In some patients a change of elevated mood can be detected a few days after surgery. It may begin with an excessive feeling of gratefulness for the surgeon who is denoted as the savior and responsible for the patient's new life. Although this affection is partly comprehensible the mood may switch into a socially inappropriate euphoric state, including seeking emotional closeness to rather distant persons, and finally the development of classic hypomanic symptoms (e.g., increased levels of energy, insomnia, pressured speech, flight of ideas, marked irritability, and increased sexual activity). Risk factors have included right temporal resection and bilateral electrographic ictal foci (Carran et al., 2003).
In most cases hypomanic symptoms are identified in the early postsurgical period and typically are short-lived. Pharmacotherapy is rarely required, lest the patient does not respond to redirection over the euphoric mood and limit setting of inappropriate behavior. Low doses of atypical antipsychotic medication for a few days or up to 2 weeks may be sufficient. Of note, postsurgical hypomanic episodes may herald an undetected bipolar disorder and should alert the clinician to the cautious use of antidepressant drugs.
Anxiety symptoms occur in the early postoperative period, often before manifest depression develops (Ring et al., 1998). In fact, symptoms of anxiety and fear of variable severity have been reported to occur in about 40% of patients. In many patients anxiety is a reasonable expression of uncertainty about the future perspective of a life without epilepsy, or of fear of recurrent seizures. Postoperative anxiety, thus, is a mixed psychoreactive and organic problem, a typical constellation of many psychiatric syndromes in epilepsy patients.
The treatment of anxiety episodes includes the use of benzodiazepines (e.g., clobazam, lorazepam) for a short time period. When anxiety is accompanied with depressive symptoms an antidepressant treatment is indicated. Some of the selective serotonin reuptake inhibitors (SSRIs) are approved for the use in anxiety disorders as well, which should be considered for long-term treatment of a pure anxiety disorder.
Depression and organic asthenic disorders
A depressive disorder may be identified about 3 months after surgery and in some patients earlier in about 10–30% of patients, independent of seizure outcome. Although preoperatively depressed mood in epilepsy patients often appears with dysthymic or dysphoric affect, with short-term mood changes lasting hours or days, as described in the interictal dysphoric disorder (IDD) by Blumer (Blumer et al., 2004), the postoperative mood changes have a different quality: persisting, more severe, associated with loss of interest and pleasure, feelings of hopelessness, and decreased energy and self-drive. Therefore, postoperative depression can present as a major depressive episode, and in patients with presurgical interictal dysphoric disorder, display more severe characteristics.
Overlapping with depression many patients have a physical and mental asthenia, which is an organic sequel of the surgical procedure, as described by Malmgren et al. (2002). This kind of fatigue and lack of psychophysical energy goes along with avoidance of social contacts because communications seem arduous, stimulus-selection fails, and high sensitivity to noise leads to withdrawal from interaction.
According to the American Psychiatric Association (APA) guidelines, depression requires multimodal treatment. Of course this applies to patients with depressive disorder in epilepsy as well. Generally, to promote good disease management it is important to assess impairment of quality of life at the beginning of treatment and set adequate goals for the course of recovery. A good coordination of care with other health professionals is necessary. The use of self-rating and clinician-rating scales to monitor symptom development is recommended.
An important basis for the treatment of depression is providing information about the disease as well as an education about treatment strategies for patient and family, including an explanation of all symptoms (including emotional withdrawal from close persons) and their transient character (e.g., positive prognosis), despite the actual feelings of hopelessness. Patients should be advised not to make life-changing decisions during a depressive episode (including no definite breakup with partner). Patients and family members should also be informed about associated cognitive complaints (poor concentration, distractibility, loss of attention) as they may also be signs of depression.
Before the start of any pharmacotherapy, medical factors facilitating the depressive episode should be identified and treated. Antiepileptic drugs (AEDs) may have to be changed (e.g., AEDs with negative psychotropic properties started after surgery, such as levetiracetam, topiramate, zonisamide, and barbiturates). No changes are required, however, if patients had been taking these AEDs before the surgical intervention without any psychiatric symptoms.
The next treatment step is to introduce antidepressant medication, which has been proved to be effective in depression accompanying neurologic disorders (Price & Rayner, 2011), although no controlled placebo-controlled trials have been published in patients with epilepsy. Yet, there is a consensus that the use of antidepressants in patients with epilepsy yields a therapeutic effect and drugs of the selective serotonin reuptake inhibitor (SSRI) family have been suggested as first choice (e.g., citalopram, escitalopram, or sertraline) (Kerr et al., 2011; see also the article on Treatment of Depression in this issue).
Some patients may be reluctant to take additional medication, especially those who had been told previously that psychotropic drugs are associated with a potential proconvulsant risk. It is important to inform patients that several studies have demonstrated clinical improvement of the depressive episodes without an increased risk of seizure occurrence when using antidepressant drugs at therapeutic doses (and in some cases, a decrease in seizure frequency associated with improvement of mood has been suggested by several authors) (Hovorka et al., 2000; Kühn et al., 2003; Specchio et al., 2004).
The use of SSRIs may at times cause insomnia, in which case the drug should be administered in the mornings. Although mirtazapine has been suggested as an alternative (Noe et al., 2011), this antidepressant has been shown to have an increased proconvulsant risk (Münchau et al., 2005). In the Bielefeld surgery program, two cases of a first seizure occurrence after surgery were associated with the introduction of mirtazapine. Agomelatine, a melatonin-activating agent, may be used with sleep disorders as primary symptoms, although the magnitude of the antidepressant effect seems to be limited (Singh et al., 2011).
After remission of the depressive episode, treatment must be continued for 6 months (Kerr et al., 2011; 1999, 2010) and when discontinuation is planned, the dose of the medication should be tapered down over the course of several weeks.
If SSRIs are ineffective, a switch to a serotonin-norepinephrine reuptake inhibitor should be considered. Tricyclic antidepressants are another option, although this class of drugs is associated with a lower tolerability and higher cardiotoxicity, which can facilitate a successful suicide attempt in case of an overdose.
If depression is accompanied by delusional symptoms, antipsychotic medication should be added to the pharmacologic regimen. Blumer (Blumer et al., 1998) recommended the use of low-dose risperidone.
In treatment-resistant severe depression after epilepsy surgery, especially when suicidal risk requires rapid therapeutic changes, electroconvulsion therapy (ECT) has been used safely (Kaufman et al., 1996; Aksoy-Poyraz et al., 2008).
With respect to psychotherapy, cognitive behavior therapy (CBT) is indicated (and has been found to be as effective as antidepressant medications) for mild or moderate depression (2010). Typically, 12–16 treatment sessions are sufficient to address the obstacles posed by the depressive disorder. CBT has been successfully tested in patients with epilepsy (Macrodimitris et al., 2011; Crail-Meléndez et al., 2012). In addition, the psychodynamic approach Interpersonal Psychotherapy (IPT) has proven to be effective in the treatment of depression (Jakobsen et al., 2012). It includes four major treatment areas all of which seem highly appropriate for treatment of depressed patients with epilepsy after epilepsy surgery: grief, conflicts in relationships, problems with change of life circumstances, and social isolation. Unfortunately, limited or no access to CBT and IPT is a common problem in most countries.
The rate of de novo postoperative psychoses is low, but it is an eminently harmful condition that affects about 2% of patients after epilepsy surgery (Koch-Stoecker & Kanemoto, 2008). Postsurgical psychotic episodes often develop later than depressive episodes (>6 months after surgery), independently of seizure outcome. Their severity may range from worried-skeptical mistrust to paranoid-hallucinatory schizophrenia-like syndromes compromising survival by self-harmful actions or aggression toward others.
In some cases, psychotic episodes may evolve from a severe depressive episode, which may delay the recognition of the psychotic features. Family members need to be instructed on the natural course of the psychotic episode, while the need for inpatient hospitalization may need to be considered.
With respect to the treatment, the use of the newer atypical antipsychotic agents is indicated and should be maintained for half a year after symptom remission at a minimum. In complicated patients with a suspected thought disorder, Blumer (Blumer et al., 1998) recommends adding a low dose of risperidone (1–2 mg/day) even before overt psychotic symptoms appear.
In the case of persistent psychotic episodes, the patient should be referred to day-hospital programs, which should include family members in the therapeutic process. In addition, vocational evaluations and training in sheltered workshops can be planned before discharge.
As in the case of severe depression, there have been reports of the effective use of ECT in severe postoperative psychoses (Maixner et al., 2010). In these cases the concept of alternative psychosis associated with the surgery-related phenomenon of forced normalization (Wolf & Trimble, 1985; Schmitz, 1998) should be considered.