Depression Major

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. 

Monoamine—Oxidase Inhibitors. In the mid-1950s, tuberculosis patients with depression being treated with iproniazid (42) were occasionally reported to become euphoric. This observation led to the discovery of irreversible monoamine—oxidase (MAO) inhibiting properties. Hydrazine and nonhydrazine-related MAO inhibitors were subsequentiy shown to be antidepressants (122). Three other clinically effective irreversible MAO inhibitors have been approved for treatment of major depression phenelzine (43), isocarboxazid (44), and tranylcypromine (45). 

Pit morphology is particularly interesting. The major depression is cavernous and shows lateral propagation. However, only a small weeping perforation is present. It is tempting to speculate that once the pipe wall was breached, air in the vicinity of the perforation limited anaerobic activity, thus producing the laterally propagating pit. 

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. 

Define depression and identify symptoms of a major depressive episode. 

Depression is one of the most common psychiatric disorders. It is characterized by feeling of intense sadness, helplessness, worthlessness, and impaired functioning. Those experiencing a major depressive episode exhibit physical and psychological symptoms, such as appetite disturbances, sleep disturbances, and loss of interest in job, family, and other activities usually enjoyed. A major depressive episode is a depressed or dysphoric (extreme or exaggerated sadness, anxiety, or unhappiness) mood that interferes with daily functioning and includes five or more of the symptoms listed in Display 31-1. 

To be classified as a major depression, these symptoms should occur daily or nearly every day for a period of 2 weeks or more. The symptoms of major depression should not be the result of normal bereavement, such as the loss of a loved one, or disease, such as hypothyroidism. 

Depression is treated with the use of antidepressan t drugs. Psychotherapy is used in conjunction with the antidepressant drug s in treating major depressive episodes. The four types of antidepressants are ... 

Antidepressant drugs are used to manage depressive episodes such as major depression or depression accompanied by anxiety. These drugs may be used in conjunction with psychotherapy in severe depression. The SSRIs also are used to treat obsessive-compulsive disorders. The uses of individual antidepressants are given in the Summary Drug Table Antidepressants. Treatment is usually continued for 9 months after recovery from the first major depressive episode. If the patient, at a later date, experiences another major depressive episode, treatment is continued for 5 years, and with a third episode, treatment is continued indefinitely. 

Grant BF, Harford TC Comorbidity between DSM-IV alcohol use disorders and major depression results of a national survey. Drug Alcohol Depend 39 197-206, 1995 Grant BF, Dawson DA, Stinson FS, et al The 12-month prevalence and trends in DSM-IV alcohol abuse and dependence United States, 1991-1992 and 2001-2002. Drug Alcohol Depend 74 223-234, 2004a... 

Fyer AJ, Liebowitz MR, Gorman JM, et al Effects of clonidine on alprazolam discontinuation in panic patients a pilot study. J Clin Psychopharmacol 8 270—274,1988 Garvey MJ, Tollefson GD Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression. Am J Psychiatry 143 1601-1603, 1986... 

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). 

Chen CY, Wagner FA, Anthony JC Marijuana use and the risk of major depressive episode epidemiological evidence from the United States National Comorbidity Survey. Soc Psychiatry Psychiatr Epidemiol 37 199-206, 2002... 

Grant BF Comorbidity between DSM-IV drug use disorders and major depression results of a national survey of adults. J Subst Abuse 7 481 97, 1995 Hall W, Babor TF Cannabis use and public health assessing the burden. Addiction 95 485 90, 2000... 

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... 

Nortriptyline. Nortriptyhne, a tricychc antidepressant, has been shown in double-blind, placebo-controlled randomized trials to be superior to placebo for smoking cessation (Prochazka et al. 1998). Nortriptyline appears to have efficacy comparable to that of bupropion for smoking cessation (Hall et al. 2002). The efficacy of this agent may be improved with more intensive behavioral therapies (Hall et al. 1998). Nortriptyline s mechanism of action is thought to relate to its noradrenergic and serotonergic reuptake blockade, because these two neurotransmitters have been implicated in the neurobiology of nicotine dependence. Side effects of nortiptyline are typical of tricyclic antidepressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with a past history of major depression, and it can be recommended as a second-... 

Persons with depressive symptoms or major depression also have high rates of smoking (40%-60% prevalence), and depression appears to be a predictor of... 

Hall SM, Reus VI, Munoz RF, et al Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Arch Gen Psychiatry 55 683-690, 1998 Hall SM, Humfleet GL, Reus VI, et al Psychological intervention and antidepressant treatment in smoking cessation. Arch Gen Psychiatry 59 930-936, 2002 Hayford KE, Patten CA, Rummans TA, et al Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism. Br J Psychiatry 174 173-178, 1999... 

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. 

Lave JR, Frank RG, Shulberg HC, Kamlet MS (1998). Cost-effectiveness of treatments for major depression in primary care practice. 

Nuitjen MJC, Hardens M, Souetre E (1995). A Markov Process Analysis comparing the cost effectiveness of maintenance therapy with citalopram versus standard therapy in major depression. Pharmacoeconomics, 159-68. 

Tollefson GD, Souetre E, Thomander L, Potvin JH (1993). Comorbid anxious signs and symptoms in major depression impact on... 

Normally, circulating glucocorticoids (of which cortisol is the most prominent in humans) cause feedback inhibition of ACTH release so that cortisol secretion is, to some extent, self-limiting. However, many patients suffering from major depression have an increased concentration of plasma cortisol but reduced ACTH secretion. The latter abnormality seems to be partly due to a reduction in the number of CRF receptors in the pituitary, although it is thought that decreased ACTH secretion could provoke the adrenal hyperplasia which is common in depression. This would result in excessive secretion of cortisol and contribute to the inhibition of ACTH release (Musselman and Nemeroff 1993). 

Depression is a common problem in patients with epilepsy, with approximately 30% having symptoms of major depression at some point.34 Patients with epilepsy should be routinely assessed for signs of depression, and treatment should be initiated if necessary. Certain AEDs may exacerbate depression, for example levetirac-etam and phenytoin. Other AEDs (e.g., lamotrigine, carba-mazepine, and oxcarbazepine) maybe useful in treating depression. Changes in mood can be precipitated by addition or discontinuation of an AED. If treatment for depression is necessary, caution should be exercised in choosing an agent that does not increase seizure frequency and does not interact with AEDs. 

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