New review of clinical studies shows that antidepressants are effective, but must be given a chance to work

Depression affects millions of people worldwide.1 ref 1A It can be severely disabling, impacting general health and wellbeing, and performance at work and school.2 ref 2A Like other mental illnesses, depression can have a profound effect on social life. In fact, one in two people suffering from mental illness say they have lost friends and social supportref 3A and that their condition has affected relationships with family members.3 ref 3B

According to the South African Depression and Anxiety Group (SADAG) as many as 1 in 5 South Africans may experience a severe episode of depression at least once in their lifetimeref 3C and women are twice as likely to suffer from depression than men.3 ref 3D The challenges faced by South African youth make them particularly vulnerable. Conflict with parents, divorce, broken families, being orphaned, having an unemployed father or chronically ill parent, child abuse, lack of emotional support, domestic violence, alcohol, substance abuse, and dissatisfaction with body image may all increase the risk of depressive symptoms among young people.4  ref 4A, B

It is not surprising that depression has a considerable impact on the economy, both in terms of having to take time off work and low productivity at work. A study from the London School of Economics published in 2016 estimated that depression cost the South African economy more than R210 billion annually.5  ref 5 D,E This figure may underestimate the true costs of depression where the illness remains undiagnosed,ref 5A or where people may be reluctant to disclose their diagnosis for fearref 5B of stigma.5  ref 5C

According to the World Health Organisation, globally fewer than half of those affected by depression ever receive treatment.6 ref 6A This shocking figure may be even lower for South Africans. SADAG estimates that only around 1 in 6 people with any mental illness receive treatment!7 ref 7A

A further problem is that even among those South Africans who do get treatment, only around one third continue to take it for longer than 4 months,ref 2B which is just not long enough to treat symptoms and keep them away.2  ref 2C Possible reasons for discontinuing might include feeling better, side effects, fear of addiction and feeling that it’s not working.2  ref 2D

For a long time there has been debate and concern as to how effective and safe antidepressants really are.1  ref 1B Partly this might be because it takes time to trigger changes in brain function,ref 8A so the full effect of the antidepressant is only apparent after a few weeks of treatment ref 1C.1,8 In contrast, side effects can appear within a few days, long before the therapeutic effects appear.8  ref 8B

However, a new review of clinical studies published in the Lancet medical journal has provided convincing data that if given sufficient time, antidepressants do work,ref 1D and the benefits can outweigh the potential for side effects.ref 1E The review was published in the Lancet, a medical journal with global readership and one that publishes the most important advances in medicine.9  ref 9A In one of the most comprehensive reviews of published and unpublished data to date,ref 1F,G the researchers reviewed 522 trials of 21 different antidepressants, including 116 477 adults with depressionref 1F who were treated for around 8 weeksref 1H.1 They defined efficacy as 50% or greater reduction in symptoms ref 1I and also looked at remissionref 1J, a measure of complete resolution of symptoms.Discontinuation of treatment and patient acceptability were compared as an indicator of how well the treatments were tolerated over time.1  ref 1I All of the antidepressant types were more effective over time than placeboref 1K, but some were more effective,ref 1L different odds ratios better tolerated and more acceptable to patientsref 1M,O than others.1 One of these was agomelatine. It was among the most effective,ref 1N but stood out because it was also associated with a very low potential for side effects,ref 1O,P In terms of study drop-outs, agomelatine was one of only two antidepressants that was actually better tolerated than placebo.1  ref 1E

Agomelatine is an unusualref 10 K antidepressant, because, in addition to an effect on some of the more traditional chemical pathways in the brain (e.g., serotonin and dopamine),ref 10 J it is the only one that works by affecting the same areas of the brain as melatonin, ref 10 A,C the hormone associated with normal sleep.ref 10 B However, unlike the majority of other commonly used antidepressants, it does not directly increase serotonin.10 ref 10 C This mechanism of action may account for not only its effectiveness in treating the symptoms of depressionref 10 D and low tendency to cause side effectsref 10 E,F or withdrawal symptoms,ref 10 G but also its tendency to improve anxiety and quality of sleep.ref 10 A Sleep is often adversely affected in people with depression.ref 10 H In contrast, agomelatine is unlikely to cause sedationref 10 I and, unlike many other antidepressants, it is not associated with sexual problems or weight gainref 10 E.10

This large, well designed and thorough review of antidepressants is encouraging and provides reassurance that, if they seek help from their doctor or local clinic, effective treatment is available for people with depression. However, it is important to remember that once an appropriate medication has been started, it is necessary to stay on it in order to give it a chance to work.

  1. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018. Published online.
  2. Slabbert FN, Harvey BH, Brink CB, Lubbe MS. Prospective analysis of the medicine possession ratio of antidepressants in the private health sector of South Africa, 2006-2011. S Afr Med J 2015; 105(2): 139-144.
  3. South African Depression and Anxiety Support Group (SADAG). Depression – the silent killer. March 2017. Available at: Accessed 16 March 2018.4. Nduna M, Jewkes RK, Dunkle KL, et al. Prevalence and factors associated with depressive symptoms among young women and men in the Eastern Cape Province, South Africa. J Child Adolescent Mental Health 2013; 25(1): 43-54.
  4. Evans-Lacko S, Knapp M. Global patterns of workplace productivity for people with depression: absenteeism and presenteeism costs across eight diverse countries. Soc Psychiatry Psychiatr Epidemiol 2016; 51: 1525-1537.
  1. World Health Organisation (WHO). Depression. 22 March 2018. Available at: Accessed 6 June 2018.
  2. South African College of Applied Psychology (SACAP). Maternal health in South Africa: whose problem is it? Published online October 28 2013. Available at: Accessed 16 March 2018.
  3. Moch S. Analysing antidepressants. SAJP 2009; May: 19-25.
  4. McKibbon KA, Wilczynski NL, Haynes RB. What do evidence-based secondary journals tell us about the publication of clinically important articles in primary healthcare journals? BMC Med 2004; 2:33.    DOI:10.1186/1741-7015-2-33
  5. Deakin B. Agomelatine: a new treatment for depression. Future Prescriber 2009; 10(2): 14-19.