Depression Holistic Treatments

Destroy Depression

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

Destroy Depression Summary


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Suicidality in children and adolescents being treated with antidepressant medications

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

Antidepressants 603521 Monoamine oxidase inhibitors

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

Tricyclic antidepressants

TCAs were introduced in the 1950s and became the gold standard treatment for depression before the launch of the first SSRI, fluoxetine, in 1987. All current antidepressants rely upon the principle of enhancing monoamine neurotransmission interfering with the presynaptic transporter that reimports the neurotransmitter from the synaptic cleft once released from presynaptic nerve terminals. The classic tricyclic compounds were much less specific, representing a shotgun approach to several neurotransmitter receptors and transporters. Now they are increasingly used as a third-line therapy as the side-effect profile of second-generation SSRI antidepressants is far superior. The leading TCAs are imipramine (23), clomipramine (24), and amitriptyline (25), along with a number of other marketed products.

Predictors of Response to Cyclic Antidepressants

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

Other Antidepressants

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

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

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

Major Depressive Disorder

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

Classification and subclassification of major depression disorder and bipolar affective disorder Major depressive disorder The symptom criteria for major depression in DSM-IV-TR and ICD-10 guidelines are very similar (Table 2), although the coding systems are somewhat different.6'7 One difference is that the ICD-10 has a separate, optional subdiagnosis for depression with and without somatic symptoms. The latter is not present in the DSM-IV system. Both sets of guidelines have depressive disorder subdiagnoses for the following Table 2 Abridged DSM-IV criteria for major depressive episode C. The symptoms are not due to a physical organic factor or illness. The symptoms are not better explained by bereavement (although this can be complicated by major depression)

Herbs That May Interact with Antidepressant Medications

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


New classes of antidepressants (ADMs) and antiepileptic drugs (ACMs) have created new opportunities for the treatment of chronic nonmalignant pain. These drugs modulate pain by interacting with specific neurotransmitters and different ion channels. Newer antidepressants have been found to have varying degrees of effectiveness in the treatment of neuropathic pain (bupropion, venlafaxine, duloxetine). Older tricyclic antidepressants (TCAs) including amitriptyline, nortriptyline, and desipramine are also used for the treatment of neuropathic pain. The first-generation anticonvulsants (carbamazepine, valproic acid, and phenytoin) and newer ACMs (gabapentin, pregabalin) are also effective in the treatment of neuropathic pain (45).

Major Depression

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

Social Cost and Market

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

Psychiatric Disorders 601411 Schizophrenia

Depressive disorders Bipolar disorders Major depressive disorder Bipolar I disorder Bipolar II disorder Major depression (see 6.03 Affective Disorders Depression and Bipolar Disorders) is a chronic disorder that affects 10-25 of females and 5-12 of males. Suicide in 15 of chronic depressives makes it the ninth leading cause of death in the USA. Presenting complaints for depression include depressed or irritable mood, diminished interest or pleasure in daily activities, weight loss, insomnia or hypersomnia, fatigue, diminished concentration, and recurrent thoughts of death. The World Health Organization (WHO) has estimated that approximately 121 million individuals worldwide suffer from depression and that depression will become the primary disease burden worldwide by 2020. In the majority of individuals episodes of depression are acute and self-limiting. The genetics of major depression are not well understood and have focused on functional polymorphisms related to monoaminergic...

Clinical Trial Issues

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

Physicochemical Basis of Pain Intervention

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

Affective disorders depression and bipolar disorder

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

The Social Context of Science

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

Global depression market

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

Disease Basis 60321 Causes of Depression

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

Norepinephrine transporter polymorphisms

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

Genetic and Environmental Origins of Depression and Bipolar Disorder

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

Epidemiological Status

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

Neurogenesis creation of new neurons critical to antidepressant action

The seminal studies by Duman and co-workers14 on neurogenesis may help to explain why antidepressants typically take a few weeks to have an effect and may indicate why a rapid-acting antidepressant may not be a viable propositition.14 These workers created a strain of 5HT1A'knockout' mice that as adults show anxiety-related traits, such as a reluctance to begin eating in a novel environment. While unaffected by chronic treatment with the SSRI fluoxetine, the mice became less anxious after chronic treatment with TCAs that act via another neurotransmitter, NE, suggesting an independent molecular pathway. While chronic fluoxetine treatment doubled the number of new hippocampal neurons in normal mice, it had no effect in the knockout mice. The tricyclic imipramine boosted neurogenesis in both types of mice, indicating that the 5HT1A receptor is required for neurogenesis induced by fluoxetine but not imipramine. Chronic treatment with a 5HT1A-selective drug confirmed that activating the...

Symptoms of Depression and Bipolar Disorder

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

The role of the placebo response and future clinical trial design

Less than 50 of the active treatment arms showed a significant difference from placebo and the magnitude of the change in the placebo group had a greater influence on the drug-placebo difference than the change in the drug group. The proportion of trials in which antidepressants were shown to give a significantly better HAM-D score than placebo (P< 0.01) was 59.6 (34 57 trials) for flexible dose trials and 31.4 (11 35) for fixed dose trials. Several researchers have questioned such outcome measures and have noted that unidimensional subscales of the HAM-D are more sensitive to drug-placebo differences than is the total HAM-D score.32 Tricyclic antidepressants

New Methods of Conducting and Evaluating Clinical Trails

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

Alkene oxide substrates

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

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

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

Studies in MS and Other Conditions

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

Selective serotonin reuptake inhibitors SSRIs

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

Fields Of Expertise Within Toxicology

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

Selective norepinephrine reuptake inhibitors

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

Catechol Omethyltransferase inhibitors

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

Treatment of bipolar disorder

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

Neuropeptide approaches

SP is an 11 amino acid peptide belonging to the tachykinin family it mediates its biological actions through G tachykinin (NK1) receptors. Evidence to support a major role of the NK1 receptor system in stress-related behaviors has guided the clinical development of several NK1 receptor antagonists, including aprepitant (MK-869 72), lanepitant (73), dapitant (74), vestiptant (75), PD-174424 (76), and NBI 127914 (77). The antidepressant efficacy of the first NK1 receptor antagonist MK-0869 (Aprepitant 72) was demonstrated in patients with major depression and high anxiety, and has recently been replicated with a second compound, L759274. Aprepitant improved depression and anxiety symptoms in a quantitatively similar manner to SSRIs. However, it failed to show efficacy in Phase III clinical trials for depression.11,57 NK2 receptor ligands (e.g., NKP 608 (78), GR159897 (79)) are also under investigation for their potential role in depression and anxiety disorders.

Special Issues in Assessment of PTSD

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

CAMP response elementbinding protein CREB

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

Posttraumatic Stress Disorder

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

Obsessive Compulsive Disorder

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

Stress Management And Psychiatric Interventions

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

Mood Disorders Diagnosis

Depression is the most common mood disorder in later life. It can have serious consequences, including disability, functional decline, diminished quality of life, mortality from comorbid medical conditions or suicide, demands on caregivers, and increased service utilization (Charney et al. 2003, p. 664). Because of the seriousness of these consequences, geriatric depression has been identified as a major public health problem, yet it is undiagnosed in about 50 of cases (Mulsant and Ganguli 1999). Even when it is recognized, depression in the elderly tends to be undertreated Steffens and colleagues (2000) found that only 35.7 of elderly patients with major depression were taking an antidepressant of these, it is likely that a substantial minority were less than optimally compliant with treatment (Katon et al. 1999). Several factors contribute to this suboptimal response by the medical profession, including 1) the normative fallacy that is, the belief that symptoms of depression are...

Normal Grief Bereavement

Studies generally concur that uncomplicated grief or bereavement may include any or all of the features of major depression except suicidality, psychosis, severe loss of self-esteem and or functionality, and psychomotor retardation. Appetite and sleep disturbance, multiple somatic complaints, anhedonia, anxiety, mild feelings of self-deprecation, the passive wish to join the loved one, sadness, and other dysphoric moods are common but generally less severe than in major depression. Depressed patients are more prone to focus on themselves and their role in the loss and, consequently, are more likely to feel guilt and reduced self-esteem than are nondepressed mourners, who tend to think more of the lost object (Gallagher et al. 1982). One series of studies found that 35 of a group of 109 bereaved widows (average age 61 years) were depressed 1 month after the death of their spouse, but only 17 remained depressed after 13 months. Moreover, the best predictor was depression itself 75 of...

Stress Induced Hyperthermia

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

Social Anxiety Disorder

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

Use in Prevention and Therapy

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

Rates Of Psychiatric Disorders Among People Living With Hiv Infection

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

Monoamine Transport Inhibitors

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

Alzheimers Disease and Vascular Dementia

Although depressive symptoms are commonly seen in patients at various stages of Alzheimer's disease, major depression per se is relatively uncommon. Ballard et al. (2000) found a 1-month prevalence of 8 (on the basis of DSM-III-R criteria), compared with 19 in patients with vascular dementia. In the Alzheimer's disease group, depression was equally common at all severities, whereas in vascular dementia, depression was more frequent in patients with Mini-Mental State Examination (MMSE) scores lower than 20. Vascular dementia patients with major depression in the month prior to assessment were significantly older, more likely to have a history of depression, and less likely to have experienced a major stroke event than were those without major depression. Lyketsos and colleagues (2000) reported a similar prevalence when the Neuropsychiatric Inventory was used. They found depression in 20 of the subjects with a diagnosis of Alzheimer's disease, compared with 32 of the participants with...

Disorders Usually First Diagnosed In Infancy Childhood Or Adolescence

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

Substance Induced Mood Disorder

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

Variations in Clinical Presentation

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

Symptom Rating Scales and Depression Screening

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

Case Example Illustrating Common Obstacles

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

Cognitive and Behavioral Theories

Often expressed by elderly depressed patients (Seligman and Maier 1967). Similarly, cognitive theorists point to the interaction between these losses and subsequent activation of deeply ingrained, stable thought schemas as resulting in negative self-perceptions, negative interpretations of life events, and pessimism about the future, which lead to depressed mood (Sadavoy 1994). Contemporary research on cognitive-behavioral therapy in late-life depression (e.g., Thompson et al. 2001) accepts (with little critical analysis) negative cognitions as the proper focus of therapeutic attention, and the reported effectiveness of cognitive-behavioral therapy indirectly supports the claim that these cognitions play a role in the psychogenesis of depressive mood.

Neurobiological Theories

A consensus conference held by the National Institutes of Health concluded that the hallmark of depression in the elderly is its association with medical comorbidity (National Institutes of Health Consensus Conference 1992, p. 1023). This conclusion was based on data associating late-life depression, particularly the late-onset variant, with a broad spectrum of medical disorders, including cardiovascular, cerebrovascular, musculoskeletal, metabolic, and pulmonary illnesses and malignancies. Possible mediating mechanisms to account for these associations have focused on cerebrovascular pathology (the vascular depression hypothesis discussed earlier in the subsection Vascular Depression) and on decreases in brain volume, which have been reported in the prefrontal lobe, caudate nucleus, and hippocampus of elderly depressed subjects. Several authors (Duman 2004 Jacobs et al. 2000) have proposed that decreased neurogenesis contributes to hippocampal atrophy and thereby underlies the...

Description Of Empirical Research

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

Substance Induced Mania

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

Psychotherapy for Geriatric Depression

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

New Directions in Psychotherapy Research

One promising line of research is examining the effectiveness of brief, structured psychotherapeutic interventions for treating depression within primary care. The multisite IMPACT (Improving Mood Promoting Access to Collaborative Treatment) project has been providing either medication, psychotherapy, or combined therapies to depressed older adults identified in primary care (Unutzer et al. 2003). Choice of treatment is determined jointly by the patient, the primary care provider, a depression care manager (either a nurse or a psychologist), and a consulting psychiatrist. Problem-Solving Treatment in Primary Care (PST-PC) is the principal psychotherapeutic intervention being studied, and it is provided by a nurse, generally a nurse clinical specialist or psychiatric nurse practitioner. Specific problems are identified, and a seven-stage approach to problem solving is introduced and practiced for each problem. Typically, one problem is addressed per session for a total of four to eight...

Combined Psychotherapy and Pharmacotherapy

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

Psychopharmacotherapy for Geriatric Depression

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

First Line Agents NonSelective Serotonin Reuptake Inhibitors

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

Initiation and Dosage Adjustment of Cyclic Antidepressant Therapy

In general, starting dosages for SSRIs and other non-TCA agents are half the usual adult dosage and are increased, as side effects allow, to the full adult dosage within the first week or two of therapy. This dosage is maintained for 6 weeks before dosage increase is considered. The likelihood of obtaining improved response by increasing the dosage beyond the recommended level is generally low, but an increase is worth trying because the side effects of these agents are so benign. Initiation of TCA therapy follows the same guidelines but typically calls for a gradual increase of dosage, as limited by side effects, to produce a plasma level of 80-120 ng mL for nortriptyline, or the highest dosage that is safely tolerated for the other TCAs. Compliance is usually enhanced by minimizing the number of doses administered during any 24-hour period. In this regard, most of the antidepressants discussed in this chapter have an elimination half-life of about 24 hours and can be administered in...

Post Herpetic Neuralgia

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

Third Line Agents Monoamine Oxidase Inhibitors

As cyclic antidepressants in elderly patients, but they appear to be as effective (Georgotas et al. 1986). In the United States, phenelzine and tranylcypromine are available for treatment of depression, and selegiline, which selectively inhibits MAO B, is marketed primarily for adjunctive treatment of Parkinson's disease but also has been studied in depression. Moclobemide, one of the first reversible inhibitors of MAO A, is available in Canada but not in the United States at the time of this writing. Pretreatment physical and laboratory examinations should be conducted as described earlier for cyclic antidepressants, including determination of pre-treatment orthostatic changes in blood pressure and, based on the medical history and physical examination, assessment of the patient's likelihood of requiring sympathomimetic agents. Elderly patients with chronic asthma or bronchitis who must take indirect-acting bronchodilators and patients with Parkinson's disease who may require...

Third Line Agents Psychostimulants

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

Strategies for Antidepressant Treatment Resistance

Depressed patients whose symptoms have not responded to an adequate trial of a single antidepressant are candidates for one or more alternative treatment strategies switching, augmenting, or combining antidepressants. For pur Combining Antidepressants Combination therapy involves the simultaneous administration of two or more agents in dosages that would be expected to have antidepressant effects if administered alone. Combinations that appear, on the basis of largely uncontrolled, small studies, to be safe and to provide some enhanced effectiveness over either agent administered alone include a TCA plus an MAOI, a TCA plus an SSRI, an SSRI plus trazodone, an SSRI plus another SSRI, moclobemide (a reversible MAOI) plus an SSRI, bupropion plus an SSRI, bupropion plus venlafaxine, mirtazapine plus an SSRI, venlafaxine plus an SSRI, and reboxetine plus an SSRI (Lam et al. 2002). Combinations chosen to produce reuptake inhibition of both serotonin and norepinephrine may be most effective....

Immune allergic drug reactions

Drug-induced hepatitis is rare during therapeutic dosage regimens. Although of unknown aetiology, several features suggest an immunological basis including (i) frequent symptoms of hypersensitivity, with fever, rash and eosinophilia (ii) the presence of specific autoantibodies (iii) liver parenchymal lesions, usually including a mixed cellular infiltrate and (iv) a more rapid and more severe response following rechallenge. Several hundred commonly prescribed drugs are associated with liver toxicity. Berson et al. 7 , reviewing 71 patients treated with 41 different agents, identified no single unifying HLA association. Although none of the individual study groups was of sufficient size for HLA association studies (the maximum was seven patients), a number of interesting observations were reported for individual drugs (Table 16.1), including associations of reactions to tricyclic antidepressants with HLA A11, diclofenac with A11 and chlorpromazine with DR6. In addition, patients with...

Psychopharmacotherapy for Psychotic Depression

The proportion of depressed patients who present with delusions and or hallucinations appears to increase with age but does not seem to be related to age at onset of depression (Brodaty et al. 1997). Treatment entails the simultaneous administration of high-potency, low-dose antipsychotic medications such as haloperidol, risperidone, or olanzapine in combination with a TCA, SSRI, or other antidepressant. The Texas Medication Algorithm Project used this combination successfully to treat psychotic depression in nonelderly adults. Their algorithm specified that partial responders were switched from a TCA plus an antipsychotic to a non-TCA plus an antipsychotic or from a non-TCA plus an antipsychotic to a TCA plus an antipsychotic patients who still did not respond were switched to electroconvulsive therapy (ECT), and partial responders to ECT were treated with a previously untried antidepressant with lithium augmentation (Trivedi et al. 2004). The typical pattern of response is marked by...

Complexity and Research Strategies in Behavioral Genetics

Rather, its themes point toward complexity, multilevel interactionism, and the critical role of environment and learning in explanations of and interventions in mental disorders. Part of what motivates an interest in genetics, particularly psychiatric genetics, is the hope that identification of the gene, or more likely genes, contributing to serious mental disorders may give us information that we can use to diagnose and treat these disorders. This is based on the premise that an understanding of the molecular origin of a disorder such as schizophrenia or manic-depressive illness can simplify and clarify our approaches to existing illnesses. I have some doubts that such simplifications and clarifications will occur, but offer some suggestions for where we might look to achieve these hoped-for advances.

Psychopharmacotherapy for Bipolar Depression

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

Inflammation And Brain Serotonin

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

Electroconvulsive Therapy

ECT remains the single most effective treatment for major depression with or without psychosis in elderly patients. Remission rates in the range of 75 90 or greater can be obtained in nai've patients (i.e., those who have not tried and failed other treatments), but in the more typical elderly patient who has had an inadequate response to other treatments, response rates (defined as a decline of 50 or more in pretreatment depression ratings) are in the 80 -90 range, even in the old-old (i.e., older than 75), and side effects are usually limited to transient memory impairment (Tew et al. 1999). ECT is about equally effective in psychotic and nonpsychotic depression however, because psychopharmacological therapy has relatively limited effectiveness in psychotic depression, this condition is the strongest indication for ECT as a first-line therapy. Other indications for ECT as the treatment of first choice include

Repetitive Transcranial Magnetic Stimulation

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

Complementary and Alternative Approaches

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

Neuropsychological Evaluation

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

The Evidence for Prescription Drug Use in the Management of Chronic Pain

Recent reviews have identified several key groups of medication for which there is high quality evidence supporting efficacy in the management of chronic pain 6-9 . This evidence has been used to develop recommendations and treatment algorithms for pharmacologic management of chronic neuropathic pain 6, 9 and chronic pain in general 7, 8 . The classes of agents for which there is well-established evidence of analgesic (pain-relieving) efficacy include the non-steroidal anti-inflammatories (NSAIDs), the tricyclic antidepressants (TCAs), specific anticonvulsants and the opioids (narcotic or morphine-like drugs). The cannabinoids (cannabis derivatives) have good support to justify their use as second or third line treatment and there is growing evidence that specific topical preparations are effective as sole agents in mild to moderate pain with potential to be used in combination with systemic therapy in moderate to severe pain 8 .

N M OBrien and T P OConnor

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

Clinical Presentation

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

Treatment of insomnia

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

Depression and Suicide Risk

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

The First Step The Discovery of Adrafinil

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

For Cellbased Interventive Therapies

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

Kava Piper methysticum

Kava is an herb native to the South Seas, where it is valued for its calming and sedative properties. Double-blind studies in humans have shown efficacy for treating anxiety (8). Kava also appears to have analgesic, muscle-relaxing, and anticonvulsant effects, though these have not been scientifically proven in humans. The anticonvulsant potential of kava may be mediated via an enhancement of GABA within the brain, or possibly via blockade of sodium and calcium channels, similar to the actions of several standard AEDs (8). Rare instances of abnormal movements, acute hepatitis, liver failure, and rash (8) have been reported with kava. This herb is contraindicated in depressed patients because the danger of suicide may be increased (8).

In Search and Discovery of Potential New Therapeutic Indications

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

Screening Instruments and Rating Scales

Most brief mental status examinations do not assess frontal executive functions, and as a result, individuals with frontotemporal dementia may score in the normal range on brief examinations in the early to middle stages of disease. Several short batteries have been developed to help clinicians test for frontal lobe changes, including the Executive Interview (Royall et al. 1992) and the Frontal Assessment Battery (FAB Dubois et al. 2000). Both measures take about 10 minutes to administer and cover several different aspects of behavior, cognition, or motor function affected by frontal lobe syndromes. The FAB differentiates better between frontotemporal dementia and Alzheimer's disease than does the Mini-Mental State Examination (MMSE) (Slachevsky et al. 2004), and it is now used frequently in clinical research (e.g., Mendez et al. 2005). The Executive Interview correlates well with neuropsychological measures of executive function and is sensitive to differences in everyday functional...

Of Antidepressant Treatments

However, there are several problems with this hypothesis. First, not all antidepressants decrease levels of PAR-stimulated cAMP formation, suggesting either that this effect is not necessary for antidepressant efficacy or that different antidepressant agents have different mechanisms. Second, the time-course for downregulation of PAR-stimulated cAMP is more rapid than for the therapeutic action of antidepressants. Third, this hypothesis implies that antagonism of PAR-stimulated cAMP formation should have an antidepressant effect, but this is not the case (63,64). In fact, treatments that enhance the PAR-cAMP system are reported to have therapeutic efficacy (65). In contrast to a subsensitivity hypothesis, further studies indicate that chronic antidepressant treatment actually upregulates the cAMP system at several postreceptor-intracellular sites (Fig. 4). First, studies by Rasenick and colleagues demonstrate that certain antidepressant treatments increase the...

Evening Primrose Oenothera biennis and Borage Borago officinalis

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

Harold W Goforth Mary Ann Cohen and James Murrough

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

Adjustment Disorder with Depressive Features

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

And Repeated Maternal Separations

The elegant studies of Liu et al. (42), Meany et al. (43), and Plotsky (44) have demonstrated permanent effects of repeated maternal separation on neuroendocrine regulation and behavior. Repeated separations of neonatal rats from their mothers for 180 min compared with non-separated controls or those separated for 15 min have revealed that these animals are hypercor-tisolemic as adults, at least partly based on increased corticotropin releasing factor (CRF) excretion. Most interestingly, these animals show anxiety in open-field situations and are also more prone to the acquisition of alcohol and cocaine self-administration compared with their littermate controls. The hypercortisolemia, anxious behaviors, and vulnerability for substance abuse are all reversible with chronic treatment with serotonin-selective antidepressants. However, when these treatments are discontinued, the hypercortisole-mia and proneness to substance abuse returns.

Methods for Locating Genes

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

Changes in Gene Expression

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

Physiological Effects

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

Implications For The Future

Smith and associates (182) demonstrated that whereas some types of stressors appeared to decrease BDNF in the hippocampus, treatment with the antidepressants did the opposite, and cotreatment with antidepressants during stressor induction could block at least some of the stressor-induced changes in neurotrophic factor gene expression. These data were subsequently replicated and extended by Duman (179) and now it is apparent that there are a host of changes in gene expression induced by the antidepressants including alterations in glucocorticoid receptors (183,184) and neurotrophic factors (179,181) that could be implicated in the psychotropic effects of these agents. It is noteworthy that ECS is also capable of transiently increasing BDNF expression in the hippocampus (185) in a manner similar to that of many antidepressants and opposite to the effects of some stressors.

Differential Diagnosis

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

Traditional Views Of The Cp

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

In Bipolar Disorder

The pattern of Ca2+ changes in BD contrasts with that observed in patients with a major depressive disorder, suggesting the type of Ca2+ disturbance may be diagnostically specific. First, basal intracellular Ca2+ concentrations in platelets lymphocytes from patients with a major depressive disorder do not differ from those in matched controls, whereas they are higher in BD patients (96,102,103). Second, whereas serotonin-induced Ca2+ responses were enhanced in both BD and major depressive disorder patients (104106), higher thrombin-stimulated Ca2+ responses were evident only in the BD patients (92,102). These observations, together with the finding of lower erythrocyte membrane Ca2+-ATPase activity in patients with major depression (90), suggest altered Ca2+ homeostasis also occurs in major depression, but likely in a different form and reflecting distinct pathophysi-ological mechanisms. An important question arising out of these studies relates to the nature of the intracellular Ca2+...

What Is Complicated Grief

Bereavement and grief are universal experiences. Many features of acute grief resemble symptoms of major depression. Consequently, there is a long history of linking grief and depression in psychiatric thinking. Bereavement triggers an episode of major depression in about 20 of individuals who lose a loved one. However, not all grief-related problems meet criteria for major depressive disorder. There is a rich clinical literature describing pathological grief reactions, under various designations, including abnormal grief, unresolved grief, and complicated grief (CG). However, the absence of a reliable method of identifying the condition and or for evaluating its severity has obstructed the development and testing of treatments. This problem was addressed when Prigerson et al. developed a simple 19-item questionnaire that reliably identifies bereaved individuals who have persistent, intense grief and poor long-term outcomes (Prigerson et al., 1995a, 1995b). The condition so described,...

Ipt The Matrix For

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

Anxiety and Depression 101

Anxiety and Depression 101

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

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