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Depression & Anxiety in Epilepsy

Depression & Anxiety in Epilepsy. Katherine Inoyama, MD October 28, 2017. Overview. What are depression and anxiety, and how are they diagnosed? How common are they in epilepsy and why are they important to address? What treatments are available for these disorders in people with epilepsy?.

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Depression & Anxiety in Epilepsy

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  1. Depression & Anxiety in Epilepsy Katherine Inoyama, MD October 28, 2017

  2. Overview • What are depression and anxiety, and how are they diagnosed? • How common are they in epilepsy and why are they important to address? • What treatments are available for these disorders in people with epilepsy? DEPRESSION & ANXIETY IN EPILEPSY

  3. Major depressive episode (DSM-V criteria) • Five or more of the following symptoms nearly daily during a 2-week period • Depressed mood most of the day • Loss of interest or pleasure • Significant weight loss or gain, or change in appetite • Insomnia or hypersomnia • Fatigue or loss of energy • Feelings of worthlessness or guilt • Difficulty thinking or concentrating • Recurrent thoughts of death or suicide • Symptoms cause significant distress or impairment • Not attributable to direct effects of a substance or other condition DEPRESSION & ANXIETY IN EPILEPSY

  4. Depressive disorders • Major depressive disorder • Persistent depressive disorder (dysthymia) • Psychotic depression • Postpartum depression • Seasonal affective disorder • Premenstrual dysphoric disorder • Bipolar disorder DEPRESSION & ANXIETY IN EPILEPSY

  5. Depression • Children/Adolescence: • Irritability • Elderly • Memory impairment • Incidence of depression lower for independent elderly, but significantly higher for those in nursing homes or with other medical condition (stroke, cancer, etc). DEPRESSION & ANXIETY IN EPILEPSY

  6. Who is most likely to have Depression? • Women (2:1) • Caucasian • Younger adults Additional risk factors…. DEPRESSION & ANXIETY IN EPILEPSY

  7. (Kendler, 2002) DEPRESSION & ANXIETY IN EPILEPSY

  8. Pathophysiology- Changes within the brain • Neurotransmitters (monoamines, dopamine, GABA, glutamate, etc) • Neural networks (especially those affecting the temporal and frontal lobes) • Anatomic changes (functional imaging, postmortem cellular analysis) • Hypothalamic-pituitary adrenal axis (increased stress) DEPRESSION & ANXIETY IN EPILEPSY

  9. The Monoamine Hypothesis (Belmaker, 2008) DEPRESSION & ANXIETY IN EPILEPSY

  10. Hypothalamic-pituitary-adrenal (HPA) axis (Belmaker, 2008) DEPRESSION & ANXIETY IN EPILEPSY

  11. Anxiety Disorders • Generalized anxiety disorder • Agoraphobia • Panic disorder • Social anxiety disorder • Specific phobia DEPRESSION & ANXIETY IN EPILEPSY

  12. Generalized Anxiety Disorder (DSM-V criteria) • Excessive anxiety and worry occurring more days than not for at least 6 months • Difficult to control the anxiety • Associated with 3 or more of the following (present more days than not): • Restless or on edge • Easily fatigued • Difficulty concentrating or mind going blank • Irritability • Muscle tension • Sleep disturbance • Symptoms cause significant distress or impairment of functioning • Not attributable to substance or other medical condition • Symptoms are not better explained by another disorder DEPRESSION & ANXIETY IN EPILEPSY

  13. Risk factors for anxiety in people with epilepsy • Some studies suggest history of depression, perceived side effects, lower education level, chronic ill health, being female, and being unemployed • Some studies show higher rates of mood disorders in patients with frequent, refractory seizures, and others show that rates are similar whether seizures are well-controlled or not …overall inconsistent results. DEPRESSION & ANXIETY IN EPILEPSY

  14. Pathophysiology of anxiety:The Limbic system (Craske, 2017) DEPRESSION & ANXIETY IN EPILEPSY

  15. How common are these disorders? Major depressive disorder: General population • Lifetime prevalence 16.5% People with epilepsy • Lifetime prevalence 30-35% Anxiety disorders: General population • Lifetime prevalence 5-31% People with epilepsy • Lifetime prevalence 11-50% DEPRESSION & ANXIETY IN EPILEPSY

  16. Why is it so common? • Brain chemistry, neural networks • Medication side effects • Psychosocial factors (e.g. stigma, discrimination) DEPRESSION & ANXIETY IN EPILEPSY

  17. Neurobiology behind the relation • Anxiety: Amygdala and hippocampus • Timing of onset: Mood disorder often precedes diagnosis of epilepsy • Animal studies DEPRESSION & ANXIETY IN EPILEPSY

  18. Quality of Life Giliam. Neurology, 2002. DEPRESSION & ANXIETY IN EPILEPSY

  19. Suicide • People with epilepsy have a suicide risk 3 to 5X higher than the general population. • FDA issued black label warning in 2008 on all AEDs indicating increased risk for suicidality. • NEJM study from 2010 (Arana, et. al.) • Evaluated a U.K. database of over 5 million people, and did not find an increased risk for suicidality in epilepsy patients on AEDs DEPRESSION & ANXIETY IN EPILEPSY

  20. Treatment for depression and anxiety in patients with epilepsy • Selection of AEDs and epilepsy treatment • Psychiatric medication • Therapy (cognitive behavioral therapy) • Other non-pharmacological methods DEPRESSION & ANXIETY IN EPILEPSY

  21. Selection of AEDs and epilepsy treatments • Potential beneficial effect on mood: • Lamotrigine, valproic acid, oxcarbazepine, carbamazepine • Lyrica, gabapentin, benzodiazepines (for anxiety) • Topiramate • Vagus nerve stimulator • Potential negative impact on mood: • Levetiracetam, phenobarbital, felbamate, vigabatrin • Topiramate DEPRESSION & ANXIETY IN EPILEPSY

  22. Psychiatric medications • Selective serotonin reuptake inhibitors (SSRIs) • e.g. Fluoxetine, sertraline, escitalopram • Serotonin-norepinephrine reuptake inhibitors (SNRIs) • e.g. Duloxetine, venlafaxine • Tricyclic antidepressants (TCAs) • e.g. Imipramine, amitriptyline • Bupropion (norepinephrine-dopamine reuptake inhibitor) Seizure risk in recent study: bupropion SR (0.1%) and bupropion IR (0.4%) DEPRESSION & ANXIETY IN EPILEPSY

  23. Psychological Treatment • Cognitive behavioral therapy (CBT) • Aims to change pattern of behavior or thinking • Recommended by the International Consensus statement (group of experts) for the treatment of depression in people with epilepsy. • Evidence is mixed (e.g. a Cochrane review found no clear benefit, subsequent systematic review found possible benefit) • Small study looking at SSRIs vs CBT found benefits to depression and quality of life were comparable after 12 weeks in temporal lobe epilepsy patients. (Orjuelas-Rojas, 2015). • More studies needed! DEPRESSION & ANXIETY IN EPILEPSY

  24. Additional Non-pharmacological Treatments • Mindfulness based intervention • Meditation exercises (mindful breathing, body scan, mindful movement, etc) • Reduction in seizure frequency and seizure severity (Tang et.al., 2015) • Improvement in depression symptoms (Thompson et.al., 2010 and 2015) • Evidence is still limited • Yoga • Insufficient evidence to support benefit in epilepsy patients • Exercise • Multiple studies show benefit in symptoms of depression, quality of life and even seizure reduction. DEPRESSION & ANXIETY IN EPILEPSY

  25. References • Arida RM, Cavalheiro EA, Scorza FA. From depressive symptoms to depression in people with epilepsy: Contribution of physical exercise to improve this picture. Epilepsy Research. 2012 Mar; 99(1-2): 1-13. • Barry JJ. The recognition and management of mood disorders as a comorbidity of epilepsy. Epilepsia. 2003;44 Suppl 4:30-40. • Belmaker RH, Agam G. Major Depressive Disorder. N Engl J Med. 2008 Jan 3;358(1):55-68. • Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: a population-based case-control study. Lancet Neurol. 2007 Aug;6(8):693-8. • Craske MG, Stein MB, Eley TC, Milad MR, Holmes A, Rapee RM, Wittchen HU. Anxiety disorders. Nat Rev Dis Primers. 2017 May 4;3:170224. • Gilliam F. Optimizing health outcomes in active epilepsy. Neurology. 2002 Apr 23;58(8 Suppl 5):S9-20.  • Kendler KS, Gardner CO, Prescott CA. Toward a comprehensive developmental model for major depression in women. Am J Psychiatry. 2002 Jul; 159(7):1133-45. • Kerr MP, Mensah S, Besag F, de Toffol B, Ettinger A, Kanemoto K, Kanner A, Kemp S, Krishnamoorthy E, LaFrance WC Jr, Mula M, Schmitz B, van Elst LT, Trollor J, Wilson SJ; International League of Epilepsy (ILAE) Commission on the Neuropsychiatric Aspects of Epilepsy. International consensus clinical practice statements for the treatment of neuropsychiatric conditions associated with epilepsy. Epilepsia. 2011 Nov;52(11):2133-8. • Orjuela-Rojas JM, Martínez-Juárez IE, Ruiz-Chow A, Crail-Melendez D. Treatment of depression in patients with temporal lobe epilepsy: A pilot study of cognitive behavioral therapy vs. selective serotonin reuptake inhibitors. Epilepsy Behav. 2015 Oct;51:176-81. • Panebianco M, Sridharan K, Ramaratnam S. Yoga for epilepsy. Cochrane Database Syst Rev. 2017 Oct 5;10:CD001524. • Steinert T, Fröscher W. Epileptic Seizures Under Antidepressive Drug Treatment: Systematic Review. Pharmacopsychiatry. 2017 Aug 29. • Wood K, Lawrence M, Jani B, Simpson R, Mercer SW. Mindfulness-based interventions in epilepsy: a systematic review. BMC Neurol. 2017 Mar 20;17(1):52. DEPRESSION & ANXIETY IN EPILEPSY

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