The goal of acute treatment of MDD is remission of all symptoms. Since antidepressants may not achieve their maximum benefit for 1–2 months or longer, it is not unusual for a trial of therapy to last 8–12 weeks at therapeutic doses. The antidepressants are successful in achieving remission in about 30–40% of patients within a single trial of 8–12 weeks. If an inadequate response is obtained, therapy is often switched to another agent or augmented by addition of another drug. For example, bupropion, an atypical antipsychotic, or mirtazapine might be added to an SSRI or SNRI to augment antidepressant benefit if monotherapy is unsuccessful. Seventy to eighty percent of patients are able to achieve remission with sequenced augmentation or switching strategies. Once an adequate response is achieved, continuation therapy is recommended for a minimum of 6–12 months to reduce the substantial risk of relapse.
Approximately 85% of patients who have a single episode of MDD will have at least one recurrence in a lifetime. Many patients have multiple recurrences, and these recurrences may progress to more serious, chronic, and treatment-resistant episodes. Thus, it is not unusual for patients to require maintenance treatment to prevent recurrences. Although maintenance treatment studies of more than 5 years are uncommon, long-term studies with TCAs, SNRIs, and SSRIs suggest a significant protective benefit when given chronically. Thus, it is commonly recommended that patients be considered for long-term maintenance treatment if they have had two or more serious MDD episodes in the previous 5 years or three or more serious episodes in a lifetime.
It is not clear whether antidepressants are useful for all subtypes of depression. For example, patients with bipolar depression may not benefit much from antidepressants even when added to mood stabilizers. In fact, the antidepressants are sometimes associated with switches into mania or more rapid cycling. There has also been some debate about the overall efficacy of antidepressants in unipolar depression, with some meta-analyses showing large effects and others showing more modest effects. Although this debate is not likely to be settled immediately, there is little debate that antidepressants have important benefits for most patients.
Psychotherapeutic interventions such as cognitive behavioral therapy appear to be as effective as antidepressant treatment for mild to moderate forms of depression. However, cognitive behavioral therapy tends to take longer to be effective and is generally more expensive than antidepressant treatment. Psychotherapy is often combined with antidepressant treatment, and the combination appears more effective than either strategy alone.
B. Anxiety Disorders
After major depression, anxiety disorders represent the most common application of antidepressants. A number of SSRIs and SNRIs have been approved for all the major anxiety disorders, including PTSD, OCD, social anxiety disorder, GAD, and panic disorder. Panic disorder is characterized by recurrent episodes of brief overwhelming anxiety, which often occur without a precipitant. Patients may begin to fear having an attack, or they avoid situations in which they might have an attack. In contrast, GAD is characterized by a chronic, free-floating anxiety and undue worry that tends to be chronic in nature. Although older antidepressants and drugs of the sedative-hypnotic class are still occasionally used for the treatment of anxiety disorders, SSRIs and SNRIs have largely replaced them.
The benzodiazepines (see Chapter 22) provide much more rapid relief of both generalized anxiety and panic than do any of the antidepressants. However, the antidepressants appear to be at least as effective as, and perhaps more effective than, benzodiazepines in the long-term treatment of these anxiety disorders. Furthermore, antidepressants do not carry the risks of dependence and tolerance that may occur with the benzodiazepines.