Psychiatric Aspects of Epilepsy Arshadi HR M.D. Assis. Prof. Of Psychiatry IAUM

Psychiatric Disorders in Epilepsy Depression Depression Anxiety Disorders Anxiety Disorders Psychosis Psychosis Personality Disorder Personality Disorder Substance Abuse Substance Abuse Aggression Aggression Sexual disturbance Sexual disturbance

Prevalence estimates of psychiatric disturbance in epilepsy tend to range from 20 to 50%. Estimates are higher for specialty clinics and lowest among community based samples.

A Variety of Factors can cause the Behavioral/Psychiatric Disturbances Associated with Epilepsy A Variety of Factors can cause the Behavioral/Psychiatric Disturbances Associated with Epilepsy ictal seizure discharge/periictal state ictal seizure discharge/periictal state CNS pathology(Common neuropathology) CNS pathology(Common neuropathology) Genetic predisposition Genetic predisposition Inhibition or hypometabolism surrounding the epileptic focus Inhibition or hypometabolism surrounding the epileptic focus Alteration of receptor sensitivity Alteration of receptor sensitivity Secondary endocrinologic alterations Secondary endocrinologic alterations effects of antiepileptic drugs (AEDs) effects of antiepileptic drugs (AEDs) adverse psychosocial consequences of having epilepsy (reactive) adverse psychosocial consequences of having epilepsy (reactive) unrelated co-existence unrelated co-existence

Behavioral/Psychiatric Disturbances Associated with Epilepsy Can Differ on the Basis of Their Temporal Relationship to the Patient’s Seizures Behavioral/Psychiatric Disturbances Associated with Epilepsy Can Differ on the Basis of Their Temporal Relationship to the Patient’s Seizures Ictal state - Behaviors/emotions that are direct expressions of the epileptic seizure. Ictal state - Behaviors/emotions that are direct expressions of the epileptic seizure. Periictal State (Pre- or Postictal) - Behaviors/emotions that are temporarily associated with seizures but are not direct manifestations of epileptic discharges. Periictal State (Pre- or Postictal) - Behaviors/emotions that are temporarily associated with seizures but are not direct manifestations of epileptic discharges. Interictal Period - Behaviors/emotions that are a function of non-ictal conditions. Interictal Period - Behaviors/emotions that are a function of non-ictal conditions.

Psychosis in Epilepsy

Psychotic Disorders Appear to be Over- Represented in Epilepsy Patients, with prevalence estimates ranging from 2.5 to 8% as compared with a 1% rate among the general population.

Ictal Psychosis (Common Features) olfactory and gustatory hallucinations olfactory and gustatory hallucinations visual or auditory hallucinations (often involving poorly defined shapes or sounds, although there may be complex visual scenes or speech) visual or auditory hallucinations (often involving poorly defined shapes or sounds, although there may be complex visual scenes or speech) paranoid or grandiose thoughts paranoid or grandiose thoughts tends to be a rare occurrence tends to be a rare occurrence episodes of nonconvulsive status epilepticus can be mistaken for schizophrenia or a manic-like state. episodes of nonconvulsive status epilepticus can be mistaken for schizophrenia or a manic-like state.

Nonconvulsive partial status epilepticus can manifest as prolonged states of fear, mood changes, automatisms, or psychosis that resemble an acute schizophrenic or manic episode. While usually confused, such patients may be able to perform simple behaviors and respond to commands and questions.

Post ictal psychosis The postictal psychosis of epilepsy emerges after a lucid interval of 2 to 72 hours (mean of 1 day) during which the immediate postictal confusion resolves and the patient appears to return to normal. The postictal psychosis of epilepsy emerges after a lucid interval of 2 to 72 hours (mean of 1 day) during which the immediate postictal confusion resolves and the patient appears to return to normal. The postictal psychotic episodes last 16 to 432 hours (mean of 3 ½ days) and often include grandiose or religious delusions, elevated moods or sudden mood swings, agitation, paranoia, and impulsive behaviors but no perceptual abnormality or voices heard. The postictal psychotic episodes last 16 to 432 hours (mean of 3 ½ days) and often include grandiose or religious delusions, elevated moods or sudden mood swings, agitation, paranoia, and impulsive behaviors but no perceptual abnormality or voices heard. The postictal psychoses remit spontaneously or with the use of low-dose psychotropic medication. The postictal psychoses remit spontaneously or with the use of low-dose psychotropic medication.

Predisposing Factors for the Interictal Schizophreniform Psychosis of Epilepsy Epilepsy characteristics: - CPS with secondary GTCS - CPS with secondary GTCS - more auras and automatisms - more auras and automatisms - epilepsy presents for 11 to 15 years before psychosis - epilepsy presents for 11 to 15 years before psychosis - long interval of poorly controlled seizures - long interval of poorly controlled seizures - recently diminished seizure frequency - recently diminished seizure frequency - left temporal focus - left temporal focus - mediobasal temporal lesions, especially tumors - mediobasal temporal lesions, especially tumors Intelligence Intelligence Left-handedness, especially in women Left-handedness, especially in women

Predisposing Factors for the Interictal Schizophreniform Psychosis of Epilepsy Psychosis Characteristics: - paranoia with sudden onset - paranoia with sudden onset - psychosis alternating with seizure - psychosis alternating with seizure - preserved affective warmth - preserved affective warmth - failure of personality deterioration - failure of personality deterioration - less social withdrawal - less social withdrawal - less systematized delusions - less systematized delusions - more hallucinations and affective symptoms - more hallucinations and affective symptoms - more religiosity - more religiosity - few schneidreian first-rank symptoms - few schneidreian first-rank symptoms - no family history of schizophrenia - no family history of schizophrenia

Treatment Ictal & postctal Ictal & postctal Interictal:risperidone, molindone, and fluphenazine may have better profiles than older antipsychotic medications; clozapine has been reported to confer a particularly high risk of seizures. Interictal:risperidone, molindone, and fluphenazine may have better profiles than older antipsychotic medications; clozapine has been reported to confer a particularly high risk of seizures.

forced normalization Alternative psychosis

Depression in Epilepsy

Prevalence of Depression in Epilepsy “Depression is the most frequent psychiatric co-morbidity in epilepsy but very often remains unrecognized and untreated.” “Depression is the most frequent psychiatric co-morbidity in epilepsy but very often remains unrecognized and untreated.”

Published Prevalence Rates of Depression in Epilepsy Estimates of the occurrence of depression among patients with epilepsy range from 20 to 55% in patients with recurrent seizures and 3 to 9% in patients with controlled epilepsy. (K&S : %) Estimates of the occurrence of depression among patients with epilepsy range from 20 to 55% in patients with recurrent seizures and 3 to 9% in patients with controlled epilepsy. (K&S : %) Although these studies have methodological limitations, they suggest that depression may be at least 3 to 10 times more prevalent in association with uncontrolled epilepsy than in the general population. Although these studies have methodological limitations, they suggest that depression may be at least 3 to 10 times more prevalent in association with uncontrolled epilepsy than in the general population.

suicide Risk of completed suicide in epileptic patients is four to five times greater than among the nonepileptic population Risk of completed suicide in epileptic patients is four to five times greater than among the nonepileptic population Those with complex partial seizures of temporal lobe origin have a particularly high risk, as much as 25 times greater. Those with complex partial seizures of temporal lobe origin have a particularly high risk, as much as 25 times greater. Death by suicide occur in 3-7% epileptic patients Death by suicide occur in 3-7% epileptic patients

دلايل عدم توجه به تشخيص افسردگي در صرع ترس ب ترس بيماران از اينكه بيش از اين انگ بخورند. نشانه هاي باليني انواع خاصي از افسردگي در صرع متفاوت است. نشانه هاي باليني انواع خاصي از افسردگي در صرع متفاوت است. پزشكان معمولا علائم روانپزشكي را دربيماران مصروع جويا نمي شوند. پزشكان معمولا علائم روانپزشكي را دربيماران مصروع جويا نمي شوند. هم بيماران و هم پزشكان علائم افسردگي را بيشتر به يك فرايند انطباقي هم بيماران و هم پزشكان علائم افسردگي را بيشتر به يك فرايند انطباقي مزمن طبيعي نثبت مي دهند تا اختلال افسردگي مزمن طبيعي نثبت مي دهند تا اختلال افسردگي نگراني پزشكان از پائين آوردن آستانه تشنج توسط دارو هاي ضد افسردگي نگراني پزشكان از پائين آوردن آستانه تشنج توسط دارو هاي ضد افسردگي

Clinical Presentation of Depression in Epilepsy

Ictal Depression - Symptoms occurring as an expression of the actual seizure. Ictal Depression - Symptoms occurring as an expression of the actual seizure. Peri-ictal (Pre- or postictal) Depression - Symptoms occurring just prior to the onset of seizures or following their occurrence. Peri-ictal (Pre- or postictal) Depression - Symptoms occurring just prior to the onset of seizures or following their occurrence. Interictal Depression - Symptoms occurring that are unrelated to specific seizure episodes. Interictal Depression - Symptoms occurring that are unrelated to specific seizure episodes.

Ictal Depression This is the clinical expression of a simple partial seizure in which the symptoms of depression consist of its sole (or predominant) semiology. This is the clinical expression of a simple partial seizure in which the symptoms of depression consist of its sole (or predominant) semiology. Psychiatric symptoms are thought to occur in approximately 25% of auras, with approximately 15% of these involving affect or mood changes. Psychiatric symptoms are thought to occur in approximately 25% of auras, with approximately 15% of these involving affect or mood changes. These spells are typically brief and stereotypical and occur out of context (without environmental precipitants), and are associated with other ictal phenomena. These spells are typically brief and stereotypical and occur out of context (without environmental precipitants), and are associated with other ictal phenomena.

Ictal Depression Ictal sadness may involve the features of typical interictal depressive syndromes, such as feelings of pathological guilt, hopelessness, worthlessness, profound despair, and suicidal ideation (Marsh & Rao, 2002). Ictal sadness may involve the features of typical interictal depressive syndromes, such as feelings of pathological guilt, hopelessness, worthlessness, profound despair, and suicidal ideation (Marsh & Rao, 2002). May lead to suicide May lead to suicide

Preictal Depression This type of depression typically presents as a dysphoric mood preceding a seizure. This type of depression typically presents as a dysphoric mood preceding a seizure. Prodromal symptoms may extend for hours or even for 1 to 2 days prior to the onset of a seizure. Prodromal symptoms may extend for hours or even for 1 to 2 days prior to the onset of a seizure. These spells are typically brief and stereotypical and occur out of context, and are associated with other ictal phenomena. These spells are typically brief and stereotypical and occur out of context, and are associated with other ictal phenomena. May lead to suicide May lead to suicide

Postictal Depression Postictal symptoms of depression have been recognized for a very long time, but their prevalence has yet to be scientifically established. Postictal symptoms of depression have been recognized for a very long time, but their prevalence has yet to be scientifically established.

ويژگي هاي افسردگي در صرع تشخيص افسردگي در بيمار مصروع تحت درمان با دارو هاي ضد صرع گاه مشكل است تشخيص افسردگي در بيمار مصروع تحت درمان با دارو هاي ضد صرع گاه مشكل است يكي از دلايل همزماني برخي علائم مثل، تغييرات وزن، فقدان انرژي و تمركز است كه مي تواند عارضه مصرف دارو هاي ضد صرع باشد. يكي از دلايل همزماني برخي علائم مثل، تغييرات وزن، فقدان انرژي و تمركز است كه مي تواند عارضه مصرف دارو هاي ضد صرع باشد. شاه علامت كليدي در اين موارد وجود Anhedonia است. شاه علامت كليدي در اين موارد وجود Anhedonia است. افسردگي در صرع با پارانوئيا ي بيشتري همراه است همچنين اين بيماران تحريك پذيري و هيجان پذيري، فراز و نشيب علائم و عدم تحمل طرد را بيشتر تجربه مي كنند افسردگي در صرع با پارانوئيا ي بيشتري همراه است همچنين اين بيماران تحريك پذيري و هيجان پذيري، فراز و نشيب علائم و عدم تحمل طرد را بيشتر تجربه مي كنند

The real diagnostic/methodological challenge involves the classification of interictal depression. Several investigators have noted that a large portion of epilepsy patients with depression do not fit the current DSM psychiatric syndromes

Patients experiencing depression in epilepsy often do not meet the criteria of major depressive disorder (i.e., their symptoms are less severe) but they also typically exhibit a more intermittent course than do patients with dysthymic disorder.

Kraepelin (1923) is credited with first describing an atypical syndrome of depression in epilepsy. Blumer (1997) more recently described this syndrome, giving it the name interictal dysphoric disorder (IDD). Blumer suggested that almost one third to one half of all patients with epilepsy seeking medical care suffer from this form of depression severely enough to warrant pharmacological treatment.

Kanner continued with this research using the DSM- IV criteria. Most symptoms presented with a waxing and waning course, with symptom-free periods. He referred to this form of depression as dysthymic-like disorder of epilepsy (DLDE). Blumer (1997) feels that the symptoms of interictal dysphoric disorder have an intermittent course and can be categorized into depressive-somatoform and affective symptoms.

Interictal Dysphoric Disorder Depressive-Somatoform Symptoms Depressed mood Depressed mood anergia anergia pain pain insomnia insomnia

Interictal Dysphoric Disorder Affective Symptoms irritability irritability brief euphoric states brief euphoric states fear fear anxiety anxiety

Treatment However, antidepressants may be necessary to effectively treat depression in these patients. When an antidepressant is prescribed, the epileptogenic potential, adverse effects, and drug interactions must be evaluated. However, antidepressants may be necessary to effectively treat depression in these patients. When an antidepressant is prescribed, the epileptogenic potential, adverse effects, and drug interactions must be evaluated. Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (due to its lack of drug interactions) and multireceptor-active compounds such as nefazodone or venlafaxine are suggested as first-line treatments. Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (due to its lack of drug interactions) and multireceptor-active compounds such as nefazodone or venlafaxine are suggested as first-line treatments. Bupropion, maprotiline, and clomipramine should be avoided Bupropion, maprotiline, and clomipramine should be avoided

عوامل موثر در بروز تشنج در درمان با دارو هاي ضد افسردگي نوع دارو نوع دارو نوع اختلال روانپزشكي نوع اختلال روانپزشكي وجود اختلال نورولوژيك وجود اختلال نورولوژيك سوء مصرف و يا ترك موارد يا دارو ها سوء مصرف و يا ترك موارد يا دارو ها مصرف همزمان دارو هاي روانپزشكي ديگر مصرف همزمان دارو هاي روانپزشكي ديگر دوز دارو ( تفاوت ژنيتيك ) دوز دارو ( تفاوت ژنيتيك ) سرعت افزايش دوز سرعت افزايش دوز دوره مصرف دارو دوره مصرف دارو

ريسك تشنج درانواع دارو هاي ضد افسردگي Group 1: clomipramine, bupropion( %) Group 1: clomipramine, bupropion( %) Group 2: Maprotiline ( %) Group 2: Maprotiline ( %) Group 3: Amitriptiline, imipramine( %) Group 3: Amitriptiline, imipramine( %) Group 4: nortriptiline, desipramine, doxepine( %) Group 4: nortriptiline, desipramine, doxepine( %) Group 5: Fluxetine, sertraline, citalopram, fluvoxamine, venlafaxine, trazodone, doluxetine, mirtazapine( %) Group 5: Fluxetine, sertraline, citalopram, fluvoxamine, venlafaxine, trazodone, doluxetine, mirtazapine( %)

اثرات متقابل دارو هاي ضد افسردگي و ضد تشنج فارماكوكينتيك كاربامازپين، فنوباربيتال، فني توئين القاء كننده هاي قوي آنزيم CYP450 هستند. اين اثر روي سرترالين بارز است بطوري كه نياز به افزايش دوز دارو است. كاربامازپين، فنوباربيتال، فني توئين القاء كننده هاي قوي آنزيم CYP450 هستند. اين اثر روي سرترالين بارز است بطوري كه نياز به افزايش دوز دارو است. اكس كابازپين و توپيرامات اثرات القاء كننده گي بسيار كمتري دارند. اكس كابازپين و توپيرامات اثرات القاء كننده گي بسيار كمتري دارند. لاموتريژين و گاباپانتين هيچ اثر تداخلي روي CYP450 ندارند. لاموتريژين و گاباپانتين هيچ اثر تداخلي روي CYP450 ندارند. والپروات سديم بدليل كند كردن فعاليت انواع خاصي از CYP450 باعث بالا رفتن درصد در سطوح سه حلقه اي ها مثل نورتريپتيلين مي شود. والپروات سديم بدليل كند كردن فعاليت انواع خاصي از CYP450 باعث بالا رفتن درصد در سطوح سه حلقه اي ها مثل نورتريپتيلين مي شود. فلوكستين ، سرترالين و فلووكسامين باعث افزايش سطوح كاربامازپين و فني توئين مي شوند. اين اثر در سالمندان اهميت دارد. سيتالوپرام كمترين اثر را در اين خصوص دارد. فلوكستين ، سرترالين و فلووكسامين باعث افزايش سطوح كاربامازپين و فني توئين مي شوند. اين اثر در سالمندان اهميت دارد. سيتالوپرام كمترين اثر را در اين خصوص دارد. ونلافاكسين اثر تداخلي چنداني با دارو هاي ضد صرع ندارد. ونلافاكسين اثر تداخلي چنداني با دارو هاي ضد صرع ندارد.

اصول كلي در درمان با دارو هاي ضد افسردگي خطر خودكشي را ارزيابي كنيم خطر خودكشي را ارزيابي كنيم وجود علائم سايكوتيك را بررسي كنيم وجود علائم سايكوتيك را بررسي كنيم نياز به بستري شدن را مد نظر قرار دهيم نياز به بستري شدن را مد نظر قرار دهيم در صورتي كه علائم افسردگي در مرحله پرو درم يا پري ايكتال بروز مي كند درمان با دارو هاي ضد صرع را تقويت كنيم در صورتي كه علائم افسردگي در مرحله پرو درم يا پري ايكتال بروز مي كند درمان با دارو هاي ضد صرع را تقويت كنيم با حداقل دوز ممكن درمان را شروع كنيد با حداقل دوز ممكن درمان را شروع كنيد دارو را با فواصل يك تا دو هفته اي افزايش دوز دهيد دارو را با فواصل يك تا دو هفته اي افزايش دوز دهيد استفاده از دارو هاي SSRI و SNRI مناسب تر است. استفاده از دارو هاي SSRI و SNRI مناسب تر است. در بين SSRI سيتالوپرام كمترين تداخل را با دارو هاي ضد صرع دارا است. در بين SSRI سيتالوپرام كمترين تداخل را با دارو هاي ضد صرع دارا است. درمان هاي غير دارويي را نيز مد نظر داشته باشيم درمان هاي غير دارويي را نيز مد نظر داشته باشيم

جمع بندي افسردگي در صرع از شيوع قابل توجهي برخوردار است و معمولا ناديده گرفته مي شود. افسردگي در صرع از شيوع قابل توجهي برخوردار است و معمولا ناديده گرفته مي شود. تشخيص افسردگي در صرع نياز مند دقت است و شايد به موارد تحت سندرومي هم بايد توجه كرد. تشخيص افسردگي در صرع نياز مند دقت است و شايد به موارد تحت سندرومي هم بايد توجه كرد. ارتباط دو سويي اي بين افسردگي و صرع وجود دارد و وجود افسردگي در صرع فراتر از يك واكنش غير انطباقي رواني است و شايد به الگوي بيولوژيك مشترك بين آنها مرتبط است. ارتباط دو سويي اي بين افسردگي و صرع وجود دارد و وجود افسردگي در صرع فراتر از يك واكنش غير انطباقي رواني است و شايد به الگوي بيولوژيك مشترك بين آنها مرتبط است. در درمان افسردگي توجه به انتخاب داروي مناسب با كمترين اثرات تشنج زايي و تداخل دارويي اهميت دارد. در درمان افسردگي توجه به انتخاب داروي مناسب با كمترين اثرات تشنج زايي و تداخل دارويي اهميت دارد.

Anxiety in Epilepsy

Peri-ictal Anxiety Some patients pre-ictal anxiety states that can precede the seizure by several days. Some patients pre-ictal anxiety states that can precede the seizure by several days. Post-ictal anxiety and/or fear can last for hours or days. Post-ictal anxiety and/or fear can last for hours or days.

Ictal Anxiety Fear and anxiety are fairly common ictal affects in patients with right temporal lobe epilepsy. Fear and anxiety are fairly common ictal affects in patients with right temporal lobe epilepsy. Some studies have linked these sensations with disharges of the anteromedial temporal lobe or structures of the limbic system. Some studies have linked these sensations with disharges of the anteromedial temporal lobe or structures of the limbic system. Usually the sensation is brief, lasting only seconds to a couple of minutes. Usually the sensation is brief, lasting only seconds to a couple of minutes. Psychic phenomena, including hallucinations and feelings of déjà vu, jamais vu, and derealization and depersonalization, may be present. Psychic phenomena, including hallucinations and feelings of déjà vu, jamais vu, and derealization and depersonalization, may be present.

Interictal Anxiety Anxiety syndromes appear to occur in both TLE and generalized epilepsy. Anxiety syndromes appear to occur in both TLE and generalized epilepsy. Patients reportedly experience a variety of symptoms ranging from feelings of apprehension to DSM-IV syndromes (Panic Disorder, Generalized Anxiety Disorder, Obsessive- Compulsive Disorder). Patients reportedly experience a variety of symptoms ranging from feelings of apprehension to DSM-IV syndromes (Panic Disorder, Generalized Anxiety Disorder, Obsessive- Compulsive Disorder).

Gastaut-Geschwind syndrome A sense of the heightened significance of things. A sense of the heightened significance of things. patients are serious, humorless, overinc1usive, and have an intense interest in philosophic, moral, or religious issues. patients are serious, humorless, overinc1usive, and have an intense interest in philosophic, moral, or religious issues. In interpersonal encounters, they demonstrate viscosity (hypergraphia) In interpersonal encounters, they demonstrate viscosity (hypergraphia)

SUMMARY Psychiatric syndromes often occur in patients with epilepsy at rates that seem to exceed the normal population. Psychiatric syndromes often occur in patients with epilepsy at rates that seem to exceed the normal population. A lack of good prevalence studies makes it difficult to know whether or not prevalence rates of these syndromes exceeds that of other patient groups experiencing CNS dysfunction. A lack of good prevalence studies makes it difficult to know whether or not prevalence rates of these syndromes exceeds that of other patient groups experiencing CNS dysfunction. Symptoms sometimes occur in association with seizures episodes (either ictally or peri-ictally), and such symptomatology tends to be brief and context-free. Symptoms sometimes occur in association with seizures episodes (either ictally or peri-ictally), and such symptomatology tends to be brief and context-free.

SUMMARY Classic psychiatric syndromes tend to occur inter- ictally. Classic psychiatric syndromes tend to occur inter- ictally. Depression appears to be the most common psychiatric feature in patients with epilepsy. Depression appears to be the most common psychiatric feature in patients with epilepsy. Greater emphasis is required on developing treatment strategies specifically designed for the psychiatric (and cognitive) consequences of epilepsy. Greater emphasis is required on developing treatment strategies specifically designed for the psychiatric (and cognitive) consequences of epilepsy.