Continuation and Maintenance Periods, and Discontinuation

CONTINUATION PERIOD This period usually lasts five to eight months after the end of the acute treatment period. The goal at this phase is the prevention of relapse. There is a high risk of relapse if treatment is discontinued after the acute treatment phase, with rates of 15% after six months and 22% after 12 months. The two best predictors of relapse are a high number of previous depressive episodes (greater than three predicted relapses) and underlying dysthymic disorder.

Once a patient has responded to medication, treatment should be continued for a minimum of four to six months from the point of initial response. This period should be lengthened for the patient with a history of longer depressive episodes.

In the past, it was suggested that, on achievement of euthymia, doses could be reduced. However, it is more likely that levels similar to those needed at the acute stage of treatment will be required throughout the continuation period.

MAINTENANCE PERIOD The goal of the maintenance period is to prevent the recurrence of depression. There are a number of reasons to consider long-term prophylactic therapy for depression rather than medication withdrawal:

1. Depression is a lifelong disease, with recurrence being the norm rather than the exception

2. As the number of acute episodes increases, the risk of future episodes increases as well, and the interval between episodes shortens

3. Each subsequent episode carries a higher morbidity and disability

4. There is a fear that treatment response may decrease with an increasing number of depressive episodes

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Several factors influence the decision to maintain long- term prophylaxis for depression, including the seriousness of previous episodes, the severity of impairment caused by such episodes, the degree of response to previous treatments, and the ability of the patient to tolerate the drug. Central in the decision process is the concept of recurrent depression: that some patients are more likely than others to have a recurrence of the disease. Three previous episodes of depression make recurrent depression likely.

The best predictors of the likelihood of recurrence appear to be older age of onset and number of episodes. Long-term maintenance is the treatment of choice for the following groups of patients:

1. 50 years old or more at the time of the first depressive episode

2. 40 years old or more at first episode and have had at least one subsequent recurrence

3. Anyone who has had more than three episodes The recommended length of maintenance therapy varies from

five years of treatment to indefinite continuation. Recent studies with both acute major depression and recurrent depression have shown significantly higher relapse rates 2–3 years post-discontinuation compared with patients on maintenance treatment.

Regarding choice of agent, there are no rigorous studies comparing different antidepressants during the maintenance period. It is usually assumed that the same agent used in the acute and continuation period will also be the preferred one in the maintenance period.

Equally important in preventing recurrence of depression is the problem of maintaining adherence to medication long after the acute episode has resolved. Proper education and support will help with compliance. Toleration of side effects is important; patients are more likely to comply with agents that have more favorable side effect profiles. SSRIs or bupropion (sustained or extended release forms) are generally the best- tolerated antidepressants.

Although lower doses for prophylaxis have been recommended, there are few data to support this contention. Even

ANTIDEPRESSANTS 69 though lower doses may increase compliance, full doses should

be used until new information indicates otherwise. DISCONTINUATION OF TREATMENT

Before discontinuing treatment with an antidepressant it is important to remember that depression is often a lifelong disease with a chronic course. One should always weigh the benefits of discontinuation against the risks of recurrent depression. Patients with a single episode of acute depression and who have an onset before age 50 are the best candidates for discontinuation.

For TCAs, the usual strategy is to taper the dose at a rate of

25 to 50 mg/day every 2 to 3 days. Too rapid a decrease in dose may produce symptoms of cholinergic ‘rebound’ or supersen- sitivity (nausea, vomiting, cramps), other signs of autonomic hyperactivity (diaphoresis, anxiety, agitation, headache), and insomnia as early as 48 hours or as late as 2 weeks after discontinuation. These early symptoms may be mistaken for relapse of depression.

MAOIs may also have a withdrawal syndrome on abrupt cessation of treatment, including symptoms of psychosis; however, this is rarer than that seen with the TCAs.

Recommendations for discontinuing SSRIs depend on the particular drug. Fluoxetine has a long half-life and abrupt withdrawal should be permissible. Shorter half-life drugs, such as sertraline, citalopram, escitalopram, and paroxetine, may require a 7–10-day taper. The withdrawal syndrome with shorter-acting agents includes symptoms of fatigue, insomnia, abdominal distress, and influenza-like symptoms. The same may be true for venlafaxine and duloxetine.

A first episode of depression has a high risk of recurrence and the risk is higher in patients who have only a partial response to treatment. After discontinuation the goal is to enable early intervention if symptoms recur. The patient should be educated to recognize the symptoms of depression and seek help at an early stage.

SIDE EFFECTS Once the choice of an antidepressant has been made, the

main goal is to maximize therapeutic effects and minimize side

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effects. Good preparation and reassurance of the patient is essential. Even relatively benign side effects are a major cause of treatment nonadherence; drop-out rates ranging from 7 to 44% have been reported in various studies of TCAs, and from

7 to 23% in studies of serotonin reuptake inhibitors. Common side effects for TCAs and SSRIs are shown in Table 2-5.

Continuation and Maintenance Periods, and Discontinuation