Depressive disorder

It is helpful to first view depressive disorders as falling broadly into three primary groups reactive sadness, grief, and clinical depression. 

Reactive sadness is characterized by relatively low-grade mood changes—sadness, disappointment, despair—that occur in response to minor losses and disappointments. The emotional responses are considered to be normal and appropriate. They are transient, and, most importantly, these mood disturbances do not typically interfere with functioning that is, they have little impact on academic, occupational, or social or interpersonal functioning. 

or uncomplicated bereavement, can be a much more prolonged and intensely painful experience. Grief is a normal and emotionally necessary response to major losses, such as death of a loved one or divorce. Most normal grief reactions result in significant degrees of emotional distress for a period of six to twelve months 

Certainly, what appears initially to be a grief reaction often disintegrates into a true clinical depression, so the boundary between these disorders is not always sharply defined. When the following symptoms emerge in the wake of a serious loss, this signals that normal grief has evolved into a clinical depression  

The vast majority of individuals encountering uncomplicated bereavement do not need psychological or psychiatric treatment. However, it is estimated that 15 to 25 percent of individuals do in fact develop a clinical depression following a major loss. 

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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. 

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

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. 

Lithium compounds are used in ceramics, lubricants, and medicine. Small daily doses of lithium carbonate are an effective treatment for bipolar (manic-depressive) disorder but scientists still do not fully understand why. Lithium soaps—the lithium salts of long-chain carboxylic acids—are used as thickeners in lubricating greases for high-temperature applications because they have higher melting points than more conventional sodium and potassium soaps. 

The authors concluded that antidepressants exert a modest beneficial effect for patients with combined depressive disorder and substance use disorder. They also emphasized that antidepressants are not a stand-alone treatment for depressed alcoholic patients and that concurrent therapy directly targeting the substance use disorder is also indicated. 

Nestler EJ, Hyman SE, Malenka RC Molecular Neuropharmacology A Foundation for Clinical Neuroscience. New York, McGraw Hill, 2001 Novick DM, Pascarelli EE, Joseph H, et al Methadone maintenance patients in general medical practice a preliminary report. JAMA 259 3299—3302, 1988 Nunes EV, Quitkin EM, Donovan SJ, et al. Imipramine treatment of opiate-dependent patients with depressive disorders a placebo-controlled trial. Arch Gen Psychiatry 55 153-160, 1998... 

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... 

Depression is a common, serious, sometimes fatal illness that is chronic and recurrent in nature, impairs family life, reduces social adjustment, and is a burden on the community (Klerman and Weissman, 1992). This disease chronicity magnifies hoth its societal impact and its economic burden. It has been estimated that more than 17% of the disability associated with mental disorders is the result of depressive disorders (Rosenbaum and Hylan, 1999), and that the global burden of depression, measured in terms of disability-adjusted life years, will rank second only to ischaemic heart disease by the year 2020 (Murray and Lopez, 1996). 

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. 

Geddes JR, Freemantle N, Mason J, Eccles MP, Boynton J (1999). SSRIs versus alternative antidepressants in depressive disorder (Cochrane Review). In Cochrane Library, Issue 4. Oxford Update Software. 

The anxiety disorders are a case in point. They comprise a range of conditions contiguous with the affective disorders and the stress responses (Table 4.1). Much overlap and comorbidity exist. Furthermore, definitions and diagnostic criteria have changed substantially over the years. For example, generalized anxiety disorder is a rare condition in its pure form, but a common condition if comorbid phobic and depressive disorders are accepted. 

Evaluation of the economics of mental illness in primary care is an ongoing initiative of the UK Department of Health (Lloyd and Jenkins, 1995). A similar American study in Washington State included sub-threshold anxiety or depression, but these imposed relatively little economic load compared with disorder-level anxiety or depression (Simon et al, 1995). Mental health treatment accounted for only a small part of overall utilization, approximately 5%. Nevertheless, most patients with anxiety or depressive disorders showed considerable improvement. This was accompanied by only modest reductions in cost. 

Honorary Consultant at the Maudsley Hospital and sees patients with anxiety, sleep and depressive disorders. He is on the advisory boards of about 25 international scientific journals. 

QUESTION Does anything suggest that people who have taken these drugs or MDMA for a period of time are subject to episodes of depressive disorders or affective disorders ... 

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. 

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