Epilepsy & Behavior 19 (2010) 156–158
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Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Review
Postictal affective episodes Andres M. Kanner a,⁎, Michael Trimble b, Bettina Schmitz c a b c
Department of Neurological Sciences, Rush Medical College and Rush University Medical Center, Chicago, IL, USA Institute of Neurology, National Hospital Queen Square, London, UK Neurologische Klinik, Charite Virchow Klinikum, Humbolt Universitat, Berlin, Germany
a r t i c l e
i n f o
Article history: Received 17 June 2010 Accepted 17 June 2010 Keywords: Postictal depression Postictal anxiety Postictal suicidality Pharmacoresistant epilepsy
a b s t r a c t Despite their recognition two centuries ago, postictal depression symptoms (PDSs) and episodes (PDEs) continue to be ignored by most clinicians in their evaluation of patients with epilepsy. And yet, PDSs are relatively frequent in patients with pharmacoresistant epilepsy, having been identified in almost 50% of patients with a median duration of 24 hours. PDSs may be the expression of symptoms restricted to the postictal period (defined as the first 5 days following a seizure) and/or may be the expression of postictal exacerbation in severity of interictal symptoms of depression. In fact, a past history of depressive and anxiety disorders has been associated with the occurrence of PDSs and PSEs. PDSs and PSEs often occur together with postictal symptoms of anxiety, and the occurrence of PDSs has been associated with more severe postictal cognitive deficits. The occurrence of PDSs and PDEs has not been associated with any epilepsy-related variable (location of seizure focus, MRI findings, type of antiepileptic drug). Prevention of PDSs and PDEs can be achieved only with seizure freedom, and preliminary uncontrolled data suggest that being on antidepressant medication does not protect patients from experiencing these types of symptoms. © 2010 Elsevier Inc. All rights reserved.
The worst aspect of having seizures is the way I feel the day after. I wake up feeling so depressed, I start crying without any reason, I feel totally helpless and hopeless. I pace back and forth in my apartment and cannot focus on anything. Often I become obsessed with the thought that it would be better if I just died. I think that the only reason I never acted on these thoughts is the knowledge that these symptoms would go away after three days. The preceding is a description of a postictal depressive episode (PDE), defined as a group of symptoms of depression occurring within 5 days of a seizure (or cluster of seizures) and lasting more than 24 hours. Yet, postictal depression symptoms (PDSs) can also occur as isolated symptoms and last less than 24 hours. They are likely to occur in patients with more severe and chronic epilepsy. The clinical manifestations of PDEs are not restricted to PDSs, but also include symptoms of anxiety, as illustrated in the PDE described above. Postictal symptoms of depression and PDEs have been recognized for more than 100 years; descriptions of postictal mood changes can be found in the writings of Gowers [1] and Hughlings Jackson [2] in the 19th century and of Kraepelin [3] in the early 20th century. They can be identified in the early postictal period, that is, immediately after a seizure (or cluster of seizures), but more typically they occur following a symptom-free period between the last seizure and the first psychiatric ⁎ Corresponding author. Department of Neurological Sciences, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA. Fax: + 1 312 942 2238. E-mail address:
[email protected] (A.M. Kanner). 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.06.024
symptom, which can span from 12 hours to 7 days, with most symptoms appearing within 72 hours of the last seizure. This time gap between seizure and onset of symptoms often leads to the misinterpretation of these symptoms as interictal. Thus, most authors have considered a postictal period as encompassing the first 7 days after a seizure [4–8]. Despite their relatively high frequency and significant negative impact on the quality of life of patients with epilepsy, PDSs and PDEs are usually ignored in the evaluation of most patients with epilepsy and, not surprisingly, have been studied in a systematic manner by very few authors. The purpose of this article is to highlight the main clinical characteristics of postictal affective symptoms, which include PDSs, presenting as isolated symptoms or clustering into PDEs, and postictal hypomanic symptoms (PHMSs). Given the high comorbidity of PDSs and postictal anxiety symptoms (PASs), a review of these symptoms is also included. 1. Can the equivalent of PDSs be identified in animal models of epilepsy? Using an animal model of amygdala-kindled seizures in rats, Engel et al. [9] examined the behavioral changes observed during the postictal period and noted the occurrence of postictal aggression that presents as reactive biting. Caldecott-Hazard et al. [10,11] suggested that this postictal phenomenon may be mediated by opioids, as pretreatment with the opioid antagonist naloxone can worsen the rats’ hyperreactive behavior, whereas pretreatment with morphine can suppress it. In fact, endogenous opioids are usually released during seizures; therefore, the animal is exposed repeatedly to transient
A.M. Kanner et al. / Epilepsy & Behavior 19 (2010) 156–158
increments, creating a state of dependency. Thus, Engel et al. suggested that this postictal aggressive behavior may be the expression of endogenous opioid withdrawal [9]. These authors also noted that the transient suppression of the multiple-squeak response in the rat, the duration of which can be shortened by pretreatment with naloxone, further supports a pathogenic role of endogenous opioids and suggests that they may be the equivalent of postictal affective disturbances, as this reaction to pain has been considered to reflect a measure of affective function [12]. Whether these theories are applicable to the occurrence of PDEs in humans is yet to be established. Nonetheless, opioids have been recognized as playing a pathogenic role in interictal depression, as endogenous opioids also may play the role of natural mood elevators and have been thought to mediate, at least in part, the therapeutic effects of electroconvulsive therapy [13,14]. They support this hypothesis with data from positron emission tomography studies that used the mu opioid receptor ligand [11C]carfentanil and revealed that temporal lobe hypometabolism is associated with enhanced opioid receptor binding [15,16]. 2. Clinical manifestations Postictal depression and anxiety symptoms may present as single or cluster of symptoms restricted to the postictal period, or as an exacerbation in severity of interictal symptoms, or both. Often, symptoms can cluster to mimic a full-blown major depressive episode, which may fail to reach DSM-IV-TR diagnostic criteria only because of its shorter duration (typically between 2 and 5 days and, thus, less than the 2 weeks in DSM-IV-TR criteria). These various manifestations of postictal phenomena were demonstrated in a study of 100 consecutive patients with pharmacoresistant partial seizure disorders [4]. The presence of interictal and postictal psychiatric symptoms was investigated with a structured 42-item questionnaire, The Rush Postictal Psychiatric Questionnaire (RPPQ), designed to identify 30 postictal psychiatric symptoms, included nine PDSs, five PASs, and two PHMSs. As neurovegetative symptoms can be an expression of mood and anxiety disorders or can reflect antiepileptic drug toxicity, they were rated as a separate category of symptoms. Every patient also underwent a psychiatric evaluation to identify previous or concurrent interictal psychiatric disorders. Each question on the RPPQ inquired about the frequency of postictal and interictal occurrence of the symptom during the preceding 3 months. Only those postictal symptoms that were identified after more than 50% of seizures were included in the study, so as to reflect a “habitual” phenomenon. For symptoms identified during both interictal and postictal periods, only symptoms reported to be significantly more severe during the postictal period were included and were classified as postictal exacerbation of interictal psychiatric symptoms. Symptoms in which the severity did not differ between the interictal and postictal periods were coded as interictal symptoms. Among the 100 patients, 62 were women. Their mean age was 34.1 ± 10 years, and the mean duration of their seizure disorder was 21.1 ± 11.5 years. Seventy-nine patients had seizures of temporal origin, and 21 of extratemporal origin. Half of the patients had only complex partial seizures (CPSs), and the other half had CPSs and secondarily generalized tonic–clonic seizures (SGTCs). Seventy-eight patients had more than one seizure, and 22 had fewer than one seizure per month. A lifetime prevalence of psychiatric disorders was found in 54 patients. These consisted of mood disorders in 33 patients, anxiety disorders in 4, mixed mood and anxiety disorders in 12, and attention deficit/hyperactivity disorder in 5. No patient had a history of a psychotic disorder. Eleven patients reported one or more psychiatric hospitalizations. 2.1. Postictal symptoms of depression Forty-three patients reported a mean of 4.8 ± 2.4 PDSs (range = 2–9, median= 5). Table 1 lists all PDSs with their median durations. Of note,
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Table 1 Postictal symptoms of depression. Postictal symptom of depression
Frequency (N = 100)
Duration (h)
Poor frustration Anhedonia Hopelessness Helplessness Crying bouts Suicidal ideation Irritability Guilt Self-deprecation
36 33 25 31 26 13 30 23 27
24 (0.5–108)a 24 (0.1–148) 24 (1.0–108) 24 (1.0–108) 6 (0.1–108) 24 (1.0–240) 24 (0.5–108) 24 (0.1–240) 24 (1.0–120)
a
Median (range).
13 patients reported habitual postictal suicidal ideation; 8 experienced passive and active suicidal thoughts, whereas 5 reported only passive suicidal ideation. No patient ever acted on these symptoms. With the exception of postictal crying, the median duration of each PDS was 24 hours, whereas 32 patients experienced PDSs of at least 24 hours’ duration. In 18 patients a minimum of six PDSs clustered for periods of at least 24 hours, meeting our definition of PDE, whereas in only 6 patients was the duration less than 24 hours. As noted above, the occurrence of PDSs and PASs was high (r = 0.55, P b 0.0001), and not surprisingly, there was a high correlation between PDSs and postictal neurovegetative symptoms (r = 0.37, P b 0.0001). In addition, PDSs were identified in the seven patients who reported postictal psychotic symptoms (r = 0.3, P = 0.002). Of note, the occurrence of PDSs was associated with worse postictal cognitive disturbances, as evidenced by a greater number of postictal cognitive symptoms (P b 0.0001). Postictal symptoms of depression are identified in patients with a prior history of mood and/or anxiety disorders. Indeed, among the 43 patients with PDSs, 25 had a previous history of a mood disorder and 11 of an anxiety disorder. In fact, a significantly greater number of PDSs were identified in patients with lifetime histories of mood and anxiety disorders. Furthermore, postictal suicidal symptoms were significantly associated with a prior history of major depressive episodes and of previous hospitalizations in psychiatric units. Thus, the occurrence of this type of postictal symptom must raise the suspicion of a lifetime history of severe mood disorders. Thirteen patients who experienced PDSs were taking antidepressant medication and had no symptoms interictally (data unpublished). These “breakthrough” symptoms may reflect a resistance of PDSs to pharmacotherapy. Future prospective studies are necessary to clarify this question, however. 2.2. Postictal symptoms of anxiety Forty-five patients endorsed the occurrence of a mean of 2 ± 1 PASs (range = 1–5, median = 2). Table 2 lists the anxiety symptoms and their median durations. Of note, 29 patients experienced postictal agoraphobia; 18 (62%) attributed these symptoms to the fear of seizure recurrence even though the presence of this fear was not related to the actual occurrence of seizures in clusters.
Table 2 Postictal symptoms of anxiety. Symptom of anxiety
Frequency (N = 45)
Duration (h)
Constant worrying Panicky feelings Agoraphobic symptoms Due to fear of seizure recurrence Compulsions Self-consciousness
33 10 29 20 10 26
24 6 24 — 15 6
a
Median (range).
(0.5–108)a (0.1–148) (0.5–296) (0.1–72) (0.05–108)
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The median duration of PASs ranged from 6 to 24 hours; as in the case of PDSs, in a majority of patients (n = 30) the duration of at least one PAS was greater than 24 hours, whereas 15 patients (33%) reported a cluster of four PASs of at least 24 hours’ duration. In 15 patients PASs lasted less than 24 hours. As in the case of PDSs, there was a significant association between a history of anxiety and depressive disorders and a greater number of PASs. 2.3. Postictal hypomanic symptoms This symptom category comprises two symptoms, excessive energy and racing thoughts, which were identified in 22 patients: racing thoughts were endorsed by 15 patients and increased energy by 9, whereas both symptoms were reported only by 2. In contrast to PDSs and PASs, PHMSs had a significantly shorter duration. Indeed, their median duration was 2 hours (0.1–48 hours), and only six patients experienced PHMSs lasting more than 24 hours. The occurrence of PHMSS correlated significantly only with that of postictal psychotic symptoms. Finally, a psychiatric history was not associated with the occurrence of PHMSs. 2.4. Postictal exacerbation in severity of interictal symptoms of depression and anxiety In his description of the interictal dysphoric disorder, Kraepelin described the persistence of interictal symptoms during the postictal period [3], but did not explicitly describe an exacerbation of interictal symptoms during the postictal period. In the study by Kanner et al. [4], of the 38 patients who experienced interictal symptoms, 24 reported symptoms of depression, 4 symptoms of anxiety, and 6 both. Interictal symptoms with postictal exacerbation were a common occurrence, as they were identified in 36 of the 38 (94%) patients; in 19, all recorded symptoms were coded only as such, whereas the other 17 reported symptoms were coded both as interictal symptoms with postictal exacerbation and as interictal symptoms. Furthermore, 30 of these 36 patients (83%) also experienced de novo postictal psychiatric symptoms. In fact, the occurrence of interictal symptoms of depression and anxiety with postictal exacerbation correlated significantly with PDSs (P b 0.0001) and PASs (P b 0.0001), respectively. In fact, among these 30 patients, the number of PDSs and PASs were significantly greater than the numbers of interictal symptoms of depression (P b 0.0001) and anxiety (P b 0.002) with postictal exacerbation. 2.5. Relationship between PASs, PDSs, and epilepsy-related variables All patients who were included in this study had undergone a presurgical evaluation, which included a video/EEG monitoring study with recording of interictal epileptiform activity and clinical seizures, high-resolution brain MRI study, and neuropsychological testing. There was no relationship between the location or lateralization of ictal and interictal epileptiform activity or MRI findings and the occurrence of PDSs or PASs. These findings contrast with a significant association between postictal psychotic episodes and the presence of bilateral independent ictal foci [7,8,17,18]. In addition, there was no relationship between the occurrence of PDSs and/or PASs and the number of antiepileptic drugs or whether these had negative psychotropic properties (e.g., barbiturates, topiramate, zonisamide, levetiracetam).
2.6. Impact of PDSs and PASs on quality of life The negative impact of PDSs and PASs on the quality of life of patients with epilepsy would not come as a surprise to anyone. Yet, to date, no study has been published describing this phenomenon. In an ongoing study of 50 consecutive patients with pharmacoresistant epilepsy, the occurrence of PDSs and PASs was associated with worse scores on the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) [Kanner et al., data submitted]. 3. Concluding remarks Postictal psychiatric phenomena, presenting as PDSs or PDEs with or without PASs are relatively frequent in patients with pharmacoresistant epilepsy. Their occurrence has been associated with a past (or current) history of mood and anxiety disorders, whereas certain PDSs such as postictal suicidal ideation have been found in patients with a prior history of severe mood disorders that required inpatient psychiatric hospitalization. Thus, recognition of PDEs, PDSs, and/or PASs should serve as a red flag for an ongoing or past psychiatric history. Although it appears as if PDSs may not respond to pharmacotherapy, this question remains unanswered and must be addressed in future prospective studies. Finally, it is imperative that clinicians include an investigation of postictal psychiatric symptoms, just as they do for postictal cognitive and neurological symptoms. References [1] Gowers WR. Epilepsy and other chronic and convulsive diseases. London: Churchill; 1881. [2] Hughlings Jackson J. In: Taylor J, Holmes G, Walshe FMR, editors. Selected writings of John Hughlings Jackson. London: Hodder & Stoughton; 1931. p. 119–34. [3] Kraepelin E. Psychiatrie. 7th edition. Liepzig: Barth; 1903. [4] Kanner AM, Soto A, Gross-Kanner H. Prevalence and clinical characteristics of postictal psychiatric symptoms in partial epilepsy. Neurology 2004;62:708–13. [5] Kanner AM, Stagno S, Kotagal P, et al. Postictal psychiatric events during prolonged video-electroencephalographic monitoring studies. Arch Neurol 1996;53:258–63. [6] Logsdail SJ, Toone BK. Postictal psychosis: A clinical and phenomenological description. Br J Psychiatry 1988;152:246–52. [7] Devinsky O, Abrahmson H, Alper K, et al. Postictal psychosis: A case control study of 20 patients and 150 controls. Epilepsy Res 1995;20:247–53. [8] Umbricht D, Degreef G, Barr WB, et al. Postictal and chronic psychosis in patients with temporal lobe epilepsy. Am J Psychiatry 1995;152:224–31. [9] Engel Jr J, Bandler R, Griffith NC, et al. Neurobiological evidence for epilepsy induced interictal disturbances. Adv Neurol 1991;55:97–111. [10] Caldecott-Hazard S, Ackermann RF, Engel Jr J. Opioid involvement in postictal and interictal changes in behavior. In: Fariello RG, Morselli PL, Lloyd K, et al, editors. Neurotransmitters, seizures and epilepsy II. New York: Raven Press; 1984. p. 305–14. [11] Caldecott-Hazard S, Engel Jr J. Limbic postictal events: Anatomical substrates and opioid receptor involvement. Prog Neuropsychopharmacol Biol Psychiatry 1987;11:389–418. [12] Carroll MN, Lim RKS. Observations on the neuropharmacology of morphine and morphine-like analgesia. Arch Int Pharmacodyn 1960;75:383–403. [13] Holladay JW, Tortella FC, Long JB, et al. Endogenous opioids and their receptors: Evidence for the involvement in the postictal effects of electroconvulsive shock. Ann NY Acad Sci 1986;462:124–39. [14] Tortella FC, Long JB. Characterization of opioid peptide-like anticonvulsant activity in rat cerebrospinal fluid. Brain Res 1988;426:139–46. [15] Frost JJ, Mayberg HS, Fisher RS, et al. Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy. Ann Neurol 1988;23: 231–7. [16] Hitzemann JR, Hitzemann BA, Blatt S, et al. Repeated electroconvulsive shock: Effect on sodium dependency and regional distribution of opioid-binding sites. Mol Pharmacol 1987;31:562–6. [17] Kanner AM, Ostrovskaya A. Long-term significance of postictal psychotic episodes: I. Are they predictive of bilateral ictal foci? Epilepsy Behav 2008;12:150–3. [18] Trimble M, Kanner A, Schmitz B. Postictal psychosis. Epilepsy Behav 2010. Epub ahead of print.
