Initial treatment choices to achieve sustained response in major depression: a systematic review and network meta-analysis

Abstract

Major depression is often a relapsing disorder. It is therefore important to start its treatment with therapies that maximize the chance of not only getting the patients well but also keeping them well. We examined the associations between initial treatments and sustained response by conducting a network meta-analysis of randomized controlled trials (RCTs) in which adult patients with major depression were randomized to acute treatment with a psychotherapy (PSY), a protocolized antidepressant pharmacotherapy (PHA), their combination (COM), standard treatment in primary or secondary care (STD), or pill placebo, and were then followed up through a maintenance phase. By design, acute phase treatment could be continued into the maintenance phase, switched to another treatment or followed by discretionary treatment. We included 81 RCTs, with 13,722 participants. Sustained response was defined as responding to the acute treatment and subsequently having no depressive relapse through the maintenance phase (mean duration: 42.2±16.2 weeks, range 24-104 weeks). We extracted the data reported at the time point closest to 12 months. COM resulted in more sustained response than PHA, both when these treatments were continued into the maintenance phase (OR=2.52, 95% CI: 1.66-3.85) and when they were followed by discretionary treatment (OR=1.80, 95% CI: 1.21-2.67). The same applied to COM in comparison with STD (OR=2.90, 95% CI: 1.68-5.01 when COM was continued into the maintenance phase; OR=1.97, 95% CI: 1.51-2.58 when COM was followed by discretionary treatment). PSY also kept the patients well more often than PHA, both when these treatments were continued into the maintenance phase (OR=1.53, 95% CI: 1.00-2.35) and when they were followed by discretionary treatment (OR=1.66, 95% CI: 1.13-2.44). The same applied to PSY compared with STD (OR=1.76, 95% CI: 0.97-3.21 when PSY was continued into the maintenance phase; OR=1.83, 95% CI: 1.20-2.78 when PSY was followed by discretionary treatment). Given the average sustained response rate of 29% on STD, the advantages of PSY or COM over PHA or STD translated into risk differences ranging from 12 to 16 percentage points. We conclude that PSY and COM have more enduring effects than PHA. Clinical guidelines on the initial treatment choice for depression may need to be updated accordingly.

Keywords: Major depression; cognitive behavioral therapy; combination therapy; maintenance treatment; network meta-analysis; pharmacotherapy; psychotherapy; sustained response; treatment choice.

Figure 1

Trial designs to examine maintenance treatment for depression. MDE – major depressive episode, COM – combination therapies, PHA – pharmacotherapies, PSY – psychotherapies, nat – discretionary treatment, R – randomization

Figure 2

PRISMA flow chart. MDD – major depressive disorder, CBT – cognitive behavioral therapy

Figure 3

Network diagram for sustained response. COM – combination therapies, PHA – pharmacotherapies, PSY – psychotherapies, STD – standard treatment in primary or secondary care, nat – discretionary treatment. The size of the node is proportionate to the number of participants allocated to that node; the width of the line is proportionate to the number of studies examining that comparison.

Figure 4

Ranked forest plot for sustained response. NMA – network meta‐analysis, OR – odds ratio, CI – confidence interval, COM – combination therapies, PHA – pharmacotherapies, PSY – psychotherapies, STD – standard treatment in primary or secondary care, nat – discretionary treatment

Figure 5

Ranked forest plot for all‐cause discontinuation. NMA – network meta‐analysis, OR – odds ratio, CI – confidence interval, COM – combination therapies, PHA – pharmacotherapies, PSY – psychotherapies, STD – standard treatment in primary or secondary care, nat – discretionary treatment

Figure 6

Ranked forest plot for sustained response with intervention subtypes. NMA – network meta‐analysis, OR – odds ratio, CI – confidence interval, STD – standard treatment in primary or secondary care, DYN – psychodynamic therapy, AD – protocolized antidepressant pharmacotherapy, MI – motivational interviewing, TAU – treatment as usual, nat – discretionary treatment, SST – social skills training, CBT – cognitive behavioral therapy, IPT – interpersonal therapy, Family – family therapy, BA – behavioral activation therapy, SUP – non‐directive supportive therapy, LRT – life review therapy, PST – problem‐solving therapy, 3W – third‐wave cognitive behavioral therapy, NT – no treatment, pl – pill placebo