Psychotherapies
As first-line treatment for patients with MDD, no clear benefit exists for medication over psychological therapy, specifically evidence-based therapies (EBTs). 11,12 The best studied and known EBTs are cognitive behavioral therapy for depression (CBT-D) and interpersonal therapy (IPT). Both are brief, targeted therapies with clear rules and expectations as opposed to more traditional long-term therapies, such as insight-oriented psychotherapy. These therapies generally involve weekly meetings with a therapist for about 12 weeks. They both require the patient to do homework during the therapy period; therefore, it is important for the patient to be a willing participant in these treatments to receive the maximum benefit. Many patients prefer not taking medication for depression, so psychotherapy is an excellent option. It is widely believed, although without clear evidence at this time, that the combination of medications and EBT offers improved outcomes. There are no contraindications to combining antidepressant medication and EBT.
Medications
Given the realities of practice settings and patient preferences, medication is often the most practical first-line treatment choice. The newer antidepressant medications are the most likely choices in the primary care setting for treating depression, because they offer effective treatment with less severe adverse effects (AEs) and are much safer than the early tricyclic antidepressant and monoamine oxidase inhibitor medications. There are numerous metaanalyses comparing the effectiveness of the commonly prescribed newer antidepressants that consistently show there is no absolutely best choice antidepressant. A number of studies have tried to identify predictors of response for a particular antidepressant, but these have not yielded clinically significant results. Additionally, there is little difference between an antidepressant’s rate of response and tolerability on a population scale. 13 Therefore, it is the AE profile and alternate uses that usually drive the choice of which to use for a particular patient.
Before discussing antidepressant medications with patients, it is important to note the FDA-required black box warning for increased risk of suicidal ideation in young people aged ≤ 24 years. The data that led to this warning did not show an increased risk of suicide. 14 In patients aged > 24 years, there is no difference in risk of suicidal ideation, and in patients aged > 65 years, the risk of suicidal ideation decreases with the start of antidepressant medication. 1
SSRIs
Selective serotonin reuptake inhibitors (SSRIs) are a common first-line treatment for MDD. Of interest, all SSRIs share the same mechanism of action (MOA), so failure of a single agent does not preclude a trial of a second agent of the same class, because the chance of response is essentially the same as switching the patient to another class. However, after a second failure, there is less chance of response to another SSRI. 5 These agents are used for depression, anxiety (long term not acute), posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder. The AEs include nausea, headache, insomnia, dry mouth, and loss of emotion. Other than feeling emotionally blunted, most of these AEs are usually temporary and resolve in days. Sexual dysfunction is often the AE of SSRIs that draws primary concern from patients. The most frequently experienced sexual AE is delayed orgasm. A review of FDA package inserts showed rates from 7% (sertraline) to as high as 28% (high-dose paroxetine).16,17 Impotence or decreased libido is often more concerning for patients and occurs at 3% to 6%. A common concern for patients is weight gain, and SSRIs are considered weight neutral. There has been no demonstrated benefit from combining these medications or using them with selective serotonin norepinephrine reuptake inhibitors (SNRIs), which only exposes patients to increased risk of AEs.