Does Insight Affect the Efficacy of Antipsychotics in Acute Mania?

Abstract

Patients having an acute manic episode of bipolar disorder often lack insight into their condition. Because little is known about the possible effect of insight on treatment efficacy, we examined whether insight at the start of treatment affects the efficacy of antipsychotic treatment in patients with acute mania. We used individual patient data from 7 randomized, double-blind, placebo-controlled registration studies of 4 antipsychotics in patients with acute mania (N = 1904). Insight was measured with item 11 of the Young Mania Rating Scale (YMRS) at baseline and study endpoint 3 weeks later. Treatment outcome was defined by (a) mean change score, (b) response defined as 50% or more improvement on YMRS, and (c) remission defined as YMRS score less than 8 at study endpoint. We used multilevel mixed effect linear (or logistic) regression analyses of individual patient data to assess the interaction between baseline insight and treatment outcomes. At treatment initiation, 1207 (63.5%) patients had impaired or no insight into their condition. Level of insight significantly modified the efficacy of treatment by mean change score (P = 0.039), response rate (P = 0.033), and remission rate (P = 0.043), with greater improvement in patients with more impaired insight. We therefore recommend that patients experiencing acute mania should be treated immediately and not be delayed until patients regain insight.

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

“…A very important posthoc analysis of individual patient data reported that patients with impaired insight (as measured with the use of item 11 of the YMRS) responded better; therefore treatment should be initiated immediately and the therapist should not wait until the patient gains sufficient insight (Welten et al, 2016). …”

Two randomized, double-blind, placebo-controlled trials and one open-label, long-term trial of brexpiprazole for the acute treatment of bipolar mania

“…The post hoc analysis (as conducted by Welten et al, 2016 ) of both studies pooled showed that baseline level of insight significantly modified the efficacy of treatment as measured by YMRS mean change score ( p = 0.0013) and response rate ( p = 0.0298), with greater improvement in patients with “impaired” or “no insight” than in patients with “excellent insight.”…”

“…When pooling the studies and presenting baseline insight scores by region, a total of 282 (63.2%) US patients had “excellent insight,” 101 (22.6%) had “good insight,” 40 (9.0%) had “moderate insight,” 17 (3.8%) had “poor insight,” and six (1.3%) had “no insight.” Thus, insight was impaired or absent (as defined by Welten et al, 2016 ) in 36.8% of the US patients. In contrast, insight was impaired or absent in 95.1% of the EU patients: 10 (4.9%) EU patients had “excellent insight,” 52 (25.6%) had “good insight,” 90 (44.3%) had “moderate insight,” 44 (21.7%) had “poor insight,” and seven (3.4%) had “no insight.”…”

“…Insight was impaired or absent at baseline in 95.1% of EU patients, but only in 36.8% of US patients. This is potentially an important finding, as baseline insight has been shown to modify the efficacy of dopamine/serotonin/noradrenaline receptor antagonists in acute mania, with treatment being more efficacious in patients with impaired or no insight than in patients with excellent insight ( Welten et al, 2016 ). Similarly to Welten et al, we found that that the baseline level of insight significantly modified the efficacy of treatment as measured by YMRS mean change score ( p = 0.0013) and response rate ( p = 0.0298), with greater improvement in patients with impaired or no insight (predominantly EU patients) than in patients with excellent insight (predominantly US patients).…”

“…Prompted by findings by Welten et al (2016) , a post hoc analysis was performed, assessing whether YMRS item 11 (“insight”) modifies the effect of brexpiprazole compared to placebo on the mean change in YMRS score from baseline to endpoint.…”