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Keywords:

  • Epilepsy;
  • Psychosis;
  • Interictal psychosis;
  • Duration of psychotic episodes;
  • Treatment

Summary

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Disclosures
  7. References

Purpose:  There have been few reports showing the distribution of the duration of interictal psychosis (IIP) episodes and their association with clinical characteristics. To clarify the nature of IIP, we studied the duration of IIP episodes and their related factors.

Methods:  One hundred fifty-five patients with epilepsy exhibited 320 IIP episodes during our follow-up period (mean 16.9 years). The duration of all the episodes and the longest episode in each patient during the follow-up periods were studied. Characteristics of the patients (e.g., epilepsy type, age of onset, and family history of psychosis) and episode-specific factors (e.g., age of the episode, seizure frequency, administrations of antiepileptic drugs [AEDs] and antipsychotic drugs [APDs]) were analyzed in association with the duration of the episodes.

Key Findings:  Mean duration of the 320 IIP episodes was 82.7 weeks and that of the longest IIP episodes was 150.1 weeks. During the follow-up period, 17 patients (11.0%) showed all episodes remitting within a month and 54 (34.8%) showed all episodes lasting for 6 months or longer. The IIP episodes that occurred at a younger age were often prolonged. Patients with a family history of psychosis or with early onset of psychosis tended to have more prolonged IIP episodes. Among the episodes treated with APDs, early administration of APDs was significantly associated with shorter IIP duration.

Significance:  The distribution of the duration of IIP episodes indicated the broad spectrum and heterogeneity of the IIP phenomena. The individual vulnerability to psychosis may be associated with prolonged episodes. Administration of APDs soon after onset of the episodes appeared to be effective in controlling them. These findings support empirical treatment principles for IIP to administer APDs at an early stage of its development.

Psychotic episodes in patients with epilepsy that occur without direct relation to seizures have been diagnosed as interictal psychosis (IIP) (Mellers et al., 1998; Adachi et al., 2000, 2002). In patients with IIP, their psychotic episodes negatively affect their quality of life as much as do their seizures per se. Whereas IIP often causes serious consequences, its nature remains uncertain. In general, as seen in functional psychoses, the duration of psychotic episodes is associated with multiple issues, for example, individual and environmental characteristics and treatment strategies (Hafner & an der Heiden, 2003). Despite the long history of clinical studies of epilepsy psychosis, there has been little evidence showing associations between the duration of IIPs and clinical characteristics.

IIP has often been categorized into two subclassifications, that is, acute/transient/brief (called “acute” hereafter and chronic, which may facilitate further clinical and pathophysiologic investigations (Sachdev, 1998; Adachi, 2006). No standard criteria, however, have been established. Conventional criteria defined episodes lasting days or weeks as acute-episodic IIPs and those lasting for months or years as chronic IIPs (Bruens, 1974; Sachdev, 1998). Some Japanese studies regarded psychotic episodes for 3 months (Kanemoto et al., 1996) or longer (Onuma et al., 1991; Matsuura et al., 1993) as chronic psychosis. More recent studies used the criteria set for diagnosis of schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV (American Psychiatric Association, 1994) for chronic IIPs in patients with epilepsy (Mellers et al., 1998). These criteria were set arbitrarily without any examination of validity and clinical relevance of the cutoff timing. Furthermore, the current diagnostic schemes for IIP do not address cases with multiple episodes with varying durations.

In the current study with a large number of IIP episodes, we reported the distribution of the duration of IIP and its relation to various clinical characteristics in view of disclosing the nature of IIP.

Methods

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Disclosures
  7. References

Definitions

IIP episodes were defined as the presence of hallucinations, delusions, or a limited number of severe behavioral abnormalities in accordance with the International Classification of Diseases (ICD)-10 Classification of Mental and Behavioral Disorders (World Health Organization, 1992). The definition of interictal psychosis is as follows in accordance with Slater and Roth (1969) description and subsequent studies: the first psychosis occurs after the development of epilepsy; their psychotic episodes occur without a decisive antecedent seizure or cluster of antecedent seizures; and the episodes occur under clear consciousness. Although some episodic manifestations of IIP 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 for the reliability of evaluation.

Subject selection

IIP episodes have been registered consecutively into our study database in a series of multicenter studies involving neuropsychiatric wards for epilepsy or epilepsy outpatient clinics of National Centre Hospital for Mental, Nervous and Muscular Disorders, Musashino Kokubunji Clinic, Tenshi Hospital, or Adachi Mental Clinic since January 1980. Our epilepsy patients with psychosis attended their clinics every 2–4 weeks in accordance with the national healthcare guidelines. The decision-making process for the treatment for IIP episodes was described in detail in our previous articles (Onuma, 1987; Adachi, 2005). In brief, our treatment strategies are as follows: (1) establishing a diagnosis of IIP episodes by excluding ictal/perictal/postictal psychotic phenomena, and evaluating the level of their disturbances; (2) assessing the patient’s capacity to give the clinician’s consent to treatment and/or to participate in the decision-making process, and seeking views from family members when necessary; (3) deciding treatment strategy, that is, psychotherapy or watchful wait in outpatient clinics, or pharmacologic treatment (with or without other treatment options) in outpatient clinics, or in neuropsychiatric wards; (4) optimizing antiepileptic drug (AED) regimens where possible by reducing polypharmacy and adjusting the dose to aim for therapeutic serum levels; and (5) when administration of neuroleptics is decided, butyrophenones and benzamides can be used as first-line antipsychotic drugs for IIP episodes. However, for serious psychomotor excitement, any neuroleptics can be used to control them rapidly. When nonpsychotic symptoms are evident, other psychotropics, for example, mood stabilizers, benzodiazepines, or antidepressants, may also be used. More detailed clinical settings of these institutions were described elsewhere (Adachi et al., 2010). All IIP episodes were assessed and treated by consultant psychiatrists qualified in clinical psychiatry and epileptology. Patients with progressive brain diseases, dementing process, or substance misuse were excluded. The study was approved by the relevant ethics committees of the institutions that participated.

Duration of IIP episode

Psychotic symptoms that lasted for 12 h or longer were assessed. Episodes of duration of 12–36 h were counted as 1 day. Episodes lasting longer than a week were measured by weeks. In most cases, the timing of the end of IIP episodes was specified. In the remaining cases, when the distinct timing of the remission was unclear, the day of consultation on which the last description of psychotic symptoms was recorded was regarded as the timing of its remission. Episodes during which patients showed excitement, disinhibition, or displeasure without distinct psychotic symptoms were not included. In some cases where the termination of IIP episodes could not be confirmed when the patients were transferred to another institution or their episodes were still ongoing at the study endpoint, the period between the onset of IIP and the last assessment was operatively regarded as the duration of the episode. For analysis, we used two sets of data: the duration of the all IIP episodes and each individual’s longest episode during the follow-up period.

Investigation items

As for patient’s characteristics, the following items were recorded: (1) age at onset of epilepsy (the age of the first afebrile seizures); (2) years of follow-up, from the first visit to the institutes after the development of interictal psychosis until December 31, 2006; (3) type of epilepsy, based on ictal semiology, electroencephalography (EEG), and neuroimaging in accordance with the International Classification of Epilepsies (Commission on Classification and Terminology of the International League Against Epilepsy, 1989); (4) cause of epilepsy: presence of known cause for epilepsy as symptomatic and absence as cryptogenic; (5) lateralization of epileptiform discharges (spikes and sharp wave variants), divided into four categories: left, right, bilateral, and none. Our criteria for lateralization are detailed elsewhere (Adachi et al., 1998); (6) the presence of mesial temporal sclerosis (MTS) in brain magnetic resonance imaging (MRI) scans: MTS was assessed qualitatively and MRI was performed in accordance with our routine protocol (Adachi et al., 2005); (7) family history of psychosis or any psychotic disorders in their first-degree relatives (Kitamura et al., 1984); and (8) intellectual function: mental retardation (full scale Wechsler Adult Intelligence Scale-Revised IQ [FIQ] 70 or below); borderline intellectual functioning (FIQ 71–84); or normal (FIQ 85 or above) in accordance with the DSM IV (American Psychiatric Association, 1994).

As for episode-specific factors of each IIP episode, the following were recorded.

  • 1 Age at IIP episode

  • 2 Frequency of habitual seizures around the episode, classified into six categories, that is, daily, weekly, monthly, yearly, less than yearly, seizure free for more than 3 years (Adachi et al., 1998)

  • 3 The number of AEDs taken;

  • 4 AED regimen (the number of AEDs or dosage) within 1 month before onset of the IIP episode, categorized into increased, decreased, changed in multiple ways (some increased and others decreased), or unchanged

  • 5 Treatment with antipsychotic drugs (APDs), any APDs taken before or after the beginning of the IIP episodes were noted. Prescribing of APDs (timing, kinds, dosages) was left to the patient’s consultant who made a decision based on clinical demand in accordance with the treatment strategy for IIP described above (Onuma, 1987; Adachi, 2005)

  • 6 APD time-lag, the duration between onset of the IIP episode and start of APD administration was noted.

Analysis

Differences in duration of the IIP episodes by each condition were analyzed with analysis of variance (ANOVA). The relation between duration of the IIP episode and liner/rank-ordered clinical factors was analyzed with Pearson’s or Spearman’s rank correlation coefficient. Significant level was set <0.05. Bonferroni correction was used to avoid risk of multiple comparisons: that is, 0.05/8 (approximately 0.0063) patient’s characteristics and 0.05/6 (approximately 0.0083) for episode-specific factors of each IIP episode. SPSS version 14.0 (SPSS Inc., Chicago, IL, U.S.A.) was used for all statistical analyses.

Results

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Disclosures
  7. References

Episodes and patients profiles

In 155 patients with epilepsy (89 men and 66 women), 320 IIP episodes were observed in our institutions. The total follow-up period of the 155 patients was mean 15.9 years (standard deviation [SD] 10.6, median 13, range 1–55). The duration between the initial IIP episode and the endpoint was mean 12.2 years (SD 8.7, median 10, range 1–40). The patients had mean 2.1 IIP episodes (SD 1.4, median 2, range 1–8); 68 patients had single IIP episodes and 87 patients had multiple IIP episodes (12 patients developed IIP episodes five times or more).

Age of onset of the IIP episode was mean 30.9 years (SD 10.5, median 28, range 14–66) and interval between onset of epilepsy and that of the IIP episode was mean 18.3 years (SD 9.0, median 17, range 0–55). Seizure frequencies at onset of the IIP episode were as follows: seizure free in 68 patients, less than yearly in 26, yearly in 77, monthly in 68, weekly in 63, and daily in 18. The number of AEDs taken was mean 2.2 (SD 1.3, median 2, range 0–7). In 47 IIP episodes (14.7%), AED regimen was changed within 1 month before episode onset (increased in 20, decreased in 20, and multiply changed in 7), whereas 273 episodes occurred on the same AED regimen. Of the 320 IIP episodes, 48 episodes were treated without any APD throughout the episode (non-APD group). The remaining 272 episodes were treated with some APDs during the course of episodes (APD group): 118 episodes occurred when the patients were on prophylactic treatment with APDs and continued the treatment throughout the episode (prophylactic APD group) and 154 episodes were treated with some APDs after their onset (APD add-on group). Of the APD group, APD time-lag between onset at the IIP episode and the time APDs were started was mean 9.7 weeks (SD 25.9, median 0.6, range 0–221).

Of the 155 patients, age at onset of epilepsy was mean 12.4 years (SD 8.6, range 0–49) and age of onset of psychosis was mean 28.5 years (SD 10.5, range 14–66). One hundred thirty patients had partial epilepsies (PE): temporal lobe epilepsy in 69, frontal lobe epilepsy in 31, parietal lobe epilepsy in 7, occipital lobe epilepies in 6, multilobe/undetermined lobe epilepsy in 14, and benign epilepsy of childhood with centrotemporal foci in 3. Twenty-five patients had generalized epilepsies (GE) idiopathic generalized epilepsy (IGE) in 17, symptomatic generalized epilepsy (SGE) in 3, and special epilepsy syndromes (e.g., progressive myoclonus epilepsy) in 5. In addition to IIP episodes, seven patients had separate postictal psychosis during their course of illness (bimodal psychosis). The lateralization of scalp EEG abnormalities was left in 60 patients, right in 60, and bilateral in 35. MTS was found on the left in 19 patients, on the right in 14, bilaterally in 4, and unremarkable in 118. Intellectual functioning was normal in 61 patients, borderline in 34, and in the range of mental retardation in 60.

The duration of the IIP episodes observed

The duration of all the 320 IIP episodes from the 155 patients was mean 82.7 weeks (SD 194.3, median 17, mode 2, range 0.2–1,874). The distribution of the duration of all the IIP episodes was shown in Fig. 1: IIP episodes subsided within 1 month in 82 episodes (25.6%), over 1 month within 3 months (1–3 months) in 63 episodes (19.7%), 3–6 months in 43 (13.4%), 6–12 months in 39 (12.2%), 12–24 months in 36 (11.3%), 24–60 months in 25 (7.8%), and 60 months or longer in 32 (10.0%). Thirty patients still had IIP episodes at the last follow-up consultation: 12 patients continued experiencing IIP episodes at the study endpoint, 8 were transferred to another institution, 5 discontinued attending the clinic without notices, 2 had a sudden unexpected death, and 3 committed suicide.

image

Figure 1.   IIP episodes subsided within 1 month (4 weeks) in 82 episodes (25.6%), over 1 month within 3 months (5–13 weeks) in 63 episodes (19.7%), 3–6 months (14–26 weeks) in 43 (13.4%), 6–12 months (27–52 weeks) in 39 (12.2%), 12–24 months (53–104 weeks) in 36 (11.3%), 24–60 months (105–260 weeks) in 25 (7.8%), and 60 months or longer (260 weeks+) in 32 (10.0%).

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The duration of the longest IIP episodes of each patient during the follow-up period was mean 150.1 weeks (SD 260.9, median 52, mode 4, range 0.6–1,874). The longest IIP episodes were for 1 month or less in 17 patients (11.0%), over 1 month to 3 months (1–3 months) in 18 (11.6%), 3–6 months in 19 (12.3%), 6–12 months in 24 (15.5%), 12–24 months in 25 (16.1%), 24–60 months in 21 (13.5%), and 60 months or longer in 31 (20.0%).

A longitudinal aspect of the duration of IIP episodes

Provided that the period of acute-episodic psychosis is defined as a duration of 1 month or shorter, 17 (11.0%) of the 155 patients showed all episodes acute, 102 (65.8%) showed all episodes chronic, and 36 (23.2%) showed both acute and chronic episodes. When the maximum duration for acute psychoses is set at 3 months, 35 (22.6%) of the patients showed all episodes acute, 75 (48.4%) showed all episodes chronic, and 45 (29.0%) showed both acute and chronic episodes. When the maximum duration is set at 6 months or less, 54 (34.8%) of the patients showed all episodes acute, 54 (34.8%) showed all episodes chronic, and 47 (30.3%) showed both acute and chronic episodes.

Relation between episode-specific factors and the duration of each IIP episode

Relations between episode-specific factors and the IIP duration were shown in Table 1. Two age-related factors showed weak associations with the IIP duration. As age of onset of IIP episode advanced, the duration of the episode became shorter. When the interval between onset of epilepsy and that of the IIP episode was longer, the duration of the episode tended to be slightly shorter, although it did not reach a significant level. Seizure frequency at onset of the IIP episode did not correlate significantly with the duration of the episode. The number of AEDs taken correlated slightly with the IIP duration, although it did not reach a statistically significant level. Changes of the AED regimen were not associated with the IIP duration. The IIP duration differed significantly between the groups regarding APD treatment: the APD group had a longer duration than did the non-APD group. Among the 272 episodes with APD treatments, the prophylactic APD group had shorter duration than the APD add-on group. As APD time-lag prolonged, the IIP duration became longer significantly.

Table 1.   Relations between episode-specific factors and the duration (weeks) of each IIP episode
Temporal factors (n)Duration (weeks) Mean, SD, median, rangeStatistics
Age at onset of IIP episodes (320) r = −0.186, p = 0.001
Interval from onset of epilepsy (320) r = −0.107, p = 0.056
Seizure frequency r = 0.026, p = 0.647
 Free (68)65, 136.3, 13.5, 1–810 
 Less than yearly (26)81.6, 159.7, 23.5, 2–754 
 Yearly (77)77.1, 221.3, 17, 0.2–1,794 
 Monthly (68)71.3, 114.6, 17.5, 0.2–546 
 Weekly (63)129.1, 291.2, 15, 0.3–1,874 
 Daily (18)56.0, 85.2, 21.5, 0.4–286 
Antiepileptic drugs (AEDs): number (320) r = 0.099, p = 0.079
Changes of AED regimens F = 1.51, p = 0.213
 Increased (20)39.5, 79.5, 10, 0.2–323 
 Decreased (20)22.3, 28.1, 9.5, 0.4–95 
 Multiply changed (7)168.4, 124.7, 4, 2–897 
 Unchanged (273)88.1, 201.7, 18, 0.2–1,874 
Antipsychotic drugs (APDs) F = 4.38, p = 0.037
 Non-APD (48)28.9, 38.0, 10.5, 0.2–173 
 APD (272)92.2, 208.8, 17, 0.2–1,874 
Timing of APD administration F = 5.32, p = 0.022
 APD prophylactic (118)59.1, 195.0, 10, 0.2–1,874 
 APD add-on (154)117.6, 216.0, 34, 1–1,794 
APD time lag (272) r = 0.43, p = 0.000

Relation between patients’ characteristics and the duration of the longest IIP episode

Relations between individual characteristics and the longest duration were shown in Table 2. The duration of the longest IIP episode showed a slight inverse correlation with age of onset of psychosis, whereas age of onset of epilepsy and the duration between onset of epilepsy and that of psychosis were not correlated with each other. The IIP patients with a family history of psychosis showed a slightly longer duration of the longest IIP episodes than did those without, although there was no significant difference. There was no difference in the longest duration between IIP patients with a family history of epilepsy and those without. There was no difference in the longest duration between IIP patients with a history of postictal psychosis and those without. Patients with partial epilepsy tended to have a slightly longer duration than patients with GE, although the difference was not statistically significant. There was no significant difference in the lateralization of EEG abnormalities, MTS on MRI, or intellectual functioning.

Table 2.   Relation between patients’ characteristics and the duration (weeks) of the longest IIP episode
Clinical characteristics (n)Duration of the longest IIP Mean, SD, median, RangeStatistics
Age of onset of epilepsy r = −0.04, p = 0.613
Age of onset of psychosis r = −0.15, p = 0.058
Duration between epilepsy-psychosis r = −0.03, p = 0.673
Family history of epilepsy F = 0.30, p = 0.586
 Presence (12)189.6, 506.0, 53, 4–1,794 
 Absence (143)146.7, 232.0, 52, 0.6–1,874 
Family history of psychosis F = 3.16, p = 0.077
 Presence (14)267.5, 464.2, 122, 1–1,794 
 Absence (141)138.4, 231.0, 48, 0.6–1,874 
Postictal psychotic episode F = 2.10, p = 0.150
 Presence (7)11.0, 8.7, 13, 1–23 
 Absence (148)156.6, 265.3, 59, 0.6–1,874 
Epilepsy type F = 3.14, p = 0.078
 Partial epilepsies (130)165.6, 279.5, 58, 1–1,874 
 Generalized epilepsies (25)65.5, 82.0, 30, 0.6–334 
Subtypes of partial epilepsies F = 1.98, p = 0.087
 Temporal lobe epilepsy (69)193.6, 348.2, 61, 1–1,874 
 Frontal lobe epilepsy (31)83.1, 102.5, 38, 1–364 
 Parietal lobe epilepsy (7)322.7, 207.5, 268, 36–650 
 Occipital lobe epilepsy (6)242.7, 166.7, 245, 32–432 
 Multilobular/undetermined lobe epilepsy (14)62.2, 88.5, 30, 6–320 
 BECCT (3)368.0, 392.5, 234, 60–810 
Subtypes of generalized epilepsies F = 0.46, p = 0.635
 Idiopathic generalized epilepsies (17)67.9, 67.5, 56, 0.6–238 
 Symptomatic generalized epilepsies (3)24.3, 29.3, 11, 4–58 
 Progressive myoclonus epilepsies (5)82.0, 141.8, 30, 3–334 
Cause of epilepsy F = 0.02, p = 0.901
 Symptomatic (57)153.5, 289.6, 39, 2–1,794 
 Cryptogenic (98)148.0, 244.3, 60.5, 0.6–1,874 
EEG; lateralization of abnormalities F = 1.09, p = 0.339
 Left (60)172.4, 296.3, 54, 1–1,874 
 Right (60)159.2, 270.3, 60.5, 1–1,794 
 Bilateral (35)93.3, 154.7, 34, 0.6–810 
MRI; mesial temporal sclerosis F = 0.04, p = 0.848
 Presence (37)156.6, 311.6, 52, 2–1,794 
 Absence (118)147.2, 243.8, 53, 0.6–1,874 
Intellectual functioning r = −0.02, p = 0.835
 Normal (61)136.7, 254.3, 60, 0.6–1,794 
 Borderline (34)108.3, 163.6, 3–650 
 Mental retardation (60)185.6, 306.5, 1–1,874 

Discussion

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Disclosures
  7. References

The current study demonstrated that the duration and related factors of a large number of IIP episodes showed a broad spectrum, suggesting heterogeneous characteristics of IIPs. Although the duration of IIP episodes tended to be prolonged, the timing of APD treatment was strongly associated with their duration. Because evidence on these issues is scarce, the findings may provide invaluable information from clinical and pathophysiologic perspectives.

The duration of each IIP episode

Mean duration of the episode was approximately 80 weeks, and one half of the IIP episodes lasted for 4 months or more, whereas their duration was distributed widely from a day to more than 30 years (Fig. 1). This broad distribution of the episode duration, one of the core elements in the diagnostic process, can lead to difficulty in understanding IIP by looking into the duration solely. This contrasts strikingly with the duration of postictal psychosis (PIP), almost all of whose episodes end within a month (Adachi et al., 2007).

This study considered only psychotic symptoms in accordance with the conventional definition of IIP. Psychiatric negative symptoms, for example, psychomotor retardations, blunted affects, and emotional withdrawal in epilepsy patients with psychosis have long been ignored. In his landmark study, Slater et al. (1963) observed that a significant number (40%) of IIP patients showed negative symptoms. These findings were, however, not noticed for a long time until we revisited this issue and reported the presence of psychiatric negative symptoms in some patients with IIP (Adachi et al., 2000; Adachi, 2006). Negative symptoms generally outlast positive symptoms in patients with functional psychosis (Lenzenweger & Dworkin, 1996). Furthermore, thought disorders in patients with epilepsy with psychosis have not been systematically studied. Among various thought disorder symptoms, delusions were clarified as disordered content (Cutting & Murphy, 1988); therefore, we were able to assess them in this study. In contrast, the other symptoms of thought disorder, that is, disordered forms, including disorder of the mechanisms of thinking and disorder of language and speech (Cutting & Murphy, 1988), were not well evaluated. If the duration of negative symptoms and/or thought disorders was also measured, their duration of illness should be prolonged.

A longitudinal aspect of IIP episodes

During the follow-up period (mean 10 years), approximately 90% of the patients had IIP lasting for more than 1 month. If the conventional duration-related classification (Bruens, 1974; Sachdev, 1998) was used, the majority of IIP episodes were classified into “chronic” psychosis. Two thirds of the IIP patients had psychoses lasting more than 6 month, which fulfilled the DSM IV criteria for schizophrenia regardless of the presence of negative symptoms. Previous studies have also shown long-lasting psychosis in many patients with epilepsy (Slater et al., 1963; Bruens, 1971; Onuma et al., 1991). Therefore, IIP tends to take a long-lasting course, which is similar to other functional psychoses (White et al., 2009). On the other hand, the prevalence (10%) of brief psychotic disorder among the patients with IIP appeared to be a little higher in comparison with the reported figures of brief psychotic disorders, accounting for 1–6% of all psychotic disorders (Susser & Wanderling, 1994; Perala et al., 2007). These findings may indicate the heterogeneous nature of IIP phenomena.

The relation between episode-specific factors and the duration of IIP

The use of APDs was significantly associated with the duration of IIP. Particularly, those patients who were treated with APDs during their IIP episodes (the APD add-on group) showed the longest duration. Although the use of APDs was a consequence of psychopathologic as well as psychosocial aspects of each episode, the use of APDs definitely reflects acuity and severity of the episodes (Adachi et al., 2007). Among the episodes treated with APDs, earlier APD administration shortened the IIP duration significantly. This is similar to findings in functional psychosis where prognosis is poorer if the first-episode psychosis becomes prolonged without appropriate treatment (White et al., 2009). These findings support empirical treatment principles for IIP to administer APDs at an early stage of its development (Onuma, 1987).

There were some aging effects on the duration of the episodes: the younger the patient was at the onset of the IIP episode, the longer was the duration. This is in line with findings in studies of functional psychosis (Borga et al., 1991; Haro et al., 1994), in that those who developed psychoses at a younger age showed more chronic and poorer outcome. Likewise, IIP episodes tended to be shorter when occurring after a long period since onset of epilepsy. This may be another age-related finding, mirroring that the duration became shorter as age advanced.

The relation between patients’ characteristics and the longest duration of IIP

Although none of the clinical characteristics were significantly associated with the longest duration of the IIP, patients with a family history of psychosis or with onset of psychosis at a younger age tended to have longer duration of psychosis. These factors likely reflect individual vulnerabilities to psychosis. People with a family history of psychosis tend to have an increased risk of psychosis and to exhibit their first psychotic symptoms earlier than do those without (Nicholson & Neufeld, 1992; Albus & Maier, 1995). Patients with early onset of psychosis are also known to show poor outcome (Sato et al., 2004; Malla & Payne, 2005). In contrast, slightly longer IIP duration in patients with partial epilepsy may be associated with brain damage or epilepsy-related adversities (e.g., intractable seizures and multiple AED administrations) (Adachi et al., 2010).

Limitation of the study

The current study had several limitations. First, whereas most information used for analysis in this study was retrieved from the database in that data were entered in a prospective manner, some additional data were collected retrospectively. Diagnosis and descriptions of psychopathologies were recorded by qualified neuropsychiatrists, who were proven reliable in our previous studies (Adachi et al., 2000; Adachi, 2006); however, data collected retrospectively might have inconsistencies. Even if this was the case, minor assessment instabilities cannot account for the findings because data entry had been completed before study-specific hypotheses were formulated or data analyses were carried out, and the findings were obtained from our large cohort of patients. Second, the duration of IIP episodes could change with environment and treatment, particularly with APDs. To our knowledge, evidence for effective IIP treatment has been scarce and there has been no standardized treatment guideline for IIP. Because regimen and doses of APDs were determined on the basis of clinical needs, thus not controlled, effects of APDs on the IIP duration could not be analyzed. To confirm our findings, controlled studies with the APD administration should be undertaken. Third, because some IIP episodes did not remit at the last follow-up consultation, mean duration can be longer than reported. The proportion of the patients whose duration was operatively determined, however, was fairly small; therefore, the duration of IIP episodes that did not remit would not have affected the findings significantly.

The current study showed the distribution of IIP duration and its related factors. Our findings, in particular effects of the timing of APD administration, would contribute to our understanding of the nature of the IIP phenomena. Further studies with prospective approaches are required to confirm our results and develop more evidence-based strategies in the treatment and management of IIPs.

Disclosures

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Disclosures
  7. References

None of the authors have any conflicts of interests. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

References

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Disclosures
  7. References
  • Adachi N. (2005) Treatment for psychiatric symptoms of epilepsy patients. Jpn J Psychiatry Treat 20(Suppl.):370373. (Japanese).
  • Adachi N. (2006) Epilepsy and psychosis. Issues on clinical research in epilepsy psychosis. Seishin Shinkeigaku Zasshi 108:260265. (Japanese).
  • Adachi N, Alarcon G, Binnie CD, Elwes RDC, Polkey CE, Reynolds EH. (1998) Predictive value of interictal epileptiform discharges during non-REM sleep on scalp EEG recordings for lateralization of epileptogenesis. Epilepsia 39:628632.
  • Adachi N, Nishiwaki S, Onuma T, Murauchi S, Akanuma N, Ishida S, Takei N. (2000) Interictal and postictal psychoses in frontal lobe epilepsy: a retrospective comparison with psychoses in temporal lobe epilepsy. Seizure 9:328335.
  • Adachi N, Matsuura M, Hara T, Oana Y, Okubo Y, Kato M, Onuma T. (2002) Psychoses and epilepsy: are interictal and postictal psychoses distinct clinical entities? Epilepsia 43:15741582.
  • Adachi N, Kanemoto K, Muramatsu R, Kato M, Akanuma N, Ito M, Kawasaki J, Onuma T. (2005) Intellectual prognosis after status epilepticus in adult epilepsy patients. Analysis with Wechsler Adult Intelligence Scale-Revised. Epilepsia 46:15021509.
  • Adachi N, Ito M, Kanemoto K, Akanuma N, Okazaki M, Ishida S, Sekimoto M, Kato M, Kawasaki J, Tadokoro Y, Oshima T, Onuma T. (2007) Duration of postictal psychotic episodes. Epilepsia 48:15311537.
  • Adachi N, Akanuma N, Ito M, Kato M, Hara T, Oana Y, Matsuura M, Okubo Y, Onuma T. (2010) Epileptic, organic, and genetic vulnerabilities for timing of the development of interictal psychosis. Br J Psychiatry 196:212216.
  • Albus M, Maier W. (1995) Lack of gender differences in age at onset of familial schizophrenia. Schizophr Res 18:5157.
  • American Psychiatric Association. (1994) Diagnostic and statistical manual of mental disorders. 4th ed. American Psychiatric Association, Washington DC.
  • Borga P, Widerlov B, Cullberg J, Stefansson CG. (1991) Patterns of care among people with long-term functional psychosis in three different areas of Stockholm County. Acta Psychiatr Scand 83:223233.
  • Bruens JH. (1971) Psychoses in epilepsy. Psychiatr Neurol Neurochir 74:174192.
  • Bruens JH. (1974) Psychoses in epilepsy. In Vinken PJ, Bruyn G.W (Eds) Handbook of clinical neurology. vol. 15. North Holland, Amsterdam, pp. 593610.
  • Commission on Classification and Terminology of the International League Against Epilepsy. (1989) Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 30:389399.
  • Cutting J, Murphy D. (1988) Schizophrenia thought disorder. Br J Psychiatry 152:310319.
  • Hafner H, an der Heiden W. (2003) Course and outcome of schizophrenia. In Hirsch SR, Weinberger D (Eds) Schizophrenia. 2nd ed. Blackwell Science Ltd, Oxford, pp. 101141.
  • Haro JM, Eaton WW, Bilker WB, Mortensen PB. (1994) Predictability of rehospitalization for schizophrenia. Eur Arch Psychiatry Clin Neurosci 244:241246.
  • Kanemoto K, Kawasaki J, Kawai I. (1996) Postictal psychosis: a comparison with acute interictal and chronic psychoses. Epilepsia 37:551556.
  • Kitamura T, Shima S, Sekino E, Kato M. (1984) Reliability study on Family History-Research Diagnostic Criteria (FH-RDC) by using case vignettes. Jpn J Soc Psychiatry 7:308312. (Japanese).
  • Lenzenweger MF, Dworkin RH. (1996) The dimensions of schizophrenia phenomenology. Not one or two, at least three, perhaps four. Br J Psychiatry 168:432440.
  • Malla A, Payne J. (2005) First-episode psychosis: psychopathology, quality of life, and functional outcome. Schizophr Bull 31:650671.
  • Matsuura M, Senzaki A, Terasaki O, Ohbayashi S, Matsushima E, Okubo Y, Toru M. (1993) Classification of the clinical course of delusional and/or hallucinatory states in epilepsy. Jpn J Psychiatry Neurol 47:363365.
  • Mellers JDC, Adachi N, Takei N, Cluckie A, Toone BK, Lishman WA. (1998) A SPET study of verbal fluency in schizophrenia and epilepsy. Br J Psychiatry 173:6974.
  • Nicholson IR, Neufeld RW. (1992) A dynamic vulnerability perspective on stress and schizophrenia. Am J Orthopsychiatry 62:117130.
  • Onuma T. (1987) Therapeutic approach to epileptic patients with psychiatric symptoms. Jpn J Psychiatry Treat 2:553560. (Japanese).
  • Onuma T, Adachi N, Hisano T, Uesugi S. (1991) 10-year follow-up study of epilepsy with psychosis. Jpn J Psychiatry Neurol 45:360361.
  • Perala J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsa E, Pirkola S, Partonen T, Tuulio-Henriksson A, Hintikka J, Kieseppä T, Härkänen T, Koskinen S, Lönnqvist J. (2007) Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry 64:1928.
  • Sachdev P. (1998) Schizophrenia-like psychosis and epilepsy: the status association. Am J Psychiatry 155:325336.
  • Sato T, Bottlender R, Schroter A, Moller HJ. (2004) Psychopathology of early-onset versus late-onset schizophrenia revisited: an observation neuroleptic-naïve patients before and after first-admission treatments. Schizophr Res 67:175183.
  • Slater E, Roth M. (1969) Mayer-Gross, Slater and Roth clinical psychiatry. 3rd ed. Bailliere Tindal, London.
  • Slater E, Beard AW, Glithero E. (1963) The schizophrenia-like psychoses of epilepsy. Br J Psychiatry 109:95150.
  • Susser E, Wanderling J. (1994) Epidemiology of nonaffective acute remitting psychosis vs schizophrenia. Sex and sociocultural setting. Arch Gen Psychiatry 51:294301.
  • White C, Stirling J, Hopkins R, Morris J, Montague L, Tantam D, Lewis S. (2009) Predictors of 10-year outcome of first-episode psychosis. Psychol Med 39:14471456.
  • World Health Organization. (1992) The ICD-10 Classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. World Health Organization, Geneva.