Suicide: Incidence, Psychopathology, Pathogenesis, and Prevention

Dietrich Blumer

Introduction

Suicide among patients with epilepsy has been widely recognized as a serious problem. In modern times, its frequency appears to approach the frequency of death from seizures. However, the frequency of its incidence is still debated, its psychopathology and pathogenesis remains unclear, and no proper method of prevention has been established.

Review of Literature

Frequency of Suicide

In a recent paper, Jallon²⁸ reviewed the significantly higher mortality of patients with epilepsy by status epilepticus, sudden unexplained death, and suicide, compared with the general population. He expressed concern that the reports on suicide were based on small samples from different populations and from highly selected groups of patients and used different methods of analysis. However, an analysis of the populations that differed in the numbers of suicide and an investigation (published in 2005) of the frequency of suicide in 29 cohorts of patients with epilepsy⁴⁴ provide answers to this concern.

Suicide is a rare event, occurring only slightly more than once among 10,000 persons annually in the United States.⁴¹ In a review of completed suicide in manic-depressive patients, Goodwin and Jamison found a mean of 19% of deaths secondary to suicide in this population.²² A similarly high suicide rate among patients with epilepsy has been documented: In a Danish study,²⁶ 164 of 2,763 patients with epilepsy suicided (an excess mortality rate of 273% compared with the number of deaths expected in Denmark); the case material included all adult patients discharged with the diagnosis of epilepsy at four neurologic clinics over 14 years, and any patient with a handicap other than epilepsy was excluded from the study. Although epilepsy was the immediate cause of death in 26%, suicide was the second leading cause of death in 20% (an excess mortality rate of 300%) at an average age at death of 32 years. According to eight reports, death by suicide occurs in 5% of patients with epilepsy, compared with 1.4% in the general population.³⁶ Based on a wider review of the literature, a fivefold increase in suicides among patients with epilepsy over the rate in the general population was found among those attending special clinics and was magnified to as much as 25-fold among patients with temporal lobe epilepsy (TLE).¹ A study by Hauser et al.,²⁴ on the other hand, included a general population of patients with epilepsy followed from the time of diagnosis, and not from the time of registration in a neurologic clinic; their patients were less severely affected, and they reported no suicides in excess of expected numbers. Suicide appears to represent a serious problem not in the general population of patients with epilepsy, but among those with more difficult epilepsy who require treatment in specialty clinics.

Since Jallon’s review, Pompili et al.⁴⁴ investigated 29 studies of suicide in epilepsy, comprising 50,814 patients, of whom 187 committed suicide. Their meta-analysis showed that suicide in epilepsy is indeed more frequent than in the general population, but with significant exceptions. A study by Cockerell et al.¹² included patients with newly diagnosed or suspected epilepsy who were ascertained when attending a general practice, with a median follow-up of less than 7 years; a single suicide was registered among 792 patients. As in the study by Hauser et al.,²⁴ few severely affected patients were included. In contrast, the largest study cited by Pompili et al., 10,739 patients from our Epi-Care Center,⁸ registered only five suicides (a rate lower than in the general population), not because of lack of severity of the epilepsy in the population, but because all patients with psychiatric complications were treated, at intake or as soon as needed, with proper psychotropic medication. This study will be fully reviewed, for a better understanding of suicide in epilepsy and to establish specific guidelines for its prevention.

Psychopathology Associated with Suicide in Epilepsy

The generally difficult psychosocial circumstances of patients with chronic epilepsy have often been considered the leading factor responsible for their elevated suicide rate, more important than the presence of psychiatric illness or the availability of drugs.¹⁵ However, in general, psychiatric illness has been identified as the nearly universal antecedent of suicide, and psychosocial circumstances cannot be considered causes for suicide.³⁵^,⁴¹ Very few reports have attempted to clarify the nature of the psychiatric disorder that may lead to suicide among patients with epilepsy.

Nilsson et al.⁴² pointed out that studies are lacking in which persons with epilepsy who have committed suicide are compared with relevant controls to identify risk factors for suicide. In their case-control study of risk factors for suicide in epilepsy, they compared 26 cases of suicide and 23 cases of suspected suicide with 171 controls, within a cohort of 6,880 registered with a diagnosis of epilepsy in the Stockholm County Inpatient Register. They found a ninefold increase of suicide with mental illness and a tenfold increase in relative risk with the use of antipsychotic drugs. They arrived at a profile of the epilepsy patient who commits suicide as one with early onset, but not necessarily severe, epilepsy and with psychiatric illness (depression, psychosis, substance abuse).

Mendez et al.⁴⁰ studied the causative factors for suicide attempts by overdose in 22 patients with epilepsy (from 711 patients hospitalized for a suicide attempt) and concluded that interictal psychopathologic factors were of primary importance. A comparison of suicide attempts among patients with epilepsy and comparably handicapped controls with other chronic disabilities found that 30% of patients with epilepsy had attempted suicide, as compared with 7% of the controls.³⁸

In 1992, Mendez and Doss³⁹ reported on the suicides in a substantial population of patients with epilepsy and included clinical details of all fatal outcomes. They documented the neuropsychiatric aspects of the four patients who died by suicide out of 1,611 patients with epilepsy followed in a neurology clinic over a period of 8 years: two male patients with chronic psychosis, depressive moods, and good seizure control; one male patient with brief psychotic episodes associated with confusion and increased bitemporal spikes and diffuse slowing on electroencephalogram (EEG) in the absence of seizures; and one female patient with episodes of profound ictal and postictal depression who suicided after three witnessed staring spells. The patient with brief psychotic episodes and one of the patients with chronic psychosis experienced voices commanding them to commit suicide. All four patients had suffered from complex partial seizures since childhood and committed suicide by medication overdose at a time when their seizures were controlled, except for the patient who suicided in a state of postictal depression.

Fukuchi et al.¹⁷ reviewed the case records of all outpatients of two epilepsy centers who had died. Patients in one center were followed for 10 years and in the second center for 7 years. Those who had unclassified epilepsy or who died as the result of an underlying disease (such as neoplasm) were excluded. More than 4,000 subjects were reviewed, and the records of 43 deceased patients with well-classified epilepsy were analyzed. Suicide occurred in six patients (14% of the deaths), all with TLE, and three suicided by throwing themselves in front of an oncoming train in the midst of an episode of postictal psychosis. The authors noted the agreement of their findings with those of Mendez and Doss.³⁹ While providing fewer details, they concluded that most suicides in epilepsy were the result of an immediate causal relationship with ictal or interictal epileptic manifestations. The authors referred to reports of violent behavior directed outward following complex partial seizures, and proposed that this violence may eventually turn into a paroxysmal self-destructive impulse.²⁰^,³¹

Suicides After Successful Treatment of Seizures and After Surgical Treatment of the Epilepsy

For an understanding of the pathogenesis of suicide in epilepsy, evidence for the role of predominant inhibition (“forced normalization”)²¹^,³³^,³⁴^,⁵¹ must be reviewed.

In 1969, Janz²⁹ stated that suicide does not occur among patients with severe epilepsy but does occur not infrequently among those patients who have just become free from seizures. With the guidance of Janz, Haltrich²³ studied the causes of death among 909 patients with epilepsy who had been treated at the neurology clinic of a German university during the preceding 8 years (1946–1953); his report includes a large number of suicides with highlights of their psychopathology. Of the 83 patients with symptomatic epilepsy, 51 died from brain tumors. The 11 recorded suicides all occurred among the 78 patients with cryptogenic epilepsy, and at 14.1% surpassed any other cause of death in this group; eight patients (10.3%) died from seizure status and six patients (7.7%) from single seizures. Among the 11 suicides, eight patients had complex partial seizures. Increased irritability was reported in six of the seven males (four with episodes of violence) and in one of the four females; four patients had a history of previous suicide attempts, and another three patients had experienced depressive moods with or without suicidal thoughts. Only one patient suicided during a psychotic state after three previous suicide attempts in psychotic or dysphoric states; he had been violence-prone and was the only patient requiring institutionalization among the 11 who suicided. Haltrich included three later cases of suicide when he reported that the 14 patients had responded well to treatment of their seizures; at the time of suicide, three had experienced only minor attacks, seven only very rare or no major seizures, and four had rare or no seizures of any type.

Taylor and Marsh⁴⁹ reported on the occurrence of suicide among 193 patients who had undergone temporal lobectomy and who were followed from 5 to 24 years. Of 37 deaths, nine were by suicide (24.3%). Including an additional six patients who died in unclear circumstances would have raised the suicide rate observed from 25-fold to 50-fold of that expected.⁴⁸ Five of the nine who definitely suicided had been rendered seizure-free by the surgery. The authors did not describe the mental state of the victims and merely documented the very high risk of suicide in their particular population.

In another series of surgically treated patients with epilepsy, Hennessy et al.²⁵ reported only one suicide among 20 deaths in their cohort of 305 consecutive patients who had TLE surgery over a 20-year period. A second patient ran onto a road and was killed by a passing car; both patients were seizure free. The authors suggested that the early series of Taylor and Marsh,⁴⁹ with its much higher postoperative suicide rate, had included many patients referred from the Maudsley psychiatric institution. However, the origin of the populations of patients surgically treated and with reports of postoperative mortality is usually not well defined. A large group surveyed from 1928 to 1973 by Jensen³⁰ includes 2,204 patients who had unilateral temporal lobectomy, with 164 postoperative deaths: due to epilepsy in 26%, suicide in 20%, and accidents in 11%; no details were provided about the suicides.

Of interest is the report by Bladin² who reported, with remarkable details of the psychosocial outcome, the results after temporal lobectomy of a series of 115 consecutive patients. They were followed as closely as possible for a mean of 4 years after temporal lobectomy. Five patients showed significant episodes of depression after the operation. In three of them, recognition and antidepressive therapy produced prompt improvement. Another patient, who was seizure-free, was rehabilitated by friends in a religious organization after two suicide attempts. The fifth patient, who lived at a distance and could not participate in the routine postoperative follow-up, was also free of seizures yet committed suicide following the unexpected death of mother and sibling. Three patients showed psychotic episodes more than 3 months after the operation and responded to appropriate therapy, including a neuroleptic. Postoperative anxiety was noted in about half the patients and responded to counseling, medication, or brief hospitalization. Increased sexual drive was reported only upon optimal seizure control. Bladin’s report is unique in its report of the use of psychotropic medication for patients with epilepsy.

Psychopathology, Pathogenesis, and Prevention of Suicide: the Study of Patients Treated at the Epi-Care Center

In Chapter 205 on affective disorders of epilepsy, we concluded that the pre-modern psychiatrists, who commonly observed patients with epilepsy on a daily basis, were correct when they
recognized the interictal dysphoric disorder with its intermittent and pleomorphic symptomatology as the predominant specific psychiatric disorder of chronic epilepsy. The interictal dysphoric disorder includes episodes of anxiety, fear, elation, insomnia, anergia, pain, explosive irritability, and depressive moods that may be intense and associated with suicidality. The disorder, in its entirety, is well treated with low doses of antidepressant medication. Subsequent to the detailed report of our experience with suicide in a large population of patients attending our epilepsy center, the psychopathology, pathogenesis, and prevention of suicide in epilepsy will be discussed.

A total of 10,739 patients with epilepsy were treated at the Epi-Care Center in Memphis during a 12-year period (1987–1999). The population included a large number of referrals from the mid-South area and beyond. About 900 patients were surgically treated during this period. The comprehensive professional team of the Center consisted of a neurologist, neurosurgeon, electroencephalographer, neuropsychologist, and the same psychiatrist (D.B.) during the entire period. The tasks of the psychiatrist included evaluating all patients admitted for intensive neurodiagnostic monitoring (as candidates for surgical treatment of medically intractable epilepsy or for clarification of the differential diagnosis between epilepsy and nonepileptic seizures) and of every patient at the center who was judged by the team to have psychiatric difficulties. Every patient in need of psychiatric assistance was followed at the Center with the appropriate psychopharmacologic and supportive treatment regardless of geographic distance, as long as the patient and family were able to come for return visits. Patients who required psychiatric hospitalization were admitted under the care of the team psychiatrist in the same hospital where the team admitted its patients for evaluation and treatment of the epilepsy. The presence of a team psychiatrist at the Epi-Care Center and the effectiveness of the psychotropic treatment employed assured prompt referral of patients with psychiatric complications, who were not routinely evaluated by the psychiatrist, for early treatment beyond antiepileptic treatment. Neuropsychological testing of all patients admitted for intensive monitoring and of a large number of outpatients, as well as a weekly case conference, greatly facilitated the teamwork and the referrals to the psychiatrist for early treatment.

The gradual development of a standardized psychiatric evaluation by a comprehensive questionnaire for seizure patients using a semistructured interview of patients and next-of-kin and of an increasingly effective psychopharmacologic treatment has been reported elsewhere.⁵^,⁹^,¹⁰^,¹¹ Initially, most patients with psychiatric complications of their epilepsy were treated by adding a modest dose of tricyclic antidepressant to the antiepileptic medication. With the development of treatment by double antidepressant medication (tricyclic plus serotonin-specific reuptake inhibitor) and the addition, if necessary, of a small dose of an atypical antipsychotic drug (risperidone), it became possible to treat successfully the vast majority of patients with any degree of psychopathology, including psychoses and suicidality.

The death of a patient with epilepsy at a treatment center is a memorable event. The number of patients who suicided was ascertained from medical records and the combined memories of the treatment team. The Epi-Care Center was the major center for treatment of epilepsy in the Mid-South and had a policy of careful follow-up of all patients. Thus, the death of one patient who had moved to a distant state about 1 year before her suicide (case 3) is included, as we had attempted to remain helpful.

Results

A total of five (four males, one female) of 10,739 patients attending the Center during the 12-year period committed suicide. The circumstances of these five treatment failures are reported here.

Case 1 (1989)

This male patient had had seizures since age 10. Following a 6-month marriage in late adolescence, he married two more times. His second wife had suicided following childbirth after 1 year of marriage; at that time, the patient became suicidal himself and required 2 months of psychiatric hospitalization. During the third marriage that lasted 4 years, he became suicidal when his wife left him with their child; he blamed his bad temper for the final breakup that had occurred 1 year prior to referral to the Center. His seizures became increasingly more frequent, occurring as often as three times daily. He was then treated by right temporal lobectomy at age 32.

After the operation, he experienced epileptic seizures on only two occasions after missing his medication. There had been a brief episode of feeling suicidal shortly after surgery, but soon he became enthusiastic about the success of the surgery, volunteered to talk to patients who were candidates for surgical treatment of their epilepsy, was active in the local chapter of the Epilepsy Foundation, and was working on a book about epilepsy. When he experienced an episode of dissociation with amnesia 12 months after his surgery, he was scheduled for psychiatric evaluation. Shortly thereafter, he developed frequent nonepileptic seizures.

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