Continuation treatment, major depression

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. 

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. 

Loss of Response. One final dilemma is the recurrence of major depression during maintenance treatment. Nearly one-third of patients who initially respond to an antidepressant will later have a recurrence despite continuing to take the antidepressant. 

Maintenance/Continuation/Extended treatment - Acute episodes of major depression require several months or longer of sustained pharmacologic therapy. Periodically reassess patients to determine the need for maintenance treatment and the appropriate dose for such treatment. 

The most common mood disorders are major depression (unipolar depression) and manic-depressive illness (bipolar disorder). Major depression is a common disorder that continues to result in considerable morbidity and mortality despite major advances in treatment. Approximately 1 in 10 Americans will be depressed during their lifetime. Of the 40,000 suicides occurring in the United States each year, 70% can be accounted for by depression. Antidepressants are now the mainstay of treatment for this potentially lethal disorder, with patients showing some response to treatment 65 to 80% of the time. 

Despite overwhelming data supporting the efficacy of ECT treatment for major depression, marked variation in the extent and pattern of its usage continues. Use of ECT declined in the 1970s but then appeared to stabilize or increase in the 1980s (J. W. Thompson et al. 1994]. ECT is used far more commonly in private hospitals than in public institutions and is more commonly administered to older patients and to women. Its more common administration to women may be the result of higher rates of depression in women (J. W. Thompson et al. 1994]. Olfson et al. [1998] similarly reported that ECT is used more often in white persons, those with higher incomes, and the elderly. 

Robinson DS, Lerfald SG, Bennett B, et al Continuation and maintenance treatment of major depression with the monoamine oxidase inhibitor phenelzine a double-blind placebo-controUed discussion study. Psychopharmacol Bull 27 31-39, 1991... 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

An adequate trial of antidepressant medication is defined as treatment with therapeutic doses of a drug for a total of 4 weeks. After 4 weeks of antidepressant treatment, patients can be divided into three groups those who have achieved a full response, those who have achieved a partial response, and those who have not responded. In the case of patients who achieve full remission, treatment should continue for a minimum of 4-6 months, or longer if the patient has a history of recurrent depression (see Maintenance Treatment of Major Depression later in this chapter). If a partial response has been achieved by 4 weeks, a full response may be evident within an additional 2 weeks without further intervention. If the symptoms do not respond at all, the dose should be increased, a different antidepressant should be used, or the therapy should be augmented with another medication (see Treatment-Resistant Depression later in this chapter). 

Several trials have been performed with antidepressants in the prevention of recurrence of major depression. In an exemplary trial of this kind, Reimherr et al. (1998) explored the optimal length of therapy in a long-term, placebo-controlled continuation study of patients who had responded to 12 14 weeks of open-label fluoxetine treatment (20mg/day) for major depression. Different maintenance schedules were represented by four treatment arms ... 

A normal response is an increase in plasma TSH of 5 to 15 pU/mL above baseline. A response of less than 5 pU/mL above baseline is generally considered to be blunted (some laboratories consider a response below 7 pU/mL to be blunted) and may be consistent with a major depression. An abnormal test is found in approximately 25% of patients with depression. A blunted TSH response (especially in conjunction with an abnormal DST) may help in confirming the differential diagnosis of a major depressive episode and support continued antidepressant treatment. An increased baseline TSH or an augmented TSH response (higher than 30 pU/mL), in conjunction with other thyroid indices, might identify patients with hypothyroidism, mimicking a depressive disorder. These patients may benefit most from thyroid replacement therapy. 

Furthermore, most psychiatric disorders are chronic, although some may go through intervals of apparent remission (e.g., major depressive disorder), whereas others are persistent but relatively asymptomatic (e.g., schizophrenia) with effective treatment. Flence, treatment with psychotropics is best considered in terms of months or years of continuous or intermittent therapy, rather than a few days or weeks. By contrast, the vast majority of the clinical trials involve short-term use. Thus, a typical database for the approval of a new antidepressant is usually based on experience with 2,000 to 8,000 patients (carefully selected as described earlier), with the majority exposed to the medication for less than 2 months. Often less than 25% will have received medication for more than 4 months, and less than 10% for more than 6 months. When a drug is marketed, most patients will be exposed to it for a minimum of 4 to 6 months. Yet, when treatment goes beyond 2 months, the database on the safety and continued efficacy of a medication is modest at best. Thus, although clinicians commonly use psychotropics for both maintenance and prophylactic purposes, an approved drug only has to be shown effective in the acute phase. 

Meanwhile, benzodiazepines became second-line treatments or augmentation treatments for these anxiety disorder subtypes in the 1990s. While buspirone continues to be recognized as a first-line general anxiolytic, it has not developed a convincing efficacy profile for anxiety disorder subtypes or for the treatment of major depressive disorder. 

Depressive illness constitutes one of the most frequently seen mental disorders. The morbidity and mortality associated with alteration of mood is one of the major problems facing behavioral health professionals, with the U.S. National Comorbidity Study of 1994 showing a lifetime prevalence of major depression of 12.7 percent in males and 21.3 percent in females. Most mood disorders are chronic and require long-term management. Pharmacotherapy continues to be a mainstay treatment of depression. Because depressant mood disorders are so prevalent in our society, antidepressant drugs are among the most frequently prescribed medications. 

Bipolar patients with so-called breakthrough major depressive episodes, despite adequate treatment, were placed in a randomized doubleblind 10-week study and treated with bupropion, sertraline, or venlafaxine augmentation (Post et al., 2001). Switches to hypomania or mania occurred in 14% of the patients. Those who responded positively to the treatment were continued for 1 year in a blinded maintenance trial, and 33% switched into hypomania or mania. In a second phase of their antidepressant augmentation studies, 18.2% switched into hypomania or... 

Bauer M, Bschor T, Kunz D, Berghofer A, Strohle A, Muller-Oerlinghausen B. Double-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression. Am J Psychiatry 2000 157(9) 1429-35. 

Kennedy SH. Continuation and maintenance treatments in major depression the neglected role of monoamine oxidase inhibitors. J Psychiatry Neurosci 1997 22 127-31. 

In addition to these subtypes, it is important to keep in mind that many, if not most, borderline personalities have comorbid Axis I disorders—especially common are major depression and substance abuse. These coexisting disorders always complicate the picture and must be dealt with in any approach to treatment. In particular, longitudinal studies following the course and outcome of borderline personality disorders over the life span suggest very clearly that those patients who continue to do poorly are those who continue to abuse alcohol and other substances. Thus treatment of chemical dependency problems must be addressed. 

A case report involving a 38-year-old female who was in a major depressive episode began taking St. John s wort at 24 gestational weeks and continued with the therapy until delivery. The pregnancy was generally unremarkable, with a relatively mild case of late onset thrombocytopenia and neonatal jaundice that developed at day 5 and responded to treatment. The child was 7 lbs 8 oz, had Apgar scores of 9 at 1 and 5 minutes, normal physical and laboratory results, and normal behavioral assessments at 4 and 33 days (92). 

Because of their continued use, narrow therapeutic range, and the nature of the iUness for which they are typically prescribed, tricyclic antidepressants may cause severe or fatal toxicity. For example, in March of 2004 the U.S. FDA issued a Public Health Advisory because of both suicidal ideation and suicide attempts in children taking antidepressant drugs for the treatment of major depressive disorder. 

The time for antidepressant onset of effect in BN is unclear. In the absence of data, the definition of a therapeutic trial from the depression hterature (4 to 8 weeks at a therapeutic dose) should be used. Since the majority of subjects will not experience a complete remission, and there are few data on predictors of response or whether switching to another class will improve response, a clear and specific target should be stated initially. Eor example, will the medication be continued if the patient has a 50% reduction in binge-purge episodes, or if abstinence from such behavior is the ultimate therapeutic goal. Optimal duration of treatment after response is also poorly defined. Most clinicians will treat for 6 months to 1 year and then re-evaluate the need for ongoing treatment. The evidence is mixed as to whether any early benefit is sustained, hence the decision to continue treatment should be made based on both initial response and the maintenance of that benefit. If the symptoms return within a few months after the antidepressant is discontinued, then the treatment may need to be reinitiated. 

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