Major depression/depressive disorder treatment

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. 

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. 

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... 

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. 

Lee, S. H., Lee, K. J., Lee, H. J. etal. (2005). Association between the 5-HT6 receptor C267T polymorphism and response to antidepressants treatment in major depressive disorder. Psychiatry Clin. Neurosci., 59, 140-5. 

Currier, M. B., Molina, G. 8c Kato, M. (2004). Citalopram treatment of major depressive disorder in Hispanic HIV and AIDS patients a prospective study. Psychosomatics, 45, 210-16. 

Kirchheiner, J., Bertilsson, L., Bruus, H. etal. (2003). Individualized medicine - implementation ofpharmacogenetic diagnostics in antidepressant drug treatment of major depressive disorders. Pharmacopsychiatry, 36, 235-43. 

Lee, H.-J., Cha, J.-H., Ham, B.-J. etal. (2004). Association between a G-protein boldbeta3 subunit gene polymorphism and the symptomatology and treatment responses of major depressive disorders. Pharmacogenomics J., 4, 29-33. 

Friedman, Michael A., Jerusha B. Detweiler-Bedell, Howard E. Leventhal, Rob Horne, Gabor I. Keitner and Ivan W. Miller, Combined Psychotherapy and Pharmacotherapy for the Treatment of Major Depressive Disorder , Clinical Psychology Science andPractice 11, no. 1 (2004) 47-68... 

Hansen, Richard A., Gerald Gartlehner, Kathleen N. Lohr, Bradley N. Gaynes and Timothy S. Carey, Efficacy and Safety of Second-Generation Antidepressants in the Treatment of Major Depressive Disorder , Annals of Internal Medicine 143 (2005) 415-26... 

Hudson, Christopher G., Socioeconomic Status and Mental Illness Tests of the Social Causation and Selection Hypotheses , American Journal of Orthopsychiatry 75, no. 1 (2005) 3-18 The Humble Humbug , The Lancet 2 (1954) 321 Hunter, Aimee M., Andrew F. Leuchter, Melinda L. Morgan and Ian A. Cook, Changes in Brain Function (Quantitative EEG Cordance) During Placebo Lead-in and Treatment Outcomes in Clinical Trials for Major Depression , American Journal of Psychiatry 163, no. 8 (2006) 1426-32 Hyland, Michael E., Do Person Variables Exist in Different Ways , American Psychologist 40 (1985) 1003-10 Hypericum Depression Trial Study Group, Effect of Hypericum Perforatum (St John s Wort) in Major Depressive Disorder A Randomized Controlled Trial , Journal of the American Medical Association 287 (2002) 1807-14... 

Keller, Martin, Stuart Montgomery, William Ball, Mary Morrison, Duane Snavely, Guanghan Liu, Richard Hargreaves, Jarmo Hietala, Christopher Lines, Katherine Beebe and Scott Reines, Lack of Efficacy of the Substance P (Neurokinini Receptor) Antagonist Aprepitant in the Treatment of Major Depressive Disorder , Biological Psychiatry 59 (2006) 216-23... 

Loo, H., Hale, A. Dhaenen, H. (2002). Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT2C antagonist, in the treatment of major depressive disorder a placebo-controlled dose range study. Int. Clin. PsychopharmacoL 17, 239-47. 

Bauer M et al. (2002). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders. Part 1 Acute and continuation treatment of major depressive disorder. World Journal of Biological Psychiatry, 3, 5-43. 

Electroconvulsive therapy A physical therapy used in the treatment of a major depressive disorder that does not respond to pharmacotherapy. 

Versiani M, Mehilane L, Gaszner P, Arnaud-Castiglioni R. Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder. J Clin Psychiatry 1999 60 400-406. 

The typical antipsychotic drugs, which for 50 years have been the mainstay of treatment of schizophrenia, as well as of psychosis that occurs secondary to bipolar disorder and major depressive disorder, affect primarily the positive symptoms[10]. The behavioral symptoms, such as agitation or profound withdrawal, that accompany psychosis, respond to the antipsychotic drugs within a period of hours to days after the initiation of treatment. The cognitive aspects of psychosis, such as the delusions and hallucinations, however, tend to resolve more slowly. In fact, for many patients the hallucinations and delusions may persist but lose their emotional salience and intrusiveness. The positive symptoms tend to wax and wane over time, are exacerbated by stress, and generally become less prominent as the patient becomes older. 

The essential feature of major depressive disorder is a clinical course that is characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. Dysthymic disorder is a chronic disturbance of mood involving depressed mood and at least two other symptoms, and it is generally less severe than major depressive disorder. This chapter focuses exclusively on the diagnosis and treatment of major depressive disorder. 

The efficacy of psychotherapy and antidepressants is considered to be additive. Psychotherapy alone is not recommended for the acute treatment of patients with severe and/or psychotic major depressive disorders. For uncomplicated nonchronic major depressive disorder, combined treatment may provide no unique advantage. Cognitive therapy, behavioral therapy, and interpersonal psychotherapy appear to be equal in efficacy. 

Monoamine reuptake inhibitors elevate extracellular levels of serotonin (5-HT), norepinephrine (NE) and/or dopamine (DA) in the brain by binding to one or more of the transporters responsible for reuptake, namely the serotonin transporter (SERT), the norepinephrine transporter (NET) and the dopamine transporter (DAT), thereby blocking the reuptake of the neurotransmitter(s) from the synaptic cleft [1], Monoamine reuptake inhibitors are an established drug class that has proven utility for the treatment of a number of CNS disorders, especially major depressive disorder (MDD). 

As the first SNRI drug approved, venlafaxine has become one of the first-line choices for depression and anxiety disorder [45,46]. An active metabolite, desvenlafaxine (19), is also under clinical development for the treatment of major depressive disorders [47], Preclinical studies also indicate that 19 may be effective in relieving vasomotor symptoms associated with menopause (e.g., hot flushes and night sweats) [47,48]. Desvenlafaxine is reported to be in clinical development for the treatment of fibromyalgia and neuropathic pain, as well as vasomotor symptoms associated with menopause [68]. 

When is medication indicated in the treatment of psychiatric illness There is no short answer to this question. At one end of the continuum, patients with schizophrenia and other psychotic disorders, bipolar disorder, and severe major depressive disorder should always be considered candidates for pharmacotherapy, and neglecting to use medication, or at least discuss the use of medication with these patients, fails to adhere to the current standard of mental health care. Less severe depressive disorders, many anxiety disorders, and binge eating disorders can respond to psychotherapy and/or pharmacotherapy, and different therapies can target distinct symptom complexes in these situations. Finally, at the opposite end of the spectrum, adjustment disorders, specific phobias, or grief reactions should generally be treated with psychotherapy alone. 

Sue is 42 years old and experiencing her second episode of major depressive disorder. She has never been on antidepressants before but this time wouid iike to try medication as part of her treatment. The initiai assessment period for her wiii be a few days to a week after starting to make sure that the medication is not producing uncomfortabie side effects. After 3-4 weeks, we expect to see some improvement in her mood if there is no change whatsoever, many physicians wouid change antidepressants after 4-5 weeks. Finaiiy, when there has ceased to be any further improvement in mood, we want to know, "is she weii or is she oniy better " if the answer is that she has oniy gotten better, but not yet weii, then we have more work to do. 

Eava M, Schmidt ME, Zhang S, et al. Treatment approaches to major depressive disorder relapse. Part 2 Reinitiation of antidepressant treatment. Psychother Psychosom 2002 71(4) 195-199. 

Eriedman MA, Detweiler-Bedell JB, Leventhal HE, et al. Combined psychotherapy and pharmacotherapy for the treatment of major depressive disorder. Clin Psychol Sci Pract 2004 11(1) 47-68. 

Appropriate management of AN also requires the early detection and treatment of any comorbid psychiatric disorders. The most common comorbid conditions associated with AN are major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and substance use disorders. At the time of presentation, over 50% of AN patients also fulfill criteria for MDD however, accurate diagnosis of depression in these patients is complicated by the fact that prolonged starvation often produces a mood disturbance and neurovegetative symptoms identical to MDD. If MDD appears to be comorbid with AN at the time of presentation, there is debate as to whether it is more prudent to withhold treatment of the depression until weight restoration has been initiated. If the depression persists despite refeeding, then treatment of the depression is likely warranted. 

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