In this paper, we have found that the negative impact of a history of abuse on response to combination treatment relative to medication monotherapy in the TORDIA study is mostly explained by a history of physical abuse.12
In those with a history of SA, the responses to combination treatment and medication monotherapy were similar, whereas in those without a history of abuse, combination treatment is clearly superior. Those participants with a history of PA had many characteristics that might be expected to predict a poorer response to treatment, namely higher self-reported depression, suicidal ideation, hopelessness, and history of PTSD, dysthymic disorder, suicide attempt, and non-suicidal self-injury. However, even after controlling for these variables, adolescents with a history of PA were still 10 times as likely to have an adequate response to medication monotherapy as to combined treatment. Thus, we are not able to identify the mechanism by which physical abuse affects treatment outcome, except to say that it is not attributable to differences in baseline characteristics, or amount or quality of treatment received.
These results should be considered within the context of strengths and limitations of this study. This study is one of the first to examine the impact of different types of abuse on treatment outcome in depressed adolescents, and randomization was preserved with respect to the rates of abuse across treatment cells. Treatment was randomly assigned and was carefully monitored for quality. On the other hand, TORDIA was not designed to examine the best modality of treating depression among youth with a history of abuse. Although the sample size of TORDIA is relatively large, the number of participants with a history of abuse is relatively small. We did not collect details about severity, frequency, duration, and timing of abuse, and the relation between victim and perpetrator. In addition, neglect, verbal abuse, and other traumatic or stressful life events, such as witnessing domestic violence, or loss of a relative or friend were not assessed, all of which have been shown to have an impact on clinical outcome.2, 29–31
The PTSD screen of the KSADS has limitations as an assessment of abuse and may miss more than 1/3 of youth with abuse histories.32
Finally, because this study excluded youth who were not living with their primary caregiver, these results might not be generalizable to children with active protective services involvement, who often receive pharmacological treatment.33
In this report, adolescents with history of PA had higher rates of PTSD than those without history of PA. It has been shown that exposure therapy, such as trauma-focused CBT (TF-CBT), is more effective that supportive treatment for the treatment of abused youth with PTSD,34–36
and in those studies, this treatment was also more efficacious in reducing depressive symptoms.35
Moreover, Cohen et al reported that augmenting TF-CBT with sertraline did not further improve PTSD symptoms as compared to TF-CBT monotherapy.37
In contrast, the depression-focused CBT in TORDIA did not include either exposure therapy or trauma-focused sessions. Nevertheless, the negative impact of a history of PA on response to combination treatment persisted even after controlling for PTSD, suggesting that this comorbid disorder alone did not explain the poorer response of CBT in those with a history of PA. Similarly, the impact of PA on outcome persisted after controlling of other negative prognosticators for outcome, such as greater depressive severity, suicidal ideation, hopelessness, dysthymic disorder, or history of non-suicidal self-injury, suggesting that the impact of PA on outcome was not just explained by higher symptomatology or more complex clinical presentation.12, 38
Fergusson and colleagues13, 39
reported that history of trauma is a marker for chronic environmental stress leading to more adverse psychiatric outcome in the adults. However, in the TORDIA combination therapy group, there was no difference between the physical and non-PA groups with respect to current family conflict. Moreover, active abuse was an exclusion from the TORDIA clinical trial. Therefore, the poorer response of physically abused participants more likely reflects an effect of abuse per se rather than of associated ongoing environmental adversity, at least with respect to family conflict, socioeconomic status, and parental self-reported depression.
Previous studies have documented a difference in response to treatment between those with and without history of abuse.7, 8
In chronically depressed adults, Nemeroff et al 7
found that a significant interaction between history of physical (but not sexual) abuse and treatment outcome. Patients with trauma history, defined as PA, parental loss, or other trauma, preferentially responded to psychotherapy versus medication. This finding is in the opposite direction of our finding in TORDIA. This difference in findings in the Nemeroff et al. study compared to TORDIA could be due to their wider definition of trauma, difference in age group, or use of a different modality of psychotherapy, cognitive behavioral analysis system of psychotherapy, which has a greater interpersonal focus than the CBT employed in this study. On the other hand, in the treatment of adolescent depression, a history of abuse, trauma, or maltreatment is associated with a less
vigorous response to CBT, whether compared to other forms of psychotherapy or to medication, although in previous reports, sexual abuse had a more profound effect than physical abuse.8–10
It is unclear why PA showed such a poor response to combination treatment, as compared to participants with a history of SA. This difference was not attributable to baseline differences in the two sub-samples. Nevertheless, even a history of sexual abuse had an impact on outcome, since those with a history of SA were half as likely to respond to combination therapy, and 1.4 times more likely to respond to medication monotherapy compared to those with no history of SA. While these findings were not as pronounced as those findings in those with a history of PA, and we were not able to demonstrate statistically significant evidence of moderation, these findings were certainly consistent with other reports in the literature.8, 10
While there were few baseline differences between those with a history of PA vs. SA, there could have been differences in important domains that were not assessed, such as frequency or severity of abuse, history of neglect, verbal abuse, intercurrent life events, family history of psychiatric disorder, attachment style, or neuropsychological functioning. Another possibility is that PA and SA actually do result in different risks for psychopathology40
and response to treatment. Unfortunately, the literature is inconsistent when comparing the impact of SA vs. PA.2, 7, 8, 10
Abuse is known to have profound developmental neurobiological effects that might in turn influence treatment response. Successful participation in CBT psychotherapy for depression involves the ability to form a relationship, to learn and remember, to participate in rewarding activities, and to face unpleasant emotions. The effects of abuse could undercut all of these domains, since abuse negatively impacts the development of interpersonal relationships, attention, executive function, working memory, and response to reward, and also increases attentional bias away
These findings are likely reflections of the impact of abuse on brain development in critical regions such as the corpus collusum, hippocampus, and prefrontal cortex.44, 45
Since many sequelae are in proportion to the current severity of PTSD, it may be the psychotherapeutic approaches that target trauma may be required prior
to engagement in CBT for depression.
In summary, these results support further investigation of the mechanisms by which maltreatment history confers an apparently greater treatment resistance to depression-focused CBT. In particular, both those with a history of PA and SA showed a lower response to combination treatment than was found in those without an abuse history, and, in the case of PA, response to medication was greatly superior to combination therapy. Furthermore, this effect of PA persisted even after adjusting for other clinical correlates known to convey treatment resistance. These data suggest that this group of patients may require a specialized approach, which could include trauma-focused CBT, and other psychotherapeutic approaches that take into account the neurpsychological profile of the depressed youth with a history of abuse. Future treatment studies should gather better information on history of abuse, other traumas, as well as the neuropsychological profile of such youth, in order to understand the processes that may moderate treatment response and to develop treatments that better target depression in youth with a history of abuse.