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Imagine you are an epilepsy health professional seeing a patient with clinical symptoms of depression. What should you do? If you have read Noble et al.’s  recent JNNP review, entitled ‘Cognitive-behavioural therapy does not meaningfully reduce depression in most people with epilepsy…’ you may have become sceptical about the potential of CBT, or psychotherapy in general, to alleviate depression in people with epilepsy (PWE). This recent systematic review pooled data from five small randomised controlled trials (RCTs), with some elements of CBT for PWE, and performed an analysis of reliable change. ‘Pooled risk difference indicated likelihood of reliable improvement in depression symptoms was significantly higher for those randomised to CBT’, but the authors focused on the finding that ‘only’ 30% of patients receiving interventions, compared to 10% of controls, could be considered ‘reliably improved’. Emphasising the fact that over 2/3 of patients did not meet this criterion for improvement, the authors suggest CBT is ‘ineffective’, has ‘limited benefit’ and could even lead to lower ‘self–esteem’ and ‘helplessness’. Notably, the latter conclusions were based on hypothetical reactions to treatment, rather than empirically supported outcomes.
Therefore, the purpose of this letter, written by the Psychology Task Force of the International League Against...
Therefore, the purpose of this letter, written by the Psychology Task Force of the International League Against Epilepsy (ILAE), is to argue that caution is needed when considering the authors’ conclusions and potential implications for the psychological care of PWE. Moreover, we offer alternative interpretations of the findings and raise the pertinent issue of how psychotherapy for PWE may continue to improve. Importantly, we hope to encourage health professionals to continue to refer patients for psychotherapy, which is an effective intervention for a substantial subgroup of PWE.
Consistent with Reuber’s  editorial commentary, Cognitive-behavioural therapy does meaningfully reduce depression in people with epilepsy, we would like to highlight the heterogeneity of the studies pooled and how this impacts the findings. First, the interventions were very diverse, and most would not be considered standardised CBT protocols for depression. Interestingly, one trial that utilised a standardised CBT protocol, resulted in 50% reliable change reductions in depressive symptoms, equivalent to CBT in the general population . Second, over 10% of patients in the analyses had depressive symptoms within the non-clinical ranges. Further, unlike previous analysis of reliable change in depression , this review failed to control for baseline levels of depression severity. Third, Noble et al. collapsed data from four different self-report depression measures, only one designed for PWE. Depression in PWE can have distinct symptomatology, given the presence of seizures (peri-ictal depression) and anti-seizure medication effects, both of which can limit the validity of generic depression measures .
Noble et al.  describe their conclusion that 30% reliable improvements in depressive symptoms across trials is ‘ineffective’ as a ‘value judgement’, illustrating subjectivity, which Reuber’s  editorial commentary argued could be interpreted completely in reverse. That is, one could conclude from the data that the treatments are ‘effective’ for PWE. There is little consensus about what we expect a ‘reliable improvement’ to be in psychological distress for PWE, or for patients with a disabling neurological disorder in general. A stated goal of epilepsy treatment is “no seizures, no side-effects.” However, many PWE continue to have seizures, and all biological treatments have potential side-effects. We argue that if just under 1 in 3 PWE reliably improve with CBT, which has no known side-effects, this is better than a possible alternative of unmanaged depression. Arguments regarding quantifying ‘reliable improvement’ aside, we do agree with Noble et al.’s  conclusions that there is ‘substantial room for improvement’ in the treatment of depression for PWE.
One important limitation of previous trials is the relatively short duration of psychotherapy offered to PWE, a factor that Noble et al.  acknowledge. Across the five RCTs, there was only an average of 7 hours (8 sessions) of psychotherapy, the adherence of which is unclear . Thus, it is very likely that participants did not receive a sufficient dosage of CBT, especially given a minimum of 12 sessions is indicated for depression in the general population . In addition, many PWE experience cognitive difficulties, including memory impairment, which may require more intensive and tailored CBT . These limitations need to be addressed and psychotherapy should be tailored to the unique needs of PWE. One advantage of CBT is that many of the behavioural skills; such as problem solving, sleep hygiene and controlled relaxation can also be tailored to assist with the self-management of epilepsy (e.g. avoidance of seizure triggers), which Noble et al. did not consider.
Another critical area for improvement is the treatment of comorbid anxiety symptoms within psychotherapy for depression. Anxiety and depression are highly comorbid, and in clinical practice it is difficult to evaluate them separately . As such, transdiagnostic treatments, which treat depression and anxiety in one protocol, are increasingly being adopted and proven to be effective in the general population. We disagree with Noble et al.’s  comments regarding the ‘disappointing’ evidence for the treatment of anxiety, as only one small trial is cited assessing the impact of CBT for depression (not anxiety), on a secondary anxiety measure. A conclusion of insufficient evidence would have been more accurate, given the state of the anxiety literature.
Depression in PWE remains underdiagnosed and treated, perhaps partially due to uncertainty about effective treatments . At worse this results in poorer quality of life and higher suicide rates in PWE. Thus, the development of more effective psychotherapies, including alternatives to CBT, is warranted. However, the ILAE Psychology Task Force believes that it is inaccurate to label CBT as ‘ineffective’ based on the findings of Noble et al.’s  review. Instead, we encourage health professionals to interpret the Noble et al.  conclusions with caution, given the concerns raised with respect to depression outcome measures, dosage and quality of the psychotherapies, and interpretation of results. Further, even with a conservative estimate of 30% responders to the psychotherapies, we posit that CBT shows promise for treating depression in PWE and should remain a strong treatment consideration for the referring clinician.
This document was written by experts selected by the International League Against Epilepsy (ILAE) and was approved for publication by the ILAE. Opinions expressed by the authors, however, do not necessarily represent the policy or position of the ILAE.
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