basic treatment principles for psychotic disorders in patients with epilepsy

Basic treatment principles for psychotic disorders

in patients with epilepsy*Naoto Adachi, †Kousuke Kanemoto, ‡Bertrand de Toffol, §Nozomi Akanuma,

†TomohiroOshima, ¶#AdithMohan, and ¶#Perminder Sachdev

*Adachi Mental Clinic, Sapporo, Japan; †Department of Neuropsychiatry, Aichi Medical University,

Nagakute, Japan; ‡Department of Neurology, Francois-Rabelais University & INSERMU 930, Tours, France;

§South London andMaudsley NHS Foundation Trust, London, United Kingdom; ¶School of Psychiatry,TheUniversity of New SouthWales, Sydney, New SouthWales, Australia; and #Neuropsychiatric Institute,

Prince ofWales Hospital, Sydney, New SouthWales, Australia

SUMMARY

In patients with epilepsy, coexisting psychoses,

either interictal (IIP) or postictal (PIP), are associ-

ated with serious disturbance in psychosocial func-

tion and well-being, and often require the care of a

specialist. Unfortunately, evidence-based treat-

ment systems for psychosis in patients with epi-

lepsy have not yet been established. This article

aims to propose concise and practical treatment

procedures for IIP and PIP based on currently

available data and international consensus state-

ments, and primarily targeting nonpsychiatrist

epileptologists who are often the first to be

involved in the management of these complex

patients. Accurate and early diagnosis of IIP and

PIP and their staging in terms of acuity and severity

form the essential first step in management. It is

important to suspect the presence of psychosis

whenever patients manifest unusual behavior.

Knowledge of psychopathology and both individual

and epilepsy-related vulnerabilities relevant to IIP

andPIP facilitate early diagnosis. Treatment for IIP

involves (1) obtaining consent to psychiatric treat-

ment fromthepatient,whenever possible, (2) opti-

mization of antiepileptic drugs, and (3) initiation of

antipsychotic pharmacotherapy in line with symp-

tom severity and severity of behavioral and

functional disturbance. Basic psychosocial inter-

ventions will help reinforce adherence to treat-

ment and should be made available. Due

consideration must be given to patients’ ability to

provide informed consent to treatment in the

short term, with the issue being revisited regularly

over time. Given the often prolonged and recur-

rent nature of IIP, treatment frequently needs to

be long-term. Treatment of PIP consists of two

aspects, that is, acuteprotectivemeasures andpre-

ventive procedures in repetitive episodes. Protec-

tivemeasures prioritize themanagement of risk in

the early stages, and may involve sedation with or

without theuseof antipsychotic drugs, and the judi-

cious applicationof localmental health legislation if

appropriate. As for preventative procedures, opti-

mizing seizure control by adjusting antiepileptic

drugsorby surgical treatment is necessary.

KEY WORDS: Epilepsy, Psychosis, Interictal psy-

chosis, Postictal psychosis, Treatment, Guideline.

Although psychotic illnesses in patients with epi-lepsy have been long studied, the literature thus farhas leaned toward descriptive psychopathology andestablishment of etiologic and neuropathologic links.In contrast, there are only a few systematic studiesthat have evaluated treatment strategies (Adachi, 2005;

Sachdev, 2007). The responsibility for initial manage-ment of these patients can fall on a range of profes-sionals in addition to epileptologists, and experience inthe management of psychotic disorders can vary,depending for instance on whether the treatment set-ting is in a tertiary referral center with access to neu-ropsychiatric expertise. We aim to propose treatmentprocedures, based on available data, for two maintypes of epilepsy-related psychoses (i.e., interictal psy-chosis and postictal psychosis), that are practical andclinically meaningful.

Address correspondence to Naoto Adachi, Adachi Mental Clinic,Kitano 7-5-12, Kiyota, Sapporo 004-0867, Japan. E-mail: [email protected]

Wiley Periodicals, Inc.© 2013 International League Against Epilepsy

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Epilepsia, 54(Suppl. 1):19–33, 2013doi: 10.1111/epi.12102

PSYCHIATRICDISORDERS IN EPILEPSY

Interictal PsychosisPeople with epilepsy have a twofold to threefold

increased risk of developing psychosis (Qin et al., 2005),which may indicate that epilepsy per se plays some role,although establishing a causal association remains contro-versial (Adachi, 2006). With regard to their temporal asso-ciation with seizures, the psychosis may be regarded asinterictal psychosis (IIP) or postictal psychosis (PIP; Sach-dev, 1998). In contrast to recent advances in clinicalresearch in PIP, studies of IIP remain limited. In particu-lar, there are few systematic studies of effective treatmentstrategies for IIP. Existing recommendations (Kerr et al.,2011) are extrapolated from those established for the treat-ment of schizophrenia and related psychotic illnesses withsome additional guidance from anecdotal evidence orexpert opinions.

A range of factors influence the choice of psychiatrictreatments for IIP patients. In this article, we summarizetreatment procedures in three stages depending on theseverity of psychotic symptoms and the level of psychoso-cial disturbance.1 Mild: Although patients clearly show some psychotic

symptoms, they are not distressed by the symptoms,and their overall psychosocial function is maintained.

2 Moderate: Patients have distinct psychotic symptoms;day to day functioning is disrupted, and overall psycho-social functioning is affected to some degree.

3 Severe: Patients have overwhelming psychotic symp-toms, behavioral consequences of these symptoms putthem or other people at risk, and their psychosocialfunction is significantly impaired.

Definition of IIPThe term psychosis encompasses a broad spectrum of

mental disturbance. Clinically, in accordance with Inter-national Classification of Diseases, Tenth Revision (ICD10) (World Health Organization, 1992), the syndrome ofpsychosis is defined by the presence of hallucinations,delusions, and/or a limited number of severe behavioralabnormalities, such as gross excitement and overactivity,marked psychomotor retardation, and catatonic behavior.Thought disorder is a salient feature of psychosis, whichmay be characterized by disordered content, as repre-sented by delusions, or disordered thought form. Disor-dered thought form broadly comprises disorders of themechanisms of thinking, that is, concrete thinking, loos-ening of associations, incoherence, overinclusion, andillogicality. There may be associated disorder of languageand speech, that is, derailment, neologisms, retarded/pov-erty of speech, pressured speech, and flight of ideas (Cut-ting & Murphy, 1988). Despite reports of frequentoccurrence in patients with epilepsy, in particular thosewith psychiatric or neurobehavioral disorders (Slateret al., 1963; Caplan et al., 1997), formal thought disorder

is not commonly considered in diagnostic workup for IIP(Adachi, 2006).

Contributions from British neuropsychiatrists (Hill,1953; Pond, 1957; Slater et al., 1963; Slater & Roth,1969) defined IIP as any psychosis in clear consciousnessthat occurs in someone who has previously been diag-nosed with epilepsy, and the psychosis is not exclusivelyduring or immediately following a seizure. This criterionis concise and practical, and has often been used forapproximately three decades. There is an implication thatthe psychosis is, in some manner, “secondary” to the epi-lepsy (Diagnostic and Statistical Manual of Mental Disor-ders, Fourth Edition; DSM-IV, American PsychiatricAssociation, 1994) or is an “organic” mental disorder(ICD-10) in line with a conceptually orthodox dichotomybetween organic and functional psychoses (Adachi et al.,2010b). Such orthodoxy is often not possible to sustain.Several recent studies have demonstrated some vulnera-bility factors, such as the presence of family history ofpsychosis (Adachi et al., 2000a; Qin et al., 2005) andimpaired intellectual functioning (Adachi et al., 2000a;Mellers et al., 2000) that are common to both “non-organic” psychosis and psychosis in epilepsy (IIP). Thesefindings have shed light on pathogenesis of psychosis inpatients with epilepsy in a wider context. Although evi-dence is still limited, recent findings suggest common vul-nerabilities among learning disability, developmentaldisorders, and psychosis (Craddock & Owen, 2010).

In this article, we have adopted Slater’s definition forpractical use. Previous authors have employed variousforms of subclassifications in IIP according to its duration(e.g., acute/brief/transient and chronic) or presumptive eti-ologies (e.g., drug-induced and forced normalization;Sachdev, 1998, 2007; Fig. 1). These subclassifications

Figure 1.

Possible pathophysiologic mechanisms for the associa-

tion between epilepsy and schizophrenia-like psychosis

(with permission from Sachdev, 2007).Epilepsia ILAE


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N. Adachi et al.

have not been validated. It needs to be kept in mind thatthe same patient can exhibit different forms of IIP at dif-ferent times, for example, drug-induced and non–drug-induced, or acute and chronic.

Diagnosing IIPPeople with epilepsy are at an increased risk of psycho-

sis. Every year, 3–4 of 1,000 adult patients with epilepsywith no past history of psychosis exhibit some psychoticsymptoms for the first time (Onuma et al., 1995; Tadok-oro et al., 2007). The risk is approximately 2–3 timeshigher than that of first-episode schizophrenia in thegeneral population aged 15–65 years. The first step formaking a diagnosis is to be aware that any patient withepilepsy can develop IIP, and to suspect IIP when theyshow unusual behavior.

Identifying IIP may be straightforward when patientsexhibit frank psychotic symptoms. It is, however, notuncommon that patients conceal their psychotic experi-ences (Koutroumanidis et al., 2010). Viron et al. (2012)proposed a set of screening questions for psychosis(Table 1). Nonverbal cues (e.g., sullen, preoccupied,monotonous, or unnatural behaviors) are vital in under-standing abnormal inner experiences, as verbally providedinformation cannot be relied upon exclusively. Obtainingcollateral history from their family, friends, and carers isalso important (Koutroumanidis et al., 2010).

To confirm the diagnosis of IIP, it is necessary toexclude ictal, preictal, and postictal psychotic phenomena.Criteria for these phenomena are detailed in the PIP sec-tion of this article. Because patients may not clearlyremember precedent seizures, clinical clues indicating thepresence of seizure activity around the time of onset of thepsychotic episode should be sought meticulously.

Associated characteristics

Constant characteristicsCharacteristics that remain constant during the course

of illness in each patient appear to be associated with vul-nerabilities relevant to the development of IIP (Fig. 1). Anumber of recent studies have shown common vulnerabil-

ities between epilepsy and psychosis (Qin et al., 2005;Adachi et al., 2011). Epilepsy patients with a family his-tory of psychosis are predisposed to developing IIP, evenin the absence of overt cerebral insult related to epilepsy(Adachi et al., 2010a). The rate of family history of psy-chosis is estimated at 3–10% in IIP (Adachi et al., 2000a,2002a; Qin et al., 2005). Because the actual risk of IIPbased on genetic vulnerabilities is difficult to calculate atpresent, the presence of family history of psychosis couldbe explored not only within the first-degree relatives as inmost genetic studies with strict criteria but also in themore extended family. Epilepsy patients with a learningdisability are more vulnerable to IIP than those without(Adachi et al., 2000a; Mellers et al., 2000). In particular,those with borderline intellectual functioning have 2–5times higher risk for various psychotic states (Adachiet al., 2002a).

Several epilepsy-related variables have been consideredin the pathogenesis of IIP (Trimble, 1991; Sachdev,1998). They include epilepsy types, seizure variables, andthe lateralization of epileptogenesis. Indeed, patients withfocal epilepsy have a higher risk of IIP than those withgeneralized epilepsy (Adachi et al., 2000a,b). It is note-worthy that 15–20% of IIP patients have idiopathic gener-alized epilepsy (Adachi et al., 2000a, 2010a). As forseizure variables, most reports have pointed to the occur-rence of complex partial seizures and in particular thoseoccurring in temporal lobe epilepsy as suggested byGibbs’s (1951) report. Patients with other forms of focalepilepsy can also develop IIP (Adachi et al., 2000b,2002b). Because most of the recent large studies failed tofind associations between left-sided epileptogenicity andIIP (Mendez et al., 1993; Kanemoto et al., 2001b; Adachiet al., 2002a), the importance of lateralization of epilepto-genesis may have been overestimated.

Inconsistent characteristicsFeatures that are subject to change, such as regimens

and doses of antiepileptic drugs (AEDs) and seizurefrequency, are also likely to affect IIP. Modifying suchconditions by appropriate medical approaches can conse-quently prevent or improve IIP.

Table 1. Screening questions for psychoses (Viron et al., 2012)

A lead-in statement helps to normalize the experiences for the patient and reduces the potential shame and embarrassment of sensitive topic, for

example:

“Sometimes when people are [under stress/feeling anxious/feeling depressed], they can have strange experiences such as trouble with their

thinking or seeing or hearing things that others don’t.” Affirmative responses to the question below should be followed by: “Tell me about that.”

Questions to elicit delusional thinking

Have you had any strange or odd experiences lately that are difficult to explain or that others would find hard to believe?

Have you felt like people are watching or following you or they want to harass or hurt you?

Have you felt like others can hear your thoughts or that you can hear another person’s thoughts?

Questions to elicit hallucinations

Do your eyes or ears ever play tricks on you?

Have there been times when you heard or saw things that other people could not?


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Treatment of Psychosis in Epilepsy

AEDs may sometimes induce psychotic symptoms. Ahigh serum level of AED, particularly in the context ofpolypharmacy, can often cloud consciousness, precipitat-ing development of psychotic symptoms (Onuma, 1987).Whereas any of the AEDs has the potential to cause psy-chotic symptoms (Schmitz, 1999), some AEDs, forexample, ethosuximide (Fischer & Pedersen, 1965), phe-nytoin (Noguchi et al., 2012), zonisamide (Matsuura &Trimble, 1997; Noguchi et al., 2012), topiramate (Mula& Monaco, 2009), and vigabatrin (Mula & Monaco,2009), seem to be more potent in this regard than others.Although most findings on AED-related psychosis havebeen based on single case reports or small series of caseswithout systematic examinations, it is arguably safer toavoid these agents in patients at high risk. Approximately30–40% of patients who had AED-induced psychosisalso developed chronic IIP or AED-unrelated IIP at dif-ferent times (Matsuura, 1999; Kanemoto et al., 2001a,b).These results may suggest that patients with individualvulnerabilities to psychosis tend to exhibit IIP irrespec-tive of types of AEDs.

The association of seizure frequency with occurrence ofIIP has been a matter of debate. Several early studies (Sla-ter et al., 1963; Flor-Henry, 1969; Kristensen & Sindrup,1978) reported a lower frequency of seizures in patientswith IIP. This is in line with the concept of antagonismbetween epilepsy (seizures) and psychosis, which may berepresented by descriptions of forced normalization (Lan-dolt, 1958) and alternative psychosis (Tellenbach, 1965).Applying these theories to clinical practice needs carefulevaluation for each IIP episode. The same individual maydevelop an episode of IIP consistent with the phenomenonof forced normalization on one occasion while having anepisode of IIP without any changes in electroencephalog-raphy (EEG) and/or seizure frequency at a different time.Furthermore, Mendez et al. (1993) reported a higher fre-quency of complex partial seizures (CPS) in IIP. System-atic study has not as yet been conducted to verify thesehypothetical theories.

Treatment principles for IIPIn the absence of specific treatment guidelines, psy-

chotic symptoms in IIP have hitherto been treated in linewith well-established treatment protocols for primaryschizophrenia and related psychotic illnesses (Kerr et al.,2011). Few data are available on the treatment of IIPspecifically.

It is not uncommon in day to day clinical practice fornonpsychiatrist epileptologists to be the first clinicians toface the management of a patient developing IIP. Aware-ness of the potential for the syndrome to develop in anyepilepsy patient and knowledge of common psychopatho-logic phenomena as described above is important.

The next step is to set a treatment target. IIP symptomscan be difficult to manage for a variety of reasons that

commonly include intractability of psychotic symptoms,the individual variation in tolerability of antipsychotictreatment, the treatment’s potential for adverse conse-quences on seizure control, and the individual’s adherenceto psychiatric treatment (Onuma, 1987; Adachi, 2005). Incases of primary psychotic episodes, at least one half ofpatients are partially or completely nonadherent (Lacroet al., 2002; Abdel-Baki et al., 2012). If this is the case,treatment modalities should be offered aiming at overallfunctional recovery and improved quality of life, ratherthan aiming at complete symptomatic remission.

There are some advantages for patients with IIP toremain in the care of their treating epileptologists at thetime of initial psychiatric treatment. The epileptologistsare positioned to observe and identify early signs of IIPeven before the individual reports it. They are also bestsuited to simultaneously manage factors common in epi-lepsy and IIP (Onuma, 1987). The existing therapeuticrelationship helps ensure that epilepsy patients with psy-chosis are more likely to be cooperative with their treatingdoctors than are patients with first-episode psychosis whoare treatment-naive (Adachi, 2005). The good doctor–patient relationship enhances therapeutic outcome (Dayet al., 2005).

A significant proportion of patients with psychosishave limited insight into their psychotic symptoms andrelated behavior, and the need for treatment (McGorry &McConville, 1999; Mintz et al., 2004). It is not uncom-mon for patients to consent to epilepsy treatment butrefuse psychiatric treatment. Assessing their capacity toprovide informed consent to treatment is important(Brabbins et al., 1996; Pollack & Billick, 1999; Capdevi-elle et al., 2009). The management of epilepsy shouldcontinue alongside regardless. At the very least, this willallow for monitoring of the evolving psychiatric presen-tation and arranging appropriate intervention whenneeded.

How to use medical treatment

Timing of initiating antipsychotic drug (APD). In general,psychosis is better managed earlier rather than at a later,more advanced stage. Early initiation of APD therapy rel-ative to time of onset of IIP shortens the duration of the IIPepisode (Adachi et al., 2012). This finding is in line withstudies on first-episode psychosis and schizophrenia(White et al., 2009). Therefore, an early introduction ofAPD is recommended where clinically indicated, inparticular if the patients present with their first episode.On the other hand, approximately 15% of IIP episodesremitted without any APD treatment (Adachi et al.,2012), indicating that a short delay in commencement ofAPDs may not be harmful for first-episode patients if theyare well supported with psychosocial interventions(Francey et al., 2010). For patients with chronic IIP, it is


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prudent to seek patient consent to continued psychiatrictreatment.

Choice of APD. The recent consensus report of the Inter-national League Against Epilepsy (ILAE) commission(Kerr et al., 2011) states that IIP can be treated with APDssimilarly to functional psychoses, for example, schizo-phrenia, brief/transient psychosis, and delusionaldisorders. APDs are often divided into two categories:first-generation (mostly typical/conventional) APDs(FAPDs); that is, butyrophenones, phenothiazines, benza-mides, and thiepins), and second-generation (atypical)APDs (SAPDs); that is, serotonin-dopamine antagonists,dibenzothiazepines, and multiacting receptor-targeted an-tipsychotics). In principle, choosing an APD depends onits efficacy and tolerability. Although some differences inefficacy have been reported, there is no conclusive evi-dence that SAPDs are more effective than FAPDs (Cross-ley et al., 2010; Girgis et al., 2011; Hara et al., 2012).The dose of APDs is often converted into chlorpromazineequivalent (CE mg/day) to help compare different APDs(American Psychiatric Association, 1998; Toru, 1998;Table 2). This is not always possible or reliable, espe-cially for some SAPDs.

Given the paucity of evidence for the relative efficacyof one APD over another in treating IIP, the choice islargely based on adverse effects. The main adverse effectsof APDs are as follows:1 Sedation, such as somnolence and hypersomnia, is the

most common side effect of APDs, either FAPDs orSAPDs. Low potency APDs except for sulpiride, for

example, chlorpromazine, are more likely to causethese effects.

2 Weight gain and metabolic syndrome occur with any ofthe APD treatments, although SAPDs are generally lessfavorable in this regard. In particular, most SAPDs(e.g., olanzapine, quetiapine, risperidone; Correll et al.,2009), with the possible exception of aripiprazole, andsome FAPDs (e.g., sulpiride) are likely to be associatedwith these problems.

3 Cardiovascular effects can occur with any APD treat-ment (Mackin, 2008). Orthostatic hypotension is themost common adverse effect of APDs, in particularwith low potency FAPDs. QTc prolongation and subse-quent arrhythmia can be caused with any APDs; how-ever, this risk is increased with pimozide, thioridazine,sertindole, and zotepine.

4 Hyperprolactinemia and sexual dysfunction are some-times in the context of treatment with most FAPDs(e.g., haloperidol and sulpiride) and some SAPDs (e.g.,risperidone and amisulpride; Rosenbloom, 2010; Holt& Peveler, 2011).

5 Extrapyramidal symptoms (EPS), such as akathisiaand parkinsonism, occur mostly with FAPDs (in par-ticular high potency agents, that is, haloperidol),although some degree of EPS can be seen with SAP-Ds. EPS can be a primary cause of noncompliancewith medication. Low doses of anti-parkinsonism/antispasmodic drugs (e.g., trihexyphenidyl 4–10 mg/day or biperiden 2–6 mg/day) can be prescribedtogether with FAPDs to ameliorate EPS (Toru,1998).

Table 2. Types of antipsychotic drugs and their chlorpromazine equivalent dosages

Generation Groups Medicines CE

First-generation APD Phenothiazines Chlorpromazine 1

Levomepromazine 2

Thioridazine 1

Properithiazine 6.7

Fluphenazine 50

Trifluoperazine 20

Perphenazine 10

Butyrophenones Haloperidol 50

Bromperidol 50

Pimozide 50

Benzamides Sulpiride 0,5

Sultopride 0.7

Thiepins Zotepine 2

Second-generation APD Serotonin-dopamine antagonists (SDA) Risperidone 67 (50–100)Perospirone 12.5

Dibenzodiazepines Quetiapine 1.4 (1–2)Clozapine 2

Multiacting receptor-targeting antipsychotics (MALTA) Olanzapine 40 (30–50)Dopamine system stabilizer Aripiprazole 40 (30–50)

Modified from American Psychiatric Association, 1998; Toru, 1998. Chlorpromazine equivalent dose (CE): 1 mg of each medicine can be converted intocertain dose (mg) of CP, for example, 1 mg haloperidol is 50 mg CP.


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Cost–benefit analyses are also important to take intoaccount, since treatment for IIP is often required over longperiods. In addition to already long-term financial com-mitment to epilepsy treatment, treatment cost for IIP couldbe a burden, becoming a barrier to adherence to treatment(Perkins, 2002; Abdel-Baki et al., 2012). In the WHOmultinational cost-effectiveness study (Chisholm et al.,2008), the most cost-effective interventions in the devel-oping world were those using typical APDs combinedwith psychosocial treatment, delivered via a community-based service.

Some AEDs, such as carbamazepine, valproate, andlamotrigine, are known to have certain psychotropiceffects; however, these are mainly for affective and not forpsychotic symptoms, and these drugs are not useful fortreating IIP per se. Minor tranquilizers (particularly ben-zodiazepines) have some antiepileptic and psychotropiceffects. Although minor tranquilizers normally suppressanxiety, irritability, and psychomotor-excitements, theyoften induce somnolence, loss of concentration, and disin-hibition and have dependence potential (Toru, 1998).Judicious use in the short term when required is necessaryto avoid such undesirable effects. Antidepressants mayhave some beneficial effects for IIP with depressive/affec-tive symptoms (Blumer et al., 2000), and judicious use ofthese drugs is recommended.

Special considerations. Concerns over the propensity ofAPDs to lower seizure threshold can lead to the under-treatment of IIP. Some APDs are recognized to increaseseizure risk more than others, including chlorpromazineand zotepine. Among SAPDs, clozapine, olanzapine, andquetiapine appear to have a higher seizure risk. It is impor-tant to bear in mind that in addition to drug-related factors,predisposing factors in the individuals contribute to drug-induced aggravation of seizures. Most reports are basedon animal studies, APD overdose cases, or patients withmental disorders who are not treated with AEDs. In epi-lepsy patients treated with AEDs, most APDs, eitherFAPD or SAPD, can be safely administered in patientswith epilepsy (Okazaki et al., 2012).

Pharmacokinetic interactions between APDs and AEDsneed to be considered (Trimble & Mula, 2008). Via cyto-chrome P450 (CYP) systems, serum concentrations willbe altered depending on the combination of the drugs ofinterest, potentially leading to adverse events or reducedefficacy. Enzyme inducers, such as carbamazepine, maydecrease the serum level of some APDs. Patients withmultiple disorders often take a combination of drugs,either enzyme inducers, enzyme inhibitors, or both. Thedrug interactions are often difficult to calculate accuratelywhen the patients are on polypharmacy, since interactionsbetween two drugs (e.g., one AED and one APD) observedexperimentally or clinically can often be altered in unex-pected directions when further drugs are added. Pragmatic

approaches are (1) to simplify medication regimens as faras possible, (2) to monitor efficacy and adverse effectsclinically, and (3) to check the serum level if appropriateand adjust the dose of the medication accordingly(Onuma, 1987; Adachi, 2005).

APD dose titration. General rules of APDs titration are tocommence at low doses, titrate slowly to a minimum ther-apeutic dose, and continue at a steady dose for a sufficientperiod of time. Of 320 IIP episodes in Japanese neuropsy-chiatric institutions, the maximum dose of APDs requiredranged from 12.5 to 3,425 mg/day CE (mean 454.7 mg/day CE; Hara et al., 2012). Empirically, for patients withmild IIP episodes, the target dose of APD ranges from 50to 300 mg/day CE. Some mild psychotic episodes disap-pear without any APD treatment; therefore, IIPs can beobserved without medication under some conditions.Examples include situations in which (1) the patients andpeople around them are not distressed or disturbed by thesymptoms, (2) the patients do not give a consent to takeAPDs and the risk profile is favorable, and (3) risks ofadministering APDs is greater than their benefits. Slowand careful titration from low dose (around 50–100 mg/day CE) can significantly reduce the occurrence ofadverse effects (Mula & Monaco, 2009). When IIPpatients show moderate episodes, which are determinednot only by symptom severity but also by functional dis-turbance, the patients with moderate episodes should take300–1,000 mg/day CE of APDs. For serious episodes, inparticular those accompanying characteristics such asexcessive psychomotor excitement or attempted suicide,they may need to take sufficient dosages (1,000–3,000 mg/day CE) of APDs. Because dose required doesnot necessarily correlate with present severity, other con-ditions, such as individual responsiveness, course of ill-ness, and history of violent behaviors, should also beconsidered. Depending on their risks to self and/or others,a transfer of care to psychiatric services, including psychi-atric emergency, may be required. Keeping up to date withmental health legislation and local procedures would min-imize delay for involvement of specialist services.

Careful titration is recommended for patients with par-ticular conditions by an international consensus study(Gardner et al., 2010). They include patients with distinctbrain damage, that is, postencephalitis and cerebrovascu-lar disease, with physical conditions, in the younger orolder age groups, or in certain ethnic groups. The startingdose should be smaller, and titration regimens should beslower than those for patients without such conditions. Forpatients with brain damage, the target dose should be setat 30–50% lower. Patients with physical diseases, such asimpaired hepatic function (�45%) and impaired renalfunction (�30%) should also be prescribed a lower dos-age. Age-related dosing changes of APD treatment shouldbe as follows; that is, children (age 6 to puberty; �60%),


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N. Adachi et al.

adolescence (�30%), and elderly (>65 years; �50%).Likewise dosages of APDs reflect ethnic metabolic char-acteristics; East Asian patients may take a 20–40% lowerdose than Western patients (Lawson, 1986; Matsunagaet al., 2009).

Duration of APD treatment. There is insufficient evi-dence on the duration of treatment with APDs for IIPepisodes. Effectiveness of APD use for maintenanceand prevention of IIP is also little known. In pharmaco-logic management in functional psychoses, it is advisedthat the patients remain on the optimized dose of APDfor at least 6 months after reaching remission for thefirst couple of episodes, and then come off medicationgradually. In patients who already have had multipleepisodes are advised to stay on medication long term.Due to its chronic nature and relatively high rate ofexacerbation, the international commission recom-mended a long-term administration of APDs after aremission of IIP (Kerr 2011). This is in line with find-ings in first-episode psychosis that the maintenance oftreatment is more effective for preventing relapse anddeterioration than targeted intermittent treatment(Gaebel et al., 2011). Sudden discontinuation of APDsmay disrupt serum levels of AEDs; thus, seizure con-trol and adverse effects of AEDs should be carefullymonitored. It is possible that IIP episodes recur afterdiscontinuing APDs (Onuma et al., 1991; Adachi,2005); careful follow-up is needed.

Psychotherapeutic approachesPsychosocial functions are adversely affected by psy-

chotic symptoms as well as nonpsychotic symptoms, thatis, apathy and neurocognitive dysfunction, which aresometimes difficult to treat with medication. Althoughthere is no systematic study on effectiveness of psycho-therapeutic approaches in epilepsy patients with psycho-ses, ample evidence in functional psychoses (Franceyet al., 2010) gives us insight into the value of such inter-ventions in the management of these patients, leading tobetter adherence to treatment and improved quality of life.Limited resources and experience in this area may be adeterrent, although basic interventions listed below couldbe provided by nonspecialists.1 Psychoeducation: It is essential to ensure that patients

understand the diagnosis of psychosis and need fortreatment over a long period (Perkins, 2002).Improved awareness and understanding of the condi-tion can help them remain motivated in continuingtreatment. Tackling stigma surrounding psychiatricconditions and their treatment may be one of the keysfor successful treatment (Iyer et al., 2011; McCannet al., 2011).

2 Self-help and reframing: Stress may play a role indevelopment of IIP. Poor coping skills could have

detrimental effects on the patients, leading to reducedquality of life and low self-esteem. Assisting thepatients in developing more helpful coping strategiescan improve their self-monitoring of the conditions,and long-term management, particularly in patientswith mildly impaired to borderline intellectual func-tioning (Harris, 1998; Adachi, 2005).

3 Support for family and carers, and networking: Goodsupport by family members, carers, and social networksis a significant determinant for adherence to medication(Rabinovich et al., 2009). In patients with schizophre-nia, the relapse rate can be reduced by 20% if relativesare involved in treatment (Addington & Addington,2008). Providing psychoeducation and practical andemotional support for family and carers often leads tobetter management of the conditions as a whole(Onuma, 1987; Adachi, 2005).

Prognosis of IIPEpisodes of IIP generally take a longer time than PIP,

lasting for months in many cases. In a large cohortstudy, approximately 75% of all IIP episodes lasted for1 month or more, regardless of APD treatment; themean duration of 320 IIP episodes in 155 patients was82.7 weeks (median 17 weeks; Adachi et al., 2012).This study considered only the periods during which thepatients manifested hallucinations and/or delusions. Epi-sodes are likely to be more prolonged if formal thoughtdisorders and/or nonpsychotic symptoms (e.g., emo-tional withdrawal, depression, anxiety, and irritability)were included.

Episodes often recur in patients with IIP. Onuma et al.(1991) reported that almost two thirds of IIP patients hadepisodes of relapse after remission or worsening ofchronic episodes during a 10-year follow-up period. Alongitudinal observation disclosed that approximately90% of the IIP patients had psychotic episodes that lastedfor 1 month or more and 65% had episodes that lasted for6 months or more (Adachi et al., 2012). In the course ofillness, patients sometimes exhibit different types of psy-chosis, for example, acute-transient and chronic (Adachiet al., 2012), AED-induced and AED-unrelated (Matsu-ura, 1999; Kanemoto et al., 2001a,b), and even IIP andPIP (Tarulli et al., 2001; Adachi et al., 2003). Some IIPsrecur after discontinuation of APD treatment (Onumaet al., 1991; Adachi, 2005).

Patients with mental disorders have an increased risk ofpremature death, from either natural or unnatural causes(Harris & Barraclough, 1998; Tiihonen et al., 2009).Patients with epilepsy also have particular risks to earlydeath, for example, sudden unexpected death, statusepileptics, suicide, and accidents, in addition to commonetiologies (Hitiris et al., 2007). It is therefore possible thatsynergism of the two conditions can lead to an increase inmortality.


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Future issuesWe have proposed treatment guidelines for IIP based

on limited data and the consensus statements currentlyavailable (Table 3). Whereas treatment systems for IIPare predominantly “borrowed” from standard treatmentsystems for functional psychoses, they have been found tobe safe and effective. Specific aspects of treatment thatwould improve outcome in IIP have not been researched.Particularly, few data are available for maintenance andprophylaxis in IIP (Adachi, 2006). Large-scale studies inpatients with IIP are required in a prospective manner,which can be challenging due to the relatively low preva-lence of IIP. In addition, despite growing interest in qual-ity of life in people with epilepsy, usefulness ofpsychosocial interventions has been rarely mentioned orinvestigated in patients with IIP. The field remains openfor more research.

Postictal PsychosisPostictal psychosis (PIP) had not drawn wide attention

until the iatrogenic provocation of seizures in seizuremonitoring units for preoperative evaluation became pre-valent (Savard et al., 1991; Devinsky et al., 1995; Kanneret al., 1996), and neurologists and neurosurgeons werefrequently confronted with PIP requiring urgent interven-tion. Pertinent knowledge of this phenomenon has there-fore become indispensable for clinicians (Trimble, 1991;Kanemoto et al., 1996a; Kanemoto, 2011). Although PIPis, in most cases, a self-remitting condition, individuals inthe midst of PIP can be astonishingly violent, extremelyagitated, or confused, such that immediate protectionunder strict custody often becomes mandatory (Devinsky,2008). PIP is a psychiatric emergency that every neurolo-gist or neurosurgeon involved in epilepsy surgery ortreatment of long-standing limbic epilepsy could beconfronted with.

Definition of PIPAs is the case for other types of epileptic psychoses,

PIP is defined by two features: its chronologic rela-tionship to seizures and the nature of the mental state.For the chronologic relationship, most authors haveadapted the criterion proposed by Logsdail and Toone(1988), that is, episodes of psychosis that developwithin 1 week after a seizure, or usually a cluster ofseizures, qualify as PIP. This operational delineation isnot as arbitrary as it seems in light of accumulateddata that now indicate that PIP generally occurs within3 days after the last seizure (Logsdail & Toone, 1988;Devinsky et al., 1995; Kanemoto et al., 1996a).Indeed, the presence of a lucid interval between thelast seizure and start of changes in mental state guar-antees a qualitative difference between PIP and simplepostictal confusion, and constitutes an integral part ofthe clinical picture of “nuclear PIP” (Fig. 2). However,inclusion of a lucid interval in the essential diagnostic

Table 3. Treatment principles for IIP

Establish a diagnosis of IIP episodes by excluding ictal/periictal/postictal psychotic phenomena; evaluate the severity of their symptoms and level of

their disturbances

Assess the patient’s capacity to give a consent to treatment and/or to participate in the decision-making process; seek views from family members

and/or carer when necessary

Make a treatment strategy, for example, psychosocial interventions or watchful wait in outpatient clinics, pharmacologic treatment (with or without

other treatment options) as an outpatient or inpatient

Optimize AED regimens where possible by reducing polypharmacy and adjusting the dose to aim for therapeutic serum levels

Administer APDs: following issues should be taken into account

Timing: early intervention is preferable

Choice of APD: any APDwith fewer or lesser adverse effects, availability, and affordability

Dose titration: 50–300 mg (CE)/day for mild episodes, 300–1,000 mg (CE)/day for moderate episodes, 1,000–3,000 mg (CE)/day for severe

episodes

Duration: long-term treatment (usually months or years) with APD is required

Provide basic psychosocial approaches, for example, psychoeducation, self-help, and reframing, and support for family and carers

CE, chlorpromazine equivalent.

Figure 2.

Definition of PIP and closely related conditions (with

permission from Kanemoto, 2011).Epilepsia ILAE


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N. Adachi et al.

criteria would exclude nearly half of the cases fromPIP (Levin, 1952; Kanemoto et al., 1996a) and mostauthors have not automatically excluded cases withouta lucid interval from their study subjects. Indeed, thelucid interval could be very short and may thereforego unnoticed.

The second part of the definition, the nature of the men-tal state, relates to the psychotic presentation. Indeed, theoriginal criteria proposed by Logsdail and Toone (1988)included the presence of delusions or hallucinations inclear consciousness. However, because a manic presenta-tion is a frequent precursor of nuclear PIP (Kanemotoet al., 1996a; Kanner et al., 1996), it seems reasonablethat postictal manic state should be included in this defini-tion. The fact that appropriate and timely therapeuticintervention can prevent subsequent transition into full-brown psychosis also shows the practical value of thisidea. In Figure 2, PIP and various related conditions areschematically summarized.

Diagnosing PIPIn seizure-monitoring units, PIP lends itself to being

easily recognized such that no specific advice seems neces-sary, except for knowing that such a state exists. However,without careful attention, an initial sign of elevated moodor emotional lability may be overlooked, which couldresult in failure to apply early intervention, and an other-wise avoidable psychiatric emergencymay ensue. It shouldbe also noted that a sensitive inquiry can disclose subtlechanges of subjective feeling such as derealization (“outerworld looks as if it was not real”) or an otherwise barelynoticeable lowering of cognitive function even in a seem-ingly normal lucid interval (Ito, 2010; Schulze-Bonhage &van Elst, 2010). In principle, it is highly advisable that acareful examination of psychiatric as well as neuropsycho-logical status should be repeated at least within 3 daysfollowing a seizure cluster in seizuremonitoring units.

As for outpatients, especially in cases of the first epi-sode of PIP, a preceding seizure or seizure cluster can beoverlooked, which may obscure the true nature of thepresentation. If an otherwise taciturn person with long-standing temporal lobe epilepsy (TLE) becomes suddenlyeloquent or if a reticent one becomes unexpectedly irrita-ble or sticky, medical personnel should be on alert, as itmay herald the beginning of PIP even if preceding sei-zures cannot be confirmed. If it is truly an initial sign ofPIP, frank psychosis or seriously annoying behavioralchanges including menacing aggression (Gerard et al.,1998; Kanemoto et al., 2010) will develop, in the absenceof appropriate intervening measures, within 48 h.

Associated characteristicsLong-standing (average duration >15 years) TLE is a

typical comorbid condition of PIP (Savard et al., 1991;Devinsky et al., 1995; Kanemoto et al., 1996a; Kanner

et al., 1996; Adachi et al., 2002a; Kanemoto, 2011).Other types of focal epilepsies, especially frontal lobe epi-lepsy, are also associated at times (Adachi et al., 2000a;Nishida et al., 2006; Alper et al., 2008). On the otherhand, coexistence of idiopathic generalized epilepsies andPIP is quite exceptional (Chakrabarti et al., 1999).

In a substantial proportion of cases, involvement of themedial temporal structures is indicated on MRI, whichmay also extend to the lateral temporal and extratemporalregions (Kanemoto et al., 1996b; Sundram et al., 2010).Furthermore, epileptiform discharges on surface EEG intemporal regions tend to be bilateral (Kanner & Ostrovs-kaya, 2008a; De Toffol, 2009). In patients with repetitiveepisodes of PIP, a specific personality trait such as hyp-erreligiosity or viscosity may supervene (Trimble, 2007;Devinsky & Lai, 2008).

Treatment principles for PIPThe therapeutic approach to PIP comprises acute protec-

tive measures and the prevention of repeat episodes (Lanc-man et al., 1994; Kanemoto, 2002; Devinsky, 2008).

Acute management of PIP or imminent PIP

Initial stage preceding PIP. In the nuclear type, elevatedmood or peculiar irritability often precedes a full-blownPIP episode (Schulze-Bonhage & van Elst, 2010). Ifpatients are successfully treated at this stage, developmentof frank psychosis might be thwarted. As noted above, PIPis closely linked with various abnormal behaviors that cando great harm to the subsequent social life of the patient.In cases of long-standing TLE, patients and familiesshould be warned beforehand to seek medical help as soonas possible and not leave the patient alone if any suspi-cious change in behavioral patterns appear after a seizureor seizure cluster (Krauss & Theodore, 2010). In the sei-zure monitoring unit, every seizure cluster or secondarilygeneralization should be taken as a possible precipitant ofPIP, and indicates the need for intensified observation.

Full-blown PIP. Once PIP develops fully, immediate pro-tective custody is unavoidable in many cases and anydelay in protection may lead to serious problems, includ-ing destructive or self-harming behavior (Devinsky et al.,1995; Kanner et al., 1996; Kanemoto et al., 1999;Fukuchi et al., 2002). In patients with a history of violentPIP episodes in the past, the risk of similar behaviors beingrepeated is particularly high. A potent sedative agent isworth trying, which may shorten the duration of the epi-sode. Paradoxically, ECT may be helpful in terminatingviolent PIP attacks in exceptional cases (Pascual-Arandaet al., 2001). Repetitive transcranial magnetic stimulationmight be more safely applied than ECT in the future,although it remains an experimental treatment for PIP atpresent (Krauss & Theodore, 2010).


27


Preventive strategy in the long termIn contrast to interictal psychosis inclusive of alterna-

tive psychosis, seizure control generally prevents recur-rence of PIP episodes (Kanemoto et al., 2001a,b). In somepatients, a simple reappraisal of pharmaceutical therapycan succeed in stopping seizures or seizure clusters, con-sequently preventing PIP episodes as well. However, aconsiderable number of patients have already tried nearlyall available antiepileptic agents by the time PIP appears,which shows a rather discouraging prospect for drug ther-apy to achieve complete seizure freedom. In addition, in aclinical setting like this, intensive antiepileptic pharmaco-therapy may be prone to induce various psychiatric symp-toms, including interictal psychosis and depression.Operative intervention, if applicable, is often the last hopefor a breakthrough in affected patients. Indeed, successfuloperative intervention leads to cessation of PIP episodesas well, except in some cases (Christodoulou et al., 2002).Nevertheless, it should be noted that epilepsy-related vari-ables associated with PIP such as structural changesbeyond medial temporal lesion and bilateral EEG focimay predict poor surgical outcome (Alper et al., 2001; DeToffol, 2009), although that has not yet been confirmed byactual investigations (Winesett & Benbadis, 2010). Anadditional cautionary note is also in order. Patients withpreoperative episodes of PIP or even prolonged postictalconfusion may have a higher risk of developing seriousdepression (or even a manic state) within 3 months aftersurgery (Kanemoto et al., 2001a,b). Furthermore, in pre-surgical evaluations of patients with a history of PIP, sei-zure cluster or secondary generalization is highly likely toreplicate similar episodes, so that every step should betaken in advance to avoid inducing PIP episodes and, oncePIP manifests, to treat it as soon as possible (Kanner,2009). Although these anticipated troubles may discour-age surgical intervention, successful surgery can dramati-cally change the life of affected patients, even moredramatically than in those with epilepsy but without PIP.Therefore, patients with PIP should not be deprived of achance for surgical intervention beforehand, as some arein fact excellent candidates.

How to use medical treatmentFor psychoses associated with epilepsy, a systemic

review of literature up to 2008 revealed only one under-powered, randomized controlled trial, from which obvi-ously few conclusions can be drawn (Farooq & Sherin,2008). When it comes to pharmacotherapy for PIP, limita-tions in the evidence should be always kept in mind, sincenearly all advice remains at the level of expert opinion. Fur-thermore, the initial target of pharmacotherapy often needsto be directed toward violent or agitated behavior, ratherthan the psychosis itself. This means that measures estab-lished for rapid tranquilization of patients with schizophre-niamay not automatically be applicable to thosewith PIP.

Acute phaseIn both the initial stage preceding PIP and during the

episode, sedative drugs are generally needed, as they notonly stop socially inappropriate behaviors but can alsoabort or alleviate symptoms of PIP. Some experts haverecommended benzodiazepines (Lancman et al., 1994),whereas others prefer a combination of both benzodiaze-pines and antipsychotics (Kanner et al., 1996). Althoughantipsychotics are known to lower seizure threshold in vi-tro, except for some notable exceptions, such as zotepineand clozapine (Devinsky et al., 1991), their proconvulsiveeffects seem to be at a tolerable level, at least as long asthey are given within a therapeutic range. In most cases,imminent need of sedation has priority over a possibleproconvulsive risk.

In some exceptional cases, early stage PIP can be man-aged and thwarted with a relatively low dose of oral ben-zodiazepines. However, in other extreme cases, sedativesshould be given swiftly as well as massively enough toforce immediate tranquilization. Depending on how seri-ous the detrimental impact is on the patient and their sur-roundings, and whether an inpatient or outpatient situationis in question, different combinations of pharmaceuticalinterventions can be chosen, as follows.1 Oral administration of benzodiazepine (e.g., loraze-

pam).2 Combined oral administration of benzodiazepine and

dopamine-blocker (e.g., risperidone, olanzapine, que-tiapine, chlorpromazine).

3 Intramuscular administration of dopamine-blocker (e.g., haloperidol plus promethazine).In cases without seriously alarming behaviors either

during precedent or current PIP episodes, regimen A maysuffice. However, even when observed signs are confinedto slightly elevated mood or irritability, the patient shouldbe kept under strict scrutiny at least for the next 24 h.Meanwhile, if any sign of increasing excitability isnoticed, a switch to regimen B may be necessary, becausebenzodiazepines alone may precipitate paradoxicalexcitement and are not as potent as dopamine-blockers forrapid tranquilization of violent or agitated patients in apsychiatric emergency (Alexander et al., 2004; Allenet al., 2005). When confronted with seriously alarmingcurrent behaviors or in the presence of past violentepisodes during PIP, if the patient is unable to cooperate,regimen C may be left as the only choice. Again, it shouldbe noted that there are no reliable data to favor one anti-psychotic over another.

Interepisodic phaseRobust manifestations of PIP usually fade away within

a week and patients seem to superficially return to theirformer selves. However, unexpected outbursts caused byminimal stimuli can occur sporadically within thenext few weeks afterward (Oshima et al., 2006). In this


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N. Adachi et al.

unstable stage, a reduced amount of regimen A or B oftenneeds to be maintained. Sedatives should be reduced grad-ually and can be tapered completely on average within4 weeks and mostly within 3 months. Except for caseswith combined chronic psychosis and severe personalitychange, continuous use of psychotropic agents is not gen-erally recommended during the interepisodic phase. Noreliable data are available to judge whether a switch of an-tiepileptic drug to one with more psychotropic efficacy,such as valproate, carbamazepine, and lamotrigine, is ben-eficial for the prophylaxis of PIP (Krauss & Theodore,2010).

Prognosis of PIPIn considering prognosis, each episode of PIP is essen-

tially a benign, self-remitting condition. Only temporarymeasures such as physical restriction or medical sedationare needed to cope with risk behaviors aimed at protectingthe safety of patients and others. In comparison with IIP,the duration of PIP is clearly shorter. In a recent collabora-tive study, approximately 95% of PIP episodes resolvedwithin 1 month (Adachi et al., 2007). In another study,PIP episodes tended to resolve within 1 week in anoverwhelming majority of patients in a seizure monitoringsetting (Devinsky et al., 1995; Kanner et al., 1996).Nevertheless, it should be noted that suicidal attempts arefrequent complications of PIP episodes and without inter-vention there may be a heightened risk of mortality(Devinsky et al., 1995; Kanemoto et al., 1996a; Kanneret al., 1996; Fukuchi et al., 2002).

In half of affected patients, PIP remains as a singleepisode. In the other half, PIP episodes tend to repeat,which may occur even quasiregularly after a cluster ofcomplex focal seizures or secondary generalization inextreme cases (Logsdail & Toone, 1988; Kanemotoet al., 1996a,b; Kanner et al., 1996; Liu et al., 2001).In some patients, repetitive PIP episodes finally developinto chronic interictal psychosis (Tarulli et al., 2001;Adachi et al., 2003; Kanner & Ostrovskaya, 2008b).

Future issuesAlthough data gathered from cases with invasive

EEG recordings during PIP are highly limited (Wieseret al., 1985; So et al., 1990; Mathern et al., 1995;Kanemoto, 1997; Seeck et al., 1999; Takeda et al.,2001; Schulze-Bonhage & van Elst, 2010), it hasbecome increasingly clear that only a limited propor-tion of PIP or related conditions correspond to ictalEEG correlates. Indeed, sporadic single photon emis-sion computed tomography (SPECT) studies have sug-gested that early frontal and late medial temporalhyperactivities may play some role in the genesis ofPIP (Fong et al., 2000; Leutmezer et al., 2003; Nishidaet al., 2006; Oshima et al., 2011). However, in asubstantial number of cases, these hyperactivities do

not seem to be directly linked with epileptiform dis-charge. Some authors have speculated that postictalalterations of neurochemical settings may be foundsomewhere in the limbic circuit. Stevens (1983)regarded these alterations as excessive inhibitory sur-round and, more specifically, Bortolato and Solbrig(2007) assumed that increased hippocampal dynorphinrelease may serve as a psychotomimetic agent viaoverstimulation of kappa opioid receptors in PIP. Froman electrophysiologic point of view, Kuba et al. (2012)recently found a unique slow rhythmicity in depth-EEGrecordings during PIP episodes, which clearly differedfrom ictal epileptiform discharge appearing in limbicstatus epilepticus. Also, as was recently suggested(Oshima et al., 2006), subcategorizing of PIP intonuclear type with a lucid interval and initial hypomanicstage and atypical periictal type may be helpful forunderstanding the underlying pathophysiology of PIP(Fig. 3A,B). Further accumulation of relevant cases ishighly anticipated.

There are genetic as well as phenomenologic data sug-gesting a close affinity of PIP with bipolar disorder (Alperet al., 2001; Kanemoto et al., 2001a,b). PIP episodes canbe well observed and investigated because of their limitedduration and clear-cut on-and-off psychotic states.Increased knowledge of how PIP develops may also helpto clarify the mechanisms related to how relevant psychi-

Figure 3.

(A) Nuclear PIP; (B) Periictal psychosis (with permis-

sion from Kanemoto, 2011).Epilepsia ILAE


29


atric disorders without epilepsy develop, which may helpbridge neurology and psychiatry.

ConclusionPsychotic disorders are not infrequent in epileptic

patients. IIP reportedly occurs in 4.5–7.0% (Trimble,1991) and PIP in <2% (Kanemoto et al., 2001b). In thosewith PEs, the incidence of PIP is doubled (Kanner et al.,1996; Kanemoto et al., 2002; Oshima et al., 2006; Falipet al., 2009), whereas the incidence is threefold in seizuremonitoring units (Kanner et al., 1996; Alper et al., 2001,2008; Falip et al., 2009). IIP and PIP are serious disorderswith significant effects on patients and their families. Anumber of cases may become psychiatric emergencies orpose significant risk to others. Such risks can be reducedor avoided if prompt and adequate treatment is put inplace. There is now international consensus amongexperts that all medical personnel involved in providinghealth care to patients with epilepsy should be well-informed about IIP and PIP (Kerr et al., 2011).

Based on the limited data and consensus statements cur-rently available, we have proposed treatment proceduresfor IIP and PIP that are concise and practical. We hope thatthis article will raise awareness of the importance of thesematters and the need for further studies. With the accumu-lation of further evidence, the proposed treatment systemsshould be refined and placed on even greater empiricalfooting.

DisclosureNone of the authors have any conflicts of interests. We confirm that

we have read the Journal’s position on issues involved in ethical publica-tion and affirm that this report is consistent with those guidelines. Thecontents of this supplement reflect the opinions of the individual authorsand do not necessarily represent official policy or position of the ILAE.

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basic treatment principles for psychotic disorders in patients with epilepsy

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