Management of depression in epilepsy

Treatment of psychiatric disorders in epilepsy is largely opinion-led, with little evidence from systematic randomized control trials (Krishnamoorthy 2003).

Pre-ictal and ictal depression do not usually require treatment; an improvement in seizure frequency reduces the occurrence of these forms of depression (Lambert 1999) Medications such as benzodiazepines e.g. clobazam, and behavioural methods such as progressive muscular relaxation, biofeedback, and yoga may abort or prevent the development of the attack. The general guidelines for management of depression in epilepsy include the following points.

Antidepressants
Management of depression in epilepsy with antidepressants involves three major issues:
  * a) effect of antidepressants on seizure threshold,
  * b) antidepressant-anticonvulsant interactions,
  * c) efficacy of antidepressants in this category of patient.
Chronic inhibition resulting in psychiatric disorders requires pharmacological intervention directed against this. The presence of dysphoric disorders in patients with epilepsy indicates the presence of marked inhibition. The proconvulsant nature of antidepressants appears to serve as effective antagonists to excessive inhibition. Patients with primary generalized seizures tend to have lower seizure thresholds, and antidepressants must be used with caution in these patients. Within certain concentration ranges, raised levels of extracellular serotonin have been shown to have converse anticonvulsant properties in animal studies (Clinckers et al. 2004).

Virtually all non-MAOI antidepressants, including the newer antidepressants such as citalopram, paroxetine, reboxetine and sertraline lower the seizure threshold in varying degrees (Trimble 1978b, Edwards 1985). Robenstein (Robenstein et al. 1993) suggested that SSRIs are less seizurogenic as compared to TCAs. Antidepressants and anti-epileptic drugs can affect each other’s levels, with anti-epileptic drugs usually reducing antidepressant levels and antidepressants increasing anti-epileptic drug levels (Robertson 1998a, Robertson 1998b). (Davis and Glassman 1989) in a recent review found that 65% patients on imipramine improved as compared with only 30% on placebo. (Trimble and Robertson 1985), in a placebo-controlled double-blind study however, showed that there were no significant differences between either active drug and placebo in the first six weeks of treatment.

Psychological therapies
Several models of cognitive behavior therapy, ranging from more generic applications to more specific models based on original research, have been applied in epilepsy. In a recent meta-analysis of psychological therapies in epilepsy however, Ramaratnam (Ramaratnam et al. 2001) concluded that, “in view of the methodological deficiencies and limited number of patients studied, we have found no reliable evidence to support the use of treatments and further trials are needed”.

The brief form of psychotherapy, group psychotherapy, patient support groups, relaxation therapy, and EEG biofeedback have all been shown to be effective.

Electroconvulsive therapy
Despite a few sporadic reports of spontaneous seizures after ECT (Devinsky 1983, Grogan et al. 1995), major studies have found the incidence of spontaneous seizures following ECTs to be lower than the incidence of epilepsy in the general population (Blumenthal 1955, Blackwood et al. 1980). ECT may be life-saving in some patients with depression, particularly severe or psychotic depression not responding to antidepressants. The efficacy of the ECT may, however, be reduced by anti-epileptic drugs. Weiner and Coffey (1993) recommend that, with the exception of patients at high risk for status epilepticus or with recent generalized tonic-clonic seizures, AEDs should be omitted the morning before each ECT treatment.

Novel treatments such as vagal nerve stimulation have recently been shown to have a positive effect on both epilepsy and co-morbid depression (Harden et al. 2000, Elger et al. 2000).

Finally, transcultural issues need to be addressed, and treatment approaches have to be tailored to meet the individual needs of the patient. Krishnamoorthy (2003), in a recent review, pointed out that while western patients and wealthier Asian patients welcome psychological explanations, patients from the lower socioeconomic groups in these settings may find these less acceptable. It is important that patients must be treated until complete resolution, as residual symptoms can impede the patient’s quality of life ( (figure 1) ).

Conclusion
Although most studies have reported a higher risk of depression in people with epilepsy as compared with normal controls, almost all studies (with a few exceptions such as Blumer 2002) report no difference between patients with epilepsy and other chronic disorders (Krishnamoorthy 2002). An argument raised by neuropsychiatrists and epileptologists is that patients with epilepsy have distinct and unique forms of psychopathology (Krishnamoorthy 2000, 2001). Neither traditional systems of classification used in psychiatry, such as the DSM or the ICD, which club the disorders under the broad umbrella of organic mental disorders, nor the ILAE classification, which does not address the psychiatric components of the disorder, do justice to these unique syndromes of “epilepsy-specific” psychopathology. The instruments used for identification of psychopathology in most studies are based on existing classification systems and are perhaps inadequate. Bear and Fedio (Bear and Fedio 1977) showed that while the MMPI failed to identify the difference between patients with TLE and other patient groups, the differences became apparent when the responses to an instrument they developed were analyzed. Blumer’s description of the interictal dysphoric disorder, seen in patients with refractory temporal lobe epilepsy, further endorses the need for a distinct classification system enabling a clearer phenomenological description of psychopathology in these patients.

Diagnosis of depressive states can be difficult. Studies have found that hospital medical and nursing staff fail to detect affective disorders in 34-72% of cases (Mayou 1986), and that General Practitioners correctly diagnose depression at first consultation in only 50% of cases (Roberts 1995). In patients with epilepsy, this problem is further compounded due to the presence of unique depressive syndromes (Hesdorffer 2000). Identification of these variants becomes important from a public health perspective. An increased prevalence of psychiatric co-morbidity in patients with epilepsy as compared with other adequately matched illness groups would warrant the creation of specific mental health resources for this patient group.

Although the first reference to epilepsy and melancholia was made by Hippocrates in 400 BC, two thousand years later, neuropsychiatrists and epileptologists are still grappling with the nuances and challenges posed by this sacred disease. A mere 7% of neurologists treating epilepsy routinely screen for depression in their outpatient clinics (Gilliam et al. 2004). With the description of a six-fold increased risk of unprovoked seizures in older patients with major depression and the possibility of a reverse causality, the relationship between affective disorders and epilepsy becomes even more intriguing (Kanner 2003). Affective disorders in epilepsy classically exemplify the expanding interface between psychiatry and neurology, the mind-body conundrum. Is it not time that neurologists and psychiatrists start talking to one another (Kanner 2003)?

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Author(s) : R Seethalakshmi, Ennapadam S Krishnamoorthy , The Institute of Neurological Sciences, Voluntary Health Services, Taramani, Chennai, India.

Summary : 1) Depression is a common and important accompaniment of epilepsy. 2) Depression in epilepsy is phenomenologically different from the usual forms of depression and it is essential that treating physicians assess for these varied forms as well. 3) Depression in epilepsy may be managed more effectively if the relationship to the ictus is better understood. 4) Other factors such as stressful life events, related or unrelated to epilepsy, may contribute to the depressive symptoms. 5) Antiepileptic drugs, particularly GABAergic agents such as vigabatrin, tiagabine, topiramate and phenobarbitone are depressogenic in nature. 6) The newer antidepressants, SSRIs such as sertraline, citalopram and paroxetine do not lower seizure threshold and can be safely used to treat depression in epileptic individuals. Fluoxetine may be avoided because of its longer half-life.

Keywords : epilepsy, depression, classification, etiology, treatment, SSRI

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