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Keywords:

  • Epilepsy;
  • Postictal psychosis;
  • Duration;
  • Time course;
  • Clinical characteristics

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. FACTORS INVESTIGATED
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Summary: Purpose: To clarify duration of postictal psychosis (PIP) episodes and identify factors that influence its duration.

Methods: Fifty-eight patients with epilepsy exhibited 151 PIP episodes during a mean follow-up period of 12.8 years. Distribution of the duration of these episodes was determined, and factors potentially affecting were analyzed. Factors analyzed included PIP-related variables (i.e., antecedent seizures and the lucid interval) and patient characteristics (i.e., type of epilepsy, lateralization of EEG abnormalities, and intellectual functioning).

Results: The mean duration of the 58 first PIP episodes was 10.5 days, and that of all 151 PIP episodes (including multiple episodes) was 9.2 days. Approximately 95% of the PIP episodes resolved within 1 month. Most PIP-related variables, except for antipsychotic drugs administered, were not associated with duration of the episodes. Several patient characteristics, i.e., history of interictal psychosis, family history of psychosis, and intellectual functioning, were associated with duration of the PIP episodes.

Conclusions: This study showed that most PIP episodes last less than 1 month. PIP episodes appear to be prolonged when individuals have an underlying vulnerability to psychosis. Clinical phenomena that can trigger PIP may not determine the course of the PIP episode.

Postictal psychosis (PIP) is a condition that follows an increased seizure frequency or intensity in epilepsy patients (Logsdail and Toone, 1988; Lancman et al., 1994; Kanemoto, 2002). Several studies have shown various risk factors for development of PIP, i.e., advanced age at the time of the episode (Adachi et al., 2002), the type and frequency of antecedent seizures (Devinsky et al., 1995; Umbricht et al., 1995; Kanemoto et al., 1996a), bilateral EEG abnormalities (Savard et al., 1991; Devinsky et al., 1995; Umbricht et al., 1995), and decreased intellectual functioning (Adachi et al., 2002).

Although many PIP episodes are self-limited in nature, some episodes evolve into disturbing or prolonged psychotic symptoms, necessitating the administration of pharmaceutical or behavioral treatment (Kanemoto, 2002; Adachi, 2005; Akanuma et al., 2005). However, few studies have shown the frequency of such prolonged episodes among all PIP episodes. Lack of evidence on its time course has prevented us from full understanding of the nature of this event.

Another important, but not yet addressed entirely, issue is whether any clinical variables are associated with the duration of the episode. Although several clinical variables and patient characteristics have been investigated as risks for the development of PIP episode (Savard et al., 1991; Devinsky et al., 1995; Umbricht et al., 1995; Kanemoto et al., 1996a; Adachi et al., 2002) as mentioned earlier, whether these factors also affect the duration of PIP episode remains a question. If we know factors related to the duration of PIP, we can estimate the course of each PIP episode more precisely and optimize our treatment strategies.

In the current study, we investigated 151 PIP episodes to reveal its distribution of the duration and factors that are related to the duration.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. FACTORS INVESTIGATED
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Definition of PIP

Psychosis was defined as the presence of hallucinations, delusions, or a limited number of severe behavioral abnormalities in accordance with the ICD-10 Classification of Mental and Behavioral Disorders (World Health Organization, 1992). PIP was defined as a psychotic episode occurring within 7 days after a decisive seizure or cluster of seizures (Logsdail and Toone, 1988; Kanemoto et al., 1996; Adachi et al., 2002). Although a PIP episode can be as short as a few hours or even minutes, the present study focused on patients who had episodes lasting at least 12 h, to ensure reliability of the evaluation. Episodes related to nonconvulsive status epilepticus or antiepileptic drug toxicity were excluded. No patients showed recent history of brain trauma, progressing brain mass regions, or alcohol or drug misuse.

Identification of PIP episodes

Psychotic episodes, either postictal or interictal, in patients with epilepsy have been registered and documented in detail consecutively in neuropsychiatry wards for epilepsy and specialist epilepsy outpatient clinics of the National Centre Hospital for Mental, Nervous and Muscular Disorders, National Utano Hospital, Aichi Medical University Hospital, Musashino Kokubunji Clinic, and Adachi Mental Clinic since January 1980. For this study, PIP episodes that occurred between January 1980 and December 2005 and that met the diagnostic criteria described above were identified in these clinical records. All PIP episodes were diagnosed, recorded, and treated in routine clinical settings by one of the authors, each of whom was serving as a consultant psychiatrist qualified in both clinical psychiatry and epileptology. Structured psychiatric interviews and formal psychiatric rating scales were not conducted. PIP episodes not adequately observed or for which records were incomplete were not included in this study.

Duration of each PIP episode

The length of each psychotic episode was quantified in terms of days. For example, a duration of 12–36 h was counted as 1 day, and a duration of 36–60 h was counted as 2 days. Periods of excitement, disinhibition, or displeasure without distinct psychotic symptoms were not included.

FACTORS INVESTIGATED

  1. Top of page
  2. Abstract
  3. METHODS
  4. FACTORS INVESTIGATED
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Patient characteristics

We investigated the following variables in each individual who exhibited PIP: (a) age at the onset of epilepsy (age at the time of the first afebrile seizure); (b) type of epilepsy based on ictal semiology, EEG, and neuroimaging according to the International Classification of Epilepsies (Commission on Classification and Terminology of the International League Against Epilepsy, 1989); (c) lateralization of epileptiform discharges (spikes and sharp wave variants) in interictal scalp EEG recordings, i.e., left, right, bilateral, or none (Adachi et al., 1998); (d) the presence of mesial temporal sclerosis (MTS) detected by MRI according to our routine protocol and assessed qualitatively (Kanemoto et al., 1996b; Adachi et al., 2005); (e) a history of interictal psychosis, the presence or absence of interictal psychotic episodes before and during the follow-up period (from the onset of epilepsy to December 2005 or to the time of their last visit to the institute); (f) comorbid psychiatric conditions were assessed in accordance with the ICD-10 (World Health Organization, 1992); (g) a family history of psychosis, i.e., any psychotic disorders of the ICD-10 (such as schizophrenia, paranoid disorders, or acute transient psychosis) (World Health Organization, 1992) in a first degree relative in accordance with the Japanese version of the Family History Research Diagnostic Criteria (Kitamura et al., 1984); and (h) intellectual function, impaired intellectual functioning (IIF, full scale Wechsler Adult Intelligence Scale-Revised IQ [FIQ] 70 or below); borderline (BIF, FIQ 71–84); or normal (NIF, FIQ 85 or above) in accordance with the DSM-IV(American Psychiatric Association, 1994).

PIP-related variables

We investigated the following variables in each PIP episode: (a) age at the time of the PIP episode; (b) frequency of habitual seizures around the time of the PIP episode, i.e., daily, weekly, monthly, yearly, less often than yearly, seizure free for more than 3 years (Adachi et al., 1998); (c) the number of antiepileptic drugs (AEDs) administered; to determine any particular effects of AEDs on the duration of PIP episodes, administration of carbamazepine, valproate, phenytoin, zonisamide, or phenobarbital/primidone was noted; (d) the type of seizures preceding the PIP episode, i.e., generalized tonic–clonic seizure (GTC), complex partial seizure, or simple partial seizures in accordance with the international classification of seizures (Commission on Classification and Terminology of the International League Against Epilepsy, 1981) and the total number of antecedent seizures; (e) the presence and duration of a lucid interval, defined as a nonpsychotic period under clear consciousness from the end of the last confirmed antecedent seizure to the beginning of the PIP episode (Logsdail and Toone, 1988; Kanemoto, 2002), noted in hours; (f) whether or not antipsychotic drugs (APDs), i.e., haloperidol equivalent 0.5 mg/day or more (American Psychiatric Association, 1997), were administered. Timing of the administration of APDs (before or after the beginning of the PIP episode) was noted. The administration of APDs (timing, type, dosage) was at the doctor's discretion, depending on the patient's need.

Analysis

To avoid analyzing variables repeatedly in patients who had multiple PIP episodes, we used only the “first” PIP episodes observed during the follow-up period for analysis of patients' demographic characteristics, and all PIP episodes observed during follow-up period were used otherwise. With respect to determining distribution of the duration of PIP, we carried out analyses with the first PIP episode and all PIP episodes separately.

The effect of each factor on the duration of PIP episodes was assessed by analysis of variance (ANOVA). Levene's homogeneity test was used to test for homogeneity of variance between groups. The relation between the duration of the PIP episode and nonparametric clinical factors was determined on the basis of the Spearman's rank correlation coefficient. A p-value of <0.05 was considered significant. SPSS 14.0 (SPSS Inc., Chicago, IL, U.S.A.) was used for all statistical analyses.

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. FACTORS INVESTIGATED
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Patient characteristics

Fifty-eight patients with epilepsy (32 men and 26 women) exhibited 151 PIP episodes during a mean follow-up period of 12.8 years (SD 7.9, range 1–31). Twenty-nine patients had a single PIP episode and 29 had multiple PIP episodes. Nine had five or more PIP episodes. Ninety-eight episodes were observed in inpatient settings, and 53 were observed in outpatient settings.

All patients suffered from localization-related epilepsy: 46 from temporal lobe epilepsy, seven from frontal lobe epilepsy, two from occipital lobe epilepsy, and three from multilobular or epilepsy of undetermined localization. Age at the onset of epilepsy ranged 1–60 years (mean 17.3, SD 12.4) and age at the time of the first psychotic episode ranged 16–69 years (mean 34.1, SD 13.5). Thirteen patients had a history of interictal psychosis, as well as PIP, during the course of epilepsy (bimodal psychosis). Thirteen patients suffered from a comorbid personality disorder; paranoid personality disorder (F 60.0) in three patients, schizoid personality disorder (F 60.1) in five, emotionally unstable personality disorder (F 60.3) in one, histrionic personality disorder (F 60.4) in two, and dependent personality disorder (F 60.7) in two. Scalp EEG abnormalities were on the left in 27 patients, on the right in 25, and bilateral in six. Thirteen patients showed left-sided MTS on MRI, five showed right-sided MTS, two showed bilateral MTS, and MRI findings were unremarkable in 38 patients. Intellectual functioning was normal in 20 patients, borderline in 24, and impaired in 14.

Duration of the PIP episodes

Duration of the 58 first PIP episodes ranged 1–63 days (mean 10.5, SD 11.2, median 7, mode 3) (Fig. 1A). Duration of all 151 PIP episodes ranged 1–63 days (mean 9.2, SD 9.1, median 6, mode 3) (Fig. 1B).

image

Figure 1. Distribution of the duration of PIP episodes. (A) Duration of the “first” PIP episodes (n = 58); 24 (41.4%) of first PIP episodes resolved within 5 days, 36 (62.1%) episodes resolved within 7 days, 40 (69.0%) resolved within 10 days, 44 (75.9%) resolved within 14 days, and 55 (94.8%) resolved within 30 days. (B) Duration of the total PIP episodes (n = 151); 72 (47.7%) of all PIP episodes resolved within 5 days, 93 (61.6%) resolved within 7 days, 108 (71.5%) resolved within 10 days, 122 (80.8%) resolved within 14 days, and 146 (96.7%) resolved within 30 days.

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To compare single and multiple PIP episodes, we analyzed the 29 episodes in the 29 patients who had a single episode and the 122 episodes in the 29 patients who had multiple episodes. Duration (mean 8.2 days, SD 6.8) in patients with a single episode was equivalent to that (9.5, 9.6) in patients with multiple episodes. The Levene test showed equal variance in duration between patients with a single episode and those with multiple episodes (Levene's statistic = 1.5, p = 0.217). Although patients with multiple episodes had often different clinical conditions such as APD treatment, further analysis of within-individual comparison will be reported hereafter.

Relation between PIP-related variables and duration of the PIP episodes

Main results were shown in Table 1. Age at the time of the PIP episode ranged 16–70 years (mean 36.5, SD 12.0). Age at the time of the episode did not significantly correlated with duration of the episode. Habitual seizures around the PIP episode occurred daily in six episodes, weekly in 49 episodes, monthly in 74 episodes, yearly in 17 episodes, and less often than yearly in five episodes. Most PIP episodes, except for six occurred following daily habitual seizures, were associated with distinct seizure phenomena. Of the six episodes following daily seizures, four developed PIP after cluster of seizures (>5) and three had no lucid interval. Frequency of habitual seizure was not significantly associated with duration of the PIP episodes. The number of AEDs administered at the time of PIP episodes (mean 2.1, SD 1.0, median 2, range 0–5) did not correlate significantly with duration of the PIP episodes. There was no significant relation between the type of AED and duration of the PIP episodes.

Table 1. Duration of the PIP episodes in relation to clinical variables
 PIP episode (SD, 95% CI)Mean duration (days) of Statisticsp-value
  1. aSpearman's correlation coefficient.

  2. bOne-way ANOVA.

  3. cPost hoc Tamhane test showed significant differences (APD add-on vs. non-APD, p = 0.000, APD vs. non-APD, p = 0.003).

Age at the PIP episode (mean 36.6 years) r =−0.135a0.098
Frequency of habitual seizures (median monthly) r =−0.07a0.380
Number of AEDs administered (mean 2.1) r = 0.143a0.079
Carbamazepine F = 1.7b0.196
 Used (n = 112)8.7 (7.8, 7.2–10.)  
 Not used (n = 39)10.9 (12.1, 6.9–14.8) 
Valproate F = 0.05b0.824
 Used (n = 22)8.8 (7.6, 5.5–12.2) 
 Not used (n = 129)9.3 (9.4, 7.7–10.9) 
Phenytoin F = 0.19b0.666
 Used (n = 87)8.9 (7.8, 7.3–10.6) 
 Not used (n = 64) 9.6 (10.7, 6.9–12.3) 
Zonisamide F = 0.01b0.936
 Used (n = 37)9.3 (6.9, 7.0–11.6) 
 Not used (n = 114)9.2 (9.8, 7.4–11.0) 
Phenobarbital/primidone F = 0.00b0.981
 Used (n = 23)9.3 (8.9, 5.4–13.1) 
 Not used (n = 128)9.2 (9.2, 7.6–10.8) 
Number of antecedent seizures (mean 3.4) r = 0.135a0.097
Antecedent GTC F = 0.51b0.476
 Present (n = 73) 
 Absent (n = 78)9.8 (8.5, 7.8–11.8) 
Lucid interval8.7 (9.7, 6.5–10.9)F = 1.0b0.315
 Present (n = 99)8.7 (8.5, 7.0–10.4) 
 Absent (n = 52)10.3 (10.2, 7.4–13.1) 
Administration of antipsychotic drugs F = 9.1b,c0.000
 APD (n = 59)9.3 (8.3, 7.1–11.4) 
 APD add-on (n = 49)12.8 (11.7, 9.4–16.1) 
 Non-APD (n = 43)5.1 (3.8, 3.9–6.2)  

The number of antecedent seizures (mean 3.4, SD 6.6, median 2, range 1–70) did not correlated significantly with duration of the PIP episodes. GTCs were observed prior to 73 PIP episodes. The duration did not differ between episodes with and without antecedent GTCs. A lucid interval was observed prior to 99 episodes (mean duration 30.3 h, SD 25.9, 95% CI 25.2–35.5). The duration of the PIP episodes with a prior lucid interval did not differ from the PIP episodes without a prior lucid interval.

APDs were administered before and throughout 59 PIP episodes (APD group). These patients were on APDs prior to the PIP episode concerned, due to previous history of interictal psychosis or recurrent postictal psychoses. In the remaining 92 episodes, APDs were administrated after the start of 49 PIP episodes (APD add-on group) and no APDs were administered before or during 43 PIP episodes (non-APD group). Duration of the PIP episodes was significantly longer in the APD group (mean 9.3 days) and in the APD add-on group (12.8 days) than in the non-APD group (5.1 days). In the APD add-on group, the mean time between the initiation of APD administration and cessation of the PIP episode was 9.8 days (SD 10.2, 95% CI 6.7–12.8). The duration of the lucid interval without prophylactic APD (non-APD and APD add-on groups) (n = 61, mean 31.0, SD25.4, 95% CI 24.5–37.5) did not differ from those with prophylactic APD (APD group) (n = 38, mean 29.2, SD 26.9, 95% CI 20.4–38.0) (F = 0.12, p = 0.735).

Relations between patient characteristics and duration of the first PIP episode

Main results were shown in Table 2. Duration of the first PIP episode did not correlate significantly with age at the onset of epilepsy, type of epilepsy, laterality of EEG abnormalities, or the presence of MTS. Duration of PIP episodes was significantly longer in patients with bimodal psychosis (16.8 days) than that in patients without bimodal psychosis (8.9 days). Patients with comorbid psychiatric disorder showed slightly longer duration of episode than did those without, although there was no statistically significant difference. PIP episodes tended to be longer in patients with a family history of psychosis than in those without. Intellectual function correlated significantly with the duration of PIP. Among the three groups regarding intellectual function, PIP episodes were shortest in patients with NIF.

Table 2. Duration of the PIP episodes in relation to patient characteristics
 Mean duration (days) of the PIP episodes (SD, 95% CI)Statisticsp-value
  1. aOne-way ANOVA.

  2. bSpearman's correlation coefficient.

Sex F = 1.06a0.309
 Men (n = 32)11.9 (10.4, 8.1–15.0) 
 Women (n = 26) 8.9 (12.1, 4.0–13.7) 
Age at onset of epilepsy r =−0.134b0.315
Type of epilepsy F = 0.46a0.711
 Temporal lobe epilepsy (n = 46)10.3 (11.5, 6.9–13.7) 
 Frontal lobe epilepsy (n = 7)14.1 (12.1,3.0–25.3) 
 Occipital lobe epilepsy (n = 2)    11.5 (10.6, −83.8–106.8) 
 Multilobular epilepsy or epilepsy of5.3 (2.1, 0.2–10.5) 
 undetermined localization (n = 3) 
Laterality of epileptiform discharges on EEG F = 0.16a0.854
 Left (n = 27)9.7 (9.4, 6.0–13.4) 
 Right (n = 25)11.4 (12.6, 6.2–16.7) 
 Bilateral (n = 6)  10.5 (13.8, −4.0–25.0) 
Mesial temporal screrosis by MRI F = 1.6a0.209
 Left (n = 13)5.2 (3.6, 3.1–7.4)  
 Right (n = 5)  9.4 (8.3, −0.9–19.7) 
 Bilateral (n = 2)  7.0 (1.4, −5.7–19.7) 
 Unremarkable (n = 38)12.7 (9.8, 8.4–16.9)  
Bimodal psychosis (history of interictal psychosis) F = 4.4a0.041
 Present (n = 13)16.1 (12.4, 8.6–23.6) 
 Absent (n = 45) 8.9 (10.4, 5.8–12.0) 
Comorbid psychiatric disorder F = 0.83a0.368
 Present (n = 13)13.0 (10.4, 6.7–19.3) 
 Absent (n = 45) 9.8 (11.4, 6.4–13.2) 
Family history of psychosis F = 4.5a0.037
 Present (n = 5)20.4 (11.1, 6.6–34.2) 
 Absent (n = 53) 9.6 (10.8, 6.6–12.6) 
Intellectual function r = 0.26b0.049
 Normal (n = 20) 8.5 (10.9, 3.4–13.6) 
 Borderline (n = 24)10.0 (7.6, 6.8–13.2)  
 Impaired (n = 14)14.4 (15.8, 5.3–23.5) 

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. FACTORS INVESTIGATED
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Of the 151 PIP episodes we studied, 72 (47.7%) lasted 5 days or less and 146 (96.7%) resolved within 1 month. These percentages are concordant with previous observations of PIP with either natural or induced seizures (Savard et al., 1991; Lancman et al., 1994; Kanner et al., 1996; Kanemoto, 2002). Our results support empirical data that PIP episodes generally last less than 1 month. The PIP episodes lasting more than 1 month appear to be exceptional (Akanuma et al., 2005).

Most PIP-related variables did not correlate with duration of the PIP episodes. The number and types of antecedent seizures, although essential to the occurrence of PIP, did not affect the overall course of the episodes. Neither presence nor duration of a lucid interval, a phenomenon unique to PIP and that may play a role in the PIP process (Kanemoto, 2002), was also associated with duration of the episodes. Although a high frequency of habitual seizures and increased number of AED administered often reflect intractability of epilepsy, these factors did not prolong the PIP episodes. These findings suggest that antecedent seizures and particular epilepsy-related variables act as triggers of PIP without influencing its successive course. Thus, once the PIP process starts, other variables, later described, may regulate the course of the episode.

Of the PIP-related variables we studied, only the condition of APD administration correlated significantly with the duration of PIP, although the administration of APD may not simply reflect the nature of PIP episode. Duration of the PIP episodes was shortest in the non-APD group, suggesting that many PIP episodes would resolve naturally even without APD treatment. Some researchers have recommended mild sedation without the use of APDs as optimal treatment for PIP (Lancman et al., 1994). In contrast, PIP episodes were longest in the APD add-on group. These episodes continued for 9.5 days even after the administration of APDs, and were as long as episodes in the APD group. This may be partially due to the doctors' tendency to prescribe APDs in difficult cases, i.e., violent, recurrent, or prolonged PIP episodes. Prospective case-controlled studies might clarify the relation between the distinct effects of APDs on PIP and the intractability of some PIP episodes.

Several patient characteristics were significantly associated with the duration of PIP, even though in patients who experienced multiple PIP episodes, the duration of each episode differed. First, PIP episodes were longer in patients with bimodal psychosis than in patients with PIP alone. This is in line with our reported findings in four patients with interictal-antecedent bimodal psychosis (Adachi et al., 2003). Patients with bimodal psychosis often show characteristics associated with both postictal and interictal psychoses (Tarulli et al., 2001; Adachi et al., 2002, 2003). Second, PIP episodes tended to be longer in patients with subnormal intellectual functioning. Impaired intellectual functioning is a risk factor for development of PIP or interictal psychosis (Adachi et al., 2002). Premorbid cognitive function is generally a prognostic factor in patients with psychosis (Malla and Payne, 2005). Psychotic symptoms in schizophrenia patients with learning disability are generally more concrete and less elaborate (Reid, 1982). Last, PIP episodes were longer in patients with a family history of psychosis than in those without. This is consistent with studies on functional psychosis that have shown poor outcomes in patients with a family history of psychosis (Verdoux et al., 1996; Bromet et al., 2005). These patient characteristics likely reflect an underlying increased vulnerability to psychosis. In addition to precipitating a PIP episode, they may delay its resolution.

Our study requires some considerations. First, due to the fact that our consultants were doubly qualified in psychiatry and epileptology, there may have been a selection bias toward patients with intractable or complicated epilepsy. Patients are not often referred to a specialist clinic until their PIP episode causes serious behavioral or social problems. Second, we excluded PIP episodes lasting less than 12 h because it is very difficult to identify short-lasting PIP episodes. These easily go unnoticed or unreported in outpatient settings. Using video-EEG monitoring systems, Kanner et al. (2004) showed that approximately 40% (three of seven patients) had PIP episodes lasting 24 h or less. If we could detect PIP episodes lasting less than 12 h precisely, the distribution of PIP episodes might have shifted toward a shorter duration. Third, some variables that may affect duration of PIP, such as whether the patients had sufficient repose and sleep (Lancman et al., 1994; Kanemoto, 2002) were not analyzed in our study. Last, although PIP episodes often show a variety of psychopathological features, this study did not evaluate them in a systematic manner. Further work is necessary to investigate whether certain psychopathologies can be associated with duration of PIP.

In conclusion, we found that most PIP episodes resolve within 1 month. PIP episodes appear to be prolonged when patients have an underlying vulnerability to psychosis. Clinical phenomena that trigger a PIP episode may not determine the course of the episode. Our findings on the duration of PIP would contribute to further development of evidence-based treatment strategies.

REFERENCES

  1. Top of page
  2. Abstract
  3. METHODS
  4. FACTORS INVESTIGATED
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES
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