Depression Anxiety in Epilepsy Katherine Inoyama MD October

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? DEPRESSION & ANXIETY IN EPILEPSY

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

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

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

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

DEPRESSION & ANXIETY IN EPILEPSY (Kendler, 2002)

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

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

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

Anxiety Disorders § § § Generalized anxiety disorder Agoraphobia Panic disorder Social anxiety disorder Specific phobia DEPRESSION & ANXIETY IN EPILEPSY

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

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

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

How common are these disorders? Major depressive disorder: General population o Lifetime prevalence 16. 5% People with epilepsy o Lifetime prevalence 30 -35% Anxiety disorders: General population o Lifetime prevalence 5 -31% People with epilepsy o Lifetime prevalence 11 -50% DEPRESSION & ANXIETY IN EPILEPSY

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

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

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

Suicide § People with epilepsy have a suicide risk 3 to 5 X 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

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

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

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

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

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

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