The American Psychiatric Association’s guidelines on treatment of major depression emphasize a well-coordinated approach to the treatment of depression. They call for physicians to establish a therapeutic relationship; evaluate functional impairment; decide between pharmacologic treatments, psychotherapy, or both; identify the patient’s treatment preferences; and carefully make decisions about the length of treatment.
Dr. Neil S. Skolnik and Dr. Curtis Olson
Acute Phase
The goal of the first phase of treatment is inducing remission with return to the patient’s baseline of functioning. Antidepressant medication should be considered for all patients; antidepressants have response rates of 50%-75%. Antidepressant medications have equal efficacy between and within classes. Choice should depend on patient preference, history of prior response, safety and tolerability, side effects, possible drug interactions, co-occurring psychiatric or medical conditions, and cost. A selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), mirtazapine, or bupropion is recommended as a starting point for most patients.
Common side effects of SSRIs and SNRIs include gastrointestinal upset, insomnia, and sexual dysfunction. Weight gain also is common with SSRIs. For patients experiencing sexual side effects, switching to bupropion should be considered. Bupropion can aid in smoking cessation and does not cause weight gain. However, bupropion is less effective than are SSRIs in patients with an anxiety component. Mirtazapine can cause sedation and weight gain but may be useful in patients with initial insomnia and weight loss.
Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are not first-line treatment choices because of side effects. TCAs cause sedation, weight gain, and anticholinergic effects, and serious cardiac arrhythmias. MAOIs carry the risk of hypertensive crisis and serotonin syndrome.
Psychotherapy is an important component of depression treatment, but it can be used as monotherapy in patients with mild to moderate symptoms. Evidence supports the use of cognitive-behavioral therapy (CBT), interpersonal psychotherapy, psychodynamic therapy, and problem-solving therapy. The lack of side effects makes psychotherapy especially useful in pregnant or lactating patients, and with patients wishing to become pregnant.
The combination of pharmacotherapy and psychotherapy should be considered for initial treatment in patients with moderate to severe depression. Electroconvulsive therapy can be first-line therapy for severely depressed patients with psychotic features, catatonia, or who are at suicidal risk.
Exercise is recommended as monotherapy for mildly depressed patients, However if it is ineffective after several weeks, other treatment modalities should be pursued. Alternative treatment options, including St. John’s wort, S-adenosylmethionine (SAM-e), and omega-3 fatty acid have demonstrated some efficacy, but data are lacking for a recommendation. Folate supplementation shows efficacy when combined with fluoxetine in young women. Bright-light therapy is an option, but monitoring for mania or hypomania is required. Acupuncture is not currently recommended.
Remission is defined as at least 3 weeks of the absence of sad mood and reduced interest and no more than three remaining depressive symptoms. Some patients will show improvement after 1-2 weeks of treatment, but generally 4-6 weeks are required.
The starting dose of medication should be increased incrementally while observing symptom improvement. Patients who show some improvement in the first few weeks should be encouraged to continue with the medication for at least 4-8 weeks before changing therapies. If no improvement is observed in the first few weeks of treatment, however, it is appropriate to consider changing to another antidepressant.
In patients who do not show a complete response, augmentation should be considered. Addition of a non-MAOI medication from a different class or a non-antidepressant such as lithium, thyroid hormone, or a second-generation antipsychotic may be beneficial. Additional strategies with less evidence to support them include adding an anticonvulsant, a psychostimulant, omega-3 fatty acids, or folate. Adding an anxiolytic or sedative-hypnotic in patients with a pronounced anxiety component should be considered.
Patients should be monitored closely during treatment. The frequency is variable and will depend on the severity of the episode, social supports, and progression of symptoms. Suicide risk should be assessed at every encounter.
Continuation
Following the acute phase, all patients should receive continuation therapy for 4-9 months. Relapse is common in the first 6 months after remission, especially among those with more severe initial episodes. Treatment should be continued at the same dose, intensity, and frequency that were effective during the acute phase. If relapse occurs, acute phase therapy must be reinstated, usually with increased medication dosage.
Maintenance
Maintenance phase treatment may be lifelong and is intended for patients having had three or more prior major depressive episodes. The same medication dose that was successful in the acute and continuation phase should be continued. The frequency of psychotherapy may be decreased, whether it is monotherapy or combination therapy.