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Epilepsy and psychiatric disorders
- 1. Epilepsy and psychiatric disorders PREPARED BY: EYOB HABTAMU & MIHIRETAB MEDHIN 1
- 2. Rules of thumb for quality of life in epilepsy Patients less likely to be employed, have less education, have less income, and more likely to be single. Epilepsy/medical – most important predictors of quality of life ○ Perceived seizure frequency (lower QOL with more frequent seizures) ○ Perceived adverse effects from AEDs ○ Perceived cognitive problems due to epilepsy ○ Limitations in independence due to seizures (not driving, unemployment) ○ Psychiatric comorbidity & Presence of social stigma of epilepsy 2
- 3. 3
- 5. Epidemiology The prevalence of psychosis in the general population is around 1% . Prevalence of interictal psychosis in non-selected epilepsy population studies varies from 3.1% to 9%. Chronic and acute interictal psychoses (IIPs) and postictal psychosis (PIP) together makeup 95% of all psychosis with epilepsy. IIP and PIP are now acknowledged to be co-existent in 3–8% of PWEs. 5
- 6. Possible Pathophysiological Mechanisms Discussion has centered broadly on two mechanisms: 1) the psychosis is due to the repeated electrical discharges, either directly or through the development of neurophysiological or neurochemical abnormalities. 2) the epilepsy and psychosis share a common neuropathology that may be localized (emphasis on temporal lobe but also frontal lobe and the cerebellum) or widespread in the brain. Both mechanisms may be operative, the latter being primary and the former modifying the presentation, determining exacerbations and remissions, or being the proximate cause. The possible roles of psychological factors, neurotoxicity of anticonvulsant drugs, deficiencies (e.g., folic acid), and abnormal experiences seem to be of secondary importance. 6
- 7. Risk factors for psychosis in epilepsy Epilepsy beginning at an early age and enduring through puberty has been associated with schizophrenia-like psychosis. It is often noted that the patients who develop psychosis have a severe form of epilepsy involving multiple seizure types, a history of status epilepticus, and resistance to drug treatment. Patients who have schizophrenia-like psychosis with epilepsy generally have been reported not to have a greater than normal familial aggregation of schizophreniform disorders. A female sex bias is not generally supported. premorbid personalities are usually normal. 7
- 8. Pre-ictal Post-ictal Psychosis in epilepsy Ictal Peri-ictal Inter-ictal Chronic Acute 8
- 9. 9
- 10. the prevalence of IIP is higher in patients with TLE than in those with generalized epilepsy. A long duration of epileptic activity serves as a fertile background for development of psychosis, especially in patients with TLE 10
- 11. Psychotic patients with epilepsy have better premorbid personalities, experience more paranoid and referential delusions, showed fewer catatonic features than functional schizophrenics do and the course of the illness was more variable. 11
- 12. Staging Mild: Although patients clearly show some psychotic symptoms, they are not distressed by the symptoms, and their overall psychosocial function is maintained. Moderate: Patients have distinct psychotic symptoms; day to day functioning is disrupted, and overall psychosocial functioning is affected to some degree. Severe: Patients have overwhelming psychotic symptoms, behavioral consequences of these symptoms put them or other people at risk, and their psychosocial function is significantly impaired. 12
- 13. Ictal psychosis Is concurrently associated with epileptic discharges in the brain The majority of discharges have a focus in the limbic and isocortical components of the temporal lobe, Symptoms may reflect one of two mechanisms: 1) a positive effect of the seizure discharge, i.e., the epileptic discharge activates a behavioral mechanism represented in the area subjected to the discharge, 2) a negative effect, i.e., either a) the individual is unable to engage in a certain behavior owing to the temporary paralysis of the anatomical substrate of that behavior or b) some behaviors are released by the inactivation of structures that normally suppress them. Behavioral disturbance due to a negative effect may occur in other situations, 13
- 14. Post-ictal psychosis Episodes of psychosis that develop within 1 week after a seizure, qualifies as PIP. (generally occurs within 3 days after the last seizure and lasts b/n 24 hours and 3 months). The prevalence has been estimated to be 6-10% in patients with epilepsy. They usually follow seizure clusters or a recent exacerbation in seizure frequency (e.g. related to withdrawal of anticonvulsants) Manic presentation is a frequent precursor of PIP. If it is truly an initial sign of PIP, frank psychosis or behavioral changes including menacing aggression will develop, in the absence of appropriate intervening measures, within 48 h. 14
- 15. Between the last seizure and the psychosis there is usually a nonpsychotic period, which ranges from a few hours to a few days. Some clouding of consciousness is often present in this period, and it may extend to the initial period of psychosis or even the whole episode The psychotic symptoms are pleomorphic (persecutory, grandiose, referential, somatic, and religious delusions, catatonia, hallucinations, etc.) affective symptoms (manic or depressive) are often prominent. Post-ictal psychosis 15
- 16. The psychotic symptoms are pleomorphic (persecutory, grandiose, referential, somatic, and religious delusions, catatonia, hallucinations, etc.) and can last for weeks. affective symptoms (manic or depressive) are often prominent. some patients with recurrent episodes of post-ictal psychosis may develop an inter-ictal psychosis. Predisposing risk factors are ictal fear, bilateral epileptic foci or gross structural lesions. Mechanisms are unknown but may be related to transient neurochemical changes as a result of seizures Post-ictal psychosis 16
- 17. Post-ictal psychosis (prognosis) Each episode of PIP is essentially a benign, self-remitting condition. Approximately 95% of PIP episodes resolved within 1 month. Suicidal attempts are frequent complications of PIP episodes and without intervention there may be a heightened risk of mortality. In half of affected patients, PIP remains as a single episode. In some patients, repetitive PIP episodes finally develop into chronic interictal psychosis 17
- 18. Treatment PIP patients can be astonishingly violent, extremely agitated, or confused, such that immediate protection under strict custody often becomes mandatory. Therapeutic approach to PIP comprises: - acute protective measures - prevention of repeat episodes 18
- 19. Treatment (acute or imminent PIP) Elevated mood or peculiar irritability often precedes a full-blown PIP episode. patients and families should be warned beforehand to seek medical help as soon as possible and not leave the patient alone if any suspicious change in behavioral patterns appear after a seizure or seizure cluster. even when observed signs are confined to slightly elevated mood or irritability, the patient should be kept under strict scrutiny at least for the next 24 h. 19
- 20. Treatment ( full-blown PIP) Once PIP develops fully, immediate protective custody is unavoidable in many cases. Any delay in protection may lead to serious problems, including destructive or self- harming behavior. A potent sedative agent is worth trying, which may shorten the duration of the episode. ECT may be helpful in terminating violent PIP attacks in exceptional cases. 20
- 21. Treatment ( full-blown PIP) Depending on how serious the detrimental impact is on the patient and their surroundings, and whether an inpatient or outpatient situation is in question, different combinations of pharmaceutical interventions can be chosen; 1- Oral administration of benzodiazepine (e.g., lorazepam). 2- Combined oral administration of benzodiazepine and dopamine-blocker (e.g., risperidone, olanzapine, quetiapine, chlorpromazine). 3- Intramuscular administration of dopamine-blocker (e.g., haloperidol plus promethazine). In the interepisodic phase a reduced amount of regimen 1 or 2 is to be maintained. Sedatives should be reduced gradually and can be tapered completely on average within 4 weeks and mostly within 3 months. 21
- 22. Inter-ictal psychosis Defined as any psychosis in clear consciousness that occurs in someone who has previously been diagnosed with epilepsy, and the psychosis is not exclusively during or immediately following a seizure. Increased risk in patients with learning disabilities or a family history of psychotic illness. 22
- 23. Inter-ictal psychosis (brief) Favored description is of an alternating psychosis, i.e., a brief psychosis alternating with periods of increased seizure activity such that the seizures and psychosis appear antagonistic. Characterized by paranoid delusions and auditory hallucinations, but multiple other features, including affective symptoms, may occur. Can develop when seizures are infrequent or fully controlled & last from days to weeks. They are usually self-limiting, and their separation from postictal psychoses may be difficult, but unlike postictal psychosis, this psychosis can be ameliorated by the occurrence of one or more seizures. 23
- 24. Inter-ictal Psychosis (chronic) The prevalence is reported to be 4-10% in patients with epilepsy, mainly in those with temporal lobe epilepsy. mean age at onset is usually about 30 years old. Phenomenologically, the disorder is mostly indistinguishable from schizophrenia. risk factors that have been reported are early age of onset of epilepsy, bilateral temporal foci and a refractory course. 24
- 25. Inter-ictal psychosis (prognosis) Approximately 75% of all IIP episodes lasted for 1 month or more, regardless of APD treatment Almost two thirds of IIP patients have episodes of relapse after remission or worsening of chronic episodes during a 10-year follow-up period. 25
- 26. Treatment Early initiation of APD therapy relative to time of onset of IIP shortens the duration of the IIP episode. On the other hand, approximately 15% of IIP episodes remit without any APD treatment. Given the paucity of evidence for the relative efficacy of one APD over another in treating IIP, the choice is largely based on adverse effects. Some APDs are recognized to increase seizure risk more than others, including chlorpromazine, zotepine, clozapine, olanzapine, and quetiapine appear to have a higher seizure risk. 26
- 27. In order to avoid drug interactions: (1) simplify medication regimens as far as possible, (2) monitor efficacy and adverse effects clinically, (3) check the serum level if appropriate and adjust the dose of the medication accordingly Commence at low doses, titrate slowly to a minimum therapeutic dose, and continue at a steady dose for a sufficient period of time. For patients with brain damage, the target dose should be set at 30–50% lower. Treatment (2) 27
- 28. There is insufficient evidence on the duration of treatment with APDs for IIP episodes. Due to its chronic nature and relatively high rate of exacerbation, long-term administration of APDs is recommended after a remission of IIP. Psychosocial support and family education are also important. Treatment (3) 28
- 29. 29
- 31. Anxiety 2nd most common psychiatric disorder in patients with epilepsy. 10 to 50% of patients with active epilepsy meet criteria for anxiety disorder. Anxiety symptoms are frequently comorbid with symptoms of depression, & they can be ictal, postictal, or interictal. There is an increased association of anxiety symptoms with female gender, unemployment, perceived side-effects of AEDs and chronic ill health, as well as lower educational attainment. 31
- 32. Anxiety Anxiety in epileptic patients may occur as • An ictal phenomenon • Normal interictal emotion • A part of an accompanying anxiety disorder or depressive disorder • A part of an underlying primary anxiety disorder
- 33. Anxiety Panic disorder can produce paroxysmal symptoms, which can be confused with epileptic events and may go unrecognized in patients with epilepsy. Symptoms of anxiety in epilepsy may result or be exacerbated by psychological reactions, including responses to the unpredictability of seizures and restrictions of normal activities. fear occurs as an aura in as many as 15% of patients Treatment is the same as for GAD. 33
- 35. Treatment related disorders Depression, anxiety, behavioral or cognitive problems are more likely to occur due to treatment than psychosis. Phenobarbitone, primidone, tiagabine, topiramate, vigabatrin and felbamate have been associated with depression. Whereas any of the AEDs has the potential to cause psychotic symptoms some AEDs, for example, ethosuximide, phenytoin, zonisamide, topiramate, and vigabatrin seem to be more potent in this regard. The risk may be higher in patients who are on polytherapy, become seizure free abruptly, or if there is a past psychiatric history 35
- 36. 36
- 37. 37
Editor's Notes
- - Interictal psychoses occur between seizures and cannot be linked directly to the ictus. They are also frequent than the peri-ictal psychoses and account for 10.30% of diagnosis in unselected case series. Interictal psychoses are, however, clinically more significant in terms of severity and duration than peri-ictal psychoses, which are short lasting and often self-limiting.
- Usually Epilepsy has often been present for more than 10 years before the onset of psychosis - Many years (usually 10– 14) are said to intervene between the onsets of epilepsy and schizophrenia-like psychosis
- 12hrs-72hrs in one study and 1 week in another. - Resolution is aided by neuroleptic medication, usually in small doses. A further seizure may exacerbate the psychosis, and anticonvulsant treatment should be carefully monitored. The brief psychosis may recur, at a frequency of 2–3 episodes per year in two studies (27, 30), and in some patients—15% in one study (23)— these episodes may become chronic. - Bullet one the duration is the common criteria used but commonly it lasts less than one week and rarely goes beyond 2 weeks.
- - Treatment of acute post-ictal psychosis may require short courses of benzodiazepines or antipsychotics. Improving seizure control would be the long-term goal.
- If patients are successfully treated at 1st stage, development of frank psychosis might be thwarted.
- - In patients with a history of violent PIP episodes in the past, the risk of similar behaviors being repeated is particularly high -Acute phase In both the initial stage preceding PIP and during the episode, sedative drugs are generally needed, as they not only stop socially inappropriate behaviors but can also abort or alleviate symptoms of PIP. Some experts have recommended benzodiazepines (Lancman et al., 1994), whereas others prefer a combination of both benzodiazepines and antipsychotics (Kanner et al., 1996). Although antipsychotics are known to lower seizure threshold in vitro, except for some notable exceptions, such as zotepine and clozapine (Devinsky et al., 1991), their proconvulsive effects seem to be at a tolerable level, at least as long as they are given within a therapeutic range. In most cases, imminent need of sedation has priority over a possible proconvulsive risk. In some exceptional cases, early stage PIP can be managed and thwarted with a relatively low dose of oral benzodiazepines. However, in other extreme cases, sedatives should be given swiftly as well as massively enough to force immediate tranquilization.
- - Robust manifestations of PIP usually fade away within a week and patients seem to superficially return to their former selves. However, unexpected outbursts caused by minimal stimuli can occur sporadically within the next few weeks afterward
- Treatment with antipsychotic medications is usually long term. The atypical antipsychotic drugs are potentially less likely to reduce seizure threshold (with the exception of clozapine) or cause extrapyramidal side effects. Lower doses than those used in primary schizophrenia seem to be effective. Psychosocial support and family education are also important. - Patients with SLPE may lack the pre-morbid personality abnormalities seen in patients with schizophrenia [16], may exhibit a greater degree of affective symptomatology than is typical in schizophrenia [18], may be less likely to demonstrate negative symptoms, and may be more responsive to lower doses of neuroleptics
- - 1 Sedation, such as somnolence and hypersomnia, is the most common side effect of APDs, either FAPDs or SAPDs. Low potency APDs except for sulpiride, for example, chlorpromazine, are more likely to cause these effects. 2 Weight gain and metabolic syndrome occur with any of the APD treatments, although SAPDs are generally less favorable in this regard. In particular, most SAPDs (e.g., olanzapine, quetiapine, risperidone; Correll et al., 2009), with the possible exception of aripiprazole, and some FAPDs (e.g., sulpiride) are likely to be associated with these problems. 3 Cardiovascular effects can occur with any APD treatment (Mackin, 2008). Orthostatic hypotension is the most common adverse effect of APDs, in particular with low potency FAPDs. QTc prolongation and subsequent arrhythmia can be caused with any APDs; however, this risk is increased with pimozide, thioridazine, sertindole, and zotepine. 4 Hyperprolactinemia and sexual dysfunction are sometimes 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 akathisia and parkinsonism, occur mostly with FAPDs (in particular high potency agents, that is, haloperidol), although some degree of EPS can be seen with SAPDs. EPS can be a primary cause of noncompliance with medication. Low doses of anti-parkinsonism/ antispasmodic drugs (e.g., trihexyphenidyl 4–10 mg/ day or biperiden 2–6 mg/day) can be prescribed together with FAPDs to ameliorate EPS (Toru, 1998).
- - Increase the risk of seizures: • High risk: bupropion, clomipramine, chlorpromazine, clozapine • Intermediate risk: tricyclic antidepressants, venlafaxine, thioridazine, olanzapine, quetiapine • Low risk: fluoxetine, sertraline, paroxetine, trazodone, haloperidol, risperidone.
- Carbamazepine can induce absence status epileptics in patients with generalized seizure disorders. * Ictal psychosis can present as a psychotic episode in status epilepticus without convulsions.*