Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder

Abstract

Bright light therapy is an evidence-based treatment for seasonal depression, but there is limited evidence for its efficacy in nonseasonal major depressive disorder (MDD). OBJECTIVE To determine the efficacy of light treatment, in monotherapy and in combination with fluoxetine hydrochloride, compared with a sham-placebo condition in adults with nonseasonal MDD. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-and sham-controlled, 8-week trial in adults (aged 19-60 years) with MDD of at least moderate severity in outpatient psychiatry clinics in academic medical centers. Data were collected from October 7, 2009, to March 11, 2014. Analysis was based on modified intent to treat (randomized patients with Ն1 follow-up rating). INTERVENTIONS Patients were randomly assigned to (1) light monotherapy (active 10 000-lux fluorescent white light box for 30 min/d in the early morning plus placebo pill); (2) antidepressant monotherapy (inactive negative ion generator for 30 min/d plus fluoxetine hydrochloride, 20 mg/d); (3) combination light and antidepressant; or (4) placebo (inactive negative ion generator plus placebo pill). MAIN OUTCOMES AND MEASURES Change score on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the 8-week end point. Secondary outcomes included response (Ն50% reduction in MADRS score) and remission (MADRS score Յ10 at end point). RESULTS A total of 122 patients were randomized (light monotherapy, 32; fluoxetine monotherapy, 31; combination therapy, 29; placebo, 30). The mean (SD) changes in MADRS score for the light, fluoxetine, combination, and placebo groups were 13.4 (7.5), 8.8 (9.9), 16.9 (9.2), and 6.5 (9.6), respectively. The combination (effect size [d] = 1.11; 95% CI, 0.54 to 1.64) and light monotherapy (d = 0.80; 95% CI, 0.28 to 1.31) were significantly superior to placebo in the MADRS change score, but fluoxetine monotherapy (d = 0.24; 95% CI, −0.27 to 0.74) was not superior to placebo. For the respective placebo, fluoxetine, light, and combination groups at the end point, response was achieved by 10 (33.3%), 9 (29.0%), 16 (50.0%), and 22 (75.9%) and remission was achieved by 9 (30.0%), 6 (19.4%), 14 (43.8%), and 17 (58.6%). Combination therapy was superior to placebo in MADRS response (β = 1.70; df = 1; P = .005) and remission (β = 1.33; df = 1; P = .02), with numbers needed to treat of 2.4 (95% CI, 1.6 to 5.8) and 3.5 (95% CI, 2.0 to 29.9), respectively. All treatments were generally well tolerated, with few significant differences in treatment-emergent adverse events. CONCLUSIONS AND RELEVANCE Bright light treatment, both as monotherapy and in combination with fluoxetine, was efficacious and well tolerated in the treatment of adults with nonseasonal MDD. The combination treatment had the most consistent effects. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00958204

When our body clocks run late: does it make us depressed?

“…This large antidepressant effect supports the theory of a causal role of phase delays in depression and more specifically, delayed melatonin offset. Combined, bright light and antidepressant provided even more benefit than either antidepressant or bright light alone (17). Indeed, the two treatments appeared possibly synergistic.…”

“…Growing proof of the antidepressant power of early morning bright light is now available. Most recently, Lam et al compared randomized early morning bright light treatment with a dummy treatment, with fluoxetine (a standard antidepressant), and with all-placebo treatment (17). Effects of early morning bright light alone over 8 weeks produced several times as much benefit as the antidepressant drug.…”

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments

“…18 Light therapy is generally well tolerated, 17 with common side effects being eye strain, headache, agitation, nausea, and sedation. 19 Since 2009, 2 meta-analyses, 16,20 4 systematic reviews 17,19,21,22 and 3 RCTs [23][24][25] have been generally confirmatory of recommendations in the 2009 guidelines (see Suppl. Table S1).…”

“…20 In addition, an RCT reported that LT monotherapy and LT combined with fluoxetine were superior to placebo in nonseasonal MDD, with the combined treatment showing the most consistent effects. 23 Similarly, medication paired with chronotherapeutic techniques (LT, sleep deprivation, and sleep time stabilization) led to superior remission rates in nonseasonal MDD compared to medication combined with exercise at both 9-week and 29-week follow-up. 24,27 In summary, the updated evidence continues to support LT as a first-line monotherapy for seasonal depression and as a second-line monotherapy or adjunctive treatment for mild to moderate nonseasonal MDD ( Table 2).…”

Use of Light Therapy by Office-Based Physicians

“…LT has been employed for the treatment of seasonal affective disorder (SAD) in particular [5,6]. However, studies have also been conducted on the effectiveness of LT for other psychiatric disorders, such as non-seasonal major depressive disorder [7,8], premenstrual dysphoric disorder [9,10], antepartum depression [11], circadian disturbances in shift workers [12,13], jet lag syndrome [14,15], alcohol withdrawal syndrome [16], negative symptoms in schizophrenia [17,18], cognitive and behavioural symptoms in Alzheimer's disease [19], and Parkinson's disease [20,21]. …”