Natural Solution for Depression Found

Destroy Depression

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

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Somatic Treatments For Major Depression Electroconvulsive Therapy ECT

There is no widespread agreement on the underlying mechanism of action of ECT. Electrophysiological studies (Ishihara and Sasa, 1999) have shown that ECT increases the sensitivity of 5-HT3 receptors in the hippocampus, resulting in an increased release of glutamate and GABA. However, tryptophan depletion failed to reverse the improvement in mood seen in depressed patients after ECT (Cassidy et al., 1997) and does not support a primarily 5-HT-dependent mechanism. ECT has been shown to decrease the sensitivity of the noradrenergic and DA autoreceptors in the locus coeruleus and substantia nigra, resulting in an increased release of NE and DA (Ishihara and Sasa, 1999). Support for a noradrenergic mechanism also arises from a study showing a normalization of platelet alpha-2 receptors after a course of ECT (Werstiuk et al., 1996). However, the fact that ECT has efficacy in patients that fail treatment with medications argues against ECT having a similar mechanism of action (Persad, 1990)....

Figure 192 The frequency of suicidal thoughts and plans among patients with stroke Mi Sci or brain trauma The frequency

Multivariate analysis of neuropsychiatric examination findings demonstrated that the existence of a depressive disorder was the only significant risk factor for suicidal thoughts. Examination of specific vegetative and psychological symptoms of depression among suicidal and non-suicidal patients using logistic regression demonstrated that social withdrawal (p 0.01) and ideas of reference (p 0.016) were independent factors associated with presence of suicidal plan. Hopelessness was found to have a trend association with suicidal plans among patients with major depression (p 0.052). Among the 33 suicidal patients at the initial in-hospital evaluation, 22 (9 stroke, 2 TBI, 3 MI, and 8 SCI) had at least one follow-up evaluation over the 2 years following onset of illness (Kishi et al. 2001b). Among the 16 patients in this group who were depressed (i.e., 73 of suicidal group), the depression had improved at follow-up in 11 and they were no longer suicidal. The patients whose depressive...

Tricyclic Antidepressants

The tricyclic antidepressants were first introduced in the early 1960s and soon became widely used for the treatment of depression. The introduction of the tricyclics, along with the development of the phenothiazine antipsychotics for the treatment of schizophrenia and the use of lithium for treatment of bipolar illness, ushered in the modern era of psychopharmacology. The robust effectiveness of the tri-cyclics is somewhat offset by their problematic side effects, and although in recent years they have been largely supplanted by the selective serotonin reuptake inhibitors (ssRis) as first line treatment, the tricyclics still remain a widely used treatment for depression and other psychiatric and neurologic syndromes.

Analysis of the Impact of the SSRIs on the Antidepressants Market

It is clearly evident from the data presented in Figure 12.2 that the antidepressants market has grown and continues to grow at a very substantial rate. In fact, between 1990 and 1997 total world sales of antidepressants increased by an average of 34 year on year, and in 1992, sales increased by a staggering 67 . Based on 1997 figures, the current value of worldwide sales of antidepressants is estimated to be (sterling)3.5 billion. It is also apparent from these figures that the USA accounts for 70 of total worldwide antidepressant sales and it has been the major contributor to growth in this sector. The reasons for this market expansion are three-fold. The first is the cost of the SSRIs relative to the tricyclics. The latter were introduced as antidepressants predominantly in the 1950s and '60s and by the time of the launch of the SSRIs, many no longer had patent protection and were already available as low cost generics. As a market dominated by old products, many of which were...

Other Antidepressants

Monoamine oxidase inhibitors (MAOIs) increase the PRL response to TRP106 and the cortisol response to 5-HTP107 in depressed patients suggesting they may increase 5-HT1A 5-HT2 receptor function but more specific challenge data are unavailable. Antidepressants which lack both 5-HT and noradrenaline reuptake inhibition such as mianserin and trazodone do not enhance the PRL response to TRP108,109 indicating that this is not a universal property of antidepressant drugs. Nefazodone, related to trazodone and with a similar pharmacology, increases PRL concentrations and temperature when given acutely, an action attributed to its metabolite mCPP.110 Chronic treatment with nefazodone results in decreased responses to acute nefazodone challenge suggesting decreased 5-HT2C receptor sensitivity111 which is similar to the blunted responses to mCPP challenge seen following repeated mCPP administration.112 Lithium has antidepressant properties and has been investigated in a number of studies. PRL...

Side Effects of Antidepressants

The pharmacological properties that underlie the side effects of antidepressants have been better characterized than the properties responsible for the therapeutic effects. While newer antidepressants have provided little additional therapeutic efficacy compared to older drugs, they are unequivocally safer and much better tolerated. In general, side effects can be divided into those that occur early in the course of treatment and those that emerge gradually over continuous use. Frequently Occurring Initial Side Effects (first 1 to 4 weeks). The majority of initial side effects of antidepressant and antimanic drugs relate in a dose-dependent way to muscarinic cholinergic, histamine H1 and H2, and a1 -adrenergic antagonist properties. Some initial side effects are also caused by increasing levels of 5-HT or NE (see Bolden-Watson and Richelson, 1993, for reviews). Most early side effects diminish in intensity over time, although cardiovascular side effects may not. Side effects due to...

Phenomenology and specificity of depressive symptoms

As indicated in the first edition of this text, we have conducted several studies examining the phenomenology of poststroke depression compared with the signs and symptoms of depression in patients without brain injury. We have also examined the frequency of specific symptoms of poststroke depression compared with stroke patients who are not depressed to examine whether these symptoms may reflect physical illness or depressive disorder. The only other investigators who have specifically examined the phenomenology of poststroke depression are Spalletta et al. (2005) and Gainotti etal. (1997,1999). In Chapter 5, I compared the findings of Spalletta et al. (2005) with our findings and showed that both studies found, among patients with poststroke major depression, the frequency of virtually every symptom was significantly greater than non-depressed stroke patients (Table 5.2). The first study to examine the phenomenology with poststroke depression was conducted by our group examining...

Prevalence of depressive disorders

Social withdrawal, or acts of self harm are often unreliable. In addition, making a diagnosis of depression based on only observed behavior would require that these new diagnostic criteria be validated. Based on observations in patients without comprehension deficits we know that symptoms, such as insomnia, decreased appetite, decreased energy, can occur in patients who deny depressed mood (Fedoroff et al. 1991). Furthermore, although some of these patients with comprehension deficits who may have improved in some of these symptoms (e.g., insomnia) after receiving antidepressants, the diagnosis of depressive disorder still remains uncertain. Until we have a laboratory test for depression or some other non-verbal means of diagnosing depression, it will be impossible to know for sure if the patient who cannot provide reliable responses to questions about their subjective mental state has a depressive disorder. Therefore, as a result of patient exclusions in all studies of poststroke...

Comparison with Other Antidepressants

In terms of tolerability and toxicity, the SSRIs appear to be more acceptable to both patients and their physicians than older antidepressants. Some investigators, however, believe that the TCAs and monoamine oxidase inhibitors (MAOIs) are more effective than the SSRIs in certain subtypes of depression. While the data are mixed, as will be discussed below, most studies indicate that the SSRIs and TCAs are equally efficacious. Tricyclic Antidepressants (TCAs) The influential studies from the Danish University Antidepressant Group (DUAG) in 19861 and in 19902 sparked an ongoing debate on the relative efficacy of SSRIs and tricyclic antidepressants specifically, that the TCAs are superior for endogenous depression. The DUAG group compared clomipramine to citalopram in one study and to paroxetine in another, in inpatients with major depression. The first study of 114 inpatients found that 62 responded to clomipramine and 34 to citalopram. Similarly, in the second study, 46 responded to...

Antidepressant Medications

Medications effective in reducing the symptoms of major depression are called antidepressants. The Food and Drug Administration requires controlled, double-blind studies showing safety and efficacy before approving an antidepres-sant medication to be available in the United States. Major Depressive Disorder is characterized by sadness and an inability to experience pleasure. Associated symptoms include decreased self-esteem, feelings of hopelessness and worthlessness, excessive guilt, and difficulty with concentration, memory, and decision making. Anxiety manifested as fear, nervousness, or excessive worry is also common in depression. Agreater focus on bodily sensations can result in somatic symptoms. Sleep difficulties marked by reduced or excessive sleep, and a change in appetite with consequent weight loss or gain, are also present. Suicidal ideas can lead to suicidal attempts with the potential to succeed. The diagnosis of major depression requires these symptoms to be present...

Tricyclic Antidepressants TCAs

TRP challenge generally reveals a consistent picture of enhanced PRL responses by TCAs. This is seen in normal volunteers with acute clomipramine15 and chronic desipramine.84 In depressed patients similar findings occur with desipramine85,86 and amitriptyline.85,87 In the study using amitriptyline by Cowen et al87 this effect was only evident if three patients with pretreatment weight loss were excluded, probably because weight loss is itself associated with increased PRL responses to TRP in women.88 The enhancement with clomipramine occurs acutely (presumably related to acute 5-HT reuptake inhibition see also SSRIs, below) whereas chronic treatment is required with desipramine86 suggesting that a different mechanism is involved (possibly pre- or postsynaptic 5-HTiA receptor changes, but see below). The increase in PRL responses is not related to clinical response.85-87 Changes in GH responses after TCAs have been less consistent (where reported) with increases seen with acute...

Major Depressive Disorder

Major Depressive Disorder (MDD) is characterized by depressed mood or a lack of interest or pleasure in once-enjoyable activities, and associated symptoms (e.g., sleep disturbance, appetite weight disturbance, difficulty concentrating, worthlessness or exaggerated guilt). To receive a diagnosis of MDD, at least five symptoms must be present most of the day, nearly every day, for at least 2 weeks (American Psychiatric Association ApA , 1994).

Antidepressants

Drugs used for treating mental disorders accompanied by depression are called antidepressants. They are drugs that can relieve a number of symptoms that are associated with number of known psychosomatic disorders such as depression. In other words, antidepressants are capable of removing or alleviating a number of disorders in the psychoemotional realm referred to as depressive syndrome in psychoneu-rological practice. There are sufficiently acceptable, although not universally accepted classifications of depression based on their etiology. Endogenous depression is characterized by loss of interest in things once pleasurable, loss of libido, minor restlessness, and trouble sleeping. Neurotic or anxious depression is distinguished by anxiety, stress, hyperactivity to unexpected events or loss, irritability, and helplessness. Situational depression usually originates upon influence of stressful outside factors. Manic-depressive disorder is characterized by alternating expression and...

Affective Disorder Syndromes

Major depression has a lifetime prevalence of about 15 percent and is about 15 times as common as bipolar disorder (manic-depressive disorder). Major depression is about twice as common in women as in men in all countries and cultures and does not vary in occurrence among different races. It may occur at any age, but the majority of cases occur in adulthood. Studies suggest a genetic predisposition because there is an increased incidence of major depression and alcoholism in relatives of patients with this mood disorder. The diagnosis of depression is often overlooked, especially in patients with chronic neurological disease. The Diagnostic and Statistical Manual, 4th edition (DSM-IV) criteria for this diagnosis requires either that the patient have a depressed mood or that the patient have a sustained loss of interest and pleasure. Some depressed patients have a depressed affect or become withdrawn or irritable but do not admit to or complain of feelings of sadness. Almost all,...

Clinical Pharmacokinetics of SSRIs

Citalopram,1 fluoxetine,2,3 fluvoxamine,4 paroxetine5 and sertraline6 are the five antidepressants which are known as selective serotonin reuptake inhibitors (SSRIs) (Fig. 2.1). Their clinical efficacy, good tolerance and safety have been demonstrated in many studies7,8 and some of them may also be prescribed successfully for the treatment of obsessive compulsive disorder, bulimia or panic attacks. Despite their common pharmacological properties, the SSRIs differ in their metabolism by cytochrome P450 and in their interaction profile with other drugs which are also substrates of this enzyme system. Sensitive and selective (including stereoselective) methods, using high performance liquid chromatography or gas chromatography, have been introduced for their quantitative analysis in blood samples.9 These have enabled studies of their pharmacokinetics as well as investigations of the relationship between plasma concentration and clinical efficacy. This review summarizes our present...

Pharmacokinetic Interactions

The interest of clinical psychopharmacologists in cytochrome P450 arose more from the observation of pharmacokinetic interactions which involved the SSRIs and which had pharmacodynamic consequences than from the discovery of pharmacogenetic differences in the metabolism of psychotropic drugs. This interest was firstly centered on the role of CYP2D6, as this enzyme is inhibited in the interaction between fluoxetine and tricyclic antidepressants, an observation described in 1989.62 For some drugs, this enzyme obviously plays an important role despite its relatively low abundance in the human liver compared with that of other CYP isozymes such as CYP3A, CYP2C9, CYP2C19 and CYP1A2 (Fig. 2.4).63 SSRIs can interact with CYP1A2, CYP2D6, CYP2C19 and CYP3A4 to a varying degree as reviewed by many authors (Fig. 2.4).22,23,69-72 Only recently has CYP2C9 also been shown to be inhibited by some of these drugs.19 This helps to explain the earlier, albeit inconsistently, observed pharmacokinetic...

Noradrenaline Autoreceptors

Noradrenaline (NE) neurons are endowed with autorecep-tors on their cell bodies, where they exert a negative feedback role on firing rate. They are of the a2A subtype as confirmed by genetic cloning experiments. Such autoreceptors are also located on NE terminals throughout the brain, where they inhibit the release of NE. The prototypical agonist of such receptors is clonidine, which is commercialized mainly for the treatment of high blood pressure. Its hypotensive effect would not, however, be exclusively mediated by its action on autoreceptors as a2-adrenoceptors are also located postsynaptically. Yohimbine, among several agents capable of blocking a2-adrenoceptors, is a relatively selective agent used mainly to treat erectile dysfunction. The antidepressant drugs mirtazapine and mianserin antagonize a2-adrenoceptors, leading to enhanced NE release that contributes to their therapeutic actions in major depression. While mirtazapine acts in part by enhancing indirectly the activation...

Serotonin Autoreceptors

As for NE neurons, 5HT neurons are endowed with cell body and terminal autoreceptors that exert a negative feedback influence on neuronal firing and release, respectively. The somatodendritic ones that inhibit firing rate are of the 5HT1A subtype, and the ones located on terminals are mainly of the 5HT1B subtype. The former subtypes of auto-receptors play a crucial role in the antidepressant effect of 5HT reuptake blockers and monoamine oxidase inhibitors because they desensitize after 2 to 3 weeks of treatment. This permits a recovery of the firing rate of 5HT neurons to normal in the presence of inhibited reuptake or monoamine oxidase inhibition, then producing a net increase in neurotransmission. The time course for this recovery in firing activity is consistent with the onset of the therapeutic action of such drugs in major depression. This observation has recently been put to clinical use by accelerating the anti-depressant response of such drugs with the 5HT1A auto-receptor...

SSRIs in Depression Distinctive Actions

The introduction of the selective serotonin reuptake inhibitors (SSRIs) has radically changed the treatment of depression worldwide. The five currently marketed SSRIs, fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram were accepted by international regulatory agencies because these medications were found to be superior to placebo and, at least for most clinical populations, of equal efficacy when compared to the older generations of tricyclic antidepressants (TCAs). The SSRIs are considered to be equally effective for the treatment of depression and share more similarities than differences. Differences in the onset of action has been a subject of debate among the pharmaceutical houses but most clinicians believe that the timing of clinical effect is the same for each of the SSRIs. Similarly, potential differences in side-effects have been exploited by pharmaceutical advertising and marketing-directed research but, again, most clinicians believe that the side-effect...

The Beck Depression Inventoryii

The Beck Depression Inventory-II (BDI-II Beck, Steer, & Brown, 1996) is a 21-item self-report instrument for measuring the severity of depression in adolescents and adults according to symptoms corresponding to the criteria for diagnosing major depressive disorders listed in the fourth edition of the American Psychiatric Association's (1994) Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). It is the upgraded version of the amended Beck Depression Inventory (BDI-IA Beck & Steer, 1993), which, in turn, replaced the original instrument developed by Beck, Ward, Mendelson, Mock, and Erbaugh (1961). The BDI-II is scored by summing the highest rating for each of the 21 symptoms, and a 4-point scale ranging from 0 to 3 is employed for each item. Respondents are asked to rate each symptom for the past 2 weeks, through that day. This instrument generally requires between 5 and 10 minutes to complete. Beck, Steer, and Brown (1996) suggested the following cutoff score...

Alcohol And Depression

The relationship between depression and both acute alcohol-related states (such as intoxication and withdrawal) and chronic use problems (such as abuse, protracted withdrawal, and chemical dependence) has been studied. All of these alcohol-related conditions have been shown to be associated with dysphoric mood states, but the mechanism of mood depression is not well understood and may differ among various alcohol-related conditions. In addition, the length of time alcohol has been abused, amount of use, predisposing genetic factors, gender, and multiple other variables may influence the mechanism of comorbidity with depression. Likewise, the different depressive states may be caused by different underlying neurochemical mechanisms, and thus could be associated with alcoholism by different processes. Current informa The association between depression and chronic alcohol use has been another area of interest. Some studies suggest that alcohol and affective disorders occur together at...

Stimulants And Depression

Depressive disorders among 298 treatment-seeking cocaine abusers to be about 60 , which declined to approximately 30 during exclusive cocaine use. In characterizing their population, Gawin and Kleber (107) found that 33 had depressive disorders 13 with major depression and melancholia and 20 with dysthymia. Symptoms persisted for more than 10 days after last use and were consistent with previous symptoms during abstinence. Interestingly, the group with psychiatric diagnoses used less cocaine than the remainder of the sample but reported that it produced the same effect. It was postulated that the depressed group might have an increased sensitivity to the effects of cocaine, thereby using it to self-medicate dysphoria. Eight of the authors' 70 subjects reported increased severity of depressive symptoms as intensity and duration of cocaine use increased, for which they postulated an acute depletion of catecholamine neurotransmitters and supersensitivity of dopamine (DA) autoreceptors....

General Management Goals

Treatment should also include addressing complications of speech and language disorders. Depression is associated with left hemisphere injury, particularly in the deep frontal regions, and is associated with Broca's aphasia, global aphasia, or subcortical aphasia with anterior extension. y , y Treatment of depression includes support and encouragement, concentration on domains in which the patient succeeds, and antidepressant medication. Paranoid and agitated behavior is occasionally observed in patients with posterior aphasic syndromes, particularly those with Wernicke's aphasia and pure word deafness y management consists of antipsychotic drugs in a low dose. Finally, patients with associated bulbar or pseudobulbar palsy are at increased risk for aspiration and secondary lung infection and should be monitored closely and considered for percutaneous gastric feeding tube.

Reservoir of R prowazekii

The human body louse is the only established vector for R. prowazekii. Lice die of their infection with R. prowazekii and do not transmit their infection to their progeny, the main reservoir (except in the United States, where the flying squirrels are implicated) appears to be in humans. To contaminate lice and allow transmission, bacteremia may occur and be prolonged. R. prowazekii is not eradicated at the apparent end of the disease. Nicolle (47) reported that chronic asymptomatic bacteremia could be observed. Humans who contact typhus retain some rickettsiae for the rest of their lives. However, the bacterium remains present, leading immune-depressed patients to relapse, known as Brill-Zinsser disease, a milder but bacteremic form of typhus (48). The bacteremia may then allow feeding lice to become infected and to start a new epidemic. Consequently, until all humans who have had typhus are dead, typhus can constitute a threat. This fact has been highlighted in Burundi in 1997,...

SSRIs and Patient Groups with Specific Treatment Problems

Selective serotonin reuptake inhibitors (SSRIs), whilst initially launched solely as antidepressants, have been used increasingly as treatments for other disorders and in patients who are vulnerable to the adverse effects of other antidepressants. This chapter examines the role of SSRIs in two groups of patients whose age places them in the latter category (the young and the elderly), concentrating on the management of a number of psychiatric disorders specific to them. Also discussed is the efficacy of SSRIs in other groups of patients in which these compounds may turn out to be a particularly useful form of therapy.

Brainderived Neurotrophic Factor

There is some specificity of the effects on BDNF as a function of both anatomical area involved and specific type of neurotrophic factor. Thus, although stress decreases BDNF in the hippocampus, it increases NT-3, and the effects on BDNF are in the opposite direction in the hypothalamic-pituitary-adrenal axis, which hypothetically could contribute to the increased size of the pituitary and adrenal glands in patients with major depression. In neonatal rat pups, 24 hours of maternal deprivation results in substantial decrements in BDNF in the hippocampus and a doubling in the rate of the diffuse neuronal apoptosis that occurs in the 12-day-old animal. Repeated experiences of maternal deprivation for 3 hours in the first 10 days of life result in an animal that is permanently hyperactive and hypercortisolemic, as well as prone to alcohol and cocaine self-administration as compared with its non-deprived litter mates. These biochemical and behavioral defects are reversed by chronic...

Other Drugs And Depression

Crites and Schuckit (177), however, found no difference in the incidence of affective symptoms between 120 solvent-abusing adolescents and 636 other drug-abusing adolescents. Dinwiddie et al. (178) reviewed psychiatric diagnoses of 11 chronic solvent abusers, only one of whom was diagnosed with a secondary depression. Overall, the depressive symptoms associated with solvent aerosol abuse generally appear to be mild and transitory. Although hallucinogens such as lysergic acid diethylamide (LSD) and phencyclidine (PCP) generally are not associated with severe mood disturbances, reports suggest that use of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy), a hallucinogen with stimulant properties, produces depressive symptoms (179-181), possibly related to damage to serotonergic neurons (182). MDMA has been noted to increase extracellular DA and 5-HT. NE and neuropeptide levels are also affected (182), and tryptophan hydroxylase activity is reduced (183)....

Child And Adolescent Depression

Clinical depression as seen in children and adolescents is characterized by depressed mood and or loss of interest in activities as well as related symptoms such as difficulties with sleep, appetite changes, a sense of hopelessness, decreased energy, increased aches and pains, loss of self-esteem, difficulties with concentration, and thoughts of death and dying, sometimes with active suicidal plans. In some cases, young people do not complain of depressed mood or loss of interest in activities but instead have extreme irritability along with other symptoms. Most children, just like adults, have brief periods of depressed or irritable mood. Clinical depression (Major Depression) requires that several symptoms occur at the same time persist for most of the day, nearly every day for a period of at least 2 weeks and be associated with significant impairment in the child's ability to function. When clinical depression is causing impairment, parents and teachers may notice loss of interest...

Diagnosis Prevalence and Prognosis

A depressive disorder is defined by a disturbance in mood and a cluster of emotional, cognitive, vegetative, and behavioral symptoms that result in functional impairment. Typically, depressive disorders are episodic. There are two diagnoses of unipolar depressive disorders Major Depressive Disorder and Dysthymic Disorder. Major depression is a more severe disorder in terms of the number and quality of symptoms and the extent of functional impairment. Dys-thymic Disorder is less severe but longer lasting. A child may experience both of these disorders at once. orders are rare among preschool children. Among children, rates of 2 are reported for major depression and 2-3 for Dysthymic Disorder. Twenty percent of adolescents report symptoms of major depression, with the rate increasing dramatically at puberty. Females, Arican American children, and children with a medical condition or learning disability are at greater risk for developing depression. Children's depressive disorders tend...

Negative View of the Self

Depressed patients not only interpret their experiences as negative, but they devalue themselves as well. If a depressed individual does not do as well as expected on a test or a business venture, a likely immediate reaction is to think of himself or herself as ineffective and undesirable. A striking feature of the depressed patient is the tendency to overgeneralize from a particular incident. A student who had difficulty getting a date on a single occasion thought, I must be repulsive to girls. A highly successful businessman who made one transaction that lost money became obsessed by the idea that he was stupid. A mother whose child was untidy on one occasion thought, I'm a terrible parent. Depressed patients often see themselves solely in terms of their deficiencies. Further, these negative self-evaluations are usually associated with self-rejection. Patients often will not only see themselves as inferior, but will criticize, reproach, and castigate themselves for being so...

Natural course of depression

Given the number of effective treatments that are available for poststroke depression (see Chapter 20), it is increasingly difficult to conduct studies on the natural course of this disorder. Several studies, however, were conducted prior to publication of the current treatment studies. In addition, most of these pretreatment studies examined the course of poststroke depression in the setting of usual care. Thus, in these studies, a minority of patients were treated with antidepressants by their primary care physician. Since effective treatment, however, must produce more rapid improvement of symptoms than would naturally occur over time, it is essential to study the natural course of poststroke depressive disorders. Our data on the natural course of depressive disorder is based on longitudinal studies in which patients received usual care and the vast majority were not given antidepressant treatment. We have studied the natural course of poststroke depression in two studies and...

Problems with use

The metabolism of barbiturates by microsomal enzymes in the liver underlies most of the drug interactions. The rate of metabolism of warfarin, phenytoin, tricyclic antidepressants and the oral contraceptive pill is increased, and conversely MAOIs inhibit these enzymes and reduce the rate of barbiturate metabolism.

Delayedonset depression

The background characteristics of the patients are shown in Table 9.1. Patients who developed major depression during the acute poststroke period tended to be younger than those who developed delayed-onset major depression, although the age distribution across diagnostic groups was not significantly different. There was no significant difference in the frequency of major versus minor depression among patients with acute- or delayed-onset depression. There were no significant differences in any of the other background characteristics or previous history of psychiatric disorder. Similarly, there were no significant differences between groups in the use of medications that is, antihypertensives, steroids, psychotropics, or other drugs. Two of the patients with acute depressions and one with delayed-onset depression were receiving antidepressant medication. There were no significant differences in the neurological findings between the diagnostic groups. Of the 26 patients with acute-onset...

Effects of interhemispheric and intrahemispheric lesion location

Significantly greater frequency of major depression than patients with any other lesion location. We found that 44 of patients with left cortical lesions were depressed (i.e., 4 of 16 had major depression) and 39 of patients with left subcortical lesions were similarly depressed (i.e., 4 of 13 with major and 1 of 13 with minor depression). In contrast, only 11 of patients with right cortical lesions (none of nine with major and one of nine with minor depression) and 14 of patients with right subcortical lesions were depressed (one of seven with major, zero of seven with minor Major depression Minor depression *p < 0.05 LC left cortical, LS left subcortical, RC right cortical, RS right subcortical. Patients with either left cortical or left subcortical lesions had a significantly higher frequency of major depression during the acute post-stroke period than patients with right hemisphere lesions (data from Starkstein, Brain 1987). The patients were further grouped according to whether...

Indications in sleep disorders

The effectiveness of antidepressants is dependent on their REM suppressing action. Clom-ipramine is probably the most effective. 3 Cataplexy. The anticataplectic effect of some antidepressants may be mediated by their 5HT promoting action more than their noradrenergic and anticholin-ergic effects. Tricyclic antidepressants, particularly clomipramine, imipramine and protriptyline, are effective. Although SSRIs may be slightly less effective, they have fewer side-effects. SNRIs, such as venlafaxine and viloxazine, and NARIs, such as reboxetine, are probably as effective as the SSRIs. Bupropion may also be useful in controlling cataplexy.

Course Of Bipolar Disorder With

Tohen et al. (46), in a 4-year prospective follow-up study of 75 patients who recovered from an index manic episode, reported that a history of alcoholism was a predictor of poor outcome for the bipolar disorder. They found that the presence of SUDs was strongly associated with a shorter time to relapse and poor psychosocial outcome. In addition, in a sample of firstepisode patients (9), the median time to recovery was shorter for persons without drug abuse than those with comorbid drug abuse (43 days vs. 55 days, respectively p 0.045). The presence of comorbid drug abuse was also associated with a lower probability of recovery at 2 years. Recently, Tohen et al. (3) studied the 24-month outcome of 219 patients who were recruited from consecutive inpatient admissions who met DSM-III-R IV criteria for bipolar disorder manic or mixed or unipolar major depression with psychotic features. The authors did not find that substance use disorder was predictive of either syndromic or functional...

Correlation between the severity of depression and anteriorposterior lesion location

Major depression was significantly more frequent following left anterior lesions than right anterior or left posterior lesions. (Reprinted from (Robinson 2003) with permission.) In 1984, the study previously described involving a new group of 36 patients with single lesions of the right (n 14) or left (n 22) hemisphere also found a significant inverse correlation between the severity of depressive symptoms as measured by combined score on the Zung depression scale, Hamilton depression scale and total score on the present state examination and the distance from the anterior border of the lesion to the left frontal pole (r 0.92, p < 0.01). In the right hemisphere, however, the correlation was in the opposite direction with more posterior lesions being associated with more severe depressive symptoms (R +0.76, p < 0.05). Although the correlation was strongest in patients with left anterior lesions, if patients with left posterior lesions (i.e., anterior border of the...

Cost Effectiveness of SSRIs

Although treatment with SSRIs is, at face value, more expensive than with the older tricyclic antidepressants there is currently a vigorous debate as to whether overall costs to health and other services differ between treatments. Lapierre et al123 attempted a cost-effectiveness analysis of paroxetine versus imipramine. They concluded that where continuation rates for paroxetine were greater or equal to 47 it was a more cost-effective treatment than imipramine in the one-year management of patients with moderate to severe depression and that clinical trials report continuation rates of 41-65 . Hotopf, Lewis and Normand124 looked at both efficacy and cost-effectiveness of SSRIs in comparison with tricyclic antidepressants. Reviewing 105 trials they noted methodological problems that made direct comparisons difficult. They agreed with the generally held view from the trials that SSRIs are as effective as tricyclic antidepressants but slightly fewer patients drop out due to side-effects....

Diagnostic Difficulties In Patients With Bipolar Disorder And Comorbid Suds

There is a marked difficulty in diagnosing bipolar affective disorder in the presence of comorbid SUD because substantial overlap may exist between the symptoms of bipolar disorder and the intoxication and withdrawal states resulting from psychoactive substances. For example, stimulant intoxication can produce a syndrome indistinguishable from mania or hypo-mania, and substantial depressive symptoms upon withdrawal from the stimulants. In addition, the phenomenological overlap between bipolar disorder and attention deficit disorder is significant. In both disorders patients may experience hyperactivity, impulsivity, agitation, racing thoughts, and distractibility, which often makes it difficult to distinguish between the two syndromes (51).

MCA versus posterior circulation infarcts

Among the 37 patients in the PC group, 27 were found to be depressed immediately after the acute lesion (four had DSM-III major and six had DSM-III minor depression). Among the 42 patients with MCA lesions, 48 developed depression immediately after the acute infarct (11 had major depression and nine had minor depression). This higher frequency of depression among the MCA compared with the PC group just failed to reach statistical significance (p 0.054). The relationship between depression and impairment was examined by dividing MCA and PC lesion patients into those with major depression, minor depression or no depression. Among patients with PC lesions, neither intergroup comparisons using ANOVA (e.g., mini-mental state examination scores across the three diagnostic groups) nor dimensional comparisons using correlational analysis (e.g., Hamilton depression score correlated with mini-mental state examination score) demonstrated a significant relationship between depression (diagnosis...

Heather Ashton and Allan H Young

Selective serotonin reuptake inhibitors (SSRIs) have considerable advantages over earlier antidepressants, such as most tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), but like all drugs they also have adverse effects. Advantages of SSRIs include greater tolerability and safety and a wider range of clinical applications, one of which is a potential use in the treatment of drug abuse and some eating disorders (see also Chapter 4). However, recent evidence shows that SSRIs are associated with a withdrawal reaction on discontinuation after regular use. A further emerging problem is that SSRIs may themselves be entering the repertoire of polydrug abusers. Three aspects of SSRIs are considered in this chapter withdrawal effects after chronic administration, potential therapeutic value in the treatment of drug abuse and the possibility of SSRI abuse.

Depression Description

Cal disorder, Major Depressive Disorder (MDD). In order to receive a diagnosis of MDD, a person must experience marked distress and a decrease in level of functioning. In addition, the 2 weeks preceding the examination must be characterized by the almost daily occurrence of a dysphoric mood (e.g., sadness) or a loss of interest or pleasure (anhe-donia) in almost all activities. The individual must also experience at least four (only three if both dysphoric mood and anhedonia are both present) of the following seven symptoms nearly every day for the 2-week period significant weight change or change in appetite Insomnia or Hypersomnia psychomotor agitation or retardation fatigue or loss of energy feelings of worthlessness or excessive or inappropriate guilt decreased concentration or indecisive-ness and suicidal ideation, plan, or attempt (Diagnostic and Statistical Manual of the American Psychiatric Association). Related disorders (i.e., other Mood Disorders) include Bipolar I and II...

Extrahypothalamic CRH Systems

Implications for Biological Psychiatry. The evidence described above clearly points to CRH transmission within discrete regions of the amygdala in the unconditional generation and learned maintenance of fear-related behavior. At the human level, extrahypothalamic CRH has been implicated in a number of human disorders such as major depression (Gold et al., 1996 Nemeroff, 1996), PTSD (Grillon et al., 1996), and bulimia (Krahn and Gosnell, 1989). As a result, the development of novel therapeutic agents that target specific CRH receptor subtypes has become a major thrust in recent years. However, one major problem associated with the use of anti-CRH drugs to treat human clinical populations has been that most of these agents do not pass through the blood-brain barrier efficiently and thus cannot bind to CRH receptors in the necessary neural substrates to effect therapeutic change. As a result, there has been a push in the past decade toward the development of nonpeptide CRH antagonists...

Integrative Role For Brain Cytokines

Implications for Biological Psychiatry. Traditionally, psychological stress and major depression have both been associated with impaired immune function and increased susceptibility to disease. In recent years, however, it has been recognized that exposure to psychological stressors and major depressive episodes are also associated with signs of immune activation for an excellent review see Connor and Leonard (1998) . One particularly interesting facet of this immune activation is that circulating levels of proinflammatory cytokines are elevated during times of stress and in clinically depressed populations. Since proinflammatory cytokines normally produce the behavioral and physiological adjustments that occur during sickness, it has been suggested that their release may mitigate some consequences of exposure to psychological stressors and major depressive episodes (Maier and Watkins, 1998). For instance, psychological stressors, depression, and sickness due to infection all produce...

Treatment A Role Of Atypical Antipsychotic Drugs

Atypical antipsychotic drugs have been reported to be more effective than typical neuroleptics to treat positive, as well as negative and depressive symptoms (128-130). In addition, atypical antipsychotics produce significantly fewer extrapyramidal side effects than typical antipsychotic drugs do (130). Furthermore, treatment with atypical antipsychotic drugs reduces frequency of hospitalization (132,133), and treatment with clozapine has been reported to reduce suicidal attempts (134). In addition, atypical antipsychotic drugs have been reported to decrease substance abuse. For example, use of clozapine in substance-abusing schizophrenics has been reported to reduce smoking (121,122), and there have been case reports of abstinence from alcohol (135) and cocaine (136) following clozapine treatment. Lee et al. (137) have reported that reduction of substance abuse in schizophrenics was significantly higher in the clozapine-treated group than in the group treated with other antipsychotic...

Patients with left sided motor dominance

In the first study, a consecutive series of 30 patients who were left handed, without evidence of mixed motor cerebral dominance, was evaluated for depressive disorders (Robinson et al. 1985). Patients were included if they reported the predominant use of their left eye for vision, left hand for writing and eating, and left foot for kicking. Patients also had to have a single stroke lesion without a clinical history or computed tomography (CT) scan evidence of prior brain injury. The study included 18 patients with left hemisphere lesions and 12 patients with right hemisphere lesions (Table 11.1). The right and left hemisphere lesion groups were not significantly different in any background characteristics except that the right lesion patients were significantly older than patients with left hemisphere lesions (p < 0.05). Of the overall group of 30 patients, eight patients had major depression, three patients had minor depression, and 19 patients were not depressed. Among the 18...

Sleep Problems and Remedies from Ambien to Zolpidem

As flurazepam, as well as a large number of BZs as well as sedating antidepressants that are still commonly used for sleep problems (Table 4.1). Also, there is vigorous research activity to develop slow-release forms of the fast-acting agents, as well as natural ingredients such as melatonin, to help sustain sleep through the night. Of course, chronic use of BZs is not advised because of strong withdrawal reactions when tolerance has developed to these agents (see Chapter 16). The one highly effective over-the-counter agent is the natural hormone melatonin, whose efficacy has long been known (Arendt, 1995) but which has not been promoted by the pharmaceutical or medical community since it has not been approved by government regulatory boards. Obviously, there is little incentive for conduct of necessary efficacy trials for agents that cannot be patented. Accordingly, the search continues to identify melatonin congeners that can be patented. Even though there is now a large number of...

The effect of depression on recovery in ADL

In an effort to control for all of these factors, we studied 25 patients who had either major or minor depression following an acute stroke and some impairment in their ADL score (JHFI score > 0) compared with 38 non-depressed patients who had a comparable degree of physical impairment at the time of their initial evaluation following acute stroke (Parikh et al. 1990). Patients were included only if they had survived 2 years since stroke without subsequent stroke or other significant medical illnesses that would have effected their recovery in daily activities. Background characteristics are shown in Table 13.3 including their baseline neurological findings. There were no statistically significant differences in demographic characteristics of the depressed (major and minor depression combined) and non-depressed patients. Similarly there were no significant intergroup differences in neurological findings or in the severity of intellectual impairment or social impairment. Furthermore,...

Effect of treatment on recovery in physical impairment

The final area of investigation which has generated a surprising number of studies has involved the assessment of antidepressant medications and their effects on recovery from physical impairment or ADL impairment. The first study to demonstrate a positive effect of treatment of depression on recovery in ADLs was reported by Reding et al. (1986). During a 6-week double-blind treatment trial, 16 patients who had a positive dexamethasone suppression test (DST) showed greater improvement in their ADL scores as measured by the BI when they received double-blind treatment with trazodone (n 7) (dose 50-200 mg day) as compared with placebo (Table 13.2). Although grouping the patients based on the clinical diagnosis of major or dysthymic depressive disorder did not show a statistically significant effect of trazodone, there was a trend for actively treated depressed patients to improve their BI scores more than depressed patients treated with placebo. In an open label study,...

Effects of depression versus effects of lesion

To separate the effect of stroke from the effect of depression on cognitive impairment, we examined 13 pairs of patients who were matched for lesion size and location, but one patient of the pair had major depression, while the other was non-depressed (Starkstein et al. 1988). Patients were matched for lesion location if both of their lesions involved, either totally or partially, the same regions as those defined by Levine and Grek (1984). There were no significant group differences in background characteristics such as age, gender, years of education, or socioeconomic status. Depressed patients, however, had significantly lower mini-mental scores than non-depressed patients (Fig. 14.1). Of the 13 pairs of patients, 10 had lower MMSE scores than their respective lesion-matched controls, two had the same scores and only one depressed patient had less cognitive impairment than their non-depressed lesion-matched control (p 0.001). This study demonstrated that the greater degree of...

Effect of antidepressant treatment on cognitive function

Perhaps the most important data which addresses the question about whether cognitive impairment produces depression or depression produces cognitive impairment is treatment outcome. Prior double-blind treatment studies (Lipsey et al. 1984 Andersen et al. 1994 Robinson et al. 2000 Fruehwald et al. 2003) have all found that patients treated with active antidepressant medication had no greater improvement in their cognitive function than patients treated with placebo, in spite of the fact that active treatment significantly improved mood. This observation led Andersen to suggest that cognitive impairment may lead to depressive disorder (Andersen et al. 1996). We recently performed a merged analysis of patients from our prior treatment studies to examine whether successful treatment of depression would lead to improved cognitive function (Kimura et al. 2000). Patients from the Lipsey et al. (1984) treatment study (Baltimore) as well as the Robinson et al.study (2000) (Iowa) were included...

Multiple sleep latency tests MSLTs

The hypocretin level is inversely related to body weight and fluctuates by around 40 in a diurnal pattern. It may double after exercise, is higher in wakefulness than in NREM sleep, lowest in REM sleep and is not affected by drugs, such as antidepressants and stimulant and wakefulness promoting agents.

Aging Stress and Mental Disorders

The present cohort of older persons has lower rates of major depression, substance abuse, and some other mental disorders than younger cohorts. Older persons are at increased risk for a number of mental disorders, including the dementias (of which Alzheimer's disease is most common) and subsyndromal depressive and anxiety disorders. Future projections suggest we will see increased prevalence of late-life mental disorders when the baby boom cohort reaches advanced age. Mental disorder in older adults is distinct in that it is often comorbid with multiple physical disorders and complicating social factors. Older persons are often taking multiple medications and seeing multiple health care providers. These changes mean that mental health or behavioral health services should be carefully coordinated with medical and social services, ideally through multidisciplinary teams.

Neurotransmitter Imaging of the Serotoninergic System

The serotoninergic system is thought to be critically involved in a large number, if not the majority, of psychiatric illnesses. The most important and well studied of these is major depressive disorder (MDD). However, the serotonin system is also considered important in schizophrenia, anxiety and phobias, obsessive-compulsive disorder, eating disorders, sleep, and numerous other psychiatric conditions. Serotonin and Depression. Several studies have found evidence for an increased availability of serotonin 5-HT2A receptors in the brains of unmedicated depressed patients and suicide victims (Cheetham et al., 1988 D'Haenen et al., 1992 Stanley and Mann, 1983). The extent to which these findings exist in depressed persons without recent suicide attempts remains controversial. A 18F setoperone PET study assessed the 5-HT2 receptor binding potential in 14 depressed and 19 healthy subjects (Meyer et al., 1999b). Interestingly, the 5-HT2 binding potential was not increased in untreated...

Imaging of Other Neurotransmitter Systems

Agren H, Reibring L, Hartvig P, et al. (1991). Low brain uptake of L- 11C 5-hydroxytryptophan in major depression a positron emission tomography study on patients and healthy Volunteers. Acta Psychiatr Scand 83 449-455. Hartvig P, Agren H, Reibring L, et al. (1991). Positron emission tomography of 11C 5-hydroxy-tryptophan utilization in the brains of healthy volunteers and a patient with major depression. Acta Radiol Suppl 376 159-160. Malison RT, Price LH, Berman R, et al. (1998). Reduced brain serotonin transporter availability in major depression as measured by 123I -2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography see comments . Biol Psychiatry 44 1090-1098. Mann JJ, Malone KM, Diehl DJ, Perel J, Cooper TB, Mintun MA (1996). Demonstration in vivo of reduced serotonin responsivity in the brain of untreated depressed patients. Am J Psychiatry 153 174-182. Willeit M, Praschak-Rieder N, Neumeister A, et al. (2000). 123I -beta-CIT SPECT...

Circadian Dysregulation

Abnormal sleep is a core symptom of major depressive disorder, with sleep disruption seen at all stages in the sleep cycle (Benca, 1994). Symptoms include difficulty falling asleep, or staying asleep, as well as early-morning awakening. Hypersomnia is also described. Electroencephalography (EEG) abnormalities in depressed patients include prolonged sleep latency, decreased slow-wave sleep, and reduced rapid eye movement (REM) latency with disturbances in the relative time spent in both REM (increased) and non-REM sleep (decreased slow-wave sleep). Reduced REM latency probably is the best studied and most reproducible sleep-related EEG finding in depressed patients, and this abnormality is reversed by most antidepressants. Sleep deprivation, particularly if instituted in the second half of the night, has a similar effect, although the rapid, dramatic improvement in depressive symptoms is short lived (Wu et al., 1999). Changes in nocturnal body temperature and...

Psychiatric disorders

Excessive daytime sleepiness is common in younger subjects with depression, whereas later in life this more frequently causes insomnia. EDS may persist despite adequate treatment of low mood by anti-depressants and may even be worsened by sedative antidepressants. EDS in depression is usually associated with weight gain whereas depression and weight loss often lead to insomnia. EDS is also a feature of the seasonal affective disorder, which is associated with weight gain.

Antidepressant Drugs and Sexual Dysfunction

Reports of rates of sexual dysfunction in clinical populations vary widely (see Introduction). The main reason for such variation is the range of methods employed to collect the data. Early studies with antidepressants relied on spontaneous self-report by patients and tended to yield relatively low rates they also failed to distinguish between rates of different forms of sexual dysfunction. Higher rates are obtained when patients are asked to fill in a questionnaire, but even under these conditions people appear reluctant to divulge sexual symptoms. Thus, the highest rates for sexual dysfunction are obtained when patients are asked sympathetically but specifically about different aspects of sexual function.

Structural Abnormalities

Lesion deficit correlation studies demonstrate that certain disorders are more likely to be associated with a major depression than others (a) discrete brain lesions, as seen with trauma, surgery, stroke, tumors, and certain types of epilepsy (b) neurodegenerative diseases with regionally confined pathologies such as Parkinson's, Huntington's, and Alzheimer's diseases (c) disorders affecting diffuse or multiple random locations such as multiple sclerosis and (d) system illness with known central nervous system effects such as thyroid disease, cancer, and acquired immunodeficiency syndrome (AIDS) (Table 7.1). TABLE 7.1. Disorders Associated with Depressive Symptoms TABLE 7.1. Disorders Associated with Depressive Symptoms Major depressive disorder Despite these apparent patterns, certain paradoxes remain. First, despite comparable underlying pathologies, not all patients with a given disorder develop depressive symptoms. For instance, in Parkinson's disease and...

Functional Abnormalities

Positron emission tomography (PET) and single-photon emission tomography (SPECT) studies of both primary depression (unipolar, bipolar) and depression associated with specific neurological conditions (focal lesions, degenerative diseases, epilepsy, multiple sclerosis) identify many common regional abnormalities (reviewed in Mayberg, 1994 Ketter et al., 1996). For example, in depressed patients with one of three prototypical basal ganglia disorders Parkinson's disease, Huntington's disease, and left caudate stroke resting-state paralimbic hypometabolism (ventral prefrontal cortex, anterior cingulate, anterior temporal cortex) was found to differentiate depressed from nondepressed patients within each group, as well as depressed from nondepressed patients, independent of disease etiology (Mayberg, 1994). These regional findings, replicated in other neurological disorders (Bromfield et al., 1992 Hirono et al., 1998 Starkstein et al., 1990c), suggests involvement of...

Optimize sleep hygiene

It is important to treat depression and anxiety, which can both be either causes of insomnia or responses to it, before more complex aspects of management are considered. Antidepressants should only be used if features of depression are present and not as a routine treatment. Sedating tricyclic antidepressants, such as trimipramine, imipramine and doxepin, are particularly effective. Paroxetine is the most suitable of the SSRI antidepressants, several of which worsen insomnia even if it is due to depression (Table 7.6). The sedating action of mirtazapine is useful in treating insomnia.

Interpersonal Psychotherapy

IPT was developed in the early 1970s by the late Gerald L. Klerman, MD Myrna M. Weissman, PhD and their colleagues at Harvard and Yale. In planning a medication treatment study for outpatients with Major Depressive Disorder (serious clinical depression), and recognizing that many patients in clinical practice received talking therapy as well as pills, Klerman and Weissman decided to add a psychotherapy to their study. Being researchers, they developed a manual-based treatment that relied on known psychosocial aspects of depression. They knew that serious life events can trigger depressive episodes in individuals who are vulnerable to developing depression, and that, once depressed, many individuals have difficulties in interpersonal functioning that result in further demoralizing life events. In other words, life events affect mood, and mood affects life circumstances, in a potentially vicious cycle. Further, research had shown that social supports provide protection against...

John A Henry and Carol A Rivas

The selective serotonin reuptake inhibitors (SSRIs) have increased in popularity and extent of use since their introduction. At the same time, our knowledge concerning the relationship between suicide and depression has increased. The impact of this group of drugs on this knowledge has been considerable. An additional consideration is that, as with all drugs and particularly with antidepressants, they are liable to be taken in overdose. This chapter reviews some of the links between the SSRIs and depression, overdose and suicide.

Pharmacological Mechanisms of Antidepressant Drug Action

Most antidepressants have potent pharmacological effects that cause increased synap-tic levels of the monoamine neurotransmitters NE and or 5-HT and in some cases DA. Levels of monoamines can be increased by blocking their reuptake as well as by inhibition of their metabolism by the enzyme MAO. However, while levels of monoamines increase within hours of ingestion of the first dose of an antidepressant, the therapeutic response does not begin until 2 to 4 weeks later. This lack of temporal relationship between increased synaptic levels of monoamines and clinical response has led to a search for other effects of these medications that correlate more closely with therapeutic response. Composite results from multiple studies are presented in Figure 8.1. One of the most striking findings is that antidepressant responses can be rapidly but transiently reversed, with the response being dependent on the class of antidepressant. About 80 percent of patients who were taking an SSRI for...

Comparison of Consequences of Overdose of SSRIs versus Other Antidepressant Agents

Comparing the toxicity of antidepressants in overdose is not a simple matter because the mechanisms of toxicity vary between classes of drugs and also between individual drugs in the different classes. Animal experiments often give a strong indication of potential toxicity and, in some cases, correlate well with the estimates of human toxicity, but their predictive value for newly marketed drugs cannot be relied upon. Epidemiological studies from several countries have provided evidence of marked differences in overdose toxicity between drug groups and, in some cases, between individual drugs, with some of the older tricyclic drugs being the most toxic. Eighty percent of all deaths arising from overdose of antidepressant medication in the UK are caused by two TCAs amitriptyline and dothiepin. These drugs are each associated with around 50 overdose deaths per million prescriptions while the TCAs as a group are associated with 36 deaths per million prescriptions in Britain.35 Taken...

Treatment of morbidity and mortality related to poststroke depression

Our study, described in Chapter 22, Treatment of poststroke depression, included 56 patients with DSM-IV defined major or minor depressive disorder. In addition, this study included 48 patients who were not depressed (i.e., no depressive diagnosis and Ham-D score < 12) at the time of enrollment in the treatment trial (Table 18.1). DSM-IV major depressive disorder Intention to treat analysis revealed that 42 of 71 patients (59.2 ) initially assigned to received antidepressants, were alive at the 9-year follow-up compared with 12 of 33 patients (36.4 ) who were assigned to receive placebo (p 0.03). Kaplan-Meier survival analysis show that the probability of survival was significantly greater in the patients assigned to the antidepressant group than the placebo group (p 0.03) (Fig. 18.3). An efficacy analysis of the patients who completed the 12-week treatment protocol (n 81) showed that 36 of 53 patients (67.9 ) given antidepressants were alive at the 9-year follow-up compared to 10...

Remission and Recovery

An episode of major depression appears to be self-limiting, in that most cases remit in approximately 6 to 8 months, even if untreated. Recovery rates appear to be similar across children and adult samples. For example, Kessler and Walters (1998) found that, in a community sample of adolescents and young adults, the average length of the longest episode an individual had suffered was 32.5 weeks. Similarly, Ko-vacs and colleagues (1984a) reported a mean length of 32 weeks for a sample of depressed children. Within 1 year of onset of a major depressive episode, 78 of adults will have recovered (Keller, Lavori, Rice, Coryell, & Hirschfeld, 1986).

Antipsychotic and Atypical Antipsychotic Drugs

Olanzepine, risperidone, and quetiapine are all being studied as both monotherapy and as an adjunctive therapy for treatment of acute mania. Of the three, olanzapine is the best studied, with double-blind comparator trials as well as doubleblind placebo-controlled trials showing significant efficacy (Tohen et al., 1999) in acute mania. All atypical antipsychotic drugs are being widely used in the United States for the treatment of agitation and psychosis in manic or psychotically depressed patients, in spite of the absence of controlled data. Interestingly, olanzapine and risperidone have both been reported to cause mania in some patients with schizophrenia, schizoaffective, or bipolar disorder. At this point, none of these drugs should be used for long-term monotherapy of bipolar disorder in patients who have been tried on other available agents since no long-term studies have been completed.

Ian M Anderson and Christopher Mortimore

The hypothesis that altering monoamine function can treat the depressed state. The second hypothesis suggests that changes in monoamine function are sufficient, or possibly even necessary, to alleviate depression and, by extension, implies that a common mechanism could underlie the action of all antidepressant drugs in spite of differences in their acute pharmacology. In this chapter we will explore an aspect of the second hypothesis by reviewing human data investigating the effect of antidepressants on serotonin (5-hydroxytryptamine, 5-HT) function using neuroendocrine challenge tests.

Mechanisms of poststroke depression

In considering the mechanisms of poststroke depression, it should be kept in mind that important clinical findings such as cognitive impairment is associated with major, but not minor depression, following the left, but not right, hemisphere stroke (Chapter 14) need to be integrated or explained by the proposed mechanisms of depression. Additional clinical findings include depression is significantly associated with left frontal and left basal ganglia lesions but not comparable lesions of the right hemisphere during the acute period following stroke (Chapter 10). Furthermore, major depression is associated with proximity of the lesion to the frontal pole while minor depression is associated with posterior lesions of the left hemisphere during the acute poststroke period (Chapter 10). Delayed-onset depression is more strongly associated with social impairment than acute onset depression (Chapter 9). Thus, it seems likely that there are multiple kinds of depression following stroke and...

Preclinical Background

The detailed pharmacology of a drug or class of drugs can be studied in animals and the findings extrapolated to humans. However species differences necessitate caution, e.g., the absolute and relative affinity of antidepressants for the human monoamine transporter is not identical to that seen in rats.1 Any attempt to relate pharmacology to clinical efficacy must eventually be tested in humans with psychiatric conditions. The investigation of pharmacological endpoints of antidepressant action by measuring the effect of chronic administration of these compounds on receptor number and function in animals has revealed a few more or less consistent changes, particularly downregulation of P-adrenoceptors and 5-HT2 receptors in the cerebral cortex.2 However it has become apparent that many newer antidepressants including selective serotonin reuptake inhibitors (SSRIs) have less consistent effects on receptor numbers3 suggesting that effects downstream from the receptor may be equally or...

HT Challenge Tests in Humans

Table 8.1 summarizes the hormonal responses to, and the putative receptor mediation of, 5-HT drugs used in human pharmacological challenge tests to investigate the effects of antidepressants on 5-HT function. As will be seen from the data presented below, characterization is patchy and relies in many cases on single studies (albeit backed up by animal data) so that the receptor mediation must be taken as provisional. A broad categorization of the challenges into those acting presynaptically (precursors, uptake inhibitors releasers) and postsynaptically (agonists) can be made although as discussed below the distinction is often less certain than it at first appears. With regard to particular 5-HT pathways, the challenges can be principally divided into those believed to act via 5-HT1A receptors or 5-HT2 receptors.

Pharmacological treatments

Anecdotal reports in the literature since the early 1980s have suggested the efficacy of antidepressant treatment for poststroke depression (Ross and Rush 1981). The first controlled treatment trial was conducted by our group and published in 1984 (Lipsey et al. 1984). The study included 39 patients who were in an acute stroke hospital, a rehabilitation hospital or were outpatients who met Diagnostic and Statistical Manual (DSM-III) diagnostic criteria for either major or minor (dysthymic) depressive disorder who were treated with nortriptyline (n 17) or placebo (n 22). The patients were not significantly different in their mean age, racial mix, social class, gender, marital status, or time since stroke. Mean age was 62 9 years in the nortriptyline and 60 12 years in the 20 placebo patients. The mean time since stroke was 261 days 437 SD in the nortriptyline group and 128 190 SD in the placebo group. Since fluoxetine was not found to be superior to placebo in this treatment study,...

Negative Affect Hypothesis

Depression represents another emotion that comprises negative affect. Unlike anxiety and anger, which are thought to be associated with increased physiological arousal or irritability, depression is commonly associated with under-arousal or the lack of activity. Depressed individuals often sleep more and engage in less activity than nondepressed counterparts, and this inactivity is often associated with increased complaints of fatigue and loss of energy. If we recall the defense and defeat reactions described by Henry and Stephens (1977) in Chapter 3, anger and anxiety appear to be classic defense reactions, while depression would be categorized as a defeat reaction. Based upon observations of psychiatric outpatients that revealed an increased incidence of essential hypertension associated with diagnoses of depression (Rab-kin, Charles, and Kass, 1983), speculations that perhaps a causal relation existed between depression and hypertension have been entertained (Dilsaver and Coffman,...

Transcranial magnetic stimulation therapy

We have recently completed a small study of rapid transcranial magnetic stimulation (rTMS) in the treatment of poststroke depression. This study included 10 patients given rTMS and 10 given sham rTMS using double-blind methodology (Jorge et al. 2004) (Table 22.1). There were no significant intergroup differences in either their background characteristics or risk factors for depressive disorder. Patients were entered in the study only if they had failed treatment on at least one occasion. In fact, the active treatment patients had failed a mean of 3.8 1.4 SD prior treatment trials with adequate doses of antidepressant medications while the sham-treated group had failed a mean of 3.8 1.1 SD prior treatments. The initial Ham-D scores were 20.1 6.7 in the active treated group and 20.8 + 6.0 in the sham-treated group. Eighty percent of the active treated patients (8 of 10) had major depressive disorder as did 90 of the sham-treated group. The remaining three patients met DSM-IV criteria...

Effect of Antidepressant Treatment on Responses to 5HT Challenge Tests

Studies of the effect of antidepressants on 5-HT challenge tests have been carried out in volunteers and patients with depressive disorder and obsessive-compulsive disorder (OCD). Normal volunteer studies avoid the possible confound of alteration in state-dependent 5-HT abnormalities that have been described in both depressive disorder14 and OCD.80,81 It is also possible that effects in depressed and non-depressed subjects might differ (e.g., ref. 82). Studies in both different patient groups and healthy volunteers therefore provide complimentary information.

Prevention and Treatment

Most osteoporotic fractures result from a fall. Risk factors for falling include visual or hearing problems, gait disturbances, underlying conditions that predispose the patient to syncope, cognitive impairment, and the use of certain medications such as diuretics, anti-hypertensive, benzodiazepines, and antidepressants. Home safety precautions may help to prevent falls. External hip protectors have been shown to provide protection against hip fractures in frail elderly adults.

Use of random effects models

Another simple use of the models would be in a sample survey, for example to find out levels of depression in primary care. A random sample of practices is chosen and within them a random sample of patients. The effect of being cared for by a particular practice on an individual is not of prime interest. If we repeated the study we would have a different set of practices. However, the variation induced on the estimate of the proportion of depressed patients by different practices is of interest, because it will affect the confidence interval. Thus we need to allow for between practice variation in our overall estimate.

Neuropsychiatric Syndromes

The relationship between psychotic bipolar disorder and schizophrenia is unclear, but certainly within schizophrenia, full-fledged manic syndromes occur and serious depressive episodes are common. These can occur either during psychotic episodes or when psychotic symptoms are either absent or stable. The lifetime risk for major depression is very high, with perhaps a third to a half of patients experiencing at least one such episode. This problem contributes to the very high risk of suicide in schizophrenia approximately 10 percent of patients may kill themselves.

Prevention of poststroke depression

The mean interval from stroke to beginning of the study was 14.3 days. Ten patients on placebo and 9 on mianserin discontinued the treatment study prematurely. The 10 patients on placebo stopped due to lack of efficacy (3 patients), lack of compliance (3 patients), side effects (3 patients) and death (1 patient). Nine patients on mianserin discontinued the treatment prematurely due to lack of efficacy (one patient), lack of compliance (one patient), side effects (six patients) and death (one patient). At the time of enrollment in the study, three patients receiving mianserin and two patients receiving placebo had a major depressive disorder. During the course of the treatment study, there were no significant differences between the treatment groups in the frequency of major depression. At 2 months, two patients receiving mianserin and five on placebo had major depression, at 6 months, four patients on mianserin and three on placebo had major depression and, at 12 months, five...

Treatment and Prevention of Essential Hypertension

Like many other early medicines, the first known antihypertensive medication, reserpine, was uncovered more or less by accident during investigations of the medicinal properties of common plants and herbs. Reserpine is a pharmaceutical compound derived from the Indian snakeroot, Rauwolfia serpentine, whose antihypertensive properties were first described by Bhatia in 1942. After years of use, reserpine's mechanism of action was determined to be associated with its ability to deplete storage of norepinephrine in neurons (Cohen et al., 1968), leading to a reduction in sympathetic nervous system activity and vascular resistance. In this regard, it is of interest that the very first antihypertensive medication to be used regularly exerted its effect via sympathetic nervous system involvement. Unfortunately, the norepi-nephrine depletion responsible for reserpine's antihypertensive effect also led to severe clinical depression in a substantial number of patients, resulting in reduced...

Huntingtons Disease

DA receptor-blocking agents (e.g., haloperidol or fluphenazine) and dopamine-depleting agents (e.g., tetrabenazine, reserpine) reduce the choreic movements but may not improve other symptoms of Huntington's disease. Because of their potentially serious side effects, including tardive dyskinesia (neuroleptics), depression (dopamine-depleting drugs), and parkinsonism (both drug classes), the antidopaminergic drugs should be reserved for patients with disabling chorea or serious psychosis. Xhe tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRI) are often helpful in ameliorating the affective disorders but may precipitate myoclonus. Antiglutaminergic drugs and facilitators of mitochondrial metabolism are currently being tested in clinical trials. Psychological support, genetic counseling, long-term planning, and access to social service agencies are important elements of patient management.

SSRIs Plus Pindolol Combinations Clinical Studies

Tertatolol), pindolol antagonizes 5-HTia receptor-mediated responses in humans.79,80 Pindolol has been used subsequently by several other groups in open-label and placebo-controlled studies to examine whether it can accelerate the effects of SSRIs and other 5-HT-acting antidepressants.

Right hemisphere lesion location

In our previously described study of patients with mania, poststroke depression, and no stroke-related disorder (Robinson et al. 1988), patients were also compared for the nature, localization, and volume of brain injury associated with mania or depression. Patients with secondary mania included those with brain tumors (n 6) predominantly frontal meningiomas) or closed head injuries (n 2). There were, however, no statistically significant differences in the volumes of the lesions between the patients with secondary mania, depression, and no mood disturbance. The hemispheric location of lesion was established by means of computed tomo-graphic (CT) or MR scan, or clinical neurological examination. In the secondary mania group, 12 of the 17 patients had a lesion restricted to the right hemisphere while only one patient had a left hemisphere lesion (Fig. 25.2). Of the patients with major depression, 19 of the 31 had lesions involving the left hemisphere, while 9 of the 28 patients in the...

Assessment and Treatment of PTSD

Pharmacotherapy for PTSD generally targets symptoms of the disorder that it shares in common with the other anxiety disorders and major depression (i.e., hyperarousal, sleep disturbance, and anhedonia) and many medications developed for the treatment of these other disorders have been used to treat PTSD. Although clinical drug trials have shown fairly modest results overall, results suggest that some individuals with PTSD may benefit greatly from pharmacotherapy. The SSRIs (including sertraline, fluoxe-tine, and paroxetine) are currently the medications of choice for the treatment of PTSD.

Depression Mania and Suicide

Isolation, lack of social support, bereavement, and the marginalization and stigma associated with AIDS may also contribute to depression (98-101). Fukunishi et al., in Japan, have shown that the lack of social supports provided to HIV-positive patients has a significant effect on the reporting of depressive symptoms and may be associated with avoidant coping behaviors, which may lead to further isolation and delay in effective medical care (98,102). There is conflicting evidence about whether depression increases the progression of the HIV illness. HIV-seropositive homosexual men without AIDS who entered the Multicenter AIDS Cohort Study in 1984 or 1985 were followed for a total of 8 years. Data from this study yielded no evidence that depressive symptoms predicted worsening of HIV disease (107). Burack et al., in a study controlled for drug and alcohol use, found evidence favoring a correlation between the rate at which CD4 levels decline and severity of depression (108), but this...

Direct Receptor Interactions

Alternatively, SSRIs could bind to receptors for other neurotransmitters which modify monoamine release (heteroceptors). A great deal of attention has been devoted to the binding of SSRIs to Hi, muscarinic and ai-adrenoceptors. This is understandable because a major objective in their development was to avoid the orthostatic hypotension, cardiotoxicity and sedation which were only too evident with the tricyclic antidepressants and which are a direct result of, or aggravated by, antagonism of these receptors. Binding of SSRIs to other transmitter receptors, particularly those for monoamines, has attracted less attention but details of their affinities for a range of monoamine and other neurotransmitter receptors are given in Table 10.5. It is clear that, when compared with the other SSRIs, fluoxetine binds appreciably to 5-HT2a 2C receptors while sertraline has a relatively high affinity for a1 and a2-adrenoceptors (Table 10.6). Although binding studies alone give no clues to receptor...

Hormones Mood and Cognition

Most hormones play a significant role in affect and cognition. An example is cortisol, which is secreted by the adrenal cortex under the influence of the anterior pituitary peptide adrenocorticotropin hormone (ACTH). Cortisol hypersecretion, such as in Cushing's disease, produces psychological changes ranging from hyperphagia, insomnia, and euphoria to anxiety, panic, and mania. On the other hand, a significant number of individuals diagnosed with major depression present signs of adrenal hypertrophy and increased circulating levels of cortisol. The mechanisms hypothesized to mediate increased cortisol levels in clinically depressed patients have implicated increased activity at the level of the hypothalamus, and dysregulation of brain serotonergic and noradrenergic systems. A reduction of circulating cortisol levels, observed in patients with Addison's disease (adrenal atrophy and insufficiency), is itself correlated with irritability, apprehension, mild anxiety, and inability to...

Rapid Eye Movement Rem Sleep

Sleep and dreaming have long been an area of clinical and scientific interest in psychology, psychiatry, and neuroscience (Nofzinger et al., 1999). For example, the similarity between hallucinations and the often bizarre and strange content of most dreams naturally stimulated interest in studying REM sleep in patients with schizophrenia and other psychiatric disorders. Although such studies did not support the hypothesis that hallucinations represent waking dreams, further research in depression often found that REM latency is shortened to less than 60 minutes, REM density and the amount of REM sleep are increased, and the distribution of REM sleep is shifted to the earlier part of the night, compared to normal subjects. These findings had been considered a potential biological marker for depression, but shortened REM latency also has been found in some patients with other psychiatric disorders. Patients with schizophrenia and psychotic depression can have extremely short REM...

Depression and Behavioral Disorders

Similar results have been found with older survivors of childhood cancer. In general, young adult survivors' rates of depressive symptoms are comparable to those of peers 34 or norms 52 . Although the large multi-site Childhood Cancer Survivors Study (CCSS) identified higher levels of depressive and somatic symptoms in survivors than in their siblings, survivors' rates of depressive and somatic symptoms were still in the normal range 63 . Similarly, in a large study of Danish survivors, overall rates of depression and other psychiatric disorders in survivors of childhood cancers other than brain tumor were consistent with national norms. Only brain tumor survivors evidenced higher levels of depression and other presumably organic disorders (e.g. psychoses, schizophrenia), as well as a higher

Lori L Davis Kimberly A Yonkers Madhukar Trivedi Gerald L Kramer and Frederick Petty

The introduction of the selective serotonin reuptake inhibitors (SSRIs) into medical treatment in the 1980s revolutionized psychiatric practice and fueled the interest in the role of serotonin (5-hydroxytryptamine, 5-HT) in the underlying neurobiology of the psychiatric disorders. In reviewing the literature, one is struck by a curious and interesting dichotomy between the fairly selective effect that these drugs have on the serotonergic system and the remarkably 'non-selective' manner in which they are used clinically. In actuality, these compounds vary considerably regarding their relative 'selectivity' for 5-HT reuptake, and some SSRIs have significant action on other biogenic amine neurotransmitter systems (for further details see Chapter 10). However, there is no doubt that the SSRIs are a marked and significant improvement on our previous attempts to selectively increase 5-HT neurotransmitter function with precursors such as tryptophan. Certainly, the SSRIs are far more...

Preclinical Models of Depression and Relationship with 5HT

One approach to understanding the behavioral effects and mechanism of action of SSRIs involves study of animal models of human psychopathology. An established and valid animal model of depression, extensively studied by our laboratory, is 'learned helplessness' which is a stress-induced behavioral depression. The basic paradigm involves an exposure, usually of rats, to uncontrollable, inescapable stress followed by a subsequent test, usually involving a task in which the stress can be terminated by the animal. An attractive aspect of the learned helplessness model is that not all animals develop learned helplessness after inescapable stress (just as not all humans become depressed following stressful life events). This variability in outcome after stress, considered a possible model for 'coping,' allows comparisons to be made between animals that receive identical stress but have different behavioral reactions to stress helpless versus non-helpless. Animals with learned helplessness...

Comparison of SSRIs and Other Antidepressant Agents

Tricyclic antidepressants have also been shown to reduce the sensitivity of 5-HT1A receptors. However this may occur postynaptically rather than at the terminal autoreceptor. The difference in loci of influence at the receptor level may explain why some patients respond to one class of antidepressants as opposed to another.

SSRI Spectrum of Therapeutic Action

The efficacy of SSRIs in the treatment of major depression, panic disorder, and obsessive-compulsive disorder has clearly been demonstrated. In addition, data is accumulating on the therapeutic effects of SSRIs in conditions of obesity, eating disorders, post-traumatic stress disorder, social phobia, premenstrual dysphoric disorder and trichotillomania. How can one class of medications work for such a seemingly diverse group of illnesses Are these agents in fact nonspecific and work as a steroid might for a multitude of inflammatory conditions Or alternatively, is there an underlying psychopathology, relating to 5-HT, that represents a common neurochemical theme among these conditions Our methods of classification in psychiatry are clinical and descriptive and may relate poorly to actual brain function.

Monoamine and Brain Homeostasis A New Hypothesis in Understanding Psychiatric Disorders

The simplistic monoamine depletion hypothesis as an explanation for major depression or any psychiatric disorder is rapidly undergoing critical re-evaluation and restructuring. Of course, it is illogical to think that one neurotransmitter is responsible for one diagnostic category. In addition, our categorical style of making diagnoses is imperfect. Perhaps major depressive disorder is the end-stage syndrome with a multitude of originating etiologies, both psychological and physiological. In addition, there is overlap, not only in illness comorbidity, but also overlap with one individual illness symptomatology and another based on DSM-IV criteria. A good example is major depressive disorder and post-traumatic stress disorder (PTSD). Both illnesses indeed frequently occur together in the same patient. Even though the criteria may seem to separate these diagnoses, in real clinical practice, it is unusual to make the diagnosis of PTSD in a treatment-seeking patient without also...

Biological Abnormalities in 5HT and Theories of Depression

We have discussed how and whether animal models of stress-induced depression can provide insights into serotonergic function correlated with depression and into the mechanisms of action of SSRIs. To what extent do clinical research findings in humans support the animal data Of course, biological abnormalities in the symptomatic depressed state include a range of disturbances in noradrenergic, serotonergic, dopaminergic, and GABAergic neurotransmitter systems, as well as secondary effects in several neuroendocrine systems.14 The complex dynamic interactions and inter-regulation of neurotransmitter systems suggest that it is more important to consider the relative balance of neurotransmitters than their absolute independent effects. Much pharmacological data also supports the concept of biological heterogeneity in depression, evidenced by the fact that some patients respond primarily to antidepressants acting principally on the noradrenergic system, while others respond preferentially...

Serotonergic System and Relevance to Disease and Therapy

Nal, are frequently effective in treating depression, anxiety, and OCD. Moreover, recent studies suggest that combined 5-HT2A- and 5-HT2C-receptor antagonists such as clozapine alleviate some of the symptoms (especially negative symptoms) of schizophrenia and that aberrant function of the serotonergic system may indeed be a major component of the disease. Moreover, alterations in serotonin uptake have been demonstrated in postmortem tissue studies in the lim-bic systems of schizophrenic patients. In addition, there is some evidence to suggest that there may be serotonergic dysfunction in at least some patients with anorexia nervosa. Animal studies using the motoneuron disease model (Wobbler mouse) suggested that sprouted serotonergic fibers in the cervical spinal cord could have excitotoxic effects on motoneurons and thus be causal to the loss of moto-neurons (Bose & Vacca-Galloway, 1999).

Functional Brain Imaging Studies of the Serotonergic System in Depression

Few data exist regarding direct imaging of 5-HT receptors in depressed subjects. Mayberg et al,22 using PET imaging of methylspiperone, found that patients after right, but not left-sided strokes had greater ipsilateral than contralateral abnormality in 5-HT2 receptors in undamaged temporal and parietal regions. Additionally, in subjects with left-sided strokes, the ipsilateral contralateral temporal lobe 5-HT2 receptor ratio correlated inversely with depression scores, suggesting that a failure to up-regulate ipsilateral 5-HT2 receptors after left-sided strokes could be related to the development of depression. D'Haenen et al,23 utilizing ketanserin as a 5-HT2 receptor ligand imaged by SPECT, reported higher uptake of the tracer in the parietal cortex of patients with depression. They also noted asymmetry (right greater than left) in the infero-frontal region in depressed subjects and not in control subjects, thus indicating a 5-HT2 receptor change in major depression. Mann et...

Cognitive Behavioral Treatment Studies

Very few studies have assessed the efficacy of CBT in addition to antipanic medication. Marks et al. (1993) evaluated the comparative efficacy of alprazolam and CBT, both alone, and in combination in patients with panic and agoraphobia, and found that alprazolam dampened patients' response to CBT. In the recent multicenter treatment trial that extended over 7 years, CBT alone was compared with placebo, imipramine alone, the combination of both CBT and imipramine, and CBT plus placebo for panic disorder (Barlow et al., 2000). In this study, all active treatments produced responses superior to placebo, but the combined treatment cell was not significantly superior to either CBT or imipramine alone after the active treatment phase. However, the combination of CBT and imipramine conferred more substantial advantage than either treatment alone by the end of the 6-month maintenance phase of the study. The major limitation of this important multicenter study is that the patients studied had...

Unipolar Depression and Hypothyroidism

Most cases of unipolar or major depression are caused by life circumstances and or situations. For this reason, the term situational depression is used by mental health experts to describe most cases of mild, moderate, or even severe unipolar depression. In the absence of thyroid disease, one out of five people in North America suffers from at least one episode of depression in their lifetime. At least twice as many women suffer from depression as men, perhaps because of the social roles women play in our society. For example, in 1994 through 1997, 72 percent of reported depressive episodes were in women.

Natural Depression Cures

Natural Depression Cures

Are You Depressed? Heard the horror stories about anti-depressants and how they can just make things worse? Are you sick of being over medicated, glazed over and too fat from taking too many happy pills? Do you hate the dry mouth, the mania and mood swings and sleep disturbances that can come with taking a prescribed mood elevator?

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