‘I’m feeling a bit depressed today.’ While mental health professionals may feel frustrated at a perceived overly-casual use of the word ‘depressed’, it is in fact true that 11% of the population experience subthreshold symptoms of depression (Zhang et al., 2023).
In fact, having subthreshold symptoms of depression triples your risk of developing clinical depression compared to people with no symptoms (Zhang et al., 2023). Preventative intervention at this stage can therefore limit the significant negative impact that depression has on the individual and society, especially as its prevalence continues to increase worldwide (World Health Organisation, 2017; Richter et al., 2019).
To determine the effectiveness of psychological prevention at this stage, a recent systematic review (Buntrock et al, 2024) analyses the effect of psychological interventions on people with subthreshold depressive symptoms, particularly in terms of the incidence of major depressive disorder (MDD).
Importantly, while most systematic reviews simply use summarised data from included studies for their analyses, this paper uses individual participant data from the selected studies to produce a large, pooled sample. This increased detail allows intervention effects to be estimated more precisely. This is the first systematic review to have used this approach to study the effect of interventions on MDD onset, making it a significant contribution to our knowledge.
Subthreshold depression is more common than people realise. Can early psychological intervention help with the prevention of major depression?
Methods
Using a comprehensive search process spanning multiple databases, randomised controlled trials were selected that compared:
- A preventative psychological intervention, and
- A control group, which could be care as usual, antidepressants, a placebo, or a waitlist.
The primary outcome was the onset of major depressive disorder (MDD).
The inclusion criteria was adults aged 18 or older with subthreshold MDD, defined by the authors as “scoring higher than a cut-off score on a self-rating depression questionnaire; scoring higher than a cutoff score on a clinician-rated instrument; or meeting criteria for minor depression according to the DSM-IV or ICD”.
Psychological intervention was defined as “application of psychological mechanisms and interpersonal stances derived from psychological principles for the purpose of assisting people to modify their behaviours, cognitions, emotions and/or other personal characteristics in directions that the participants deem desirable”.
Results
In total, 30 trials were identified, with a total of 7,201 participants. Most trials (24 out of 30) were rated as having a low risk of bias.
Psychological interventions significantly reduced MDD incidence at 3 time points:
- post-treatment (Incidence Rate Ratio 0.57, 95% CI [0.35 to 0.93]),
- 6 months after intervention (0.58 [0.39 to 0.88]), and
- 12 months after intervention (0.67 [0.51 to 0.88]).
There was no significant effect at the 24-month time point (1.16 [0.66 to 2.03]), though note that the first 3 results above were calculated using data from 18-19 studies, the 24-month time-point only had data from 6 studies.
Similar findings were obtained for the secondary outcomes. For example, there was a reduction in depressive symptom severity at post-treatment (standardised mean difference -0.49 [-0.66 to -0.32]), 6 months (-0.26 [-0.41 to -0.11]), and 12 months (-0.27 [-0.40 to -0.24]). This analysis was conducted with participant data from 28 studies, 23 studies, and 23 studies respectively. There was again no effect at 24 months, but this only involved participants from 11 studies (-0.14 [-0.32 to 0.04]).
There were also similar significant increases in the number of participants with 50% symptom reduction, symptom-free status, and reliable improvement, and there were significant decreases in reliable symptom deterioration.
Interestingly, there was no effect of type of intervention on effectiveness (p = 0.374), and people with no previous psychotherapy experienced about 2.3 times more benefit (effect size of 2.292, p = 0.029).
Psychological interventions reduced the risk of developing major depression for up to a year, regardless of therapy type.
Conclusions
For adults with subthreshold depression, preventative psychotherapeutic interventions were effective for up to 12 months in reducing the incidence of future major depressive disorder (MDD) as well as the severity of existing depressive symptoms.
Preventative interventions show clear benefits for people with subthreshold depressive symptoms, supporting early therapeutic engagement.
Strengths and limitations
Strengths
The sample size was large, and study search was comprehensive. 30 randomised controlled trials with a total of 7201 patients were included, increasing the validity of the results. This is especially since RCTs already provide the highest quality evidence in the Evidence-Based Medicine pyramid apart from systematic reviews themselves (see pyramid here). Study search was comprehensive; the Metapsy research domain covers 4 large and established databases (PubMed, EMBASE, PsycINFO, and Cochrane Central). Many efforts were also made to obtain individual participant data, as corresponding authors were contacted up to 3 times.
There was low risk of bias with both the studies included and the systematic review itself. For the selected studies, risk of bias was assessed with the Cochrane RoB2 tool and was overall low (24/30 studies had low risk). Bias in study inclusion was reduced by how they were selected by two independent researchers. The systematic review itself was pre-registered, which is a well-established method to reduce reporting bias. Pre-registration here means declaring primary and secondary outcomes and methods prior to conducting any data analysis. This means that the authors cannot simply change their analysis methods or outcomes of interest to obtain a more significant or positive result.
The results remained valid under all robustness checks. These checks involve assessing if the results hold after controlling for possible confounding factors, i.e. factors which may affect the outcome being measured. In this case, the authors accounted for demographics, baseline depression and anxiety symptom severity, history of MDD, antidepressant use, previous psychotherapy and chronic medical conditions. They found controlling for these did not affect the results. The results also remained robust under all methods of accounting for missing data. Data analysis methods were also appropriately selected e.g. a Poisson model for analysing MDD onset, as a Poisson model is suitable for count data which may be infrequent.
Lastly, the authors involved people with lived experience in designing and implementing the study, which should be commended, as it helps us meet their needs better.
Limitations
The studies varied in what intervention was used, how it was delivered, and the type of control used. Indeed, the authors report that in many analyses, between-study heterogeneity was moderate-to-large. The most common intervention was Cognitive Behavioural Therapy (n = 16), but problem-solving therapy (n = 4), behavioural activation (n = 4) and stepped care (n = 5) were also included. Similarly, the most common delivery method was face-to-face (n = 12), but Internet-based interventions (n = 8) were also included. As the authors state, this means that “true effects may differ across contexts”.
It is unclear if the effect persists after a year. As discussed previously, no significant effect was found at the 24-month timepoint, despite significance at 12 months. It is unclear whether this is due to a true negative effect, meaning that the benefits of intervention have faded after 2 years, or because there is a lack of studies.
The studies were mostly in high-income countries. Unfortunately, this is a problem present across scientific research, and reflects a broader issue of WEIRD populations – Western, Educated, Industrialised, Rich and Democratic – being over-represented. Although the UK is indeed a high-income country, this still warrants a mention as this means it may not be applicable to all patient groups should broader implications be considered.
This review is robust and comprehensive, but variability in interventions and a lack of long-term data leave questions unanswered.
Implications for practice
This systematic review demonstrates that, contrary to concerns about overtreating the “worried well”, psychological interventions can indeed prevent major depressive disorder (MDD) onset in people who have some symptoms but are not experiencing a depressive episode. For clinicians, this means that psychotherapy can continue to be suggested for less severe depression (which includes both subthreshold and mild depression), as seen in the current National Institute for Health and Care Excellence (NICE) guidelines (NICE, 2022, last reviewed 2024).
Given that the study shows that intervention type has no significant effect on experienced benefits, this justifies the decision (as seen in the image below) to first recommend more cost-effective methods such as group therapies, given the context of limited health and social care funding.
However, some practical questions still need to be answered. First, when exactly should subthreshold depression warrant intervention – would it be when it persists for more than 2 weeks, like for depression? Does this change depend on how far from the threshold these subthreshold symptoms are? The authors state that considerations about how to “integrate these interventions into routine care” should be prioritised, but this may be difficult given that there are already high thresholds to qualify for treatment, and access is patchy, often termed a “postcode lottery” (Mind 2013, Rethink Mental Illness 2024). If people with even major depression have difficulties accessing therapy on the NHS, how can interventions for subthreshold depression be justified? As such, we may well recommend that clinicians suggest that these patients seek therapy, but these patients would be unlikely to receive it on the NHS.
This does lead to more complex questions about whether preventative approaches, while seemingly harder to justify on the surface, may actually be more cost-effective in the long term. The same way preventing diabetes early can prevent costly hospital admissions due to a cardiac event, perhaps preventing mental health crises can prevent costly hospital admissions due to suicide attempts and other acute mental health crises.
That said, public-level psychoeducation is always an option. For those who can access private therapy, or therapy through work or education, destigmatising psychotherapy as something to consider even if you do not have clinical depression could nudge them to seek help before their symptoms worsen. While receiving therapy seems to have become less stigmatised over the years – well-known figures such as Prince Harry have openly shared having had therapy – this adds another piece of evidence that aids with destigmatisation. The fact that one benefits regardless of intervention type can also be included in public health messaging, as this means that people can choose the intervention that best suits their preferences and life e.g. cost.
With early intervention showing promise, clinicians and policymakers must consider how best to integrate the findings into routine care. [View full-size image]
Statement of interests
No conflicts of interest.
Links
Primary paper
Buntrock C, Harrer M, Sprenger AA, Illing S, Sakata M, Furukawa TA, Ebert DD, Cuijpers P, Adriaanse MC, Albert SM, Allart E. (2024) Psychological interventions to prevent the onset of major depression in adults: A systematic review and individual participant data meta-analysis. The Lancet Psychiatry. 2024 Dec 1;11(12):990-1001.
Other references
Mind. (2013). We still need to talk: A report on access to talking therapies. Mind. https://www.mind.org.uk/media-a/4248/we-still-need-to-talk_report.pdf
National Institute for Health and Care Excellence (Great Britain). (2022). Depression in adults: treatment and management. National Institute for Health and Care Excellence (NICE).
Rethink Mental Illness. (2024, June 25) New survey reveals stark impact of NHS mental health treatment waiting times. https://www.rethink.org/news-and-stories/media-centre/2024/06/new-survey-reveals-stark-impact-of-nhs-mental-health-treatment-waiting-times/
Richter D, Wall A, Bruen A, Whittington R. (2019) Is the global prevalence rate of adult mental illness increasing? Systematic review and meta‐analysis. Acta Psychiatrica Scandinavica, 140(5), 393-407.
World Health Organization. (2017) Depression and other common mental disorders: global health estimates.
Zhang R, Peng X, Song X. et al (2023) The prevalence and risk of developing major depression among individuals with subthreshold depression in the general population. Psychological Medicine, 53(8), 3611-3620.
