of health services

One of the major challenges for psychiatry presented by epidemiological studies of depression has been the consistent finding that the majority of cases of depression in the community are neither recognized, diagnosed, nor treated. In the ECA study, it was found that 65 to 70 per cent of people with depression had visited a health professional in the last 6 months, but only 15 to 20 per cent had had a visit for a mental health reason and only about 10 per cent had seen a mental health specialist. Ormel et a .(29 found that patients with depression who present with largely somatic rather than psychological symptoms are extremely unlikely to be recognized by general practitioners. Similar findings have also been reported in England. (39 Even if major depression is recognized in the primary care setting, it is often not adequately treated. Even when major depression is treated in primary care, there is evidence to suggest that the outcome is worse if treated by the primary physician than...

Serotonin markers and affective disorders

Dysfunction of the serotoninergic system has long been suspected in major depression and related disorders. Depression can successfully be treated with selective drugs which target serotonin receptors. The serotonin transporter may also be involved in susceptibility to affective disorders and in the response to treatment with these drugs. Allelic association has been suggested between the serotonin transporter gene (located on chromosome 17q11.1-12) and unipolar affective disorder. (48) The presence of one allele of this gene was significantly associated with a risk of unipolar affective disorder. This study also included a group of bipolar affective disorder patients, although no associations were found with this marker in this patient group compared to normal controls. This preliminary finding may add to our understanding of the possibility of polygenic inheritance in affective disorders. These findings were replicated in two different samples, again showing an association between...

Impairment in social and familial relationships

Difficulties in social functioning are concomitant to depressive disorders. (5,Z,62) Previous research found that patients experienced a reduction of social relationships, with feeling of social discomfort, loneliness, and boredom.(6) Depressed patients seem lower in social self-confidence, they socialize less, and participate in social interaction less fully than do never-depressed persons.(62) In other words, depressed individuals do not make active effort to develop and sustain reciprocally supportive social relationships. The concept of social support has been widely used to predict general health and more specifically psychiatric symptoms. (63 Previous research revealed that the degree of integration in a social network, or structural support, have a direct positive effect on well being, reducing negative outcomes in both high- and low-stress life events. Among depressed individuals, dysfunctioning in social activities has been found to persist a long time after remission from...

Dysfunctional cognition

According to the helplessness model of depression,(89) vulnerability to depression derives from a habitual style of explaining the causes of life events, known as attributional style. A large body of research found that individuals suffering from depression think more negatively than healthy individuals. Specifically, depressed patients have a tendency to make internal, stable, and global causal attributions for negative events, and to a lesser extent, the attribution of positive outcomes to external, specific, and unstable causes. In other words, depressed patients have a low self-esteem.(9 Thus, when thinking about the self, past, current, and future circumstances, depressed patients emphasize the negative, and this process is likely to contribute to the perpetuation of their depressed mood. However, the role of self-esteem in depression has not yet been well established. A controversy persists as to whether low self-esteem is a consequence of depression or a vulnerability factor of...

Temperament and behaviour

The model of temperament developed by Eysenck(128) approaches temperament in terms of cortical arousal. Eysenck suggested that individuals differ in their basic arousability and therefore in their optimal level of stimulation. These physiological differences give rise to the primary personality dimension of introversion-extraversion. Introverts are said to possess relatively reactive reticular systems, and thus to attain their optimal level of cortical arousal at relatively low level of stimulation. As a result of their low optimal arousal level, introverts are expected to prefer and seek out mild forms of stimulation and to avoid more intense and novel form of stimulation. In contrast, extraverts are said to possess relatively unreactive reticular systems, to have correspondingly high optimal levels of cortical arousal, and to therefore approach more intense and novel forms of stimulation. While this central form of arousal is seen to influence the affective quality of experience,...

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