Can-SAD

Published

Lam RW, et al. "The Can-SAD study: A randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder". The American Journal of Psychiatry. 2006. 165(5):805-812.
PubMed • Full text • PDF

Clinical Question

Among patients with seasonal affective disorder, how does light therapy compare with fluoxetine for clinical response and remission rates?

Bottom Line

In this small study of patients with major depressive episodes with a winter pattern, light therapy was similar to fluoxetine in terms of reducing patients' self-reported depression scores. Light therapy is a reasonable first-line therapy for seasonal affective disorder.

Major Points

Trials in the late 1990s demonstrated the efficacy of light therapy in the treatment of seasonal affective disorder (SAD). Large head-to-head comparisons of light therapy versus antidepressants were lacking.

Published in 2006, the Can-SAD study randomized 96 patients with SAD to light therapy or fluoxetine therapy in a double-blind fashion. Of those randomized, 81 completed the study. Patients at baseline were severely depressed by the Hamilton Depression Rating scale with a mean score of 30. At 8 weeks of follow-up, both groups had improvements in their depression, with scores correlating with mild severity (mean score of 12). Both groups experienced a similar frequency of adverse events, with about a third of each group experiencing a self-reported severe adverse event. The SSRI group had more frequent reports of agitation, sleep disturbances, and palpitations. This trial is limited by is under-reporting of trial design (eg, goal enrollment based upon power calculations), small size, and incomplete reporting of adverse event details.

A 2011 Cochrane meta-analysis found light therapy to be equivalent to SSRI therapy in SAD, though this was based on two trials only.

Guidelines

American Psychiatric Association Major Depression (2010, adapted)

• Light therapy appears to be effective for SAD and nonseasonal MDD. It is low-risk and low-cost. (No specific grading or recommendations given.)

Design

• Multicenter, double-blind, randomized, controlled trial
• N=81
  • Light therapy (n=41)
  • Fluoxetine (n=40)
• Setting: Four centers in Canada
• Enrollment: Three winter seasons (September 15-February 15) 2000-2003
• Follow-up: 8 weeks
• Analysis: Intention-to-treat
• Primary outcome: Hamilton Depression Scale score

Population

Inclusion Criteria

• 18-65 years
• Major depressive episodes with a winter pattern as determined by a modified Structured Clinical Interview for DSM-IV
• Hamilton Depression Rating Scale score ≥20 if 17 items or ≥14 if 17 items if score on 24 item was ≥23

Exclusion Criteria

• Pregnant or lactating
• Sexually active women without effective contraception
• Serious suicidal risk by the judgment of the investigator
• Meeting DSM-IV criteria for organic mental disorders, substance use disorders in the prior year, schizophrenia, paranoid disorder, delusional disorder, psychotic disorder, bipolar I disorder, panic disorder, GAD not otherwise concurrent with major depressive episodes
• Unstable, serious medical illness
• Retinal disorder precluding treatment with light therapy
• Severe allergies or multiple drug adverse reactions
• Use of other psychotropic medications (including St. John's wort or melatonin)
• Beta blocker therapies
• Use of antidepressants or mood-altering medications in prior week
• Prior treatment with fluoxetine or light therapy
• CBT or interpersonal psychotherapy in prior 3 months
• "Shift work" or traveling south during the protocol

Baseline Characteristics

From the light therapy group.

• Demographics: Female 64.6%, age 42.3 years, married 50%
• Psychiatric diagnoses and history: Bipolar II disorder 4.2%, prior psychiatric contact 27.1%, prior hospitalization 4.2%, family history of mood disorders 41.7%, previous antidepressants 45.8%, previous psychotherapy 22.9%
• SAD details: Atypical features 31.3%, prior episodes 11, CGI severity 4.2, Global Assessment of Functioning score 57.2
• Hamilton Depression Rating Scale score:
  • Total (24 items): 30.2
  • Typical symptoms (17 items): 17.3
  • Atypical symptoms (7 items): 13.0
• Beck Depression Inventory II: 24.5

Interventions

• 1 week of sleep adjustment in which patients were instructed to sleep only between 10PM and 8AM
• Patients who had <25% improvement in their depression scores were randomized to a group for 8 weeks:
  • Light therapy - 10,000 lux fluorescent light box at 14 inches from the corena for 30 min between 7-8AM
  • SSRI - Fluoxetine 20 mg PO qday between 7-8AM
• Both groups were given placebo agent for the other arm

Outcomes

Presented as light therapy vs. fluoxetine at 8 weeks except where noted.

Primary Outcome

Hamilton Depression Rating Scale score

Total score: ≤9 not depressed; 10-19 mildly depressed; 20-29 moderately depressed; ≥30 severely depressed.

Total (24 items): 11.6 vs. 11.6 (NS)

Typical symptoms (17 items): 6.4 vs. 6.5 (NS)

Atypical symptoms (7 items): 5.2 vs. 5.1 (NS)

Secondary Outcomes

Beck Depression Inventory-I

0-13 minimal depression; 14-19 mild depression, 20-28 moderate depression; 29-62 severe depression.

9.1 vs. 11.2

Primary outcome at 1 week

Total (24 items): 20.7 vs. 22.2 (P<0.05)

Adverse Events

Any

77% vs. 75%

Severe, by self-rating: 33% vs. 35%

Any increase from baseline

Abdominal pain: 6.3% vs. 8.3%

Nausea: 4.2% vs. 10.4%

Diarrhea: 4.2% vs. 10.4%

Constipation: 8.3% vs. 6.3%

Decreased appetite: 14.6% vs. 14.6%

Increased appetite: 8.3% vs. 14.6%

Weight loss: 2.1% vs. 6.3%

Anxiety: 12.5% vs. 25.0%

Nervousness: 12.5% vs. 10.4%

Agitation: 0% vs. 12.5% (P<0.05)

Tremor: 2.1% vs. 6.3%

Irritability: 4.2% vs. 8.3%

Sleepiness: 8.3% vs. 12.5%

Increased sleep: 12.5% vs. 18.8%

Decreased sleep: 22.9% vs. 20.8%

Sleep disturbance: 2.1% vs. 29.2% (P<0.01)

Headache: 16.7% vs. 10.4%

Decreased sex drive: 14.6% vs. 16.7%

ED in males: 4.7% vs. 6.3%

Delayed orgasm in women: 0% vs. 6.3%

Faint feeling: 6.3% vs. 0%

Palpitations: 0% vs. 10.4% (P<0.05)

Sweating: 6.3% vs. 10.4%

Muscle pain: 12.5% vs. 12.5%

Weakness/fatigue: 16.7% vs. 16.7%

Rash: 0% vs. 6.3%

Dry mouth: 18.8% vs. 14.6%

Flushing: 6.3% vs. 4.2%

Dropout

8 vs. 7 participants (P=1.00)

Due to an adverse event: 1 vs. 2 participants (P=1.00)

Criticisms

• Small study
• The authors did not report their power calculation or if they met their enrollment goal
• No report of what constituted a severe adverse event

Funding

• Canadian Institutes of Health Research (CIHR) grant
• CIHR/Wyeth Postdoctoral Fellowship Award
• Uplift Technologies provided light therapy boxes
• Authors with multiple financial disclosures