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Depression is a serious and common mental health problem. Although a number of psychological and pharmacological treatments are available for this serious psychiatric condition, there is still a lot of room for improvement. As is true for virtually all mental disorders, the most common and comparatively most effective form of psychological treatment for depression is cognitive behavioral therapy (CBT).1
To advance and understand the treatments for this disorder, it is important to know when, how, and for whom a treatment works. In line with such a personalized approach to therapy, in this issue of JAMA Psychiatry, Cuijpers and colleagues2 conducted a meta-analysis to answer the question whether psychotherapies (primarily CBT) for depression have comparable outcomes in all age groups across the life span. Based on a meta-analytic review of 366 randomized clinical trials, this study found that treatments were less effective in children and adolescents compared with adults. The authors called for better psychological treatments in children and adolescents.
What might account for the observed results? What factors might have accounted for these findings aside from age? If age was in fact the primary reason for the results, why is psychotherapy in children and adolescents less effective? Is it possible that depression in children and adolescents is more severe and treatment resistant than the other age groups? These are the questions I will address in this commentary.
As is true for all meta-analyses, decisions have to be made that might have influenced the results. The study2 allowed different treatment formats, including individual sessions, group therapy, telephone consultations, and guided self-help treatments through the internet. It is quite reasonable to assume that the treatment formats are not used to the same extent by all age groups. Children are unlikely to use self-help guides, and very young children and older adults might be less likely to use the internet for their treatments than young adults, for example. We also know that some of these treatment formats are not as effective as others. Self-help guides, for example, may not be as effective as face-to-face treatments. This difference in treatment use might be an alternative explanation for the pattern of results.
There is also a well-known age-by-sex difference in the prevalence of depression.3 Until age 13 years, depression is equally common among boys and girls. After that age, depression becomes a lot more common in women and girls than men and boys. Therefore, any differences in the treatments between different age groups could also be attributable to differences in sex proportions between these groups. Similar arguments could be made for differences in socioeconomic status, social support, and even culture.
Finally, the number of studies included in the various age-group categories differ dramatically, with 242 studies examining middle-aged adults and only 13 studies examining children and 10 studies examining older adults.2 Not surprisingly, the 95% CI was a lot smaller for the treatment effect size for studies of the middle-aged adults compared with the treatment effect sizes of studies of the children and older adults. This may have also contributed to the pattern of results. Meta-analyses are powerful tools that need to be handled with great care.
Assuming that the findings2 are not explained by an artifact of some other variable, such as treatment use or sex, what could the results mean? Is it possible that depression is not the same disorder for all age groups? The DSM-5 distinguishes major depressive disorder, persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, other specified depressive disorder, and unspecified depressive disorder. For all of these categories, age is a factor, and children with mood disorders have posed a number of diagnostic challenges. Perhaps one of the most controversial issues during the development of the DSM-5 was the diagnosis of bipolar disorder in children. To attempt to avoid the overdiagnosis of and treatment for bipolar disorder in children, the DSM-5 created a new diagnosis: disruptive mood dysregulation disorder. This diagnosis typically describes children 12 years or younger who show persistent irritability and frequent episodes of extreme behavioral dyscontrol.
There are other obvious age-associated differences in mood disorders. Children are much less likely to use substances of abuse than adults. Yet, we know that a large number of substances of abuse, such as some prescribed medications, as well as several medical conditions, can be associated with depressionlike phenomena. This fact is recognized in the diagnoses of substance/medication-induced depressive disorder and depressive disorder due to another medical condition. These patients will obviously require an intervention that also addresses the substance or medication to effectively target the depression. It is unclear how many patients in the meta-analysis met criteria for a substance-associated depression. Those patients were unlikely to be children.
The DSM-5 recognizes that in children and adolescents, the mood may be irritable and cranky rather than sad.4 A more chronic form of depression is diagnosed when the mood disturbance continues for at least 2 years in adults but only 1 year in children. Age further defines different subtypes of dysthymia, based on whether the onset is early (before age 21 years) or late (after age 21 years). These differences in age at onset and time course are fairly arbitrary, but they emphasize the importance of age when making a diagnosis.
Of particular relevance in the context of the study is the onset specifier. This specifier was in large part the result of studies conducted by Akiskal,5 who proposed that early-onset dysthymia is a low-grade characterological form of depression that develops gradually, whereas late-life dysthymia is an acute and more severe form of the disorder.
Although the early-onset vs late-onset specifier was not included for major depressive disorder, it has been suggested that a similar distinction should also be made for this disorder.6 Accordingly, early-onset chronic major depression might be a more severe form and associated with greater comorbidities than the late-onset subtype. This would explain why treatments are less effective in early-onset subtype of the disorder and therefore also in children and adolescents.
It is unclear why age appears to distinguish different forms of depressive states. It is quite possible that hormonal changes, and especially the influence of estrogen and testosterone on brain function and development among girls around puberty, might explain some of the results.7 Other possible explanations might be associated with the physical changes that occur during sexual maturity and the associated social conflicts and stress around gender roles.3 Whatever the reason, age (and sex) is a critical factor that needs to be considered for the diagnosis and treatment of depression. It is quite possible that we are dealing with different disorders, depending on the age and sex of the patient.8 Therefore, the same treatment might not be equally effective for all individuals at all ages. This questions the idea that depression is a monolithic entity and supports the call for a paradigm shift toward precision medicine in psychiatry.
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