Is it possible to prevent the onset of depressive disorders in people who do not currently have a disorder?

In the 1970s this was considered impossible (Lobel & Hirschfeld, 1984). Because the causes of depression are unknown, the mainstream idea was that it was not possible with the knowledge at that time to prevent it. Nowadays we know that this reasoning is not correct and that it is possible to prevent depressive disorders in some cases. It is not necessary to understand the causes of a disorder before one can do a randomized trial on preventing it.

In this blog, I will give a brief overview of the current knowledge on prevention of depression, which I also present in the webinar that you can watch below. You can also catch up on all of blogs and webinars in #DepressionSolvingTheToll series.

How to reduce the impact of depression at the population level?

Depression is an important problem from a public health perspective, because of the very high prevalence ratesacross the world, the high levels of personal suffering in patients and their families, and the enormous costs associated with depression. There are about 280 million people across the world with a depressive disorder, and 5.6% of all ‘years lived with disability’ can be attributed to depression (World Health Organization, 2022). The total costs are estimated to be nearly US$1 trillion per year (Chisholm et al., 2016), mostly because of production losses. Furthermore, current treatments are effective, but can only reduce the disease burden of depression by about one third, even in optimal conditions of 100% uptake and delivery of evidence-based treatments (Andrews et al., 2004).

It is important to continue to treat people with depression with these evidence-based therapies, because that can reduce the personal suffering and the disease burden at the population level considerably. But there are several other approaches that can be used to reduce the disease burden of depression at the population level:

• One approach is to develop more effective treatments.
• Another is to improve the uptake of treatments because many people with depression currently receive no treatment. This is especially important in low- and middle-income countries (Cuijpers, 2023), where 80% of the world’s population live and where evidence-based treatments are extremely scarce, but also in high-income countries because the uptake there is also low.

I will discuss these solutions to reduce the disease burden of depression in other blogs and webinars in this series

Prevention of depression

Another approach that may lead to a reduction of the disease burden at the population level is prevention. If we can prevent the onset of depression altogether, that will have a considerable impact on the disease burden of depression. There are three types of prevention (Mrazek and Haggerty, 1994; Institute of Medicine, 2009; National Academies of Sciences, Engineering, and Medicine, 2019):

1. Universal prevention, aimed at a whole population, regardless of its risk status (such as school programs, or mass media campaigns);
2. Selective prevention, aimed at high risk groups (such as children of depressed parents, unemployed people, caregivers of people with general medical disorders, and people with general medical disorders themselves); and
3. Indicated prevention, aimed at people with some symptoms but not yet meeting criteria for a full disorder. Interventions aimed at people with existing disorders are not considered to be prevention, but treatment.

Advantages and disadvantage of different prevention types

Each type of prevention has its own advantages and disadvantages (Cuijpers, 2023).

1. Universal prevention (advantages and disadvantages)

• An important advantage of universal prevention is that stigma is low because everyone gets the intervention, regardless of the risk status.
• Another advantage is that can often be done in specific settings, such as schools, universities, and workplaces, where participants can be reached relatively easily.
• A disadvantage of universal prevention is that it is very difficult to examine the effects of interventions in randomized trials on the incidence of depressive disorders, because of the very large sample sizes that are needed. Many universal interventions also focus on the total population, and when they find effects, these are usually found in people who already were depressed at baseline. This means that this was not a truly preventive effect, but more an ‘indirect treatment effect’ in those with depression at baseline. The most recent meta-analysis of randomized trials on preventing the onset of depressive disorders in those without a disorder at baseline, only included one trial. This means that the effects of these interventions on incidence are not yet known.

2. Selective prevention (advantages and disadvantages)

• Selective interventions are aimed at high-risk groups. An important advantage is that participants can be recruited through their risk status. Stigma is relatively low, because participants do not participate because of their (risk of) depression, but because of being in the specific high-risk group.
• A disadvantage of selective interventions is that the predictive value of most known risk factors for depression is low (Cuijpers et al., 2021). This means that despite the increased risk, most people in a high-risk group will not develop depression. This means that the incidence of depression is not as small as in universal prevention, but still small. And this means that randomized trials examining the effects still need to be very large and are therefore very expensive.
• Another problem is that most trials examining the effects of selective interventions do not measure the effects on the incidence of new depressive disorders. The most recent meta-analysis of 16 trials indicated that selective interventions are effective in reducing the incidence of depressive disorders in the coming year with 21% compared to no intervention (Cuijpers et al., 2021).

3. Indicated prevention (advantages and disadvantages)

• Indicated prevention, aimed at people with subthreshold depression (not meeting criteria for a depressive disorder) has been examined in a considerable number of trials. In our meta-analysis we identified 33 trials, which showed that if someone participates in such an intervention, the risk of developing a disorder was 19% lower compared to no intervention (Cuijpers et al., 2021).
• A main advantage of indicated prevention is that it is relatively easy in some target groups to identify potential participants through screening, so for example in perinatal care, general medical care, schools, universities, and work settings.
• One major disadvantage, however, is that the uptake is extremely low. Most people with subthreshold depression are not willing to participate in a preventive intervention, because they do not feel that their problems are serious enough for such an intervention or because they feel that they can solve it in different ways (Cuijpers et al., 2010).

How to increase the impact of prevention?

In summary:

• It is currently unclear if universal prevention works.
• Selective prevention is promising, but this may very well just indirectly ‘treat’ people with existing problems and the potential of this type of prevention is limited by the low predictive strength of risk factors.
• There is some evidence that indicated prevention works, but the uptake is too low to really make an impact on depression at the population level.

So how can the impact of prevention be increased?

First, the resources currently available for research on prevention is very low. More priority for this kind of research is very much needed. Large trials in multiple target populations are needed and these are logistically challenging and expensive. Important determinants of depression have been examined insufficiently in well-powered randomized trials, such as poor parenting, inter-parental conflict, family instability, children’s maladaptive personality traits and poor social and problem-solving skills. Effective interventions with a large impact should start early in life, and focus on children and parents. Prevention programs can only be expected to have an impact when they are long-term, structural and should be offered across the life course.

Potentially important determinants that have not been examined extensively enough include inequalities, social status, and migration. Such interventions should be embedded locally and nationally in existing public (health) institutions; like education, perinatal and childcare, health, and social work and later in the work-setting. Community intervention trials are needed to examine the effects of such programs.

A promising innovative approach to prevention is through indirect interventions (Cuijpers, 2021). Such interventions focus on a less-stigmatising problem (like sleep, stress, procrastination, perfectionism), but still teach skills to cope with mood problems and can therefore prevent the onset of depressive disorders. There is some evidence that this may be effective. This indirect approach is especially useful in communities where ‘suites’ of interventions can be developed that are co-created with members of the community; for example in college students, schools, or the workplace.

Conclusion

• Prevention of new depressive disorders is very much needed because current treatments can only reduce the disease burden of depression to a limited extent.
• Research has shown that preventive interventions are effective, especially in indicated prevention, but also selective prevention. However, the impact of these interventions is limited because the uptake is low.
• A new generation of randomized community trials are needed to examine suites of innovative preventive interventions.

This blog is part of #DepressionSolvingTheToll series written by Pim Cuijpers. Catch up on all of blogs and webinars in this series.

References

Andrews G, Issakidis C, Sanderson K, Corry J, and Lapsley H (2004). Utilising survey data to inform public policy: comparison of the cost-effectiveness of treatment of ten mental disorders. British Journal of Psychiatry 184, 526-533.

Chisholm D, Sweeny K, Sheehan P, Rasmussen B, Smit F, Cuijpers P and Saxena S (2016). Scaling-up treatment of depression and anxiety: A global return on investment analysis. Lancet Psychiatry 3, 415-424.

Cuijpers P (2021). Indirect prevention and treatment of depression: An emerging paradigm? Clinical Psychology in Europe, 3, e6847.

Cuijpers P (2023). Preventing the onset of depressive disorders in low- and middle-income countries: An overview. Global Mental Health, 10, e28.

Cuijpers P, Furukawa TA and Smit F (2021). Most at-risk individuals will not develop a mental disorder: the limited predictive strength of risk factors. World Psychiatry 20, 224-225.

Cuijpers P, Pineda BS, Quero S, Karyotaki E, Struijs SY, Figueroa CA, Llamas JA, Furukawa TA and Muñoz RF (2021). Psychological interventions to prevent the onset of depressive disorders: A meta-analysis of randomized controlled trials. Clinical Psychology Review 83, 101955

Cuijpers P, van Straten A, Warmerdam L and van Rooy MJ (2010). Recruiting participants for interventions to prevent the onset of depressive disorders: Possible ways to increase participation rates. BMC Health Services Research 10, 181.

Institute of Medicine (2009). Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press.

Lobel B, Hirschfeld RM (1984). Depression: What We Know (DHHS Publication No. ADM 84-1318). Rockville, MD, National Institute of Mental Health.

Mrazek PJ, Haggerty R (1994). Reducing risks of mental disorder: Frontiers for preventive intervention research. Washington: National Academy Press.

World Health Organization (WHO) (2022). World mental health report; Transforming mental health for all. WHO: Geneva.

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