Treatment consists of three phases:
- Acute Phase – Remission is induced (minimum 6 – 8 weeks in duration).
- Continuation Phase – Remission is preserved and relapse prevented (usually 16 – 20 weeks in duration).
- Maintenance Phase – Susceptible patients are protected against recurrence or relapse of subsequent major depressive episodes (duration varies with frequency and severity of previous episodes).
Remission and relapse have been defined by the American Psychiatric Association. Remission is the return to the patient’s baseline level of symptom severity and functioning. Remission should not be confused with significant but incomplete improvement. Relapse is the re-emergence of significant depressive symptoms or dysfunction after remission has been achieved.
Acute Phase Treatment: Severe Major Depression
The goal of acute phase treatment is to induce remission.
For patients with severe major depression, evidence supports either pharmacotherapy alone, or the combination of pharmacotherapy and psychotherapy. There is insufficient evidence that psychotherapy alone is effective for severe depression.
Patients with severe depression should be seen again in the office within 1-2 weeks of starting a new antidepressant medication for re-assessment. The combination of antidepressant medication and psychotherapy may be the initial treatment approach for patients for patients with severe depression in the presence of psychosocial stressors, interpersonal difficulties, intrapsychic conflict, and any personality disorders. Patients with depression and psychotic symptoms, catatonia, or severe impairment may be considered for combination therapy with antidepressants, antipsychotics, and / or electroconvulsive therapy (ECT). Patient with severe depression with any of the aforementioned co-morbidities are usually referred for care under a psychiatrist.
Acute Phase Treatment: Mild to Moderate
For patients with mild to moderate major depression, the initial treatment modalities may include pharmacotherapy alone, psychotherapy alone, or the combination of medical management and psychotherapy. Antidepressant medications can be used as initial treatment modality by patients with mild or moderate depression. Clinical features that may suggest that antidepressant medication is preferred over other modalities are a positive response to prior antidepressant treatment, significant sleep and appetite disturbance, severity of symptoms, or anticipation by the physician that maintenance therapy will be needed. Patient preference for antidepressant medication alone should be taken into consideration. Most primary care physicians can medically manage these patients in their practices as long as they continue to monitor the patient’s symptoms closely. The frequency of monitoring in the acute phase of pharmacotherapy is from once a week to multiple times a week. Psychotherapy alone may be considered as initial treatment modality for patients with mild to moderate depressive disorder. Clinical features that suggest the use of psychotherapy are the presence of psychosocial stressors, interpersonal difficulties, intrapsychic conflict, and personality disorders. In addition, patient preference for psychotherapy alone should be taken into consideration, as well as a woman’s desire to get pregnant, be pregnant, or to breastfeed. Most primary care physicians will refer these patients to a professional psychotherapist for management. The frequency of monitoring in the acute phase of psychotherapy is from once a week to multiple times a week.
The combination of antidepressant medication and psychotherapy may be the initial treatment approach for patients with moderate depression in the presence of psychosocial stressors, interpersonal difficulties, intra-psychic conflict, and personality disorders. Combination therapy may also be appropriate for patients with only partial remission on one type of treatment, or with a history of poor adherence to treatment. Most primary care physicians can medically manage these patients while referring them to a professional psychotherapist for co-management.
Assessing for Adequate Response in the Acute Phase
Although the goal of acute phase treatment is to return patients to their functional and symptomatic baseline, it is common for patients to have a substantial but incomplete response to acute phase treatment. Structured tools that measure depression severity and functional status may be used for follow up assessment (e.g., PHQ- 9, Beck Depression Inventory, etc.). It is important to not conclude treatment for these patients at this phase as it may be associated with poor functional outcomes. The degree of an “adequate response” to treatment of depression has been loosely defined: non-response is the decrease in baseline symptoms of 25% or less; partial response is a 26 – 49% decrease in baseline symptoms; partial remission is 50% or greater decrease in baseline symptoms with residual symptoms; and remission is the complete absence of symptoms). When patients have not fully responded at this phase, the most important first step is increasing the dose.
Overall, if after the initial 4 – 8 weeks there is not a moderate improvement in baseline symptoms in the acute phase, then a reassessment of the diagnosis, medication regimen and / or psychotherapy, adherence, substance or alcohol use is in order. Increasing the treatment dose is the first step to be considered. If 4 – 8 weeks after the increase of treatment dose there is not a moderate improvement in symptoms, another review should occur. Other treatment options should then be considered in consultation with a psychiatric specialist.
From our initial opening clinical case, Mr. George is a 44 year old male who you found to have major depression. Administration of a standard depression questionnaire (such as the PHQ – 9) found his depression to be of moderate severity. You started him on antidepressants. You see him 8 weeks later after starting the antidepressant medication and his appetite is back, he is sleeping well, and concentrating better at home and at work. He still feels tired but denies feeling depressed. He still has not assumed his normal social activities. You re-administer the same standard depression questionnaire, and conclude that he has achieved partial remission. Reassessment has found no issues with substance abuse or adherence issues with his medications. After this initial reassessment, which one of the following is the most appropriate first step in treatment options? (Choose the best answer.)
Continuation Phase Treatment
Patients who have been treated with antidepressant medications in the acute phase should be maintained with this regimen to prevent relapse. This “continuation phase” should last for 16 – 20 weeks after remission. “Psychiatric management” should continue in this phase. The American Psychiatric Association recommends the medication doses used in the acute phase be maintained in the continuation phase. There is increasing data to support the continued use of specific effective psychotherapy in this phase. The use of ECT in this phase has not been well researched. The frequency of visits in the continuation phase may vary. Stable patients may be seen once every 2 – 3 months. Patients in active psychotherapy may be seen several times a week.
Patients who remain stable throughout the continuation phase, and who are not candidates for the maintenance phase (e.g., recurrent relapsing chronic depression, etc.), can be considered candidates for discontinuation of treatment.
A 35 year old female returns for a follow visit after you have successfully treated her first episode of uncomplicated major depression. After 6 weeks of treatment with an antidepressant, all of her depressive symptoms have resolved. Based on the evidence, the total length of treatment with antidepressants should be at a minimum: (Choose the best answer.)
Maintenance Phase Treatment
Between 50 – 85% of patients with a single major depressive episode will have another episode. Maintenance phase treatment is designed to prevent recurrence. Issues to consider in using maintenance phase treatment are severity of episodes (e.g., suicidal ideation or attempts, psychotic symptoms, functional impairment); risk of recurrence (e.g., residual symptoms between episodes, number of recurrent episodes); comorbid conditions; side effects experienced with continuous treatment; or patient preference.
The same treatment that was effective in the acute and continuation phase should be continued in the maintenance phase. The doses of medication in the previous phases are usually maintained. The type of psychotherapy employed dictates the frequency of visits in the maintenance phase (e.g., cognitive behavioral therapy and interpersonal therapy decrease to once a month, while psychodynamic psychotherapy maintains the same previous frequency). Combination therapy (psychotherapy and pharmacotherapy) may be beneficial for some patients although it is not well studied. Patients with recurrent moderate or severe depressive episodes who don’t respond well to pharmacotherapy may be candidates for periodic ECT. Frequency of visits in the maintenance phase can vary as in the continuation phase.
The length of maintenance treatment that is optimal is unknown. Factors that may influence this period may be frequency and severity of recurrent episodes, persistence of symptoms after a period of recovery, tolerability of treatment, and patient preference. Some patients may require indefinite maintenance treatment.
For which one of the following patients is a trial of discontinuation of antidepressant medication appropriate? (Choose the best answer.)
Discontinuation of Active Treatment
The factors to discontinue treatment are based on the same considerations in deciding on using maintenance phase therapy: frequency and severity of recurrent episodes, dysthymic symptoms between episodes, the presence of other psychiatric disorders, the presence of chronic general medical disorders, or patient preference. If maintenance pharmacotherapy is discontinued, it is recommended to taper the medication over several weeks. Slow tapering may allow the physician to detect emerging symptoms and restore the medical management to full therapeutic doses. Discontinuation syndromes (e.g., mood disturbances, sleep, energy, and appetite) can appear much like relapses but are in fact due to lack of tapering of medications. Patients on short acting agents are more prone to discontinuation syndromes and should be tapered over longer periods of time. Signs and symptoms of relapse should again be reviewed with the patient once discontinuation of treatment has occurred.
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