ILLUSTRATIVE CASE
A healthy 33-year-old woman presents to your office with a 3-month history of depressed mood. She reports difficulty concentrating, insomnia, decreased appetite, and generalized fatigue. She denies suicidal or homicidal ideation, substance misuse, or history consistent with manic episodes. Her vital signs are normal and overall her physical examination is unremarkable, although the patient is tearful when discussing her mood. Using shared decision-making, you and the patient determine it is appropriate to initiate pharmacotherapy. Is there a role for combination pharmacotherapy to treat this patient’s acute depression?
Unipolar depression is a highly prevalent condition, estimated to affect 21% of US adults at some point in their lifetime.2 It is the second leading cause of disability in the United States, with an estimated economic impact of more than $200 billion annually.3
The diagnosis of unipolar depression is based on the criteria set forth in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and commonly includes depressed mood, anhedonia, sleep disturbance, appetite changes, fatigue, feelings of worthlessness or guilt, decreased ability to concentrate, and psychomotor symptoms occurring over at least a 2-week period.4 Symptoms represent a decrease in functioning from previous levels that are not attributable to another medical condition or substance, and must not include a history of past manic or hypomanic episodes. Thoughts of death and suicidal ideation are common.
Several systematic reviews and meta-analyses have shown that a combination of psychotherapy and pharmacotherapy is more efficacious for treatment of unipolar depression than either therapy alone.5-7 As for which medication is most effective and tolerable, multiple systematic reviews and meta-analyses have not demonstrated superiority of 1 second-generation antidepressant (eg, SSRIs, SNRIs) over another.7,8
General practice guidelines support titration of the dose or a switch in monotherapy medications until treatment response is achieved, prior to initiation of a second agent. When an adjunctive medication is considered, there are several options: a second-generation antipsychotic, a second antidepressant from a different class, thyroid hormone, and lithium. Special consideration is given to the adverse effect profile and potential tolerability; higher adverse effect profiles are observed with second-generation antipsychotics and lithium.9
It is not common practice to initiate 2 antidepressants for a new diagnosis of acute depression. The systematic review and meta-analysis conducted by Henssler et al1 attempted to provide evidence to support the efficacy and tolerability of specific antidepressants when used in combination for initial treatment of acute depression. Of note, a 2008 national survey showed that a majority of psychotropic medications in the United States are prescribed by primary care physicians (73.6%) rather than psychiatrists, making this analysis relevant to family physicians.10
STUDY SUMMARY
Combination pharmacotherapy yields superior efficacy in acute depression
This 2022 systematic review and meta-analysis (39 randomized clinical trials [RCTs]; N = 6751) compared the efficacy and tolerability of monotherapy to combination therapy in the treatment of patients with acute depression.1 The study also aimed to address which specific combination therapies were superior.
Continue to: Selected RCTs included...
