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Anxiety in Epilepsy

Evidence- based management of anxiety in epilepsy
Anxiety is as common a symptom observed in patients with epilepsy as depressive symptoms, and is often overlooked. It is now clear that anxiety in the presence of depression is responsible in the number of patients attempting suicide. Anxiety in patients with depression is considered to be a result the unpredictability and vulnerability of seizure episodes. This fear is said to trigger a neurobiological response from the amygdala, hippocampus and hypothalamic axis. Pharmacological treatment of anxiety symptoms in epilepsy needs to be identified, and categorized in order to benefit patients.

Classification and treatment of anxiety disorders in epilepsy

According to the fourth edition of The Diagnostic and Statistical Manual of Mental Disorders text revision (DSM-IV-TR), classification of anxiety disorders in epilepsy includes:

(i) Generalized anxiety disorders (GAD):
Treatments widely used for GAD are drug therapies and cognitive behavioral treatments. Clinically, benzodiazepines are the widely used. However, clinical evidence from a systematic review points that antidepressant drugs imipramine, venlafaxine, and paroxetine are efficacious in GAD. Short and long-term efficacy has also been evidenced with pregabalin. The role of cognitive behavioural therapy (CBT) in GAD is still being debated with mixed results from existing data.

(ii) Panic disorder (with or without agoraphobia)
Panic attacks can be triggered on a recurrent basis in patients who are concerned about future attacks. Panic can occur with or without agoraphobia (fear of public places), although many
patients with panic disorder also have agoraphobia. Panic disorder can be controlled
successfully with CBT that is a commonly employed technique. Additionally, antidepressants and benzodiazepines are also widely used. Several meta-analysis have indicated equal efficacy of selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants (TCAs) with SSRIs being better tolerated. Further, a Cochrane metaanalysis indicated that psychotherapy alongside pharmacological management could have a role in the treatment of panic disorder.

(iii) Obsessive-compulsive disorder (OCD)
In OCD, evidence points to the fact that patients respond well to CBT and clomipramine is most effective in severe cases. Clomipramine therapy must be monitored for potential complications related to the cardiovascular system, anticholinergic effects, sedation, weight gain, and sexual dysfunction. A meta-analysis suggests that clomipramine may be more efficacious than SSRIs in reducing symptom severity in more severe cases. Seizure exacerbation and pharmacodynamics interactions with AEDs must be carefully examined.

(iv) Posttraumatic stress disorder (PTSD)
Since only 1% of patients with epilepsy display PTSD, evidence regarding ideal treatment is limited. Among SSRIs, some evidence indicates that paroxetine and sertraline reduces PTSD symptoms. As far as psychotherapy is concerned, PTSD-specific CBT may be of value in severe patients with psychosis or suicidal ideation.

(v) Social anxiety disorder
Nearly 3% and 7% of epilepsy patients will exhibit social anxiety disorder. Both SSRIs and CBT have been found to be effective in controlling symptoms.

Summary points: take home messages
• Evidenced-based therapeutic strategies in epilepsy patients with anxiety disorders should be directed according to the individual symptoms, needs and tolerability
• CBT is ideal when combined with pharmacotherapy for long-term maintenance
• SSRIs vs TCAs have a better pharmacodynamics and safety profile
• In GAD, pregabalin has to be considered first choice for short-term and long-term treatment
• In SAD and PTSD, SSRIs can be considered first choice, in particular sertraline and paroxetine
• CBT has always to be considered first choice in patients with epilepsy. If CBT alone is not sufficient and drug treatment is needed, SSRIs, in particular sertraline, are preferred
• Careful clinical monitoring is necessary for potential seizure precipitation or side effects due to pharmacodynamic interactions with AEDs.

Adapted from Mula M. Treatment of anxiety disorders in epilepsy: an evidence-based approach. Epilepsia. 2013 Mar;54Suppl 1:13-8. doi: 10.1111/epi.12101.