Melatonin and agomelatine for prevention of winter depression

Why is this review important?

Many people in northern latitudes suffer from seasonal affective disorder (SAD), which occurs as a reaction to reduced sunlight. Three-quarters of those affected are women. Lethargy, overeating, craving for carbohydrates and depressed mood are common symptoms. In some people, SAD becomes a depression that seriously affects their daily lives. Up to two-thirds experience depressive symptoms every winter.

Who will be interested in this review?

• Anyone who has experienced winter depression.

• Relatives and friends of people who have experienced winter depression.

• General practitioners, psychiatrists and pharmacists.

• Professionals working in adult mental health services.

What questions does this review aim to answer?

Because of the seasonal pattern and high recurrence of SAD, melatonin/agomelatine could be used during fall and winter months to prevent the onset of depressed mood. The goal of this report is to examine whether benefits outweigh harms of melatonin/agomelatine when used in healthy people to prevent onset of SAD for those with a history of SAD who were free of symptoms when the preventive intervention started. To date, this question has not been examined in a systematic way and is of importance for those who have suffered winter depression. This is one of four reviews on the efficacy and potential harms of interventions to prevent SAD.

Which studies were included in the review?

We searched databases up to August 2015 for studies on melatonin/agomelatine for prevention of winter depression. Among 2986 records, we found no randomised controlled studies.

What does evidence from the review reveal?

Our literature search yielded no studies that addressed the efficacy of melatonin or agomelatine in preventing SAD, and we can make no recommendations in support of, or against, its use to treat individuals with SAD.

What should happen next?

Review authors recommend that future studies should evaluate the efficacy of agomelatine or melatonin in preventing SAD and should directly compare these interventions versus other effective treatments such as light therapy, antidepressants and lifestyle or psychological therapies to determine the best treatment option for prevention of SAD.

Authors' conclusions: 

No available methodologically sound evidence indicates that melatonin or agomelatine is or is not an effective intervention for prevention of SAD and improvement of patient-centred outcomes among adults with a history of SAD. Lack of evidence clearly shows the need for well-conducted, controlled studies on this topic. A well-conducted RCT of melatonin or agomelatine for prevention of SAD would assess the comparative benefits and risks of these interventions against others currently used to treat the disorder.

Read the full abstract...

Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD in the United States ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on agomelatine and melatonin as preventive interventions.


To assess the efficacy and safety of agomelatine and melatonin (in comparison with each other, placebo, second-generation antidepressants, light therapy, psychological therapy or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD.

Search strategy: 

We conducted a search of the Specialised Register of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDANCTR) to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We conducted a grey literature search (e.g. in clinical trial registries) and handsearched the reference lists of all included studies and pertinent review articles.

Selection criteria: 

To examine efficacy, we planned to include randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. To examine adverse events, we intended to include non-randomised studies. We planned to include studies that compared agomelatine versus melatonin, or agomelatine or melatonin versus placebo, any second-generation antidepressant (SGA), light therapy, psychological therapies or lifestyle changes. We also intended to compare melatonin or agomelatine in combination with any of the comparator interventions listed above versus the same comparator intervention as monotherapy.

Data collection and analysis: 

Two review authors screened abstracts and full-text publications against the inclusion criteria. Two review authors planned to independently extract data and assess risk of bias of included studies. We planned to pool data for meta-analysis when participant groups were similar and when studies assessed the same treatments by using the same comparator and presented similar definitions of outcome measures over a similar duration of treatment; however, we identified no studies for inclusion.

Main results: 

We identified 2986 citations through electronic searches and reviews of reference lists after de-duplication of search results. We excluded 2895 records during title and abstract review and assessed 91 articles at full-text level for eligibility. We identified no controlled studies on use of melatonin and agomelatine to prevent SAD and to improve patient-centred outcomes among adults with a history of SAD.