Pharmacologic And Psychotherapeutic Treatments For Depression And Anxiety

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According to the World Health Organization, by 2020 major depression will be the second leading cause of disability with cardiovascular disease as the leading cause (Michaud et al., 2001). In an editorial, Evans and Charney (2003) stated if an individual has a chronic condition and is depressed there was a poorer prognosis and even increased morbidity and mortality than from the medical diagnosis alone. Additively, co-occurring depression and anxiety is related to poorer prognosis, increased suicide risk, decreased treatment response, and increased functional impairments (Brown et al.) 1996) Sherbourne and Wells., 1997 ) Regier et al.) 1998) Kessler et al.) 1999a) Kessler et al.) 2005a, b) . Generalized anxiety disorder and major depression have been demonstrated to negatively impact quality of life more so than depression alone (Mittal et al.) 2006). Treatment of depression and anxiety will improve quality of life, reduce suicidality, and decrease functional impairments. Leaving depression and anxiety untreated only leads to poorer outcomes and prognosis.

In the epilepsy literature, a large knowledge gap exists in understanding the efficacy of pharmacologic and psychological treatments for both depression and anxiety. Notably, Kanner (2003) characterized treatment options for depression in epilepsy as remaining "unexplored territory." With this in mind, the pharmacological treatments and psychological treatment options for depression and anxiety will be summarized below.

Pharmacological treatment

There are several factors to consider before initiating any pharmacological treatments. It will be important to rule out any potential factors influencing the presentation of symptoms of depression or anxiety (Kanner, 2003). First, it is important to know if an AED has been discontinued. Ketter et al. (1994) demonstrated that AED withdrawal may result in the development of symptoms of depression or anxiety even after a gradual tapering of the antiepileptic medications. Additionally, individuals with ictal anxiety were at higher risk for developing anxiety after AED withdrawal. Second, it is important to assess if an AED with negative psychotropic properties is being used, and if there was a change in the dosing of the AED. The following medications have negative psychotropic properties: phenobarbital, primidone, tiagabine, topiramate, and vigabatrin. If appropriate, an antidepressant can be used to counteract the negative side effects of the AEDs.

When considering the introduction of an antidepressant in an individual with epilepsy on AEDs, there is concern among clinicians regarding the potential to lower the seizure threshold and increase seizure frequency and severity if an anti-depressant is utilized. There are potential risks; however, by monitoring plasma serum concentrations, introducing the antidepressant in low doses with small increments, and avoiding using antidepressants with other drugs with proconvul-sant properties the overall risks can be significantly minimized (Rosenstein et al.) 1993). There are several antidepressant drugs with proconvulsant properties that should be avoided in individuals with epilepsy. These include bupropion, maproti-line, and amoxapine (Kanner, 2003). It is important to treat depression and anxiety in epilepsy while monitoring the potential risks.

Pharmacological treatments for depression

SSRIs are recommended to be the first pharmacological treatment option for depression in epilepsy (Kanner and Balabanov, 2002; Kanner, 2003) . SSRIs have fewer side effects and a low risk of increasing seizure frequency or lowering the seizure threshold (Scicutella, 2001) . A note of caution should be made, regarding the potential interaction between SSRIs and AEDs since certain SSRIs inhibit certain CYP450 enzymes, resulting in adverse interactions with hepatically metabolized AEDs. These medications include fluoxetine, paroxetine, and fluvox-amine (Scicutella, 2001; Kanner and Balabanov, 2002). Sertraline is frequently recommended due to the minimal pharmacokinetic interactions with AEDs (Barry, 2003 ; Kanner, 2003) . Additionally, Kanner (2003) cautioned that individuals can develop a therapeutic tolerance to sertraline within a few months, resulting in the need to introduce a new SSRI in short order. Citalopram is also a possible treatment option because it does not inhibit the CYP450 enzymes (DeVane, 1999) . TCAs are a second line of drugs used to treat depression. However, TCAs have cardiotoxic effects and can easily cause an overdose. In an anecdotal study, Blumer et al. (1995) report using low dose imipramine in patients with epilepsy with positive results. There are a number of pharmacological treatment options that appear to be effective in treating depression in epilepsy, but future randomized controlled studies will shed light on the best treatment options for people with epilepsy who have depressive disorders.

Pharmacological treatments for anxiety

A number of SSRIs are approved by the Food and Drug Administration (FDA) in the United States to treat anxiety disorders. Sertraline is approved to treat panic disorder, post traumatic stress disorder and obsessive compulsive disorder, and par-oxetine is approved for treatment of panic disorder, obsessive compulsive disorder, generalized anxiety disorder, and social phobia. Obsessive compulsive disorder can also be treated by fluoxetine. In the general population SSRIs are effective, tolerated and safe for the treatment of anxiety disorders. Other drugs approved to treat anxiety disorders include: clonazepam for panic disorder, and alprazolam for generalized anxiety disorder and panic disorder. Benzodiazepines can cause sedation, psychomotor slowing, decreased attention, impaired memory and a risk for addiction. Venlafaxine is approved for use in generalized anxiety disorder (Davidson et al.; 1999) . It inhibits serotonin and NE reuptake. Venlafaxine has side effects that include nausea, nervousness, and hypertension. Additionally, in a randomized placebo controlled, double blind study, venlafaxine was demonstrated to be efficacious in the treatment of comorbid major depression and generalized anxiety disorder (Silverstone and Salinas, 2001). Buspirone, a partial serotonin agonist and propranolol, a beta blocker, have been used in the treatment of generalized anxiety disorder. No studies have investigated the pharmacological treatment of anxiety disorders in epilepsy, and no studies have examined the treatment options for co-occurring depression and anxiety in epilepsy.

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