Major depression/depressive disorder

There are two major types of depression major depressive disorder (MDD) and bipolar or manic-depressive illness. Both disorders are characterized by changes in mood as the primary clinical manifestation. Major depression is characterized by feelings of intense sadness and despair with little drive for socialization or communication. Physical changes such as insomnia, anorexia and sexual dysfunction can also occur. Mania is characterized by excessive elation, irritability, insomnia, hyperactivity and impaired judgment. It may effect as much as 1% of the U.S. population."... 

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Two recently introduced antidepressants are notable m that they are selective serotonin uptake inhibitors Citalopram (19) is reported to be as effective as amitriptyline m the treatment of endogenous depression [75, 16] Fluoxetine (20) as the hydrochlonde is approved for major depressive disorders mcludmg those with concomitant anxiety Interestmgly, it also appears useful m the treatment of obesity [17]... 

Indeed, 5-HT is also a substrate for the 5-HT transporter, itself an important player in the treatment of depression, and more recently for the whole range of anxiety disorders spectrum (GAD, OCD, social and other phobias, panic and post-traumatic stress disorders). It is the target for SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, paroxetine, fluvoxamine, and citalopram or the more recent dual reuptake inhibitors (for 5-HT and noradrenaline, also known as SNRIs) such as venlafaxine. Currently, there are efforts to develop triple uptake inhibitors (5-HT, NE, and DA). Further combinations are possible, e.g. SB-649915, a combined 5-HTia, 5-HT1b, 5-HT1d inhibitor/selective serotonin reuptake inhibitor (SSRI), is investigated for the treatment of major depressive disorder. 

In summary, research on the use of antidepressants to treat cannabis dependence, particularly among individuals with comorbid major depressive disorder, although limited, offers a promising avenue for the development of pharmacological aids to assist in the treatment of cannabis withdrawal. There are clear parallels between this literature and the existing research on the use of antidepressants in the treatment of alcohol dependence comorbid with major depressive disorder (see Chapter 1, Medications to Treat Co-occurring Psychiatric Symptoms or Disorders in Alcoholic Patients). 

Schmitz JM, Averill P, Stotts AL, et al Fluoxetine treatment of cocaine-dependent patients with major depressive disorder. Drug Alcohol Depend 63 207-214,2001 Schottenfeld RS, Pakes JR, Oliveto A, et al Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Arch Gen Psychiatry 54 713-720, 1997... 

Einarson TR, Arikian S, Sweeney S, Doyle J (1995). A model to evaluate the cost effectiveness of oral therapies in the management of patients with major depressive disorders. Clin Ther 17, 136-53. 

The anxiety disorders are common and surprisingly disabling conditions. Studies on the health economics of generalized anxiety disorder, panic disorder, social anxiety disorders and obsessive compulsive disorder document the cost to the individual and to society. Attention has focused on the major psychiatric disorders such as depression, schizophrenia and the dementias. Studies suggest that many anxiety disorders are of early onset and too often chronic they are quite common and impose a heavy burden on society. More studies will be needed to discern the fine grain in the survey material and to identify more precisely the location and type of societal costs. These factors will vary from country to country, from district to district, between men and women and between various age groups. 

Explain the etiology and pathophysiology of major depressive disorder. 

State the goals of pharmacotherapy in major depressive disorder. 

O Classic views as to the cause of major depressive disorder focus on the monoamine neurotransmitters norepinephrine (NE), serotonin (5-HT), and to a lesser extent, dopamine (DA) in terms of both synaptic concentrations and receptor functioning. 

It is not uncommon for a patient to experience only a single major depressive episode, but most patients with major depressive disorder will experience multiple episodes. 

One extremely important outcome in the treatment of major depressive disorder is the prevention of suicidal attempts. 

Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000 157(4 suppl) lM5. 

Department of Psychiatry and Behavorial Neurobiology University of Alabama at Birmingham Birmingham, Alabama Chapter 35 Major Depressive Disorder... 

Chap. 35 - Major Depressive Disorder Universal Program Number 014-999-07-051-H04... 

Kleinman (1986) claimed that neurasthenia was a cultural form of chronic somatization that outlined several different types of psychopathological disorders, the major depressive disorder included in western classifications being the one that best accounted for this disorder. This would explain the lower rate of prevalence of the diagnosis of depressive disorder among the Chinese population. 

Yu, Y. W., Tsai, S. J. etal. (2002). Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Mol. Psychiatry, 7(10), 1115-19. 

Yoshida, K. et al. (2002). Monoamine oxidase a gene polymorphism, tryptophan hydroxylase gene polymorphism and antidepressant response to fluvoxamine in Japanese patients with major depressive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry, 26, 1279-83. 

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