Topic 14.2. Management of depression in Friedreich ataxia
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
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The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.
The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.
Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.
These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.
Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.
14.2 Management of depression in Friedreich ataxia
Caroline Spencer, Alexandra Durr, George Wilmot, Susan Perlman and Louise Corben
Clinicians should be highly attuned to the possibility of depression and associated mental health issues in individuals with FRDA and ensure these issues are proactively and effectively managed. In a large cohort of individuals with FRDA (n=650), 14.2% reported depression (15). Grief and sadness are common among individuals with FRDA, particularly as they deal with significant transitional times such as ceasing to walk, and dealing with adolescence and early adulthood (11). Transitional times often highlight the sense of loss and present significant challenges to an individual’s sense of identity (11). Many of these individuals also present with irritability due to frustration of trying to perform activities of daily living. As one person with FRDA stated “Every small detail of their lives consumes more and more of the time they used to devote to work, play and other independent activity” (1).
If depression or other mental health issues are suspected in individuals with FRDA, proactive management should include referral to appropriate clinicians, instigation of pharmacological therapy if indicated and referral for counseling. In particular, given the prevalence of depression in individuals with FRDA and the impact on quality of life, clinicians should be vigilant to the possibility of depression and provide timely intervention. The clinical experience of the authors indicates there is no difference in response to antidepressant medication in individuals with FRDA compared to those without FRDA. For this reason, it is important to make sure individuals with FRDA are screened for depression, particularly as the consequences of depression are major (suicidal thoughts, hospitalization, lack of engagement in social activities and/or physical therapy programs) and clinical experience suggests that individuals with FRDA may not recognize depressive symptoms. Clinicians also need to consider both the degree of depression and the possibility of masking of symptoms by associated FRDA-related symptoms such as fatigue. As such, careful assessment of the severity of depression is warranted. Given individuals with FRDA may be reluctant to recognize symptoms of depression, the first line of clinical management may be counseling. However, it is important to explore what will work best for individual with FRDA, particularly in the context of the other aspects of their lives, such as accessibility requirements of face-to face counseling and time constraints for work/study/family. The clinician may consider treating depressive symptoms with both counseling and medication. Preventive measures such as counseling at major life stages such as going to college, or leaving home may be very helpful. Counseling may also be appropriate for parents/carers of individuals with FRDA.
Lifestyle changes (such as exercise, diet, social activities) may have a positive impact on depression. Conversely, depression may impact on the motivation to engage with lifestyle changes. This could be helped by the use of antidepressants. As such, lifestyle changes may be used in in conjunction with other treatments, particularly medication. There may, however, be significant barriers to participation related to FRDA that would need to be addressed to enable lifestyle changes and these FRDA–related factors may also exacerbate underlying depression. A multidisciplinary approach to facilitating engagement in lifestyle changes may assist. Suicidal or more severely depressed individuals with FRDA are likely to need more targeted therapy.
While it is apparent that depression and associated mental health issues may be a greater risk for individuals with FRDA, it is still not clear if the greater prevalence is due to the pathology associated with FRDA, the environmental/lifestyle changes imposed by the presence of the condition, or a combination of the two. Further research is required to understand the mechanism associated with mental health issues in individuals with FRDA. Further research is also required to identify significant periods during the disease process when an individual may be at greater risk and therefore requiring prophylactic intervention including, but not confined to, intense and targeted counseling.
Antidepressant medication
QUESTION: Should antidepressant medication versus none be used for depressed individuals with Friedreich ataxia?
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RECOMMENDATION: We conditionally recommend the use of antidepressant medication in individuals with Friedreich ataxia who present with symptoms of depression.
JUSTIFICATION: Cohort studies indicate that the presence of depressive symptoms may be greater in individuals with Friedreich ataxia than those without Friedreich ataxia. Whilst there is no published evidence in Friedreich ataxia, if treatment is efficacious then the desirable effect on individuals who are depressed would be large. Clinical experience of the authors indicates there is no difference in response rate in individuals with Friedreich ataxia compared to those without Friedreich ataxia, when they accept use of medication. Individuals with Friedreich ataxia are less likely to accept a diagnosis of depression; however, there is no reason why they would not respond to treatment after accepting that treatment may be of benefit. For this reason, it is important to make sure individuals with Friedreich ataxia are screened and clinicians are alert to the possibility of depression.
Note, the consequences of depression are major (suicidal, hospitalization) and the experience of the expert authors indicate individuals with Friedreich ataxia may not recognize depressive symptoms. Clinicians need to be very careful in considering both the degree of depression and the possibility of masking of symptoms. As such, careful assessment of severity of depression is warranted.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia and depression and should be implemented according to an assessment of the severity of depression. Balance of side effects versus efficacy needs to be taken into account when considering treatment options.
Evidence to Recommendation Table PDFCounseling for depression
QUESTION: Should counseling or therapy versus none or antidepressant prescription be used for depressed individuals with Friedreich ataxia?
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RECOMMENDATION: We recommend counseling or therapy over no counseling in individuals with Friedreich ataxia who present with symptoms of depression.
JUSTIFICATION: Cohort studies indicate that the presence of depressive symptoms may be greater in individuals with Friedreich ataxia than those without Friedreich ataxia. Whilst there is no published evidence in Friedreich ataxia, if counseling is efficacious then the desirable effect on individuals who are depressed would be large. Given individuals with Friedreich ataxia may be reluctant to recognize symptoms of depression, the first line of clinical management may be counseling. It is important that clinicians explore what will work best for individuals with Friedreich ataxia, particularly in the context of the other aspects of their lives (accessibility requirements of face to face counseling, time constraints for work/study/family, etc.). The clinician may need to consider treating depressive symptoms with both counseling and medication. In addition, it is important for the clinician to be aware of the role of fatigue in depression (and perhaps presenting as depression).
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia and depression. It may be difficult for a person with severe dysarthria to engage in counseling. Counseling may be very helpful at major life stages such as going to college, leaving home etc. Counseling may also be appropriate for parents/carers of individuals with Friedreich ataxia.
Evidence to Recommendation Table PDFLifestyle changes for depression
QUESTION: Should lifestyle changes (exercise, diet, social activities) versus none or antidepressant treatment be used for depressed individuals with Friedreich ataxia?
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RECOMMENDATION: We recommend lifestyle changes (exercise, diet, social activities) either prior to or in conjunction with other interventions, including antidepressants, for individuals with Friedreich ataxia who have symptoms of depression.
JUSTIFICATION: Lifestyle changes may have a positive impact on depression. However, the use of antidepressants may assist in facilitating participation if depression is associated with lack of motivation. Therefore, lifestyle changes may be used in in conjunction with other treatments, particularly medication. There may be significant barriers to participation related to Friedreich ataxia that would need to be addressed to enable lifestyle changes.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia and depression. Consideration should be given to the stage of Friedreich ataxia, the age of the person, and the level of depression (mild vs severe). Suicidal or more severely depressed individuals with Friedreich ataxia may need more targeted therapy.
Evidence to Recommendation Table PDFIndividuals with Friedreich ataxia may benefit from regular counseling to assist in adjusting to transitional events and possibly prevent the emergence of related depression.
Individuals with Friedreich ataxia identified with depression should be treated with established interventions including counseling +/- pharmacological agents.
The risk of suicide in individuals with Friedreich ataxia should be considered and managed proactively.
Lay summary of clinical recommendations for depression in Friedreich ataxia
Individuals with Friedreich ataxia often report mental health concerns. These issues can vary in nature throughout the person’s life, and often include depression. Mental health concerns can affect physical, emotional, and social wellbeing.
Why these recommendations?
There are various strategies that may help a person with Friedreich ataxia experiencing depression.
Medication
Due to a lack of studies, there is no direct evidence showing the benefits of medication for treating depression in individuals with Friedreich ataxia. However, if medication is effective for treating depression, the benefit to the individual would be large, so it may be worth trying. Ways to limit undesirable side effects (such as dizziness or worsening balance), which would likely have a greater impact on individuals with Friedreich ataxia than other people, should be considered.
Counselling
While there is no direct evidence for the benefits of counselling in individuals with Friedreich ataxia who have depression, we recommend counselling to treat depression. If counselling is effective, the benefit would be large and there are unlikely to be any undesirable effects.
Lifestyle changes
We recommend lifestyle changes (e.g., exercise, healthy diet, greater social activities) before, or at the same time as other treatments for depression in Friedreich ataxia. Although there is little research evidence that lifestyle changes will improve depression symptoms, the clinical experience of the authors supports the benefits of lifestyle changes.
What does this mean for you as a person living with Friedreich ataxia or caring for someone living with Friedreich ataxia?
Research shows that individuals with Friedreich ataxia experience depression more frequently than others in the general population. It is important to talk to your doctor or other healthcare professional if you feel this may be an issue for you or someone you care for. A health professional will assess whether the use of behavioural management, counselling, medication, alternative therapies and/or a specific diet may be appropriate for you.
Who are these recommendations specifically for?
These recommendations are relevant to all individuals with Friedreich ataxia who have symptoms of depression. Consideration should be given to treatments that are best suited to the age of the individual, the specific diagnosis and the severity of symptoms.
Louise Corben, PhD
Principal Research Fellow, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Email: louise.corben@mcri.edu.au
Alexandra Durr, MD, PhD
Professor of Neurogenetics, Sorbonne Université, Paris, France
Email: alexandra.durr@icm-institute.org
Susan Perlman, MD
Clinical Professor of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
Email: sperlman@ucla.edu
Caroline Spencer, PhD
Postdoctoral Fellow, Boston University, Boston, Massachusetts, USA
Email: cspencer@bu.edu
George Wilmot, MD, PhD
Associate Professor, Department of Neurology, Emory University, Atlanta, Georgia, USA
Email: gwilmot@emory.edu
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These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
It is our expectation that going forward individual topics can be updated in real-time in response to new evidence versus a re-evaluation and update of all topics simultaneously.