- OK, I WOULD LIKE TO WELCOME YOU ALL TO OUR FIFTH CALL OF THE FISCAL YEAR IN THE "INTRODUCTION TO EPILEPSY" AUDIO CALL SERIES. MY NAME IS SHAWN GAMBLE, AND I'M WITH THE EMPLOYEE EDUCATION SERVICE HERE IN ST. LOUIS, AND I'M THE PROJECT MANAGER FOR THIS SERIES. ALL THE LINES ARE GONNA BE MUTED, BUT THEY WILL BE OPENED UP AT THE END OF THE PRESENTATION WHEN WE ARE READY FOR QUESTIONS. PLEASE BE SURE TO COMPLETE YOUR EVALUATION TO GET CREDIT FOR THE PROGRAM. DEADLINE DATE IS AUGUST 17. NOW LET ME WELCOME OUR SPEAKER TODAY, DR. HAMID. GO AHEAD, SIR. - GREAT. THANK YOU. SO I'M HAMADA HAMID, AS YOU HEARD, AND I AM A CO-DIRECTOR OF THE EPILEPSY CENTER OF EXCELLENCE IN THE CONNECTICUT VA. I'M A BOARD-CERTIFIED NEUROLOGIST AND PSYCHIATRIST AND FACULTY AT YALE. AND SO TODAY'S TOPIC, AS YOU ALL KNOW, AS YOU CAN SEE FROM YOUR SLIDES, IS "DEPRESSION AND EPILEPSY." NOW, WHILE THIS TALK IS INTENDED FOR HEALTH CARE PROFESSIONALS, CERTAINLY PEOPLE WHO SUFFER FROM EPILEPSY OR PEOPLE WHO ARE CARING FOR PEOPLE WITH EPILEPSY ARE ALL WELCOME. AND AS WE EARLIER MENTIONED, WE WILL BE OPENING FOR QUESTIONS AND WE'LL OPEN UP FOR DISCUSSION AT THE END OF MY TALK. AND I'LL REMIND YOU THAT THIS IS A EDUCATIONAL TALK NOT INTENDED FOR CONSULTATION. SO IF YOU'RE A PATIENT OR A PERSON WHO IS CARING FOR A PERSON WITH EPILEPSY, PLEASE MAKE IT MORE GENERAL EDUCATION-RELATED QUESTIONS. SO, NEXT SLIDE, WHICH IS SLIDE TWO. WHAT I'LL BE TALKING ABOUT IS THE IMPACT OF MOOD ON EPILEPSY, HOW CHANGES IN MOOD IMPACT SEIZURE CONTROL AND VICE VERSA, HOW DOES SEIZURE CONTROL IMPACT MOOD. I'LL PROVIDE AN UPDATE ON OUR CURRENT UNDERSTANDING OF THE NEUROANATOMY AND NEURAL NETWORKS INVOLVED IN EPILEPSY AND DEPRESSION. I'LL DRAW FROM THE PRIMARY DEPRESSION LITERATURE AND DISCUSS HOW IT RELATES TO EPILEPSY. I'LL ALSO TALK ABOUT MEDICATION, BOTH ANTIDEPRESSANTS AND ANTIEPILEPTIC DRUGS, AND I WILL CLOSE BY DISCUSSING BRIEFLY SOME OF THE PSYCHOLOGICAL ASPECTS AND RESOURCES FOR PEOPLE WHO SUFFER FROM EPILEPSY AND DEPRESSION. SO, NEXT SLIDE. SO THE "SO WHAT" QUESTION: WHY SHOULD PEOPLE CALL IN? AND I APPRECIATE EVERYBODY CALLING IN FOR THIS IMPORTANT TOPIC. IN MY MIND, THERE'S 3 REASONS WHY WE SHOULD AS PROVIDERS BE CONCERNED ABOUT EPILEPSY AND DEPRESSION. THE FIRST IS DEPRESSION IMPACTS QUALITY OF LIFE AS WELL. WE'LL TALK ABOUT IT IN DETAIL. THE SECOND IS THAT DEPRESSION IS ASSOCIATED WITH WORSE SEIZURE CONTROL. AND FINALLY, PEOPLE DO DIE FROM SUICIDE. NOW, SUICIDE, AS YOU CAN IMAGINE, IS A PREVENTABLE CAUSE OF MORTALITY. AND SO OUR PATIENTS WITH EPILEPSY SHOULD REALLY NOT BE DYING OF SUICIDE. WE SHOULD BE PREVENTING THIS HAS MUCH AS POSSIBLE. SO, NEXT SLIDE, CLINICAL RELEVANCE. THIS SHOULD KIND OF PUT THIS IN CONTEXT. I OFFERED A CLINICAL CASE, A PATIENT THAT I SAW AT YALE-- 35-YEAR-OLD WOMAN WHO CARRIED A 15-YEAR HISTORY OF EPILEPSY, AND SHE HAD RECENTLY TRIED TO KILL HERSELF AFTER BREAKING UP WITH HER BOYFRIEND BY TRYING TO OVERDOSE ON HER ATIVAN. SHE WAS ADMITTED TO THE PSYCHIATRIC WARD AND HAD MULTIPLE GENERALIZED TONIC- CLONIC SEIZURES AND REQUIRED MULTIPLE [INDISTINCT] ATIVAN. THOSE WERE HER MEDS, INCLUDING KEPPRA, DILANTIN, AND LEXAPRO. HER EXAM WAS NORMAL. AND WHEN SHE WAS TRANSFERRED TO US, SHE HAD BEEN STABLE, WAS NOT HAVING SUICIDAL THOUGHTS AT THE TIME. SO, NEXT SLIDE. SO SOME OF THE QUESTIONS THAT EMERGED FROM THAT CASE INCLUDE, DOES LEXAPRO WORSEN SEIZURES, OR DO ANTIDEPRESSANTS IN GENERAL LOWER SEIZURE THRESHOLD? DOES KEPPRA WORSEN DEPRESSION? AND MORE GENERALLY, WHAT ANTICONVULSANTS WORSEN DEPRESSION? AND ALSO, WHAT IS THE RELATIONSHIP BETWEEN SEIZURES AND RISK FOR SUICIDE? SO ONCE WE STABILIZE HER SEIZURES, IS SHE STILL AT RISK FOR SUICIDE? WHAT'S THE RELATIONSHIP THERE? AND SO THOSE ARE THE THINGS I WANT YOU TO KEEP IN THE BACK OF YOUR MIND AS WE GO THROUGH THIS TALK. AND AGAIN--NEXT SLIDE--THIS REMINDS YOU THAT THESE ARE THE 3 ISSUES--SUICIDE, QUALITY OF LIFE, SEIZURE CONTROL--THAT WE'LL BE TALKING ABOUT NEXT. NEXT SLIDE, QUALITY OF LIFE. SO MANY OF YOU ARE FAMILIAR WITH THIS PAPER BY LAURA BOYLAN AND HER GROUP AT NYU. WHAT YOU SEE ON THE LEFT SIDE, THE X-AXIS, THE LEFT GRAPH, SHOWS SEIZURE FREQUENCY QUARTILES, 1 BEING INFREQUENT SEIZURES, 4 BEING VERY FREQUENT SEIZURES. AND THE Y-AXIS IS QUALITY OF LIFE, AND THE HIGHER THE QUALITY OF LIFE SCORE, THE BETTER THE QUALITY OF LIFE. YOU'LL SEE THAT THERE'S ABOUT AN OVERLAP, THAT THERE'S NO STATISTICAL DIFFERENCE BETWEEN SEIZURE QUARTILES AND QUALITY OF LIFE, MEANING THAT WHETHER YOU HAVE 10 SEIZURES A MONTH OR ONE SEIZURE A MONTH, YOU HAVE THE SAME QUALITY OF LIFE. AND WHAT STUDIES HAVE SHOWN IS THAT WHAT IMPACTS QUALITY OF LIFE IS NOT THE NUMBER OF SEIZURES, BUT SEIZURE FREEDOM. SO REDUCING A PERSON'S SEIZURES FROM 20 SEIZURES A MONTH TO ONE SEIZURE EVERY OTHER MONTH DOESN'T REALLY IMPROVE PEOPLE'S QUALITY OF LIFE, BUT MAKING A PERSON SEIZURE-FREE IS WHAT IMPROVES PEOPLE'S QUALITY OF LIFE. AND IF YOU THINK ABOUT IT, IT MAKES SENSE IN THAT IF YOU HAVE ONE SEIZURE EVERY OTHER MONTH, YOU STILL ARE NOT ALLOWED TO DRIVE. YOU STILL HAVE STIGMA. YOU STILL HAVE ANTICIPATORY ANXIETY ABOUT WHEN'S YOUR NEXT SEIZURE. AND SO IT'S NOT REALLY UNTIL A PERSON IS SEIZURE-FREE FOR A PROLONGED PERIOD, AND MOST PEOPLE SAY 1 TO 2 YEARS, ALTHOUGH THAT HASN'T BEEN WELL STUDIED, THAT PEOPLE'S QUALITY OF LIFE REALLY IMPROVES. ON THE GRAPH TO THE RIGHT, IT SHOWS THAT DEPRESSION SCORE DOES CORRELATE VERY WELL WITH QUALITY OF LIFE SCORE. SO AS YOU GET A WORSENED DEPRESSION SCORE, AS INDICATED BY THE X-AXIS THAT IN THIS CASE REFLECTS THE DEPRESSION INVENTORY, BDI, A HIGHER SCORE INDICATES WORSE DEPRESSIVE SYMPTOMS. THE WORSE THE DEPRESSION SCORES, THE LOWER THE QUALITY OF LIFE SCALE, AND THAT'S BEEN DUPLICATED--REPLICATED IN MULTIPLE STUDIES IN DIFFERENT SETTINGS. AND SO DEPRESSION SCORE CORRELATES MUCH BETTER WITH QUALITY OF LIFE THAN SEIZURE FREQUENCY, AND THAT'S DRAWN A LOT OF ATTENTION AND INTEREST OF CLINICIANS AND RESEARCHERS ON THE RELATIONSHIP BETWEEN DEPRESSION AND SEIZURES. SO, NEXT SLIDE. AND SO AT LEAST THIS STUDY, THIS SEIZURE STUDY, SHOWS THAT DEPRESSION SEEMS TO BE ASSOCIATED WITH QUALITY OF LIFE. I'D BE CAREFUL ABOUT--THE SLIDE SAYS DEPRESSION IMPACTS QUALITY OF LIFE. WE HAVE TO BE CAREFUL BECAUSE THESE ARE CROSS-SECTIONAL STUDIES. THEY SHOW AN ASSOCIATION, BUT WE CAN'T REALLY CONCLUDE A CAUSATIVE RELATIONSHIP. BUT BASED ON THESE STUDIES, IT SHOWED THAT DEPRESSION WAS ASSOCIATED MORE WITH QUALITY OF LIFE THAN SEIZURE FREQUENCY, EVEN ANXIETY AND SOCIAL FUNCTIONING AND SEIZURE STIGMA. NOW, I WILL SAY THERE HAVE BEEN AT LEAST TWO STUDIES THAT SHOWED THAT ANXIETY SCORES ALSO CORRELATE STRONGLY WITH QUALITY OF LIFE AS WELL. SO THAT'S SOMETHING THAT WE TEND TO OVERLOOK, IS THE ROLE OF ANXIETY IN EPILEPSY, BUT THAT'S A DIFFERENT TALK. NEXT SLIDE, THE BIDIRECTIONAL RELATIONSHIP OF EPILEPSY. NOW, THIS HAS DRAWN A LOTS OF INTEREST. WHAT DR. DALE HESDORFFER AND A COUPLE OTHER PEOPLE HAVE SHOWN IS THAT PEOPLE WITH A HISTORY OF DEPRESSION--IN OTHER WORDS, PEOPLE WHO DON'T HAVE A HISTORY OF SEIZURES OR EPILEPSY BUT HAVE A HISTORY OF DEPRESSION--ARE 3 TIMES MORE LIKELY OF DEVELOPING EPILEPSY THAN THE GENERAL POPULATION. THIS IS A LARGE POPULATION- BASED STUDY. I FORGET IF IT WAS GREENLAND OR ICELAND, BUT IN ANY CASE, THIS MAJOR STUDY SHOWED THAT PEOPLE WITH DEPRESSION ARE MORE LIKELY TO DEVELOP EPILEPSY. FURTHERMORE, PEOPLE WHO HAD A SUICIDE ATTEMPT--AND OF COURSE, THIS WAS CONTROLLED FOR TRAUMATIC BRAIN INJURY, MEDICATIONS--I MEAN, ALL THINGS WERE CONTROLLED FOR--BUT PEOPLE WHO HAD A HISTORY OF SUICIDE ATTEMPT WERE MUCH MORE LIKELY OF DEVELOPING EPILEPSY THAN THE GENERAL POPULATION, AND SO THAT HAS DRAWN A LOT OF ATTENTION BY CLINICIANS AND NEUROSCIENTISTS ABOUT THE BIDIRECTIONAL RELATIONSHIP OF DEPRESSION AND EPILEPSY. IT'S NOT JUST THAT A PERSON WITH EPILEPSY SUFFERS FROM SEIZURES, IS EMBARRASSED BY THE SEIZURES, IT IMPACTS THEIR PSYCHOSOCIAL FUNCTIONING, AND THEREFORE THEY DEVELOP DEPRESSION, BUT THERE'S ALSO SOMETHING ABOUT THE UNDERLYING SUBSTRATE OF DEPRESSION, THAT THERE'S SOMETHING SHARED BETWEEN THE EPILEPSY, SEIZURES, AND DEPRESSION. ANOTHER STUDY BY KENNETH ALPER AND HIS GROUP, AGAIN AT NYU-- WHEN THEY LOOKED AT ALL THE RANDOMIZED CONTROL TRIALS OF PSYCHOTROPICS AND LOOKED AT SEIZURE INCIDENCE IN PATIENTS WHO WERE ON A PSYCHOTROPIC DRUG VERSUS PLACEBO--IN OTHER WORDS, PEOPLE ON PLACEBO ARE PEOPLE WHO WERE ENROLLED IN A DEPRESSION STUDY, FOR INSTANCE, BUT WERE GIVEN PLACEBO. THEY WERE NOT GIVEN DRUGS. THOSE PATIENTS ON PLACEBO WERE 17 TIMES MORE LIKELY TO EXPERIENCE A SEIZURE THAN POPULATION-BASED DATA, WHICH IS VERY INTERESTING. OF COURSE, THOSE ARE PATIENTS THAT ARE MORE LIKELY TO BE REFRACTORY RESISTANT TO ANTIDEPRESSANT MEDICATION, SO THEIR DEPRESSION IS MORE SEVERE, BUT IT'S, AGAIN, INTERESTING. IT SUPPORTS THE IDEA THAT THERE IS A BIDIRECTIONAL RELATIONSHIP BETWEEN DEPRESSION AND SEIZURES. AND NOW, FOR THE BASIC SCIENTISTS IN THE AUDIENCE, THERE HAS BEEN INTEREST IN LOOKING AT, HOW DOES DEPRESSION AND STRESS MODELS--WHAT IS THAT SUBSTRATE INVOLVED? I MEAN, CERTAINLY THERE'S BEEN A STUDIES LOOKING AT SEROTONIN OF 5-HT, 1A, AND VARIOUS OTHER SEROTONIN RECEPTORS IN EPIGENESIS. IT'S VERY WELL ESTABLISHED THAT ANIMAL MODELS, PARTICULARLY MICE AND RAT MODELS, WHEN--THAT THE SSRIs, SEROTONIN REUPTAKE INHIBITORS, RAISES THE SEIZURE THRESHOLD, THAT IN EPILEPSY MOUSE MODELS, WHEN YOU GIVE THEM SSRIs, IT RAISES THEIR SEIZURE THRESHOLD. AND SO THERE IS AN INCREASED INTEREST IN THE ROLE OF SEROTONIN AND ALSO GLUTAMATE, FOR THAT MATTER, IN DEPRESSION AND EPILEPSY. NEXT SLIDE. SO WE TALKED ABOUT THE RISK OF PEOPLE WITH DEPRESSION DEVELOPING EPILEPSY. CERTAINLY THERE'S A ROLE OF DEPRESSION--OF PSYCHIATRIC FOR MANY IN DEPRESSION, IN GENERAL THROUGH THE TREATMENT OF SEIZURE AND CONTROL. THIS STUDY SHOWS THAT-- BY HITRIS, ET AL-- THAT PEOPLE WITH PSYCHIATRIC MORBIDITY WERE MORE LIKELY, OVER DOUBLE TIME-- TWICE--TWO TIMES MORE LIKELY TO BE RESISTANT TO MEDICATIONS THAN THE PEOPLE WHO DIDN'T HAVE PSYCHIATRIC MORBIDITY. AS YOU SEE, IN OUR VA POPULATION, WHERE WE SEE MORE TRAUMATIC BRAIN INJURY, THOSE PEOPLE ARE ALSO MORE LIKELY TO BE RESISTANT TO ANTIEPILEPTIC DRUGS. ANDY KANNER HAS SHOWN THAT PEOPLE WITH A PSYCHIATRIC HISTORY, PARTICULARLY DEPRESSION, HAVE WORSE OUTCOMES IN SURGERY, AND HE HAS POSTULATED THAT THERE IS MORE DIFFUSE NEURAL INJURY. AND IN FACT, WHEN HE WENT BACK AND LOOKED AT THE POST-HOC MANNER, THE EEGs OF PATIENTS WHO FAILED SURGERY WHO HAD PSYCHIATRIC INJURY, THEY MORE OFTEN HAD A DUAL PATHOLOGY OR ANOTHER EPILEPTIC FOCUS THAT WAS NOT--THAT WAS BASICALLY MISSED IN SURGERY. NEXT SLIDE. SO THIS IS A VERY IMPORTANT ISSUE THAT WE ARE--THAT'S GETTING A LOT MORE ATTENTION, IS THE RISK OF SUICIDE IN PEOPLE WITH EPILEPSY. AND WE KNOW THAT, AND PARTICULARLY TEMPORAL LOBE EPILEPSY, THAT PEOPLE ARE AT ENORMOUSLY GREATER RISK. I MEAN, WE'RE TALKING ABOUT 6 TO 25 TIMES GREATER RISK. THE GREATEST RISK OCCURS INITIALLY AT THE TIME OF DIAGNOSIS. THAT'S SOMETHING TO THINK ABOUT. OBVIOUSLY IT'S A DEVASTATING ILLNESS. PEOPLE HAVE ALL SORTS OF IDEAS AS TO WHAT IT MEANS IN TERMS OF THEIR LIFE AND THEIR PROGNOSIS, AND SO WHEN THEY FIRST ARE GIVEN THE DIAGNOSIS-- WHICH, KEEP IN MIND THAT THEY'RE AT GREATER RISK OF KILLING THEMSELVES. OBVIOUSLY, PEOPLE WITH COMORBID PSYCHIATRIC ILLNESS ARE GONNA BE AT GREATER RISK OF SUICIDE. WHAT'S PARTICULARLY INTERESTING AND IS SOMETHING THAT WE AND OTHERS HAVE PUBLISHED IS THAT EVEN AFTER SUCCESSFUL EPILEPSY SURGERY, PEOPLE EVEN AFTER BEING SEIZURE-FREE ARE STILL AT GREATER RISK OF KILLING THEMSELVES FROM SUICIDE. AND SO IT'S NOT JUST ABOUT SEIZURE CONTROL, BUT THERE'S SOMETHING ABOUT WHAT HAPPENS TO THE BRAIN--MOST LIKELY WHAT HAPPENS TO THE BRAIN--THAT LEADS TO A--TO PEOPLE KILLING THEMSELVES, SOMETHING ABOUT PERHAPS BEING MORE DISINHIBITED OR HAVING--BE MORE IMPULSIVE WHEN THEY HAVE SUICIDAL THOUGHTS THAT WE REALLY NEED TO STUDY. AND SO KEEP THAT IN MIND. IT'S NOT JUST A MATTER OF YOUR PATIENTS WHO ARE STABLE THAT ARE AT INCREASED RISK, BUT EVEN PATIENTS WHO ARE SUICIDE--I'M SORRY, WHO ARE SEIZURE-FREE, WHO ARE STILL AT INCREASED RISK OF DEVELOPING--OF KILLING THEMSELVES FROM SUICIDE. NEXT SLIDE. NOW, STUDYING DEPRESSION COMORBIDITY, AND NOW WE THINK OF IT NOT SO MUCH AS A COMORBIDITY, BUT AS SOMETHING THAT IS PART AND PARCEL TO EPILEPSY. BUT STUDYING IT IS CHALLENGING, AND I THINK SOMETIMES WE THINK OF EPILEPSY AS COMORBIDITY AS--OBVIOUSLY, EPILEPSY IS A CHRONIC DISEASE, AND ANYBODY WITH A CHRONIC DISEASE IS GONNA HAVE AN INCREASED RISK OF DEPRESSION COMPARED TO HEALTHY CONTROLS, OR HEALTHY POPULATIONS. AND SO ETTINGER LOOKED AT ASTHMA AS A MODEL TO COMPARE ANOTHER CHRONIC DISEASE TO EPILEPSY AND SEE IF THERE'S SOMETHING DIFFERENT. THE IDEA IS THAT WE WOULD THINK THAT EPILEPSY BEING MORE OF A BRAIN DISEASE, AS WE TALKED ABOUT EARLIER, ASSOCIATED MORE WITH SUICIDE, SHARING SOME OF THE NETWORKS AS WELL AS...NEUROTRANSMITTER AND NEUROCHEMICALS OF DEPRESSION THAT ARE INVOLVED IN AND THAT PERHAPS THERE'S MORE OF A RELATIONSHIP WITH EPILEPSY AND DEPRESSION THAN OTHER CHRONIC DISEASES. SO HE LOOKED AT EPILEPSY VERSUS ASTHMA AND SHOWED THERE'S AN INCREASED RISK IN EPILEPSY. ASTHMA IS AN INTERESTING MODEL-- NEXT SLIDE--BECAUSE MUCH LIKE EPILEPSY, IT'S A PAROXYSMAL DISEASE. IT'S OFTENTIMES UNPREDICTABLE. IT'S A VERY PUBLIC DISEASE IF YOU HAVE AN ASTHMA ATTACK IN FRONT OF PEOPLE. AND SO, AS YOU CAN SEE, FROM A DISTANCE, IT LOOKS LIKE THERE'S A VERY SIMILAR COMORBIDITY, BUT OVERALL THAT THERE'S PERHAPS INCREASED RISK OF SEVERE DEPRESSION FOR PEOPLE WITH EPILEPSY. SO THAT KIND OF BEGS THE QUESTION OF, WELL, IS THERE ANYTHING DISTINCT ABOUT DEPRESSION AND EPILEPSY? IS THIS JUST WITH ANY CHRONIC DISEASE, AS PEOPLE ARE SUFFERING FROM A CHRONIC ILLNESS OR SUFFERING FROM A STRESSOR, THEY'RE MORE LIKELY TO HAVE DEPRESSION, OR IS THERE SOMETHING SPECIAL ABOUT EPILEPSY, PERHAPS THE GENOTYPE? SO, NEXT SLIDE. ONE AREA OF INTEREST THAT MANY RESEARCHERS HAVE REVISITED IS THE RELATIONSHIP OF THE SEIZURE TO MOOD. AND SO, AGAIN, ANDY KANNER HAS SHOWN THAT A POST-ICTAL--THAT OFTENTIMES, POST-ICTAL SYMPTOMS CONSIST OF DYSPHORIA, DECREASED MOODS. AND WHEN I SAY POST-ICTAL, IMMEDIATE POST-ICTAL STATE WITHIN HOURS, BUT EVEN UP TO DAYS AFTER A SEIZURE, PEOPLE FEEL DOWN AND DYSPHORIC. AN AREA OF INCREASED INTEREST HAS BEEN THIS INTERICTAL DYSPHORIC PHENOMENA, THE IDEA THAT IN BETWEEN SEIZURES, THAT PEOPLE'S MOOD STATE IS MORE LABILE, THAT THERE'S MORE ANXIETY, MORE DEPRESSION, THERE'S PAROXYSMAL IRRITABILITY. AND THIS IS A PHENOMENON THAT'S CALLED INTERICTAL DYSPHORIC DISORDER. MOST OF THE PEOPLE WHO SUFFER FROM THIS, IF NOT ALL OF THEM, DON'T MEET CRITERIA FOR MAJOR DEPRESSIVE DISORDER, BUT THEY DO IN GENERAL HAVE DEPRESSED MOOD, ARE MORE IRRITABLE, AND DO HAVE A WORSE QUALITY OF LIFE THAN PEOPLE WHO DO NOT HAVE THIS ILLNESS. SO THERE MIGHT BE SOMETHING DISTINCT ABOUT THE RELATIONSHIP BETWEEN MOOD AND EPILEPSY IN THE TEMPORAL RELATIONSHIP WITH THE SEIZURE AS WELL AS THIS PHENOMENA OF INTERICTAL DYSPHORIC DISORDER. AND THERE'S SOME CASE REPORTS OF PEOPLE RESPONDING WELL WITH SSRIs IN THIS VERY POPULATION. SO, NEXT SLIDE. SO SHIFTING, WE TALKED ABOUT IMPACT OF MOOD, AND NOW WE'LL TALK ABOUT THE NEUROANATOMY OF EPILEPSY AND DEPRESSION. NEXT SLIDE. SO JUST TO REMIND ALL OF YOU WHAT THE SYMPTOMS OF DEPRESSION, OF CLINICAL DEPRESSION, AGAIN, WE ALL HAVE OUR UPS AND DOWNS, AND SO WHAT WE'RE TALKING ABOUT IS NOT JUST OUR DAILY FEELING SAD OR BAD, BUT CLINICAL DEPRESSION, AND THAT REQUIRES THE FIRST TWO SYMPTOMS-- YOU HAVE TO HAVE EITHER DEPRESSED MOOD MORE OFTEN THAN NOT FOR AT LEAST TWO WEEKS OR ANHEDONIA, THE LOSS OF PLEASURE; AND YOU HAVE TO HAVE AT LEAST 4 OF THE FOLLOWING SYMPTOMS. AS YOU CAN SEE, SOME OF THESE SYMPTOMS CAN BE CLUSTERED. WEIGHT, SLEEP, AGITATION. SOME PEOPLE CONCEPTUALIZE THIS AS INDICATIVE OF SOMATIC SYMPTOMS AND THE FEELINGS OF WORTHLESSNESS, CONCENTRATION PROBLEMS, ASSOCIATED IDEATION AS AN ATTENTION-COGNITIVE CLUSTER OF SYMPTOMS. AND THAT'S IMPORTANT--NEXT SLIDE--BECAUSE YOU CAN THINK ABOUT DIFFERENT NETWORKS ASSOCIATED WITH DIFFERENT SYMPTOMS. SO THE MOST COMMON--IN TERMS OF FROM THE PRIMARY DEPRESSION LITERATURE, THE MOST COMMON STRUCTURAL ABNORMALITY THAT'S BEEN DEMONSTRATED IS HIPPOCAMPAL ATROPHY. OF COURSE, THAT'S OF INTEREST TO US AS EPILEPTOLOGISTS BECAUSE WE KNOW THAT THEY HIPPOCAMPUS IS ONE OF THE MAJOR CAUSES OF REFRACTORY [INDISTINCT] EPILEPSY. OF COURSE, THE PATHOLOGIES ARE VERY DIFFERENT. YOU HAVE THE MOSSY SPROUTING THAT YOU DO IN EPILEPSY OR TEMPORAL SCLEROSIS, BUT IT'S INTERESTING THAT THERE IS HIPPOCAMPAL ATROPHY IN PATIENTS WITH DEPRESSION. AND THIS IS A META-ANALYSIS SHOWING THAT. ALSO, FROM THE PRIMARY DEPRESSION LITERATURE--NEXT SLIDE--IT'S NOT JUST THE HIPPOCAMPUS OR THE GRAY MATTER-- IT'S NOT JUST ABOUT VOLUME, BUT IT'S ALSO ABOUT A CONNECTION, THAT THERE HAS BEEN A LARGE LITERATURE LOOKING AT DIFFUSION TENSOR IMAGING [INDISTINCT] CONNECTIONS BETWEEN TEMPORAL AND FRONTAL REGIONS. AND MANY STUDIES HAVE SHOWN THAT THERE'S DECREASED FRACTION AND ATROPHY, OR DECREASED WHITE MATTER INTEGRITY, BETWEEN THE TEMPORAL REGIONS AND THE FRONTAL REGIONS. NEXT SLIDE. AND SO WHEN WE THINK ABOUT DEPRESSION NETWORKS, I MEAN, IT'S IMPORTANT TO CONCEPTUALIZE THAT YOU CAN'T JUST LOCALIZE DEPRESSION TO-- ATTRIBUTE DEPRESSION TO ONE REGION OF THE BRAIN, THAT THERE ARE THESE NETWORKS. AND AS I ALLUDED TO EARLIER, YOU CAN CONCEPTUALIZE DEPRESSION SYMPTOMS INTO THESE DIFFERENT CLUSTERS: ATTENTION-COGNITIVE CLUSTERS, WHICH ARE ASSOCIATED, BASED ON FUNCTIONAL IMAGING STUDIES WITH THE MORE [INDISTINCT] REGIONS OF THE BRAIN, PARTICULARLY THE DORSAL CINGULATE, POSTERIOR CINGULATE, DORSAL PARIETAL REGIONS; AND THEN THERE IS [INDISTINCT] AREAS, WHICH, AS YOU IMAGINE, THE HIPPOCAMPUS, AMYGDALA, HYPOTHALAMUS IS INVOLVED; AND THAT THE SUBGENUAL CINGULATE HAS SHOWN TO BE A REGION THAT REGULATES MOODS AND COORDINATES THESE TWO SETS OF SYMPTOMS. AND THIS IS--ALTHOUGH THIS MODEL WAS DEVELOPED BY HELEN MAYBERG BACK IN 1997, STUDY AFTER STUDY HAS SUPPORTED THIS MODEL OF DEPRESSION NETWORKS. NEXT SLIDE. TO BE A LITTLE BIT MORE NUANCED--THIS IS A BUSY SLIDE. WE CAN TELL FROM THE TOP THAT-- I MEAN, YOU CAN TELL THAT THERE'S MULTIPLE REGIONS INVOLVED IN DEPRESSION. AND AGAIN, THIS IS THE PRIMARY DEPRESSION LITERATURE. IN THE TOP PART IS THE [INDISTINCT] REGIONS. AND THE IDEA THAT, IF YOU SEE TO THE RIGHT, THE ORBITAL FRONTAL--ORBITAL PREFRONTAL CORTEX IS INVOLVED IN DEPRESSION, PARTICULARLY EMOTION DISINHIBITION. SO MANY STUDIES HAVE SHOWN THAT PEOPLE WHO ARE MORE LIKELY TO ATTEMPT SUICIDE HAVE MORE ORBITAL FRONTAL DAMAGE. THERE IS ONE STUDY THAT CAME OUT OF UCLA THAT ALSO SHOWED THAT PEOPLE WITH EPILEPSY AND DEPRESSION WHO ARE SUICIDAL HAVE MORE ORBITAL FRONTAL DAMAGE. AND SO UNDERSTANDING THE DEPRESSION NETWORKS IS IMPORTANT. THE HIPPOCAMPUS IS THOUGHT TO MEDIATE EMOTIONAL MEMORIES, AS IS THE AMYGDALA, AND SO DYSFUNCTION IN THAT REGION, AS WE SEE IN TEMPORAL LOBE EPILEPSY, CAN MAKE OUR PATIENTS MORE VULNERABLE TO DEPRESSION. AND CERTAINLY, AS YOU SEE, THE OTHER REGIONS OF THE BRAIN WHICH MAY OR MAY NOT BE INVOLVED IN EPILEPSY, PER SE, CAN ALSO CONTRIBUTE TO DEPRESSION. NEXT SLIDE. THIS IS ANOTHER MODEL--AGAIN, A KIND OF NETWORK MODEL OF HOW DEPRESSIVE SYMPTOMS ARE LOCALIZED, IF YOU WILL, TO DIFFERENT PARTS OF THE BRAIN. AND THIS MODEL LOOKS AT INTERNAL VERSUS EXTERNAL STATES. SO IF YOU LOOK IN THE BOTTOM BOX WHERE IT SAYS "INTEROCEPTION," THESE ARE THE THE PARTS OF THE BRAIN ARE INVOLVED IN YOUR SOMATIC SYMPTOMS, SO, FOR INSTANCE, THE HYPOTHALAMUS AND SLEEP, BRAIN STEM AND AUTONOMIC FUNCTION. AS YOU KNOW, THE INSULAR CORTEX IS INVOLVED IN SOMATIC COMPLAINTS. SO THAT'S THAT BOX. KIND OF HOW YOU ASSIGN SOME MOOD MONITORING THAT THE BOX TO THE RIGHT--HOW YOU ASSIGN EMOTIONS TO YOUR EXPERIENCES IS MODULATED BY THE AMYGDALA, THE THALAMUS, THE [INDISTINCT] MENTAL AREA. SO THAT'S AN IMPORTANT PART OF DEPRESSION. OBVIOUSLY, AMYGDALA IS HEAVILY INVOLVED IN EPILEPSY. AND AGAIN, MOOD REGULATION IS PREDOMINANTLY FRONTAL LOBE, WITH THE PREGENUAL ANTERIOR CINGULATE REGION IS THE CENTRAL PART OF MOOD REGULATION. AND THEN THE TOP BOX, THE ATTENTION-APPRAISAL, HIPPOCAMPUS AND CINGULATE REGIONS ARE PARTICULARLY IMPORTANT AS WELL AS THE PARIETAL CORTEX AND PREMOTOR CORTEX. AND SO THIS JUST SHOWS YOU HOW COMPLICATED THESE DEPRESSION NETWORKS ARE AND HOW MUCH OVERLAP THERE IS BETWEEN DEPRESSION AND EPILEPSY. MOVING ONTO THE NEXT SLIDE. SO THIS IS ONE STUDY THAT FRANK GILLIAM AND HIS GROUP SHOWED THAT IN TEMPORAL LOBE EPILEPSY, THE AMOUNT OF DAMAGE TO THE TEMPORAL LOBE AS MEASURED BY MR SPECTROSCOPY DID CORRELATE TO AT LEAST THIS DEPRESSIVE SCALE. SO AGAIN, IN THE HIPPOCAMPAL MODEL, TOO, DEPRESSION. AND IF YOU GO TO THE NEXT SLIDE, YOU'LL SEE THAT THERE HAS BEEN STUDIES--AT LEAST ONE STUDY--SHOWING THE SYMPTOMS OF DEPRESSION COLOCALIZING WITH SOME OF THE REGIONS WE TALKED ABOUT EARLIER--THE CINGULATE WITH ANHEDONIA, THE INSULA WITH NEGATIVE COGNITIONS. NOW, IT'S INTERESTING BECAUSE THOSE ARE NOT THE REASONS THAT WE'D PREDICT. WITH NEGATIVE COGNITIONS, WE WOULD THINK MORE FRONTAL HIPPOCAMPAL CIRCUITS, AND WE'D THINK WITH THE INSULA, IT WOULD BE MORE SOMATIC SYMPTOMS. SO I'M NOT SURE--I MEAN, THIS IS ONE STUDY, SO THIS COULD, YOU KNOW--MIGHT NOT BE REPRESENTATIVE, AND IT CERTAINLY NEEDS TO BE REPLICATED. SO I'M NOT SURE IF THAT'S REWIRING OF THE BRAIN IN PEOPLE WITH EPILEPSY OR IF THIS IS JUST AN ABERRATION. SO THIS IS AN INTERESTING AREA OF POTENTIAL RESEARCH THAT WE'RE STARTING TO GET ENGAGED IN. NEXT SLIDE. ANOTHER WAY OF STUDYING DEPRESSION NETWORKS IS LOOKING AT LESION MODELS. OF COURSE, A COMMON LESION MODEL IS EPILEPSY SURGERY. AND SO WHAT HAPPENS TO MOOD WHEN YOU TAKE A LARGE PART OF THE LIMBIC LOBE OUT OF THE PATIENT? AND THAT'S SOMETHING THAT PEOPLE CAN BE CONCERNED ABOUT, AND RIGHTFULLY SO, GIVEN THAT EVEN PEOPLE WHO BECOME SEIZURE-FREE AFTER THE SURGERY STILL ARE AT HIGH RISK OF SUICIDE. SO, NEXT SLIDE. THIS IS A STUDY THAT WE PARTICIPATED IN WITH--IT WAS A MULTICENTER STUDY IN WHICH 7 CENTERS DID A PROSPECTIVE TRIAL. AND THIS, IF YOU LOOK AT... THIS IS A KIND OF COMPLICATED TABLE, BUT IF YOU LOOK AT-- FORGET THE COLORS FOR NOW. JUST LOOK AT THE DIFFERENT GROUPS OF COLUMNS. SO...THE FAR RIGHT IS MODERATE TO SEVERE DEPRESSION. AND WHAT THIS SHOWS IS IF YOU ADD THOSE 3 COLUMNS TOGETHER, PEOPLE AT BASELINE--I'M SORRY, THE PEOPLE AT BASELINE WHO STARTED WITH--THERE'S ABOUT 20 PLUS 7 PLUS 29--ABOUT 50-SOME PEOPLE WHO STARTED OUT WITH MODERATE TO SEVERE DEPRESSION. AND IF YOU GO TO THE FAR LEFT, YOU SEE 145 PLUS 10 PLUS 9-- 164 PEOPLE STARTED WITH NO DEPRESSION. THAT'S DEPRESSION AT BASELINE BEFORE SURGERY. NOW, IF YOU LOOK AT THE COLORS-- LET'S START WITH NONE. OUT OF THE PEOPLE WHO HAD NO DEPRESSION, THAT NONE, THOSE COLUMNS, 145 CONTINUED TO NOT HAVE DEPRESSION, BUT 10 PEOPLE IN THAT RED DEVELOPED DEPRESSION. IN CONTRAST, WHICH IS INTERESTING--THERE ARE A GROUP OF PEOPLE WHO ARE GONNA DEVELOP [INDISTINCT] DEPRESSION AFTER SURGERY. BUT WHAT'S PERHAPS MORE INTERESTING IS OUT OF THE PEOPLE WHO STARTED OUT WITH MODERATE TO SEVERE DEPRESSION, THAT 50-SOME PEOPLE, 29 OF THOSE PEOPLE HAD NO DEPRESSION AFTER 5 YEARS, WHICH IS PARTICULARLY INTERESTING BECAUSE THAT MEANS ABOUT 50%, OR MORE THAN 50%, OF PEOPLE WHO STARTED OUT WITH SEVERE DEPRESSION, MODERATE TO SEVERE DEPRESSION, WERE DEPRESSION-FREE 5 YEARS AFTERWARDS. NEXT SLIDE. WE LOOKED AT, LONGITUDINALLY, HOW DID THE RELATIONSHIP BETWEEN SEIZURE CONTROL... RELATE TO PEOPLE'S DEPRESSION SCORES? SO THE Y-AXIS SHOWS CHANGE IN DEPRESSION SCORES. SO ZERO WOULD BE NO CHANGE, -1 IS A ONE-POINT CHANGE IN BDI. 2, 3, 4 AS FOLLOWS. IF YOU SEE THE BLUE LINE, THOSE ARE PEOPLE WHO WENT SEIZURE-FREE AFTER SURGERY, AND YOU SEE THAT AS A GROUP, THAT PEOPLE WHO HAD A 4-POINT DIFFERENCE IN THEIR DEPRESSION SCORES, WHICH IS A SIGNIFICANT DIFFERENCE, AND THEY SUSTAINED THAT IMPROVEMENT IN DEPRESSION IF THEY HAD--THEY WERE SEIZURE-FREE. IN CONTRAST, THE RED LINE SHOWS THAT EVEN PEOPLE WHO FAILED EPILEPSY SURGERY, THAT EVEN AFTER THE SURGERY, THEY CONTINUED TO HAVE SEIZURES--THOSE PATIENTS INITIALLY HAD A PLACEBO--I'M NOT SURE PLACEBO [INDISTINCT], BUT THEY HAD A DROP IN DEPRESSION SCORES UP TO ONE YEAR, BUT OVER TIME, THOSE DEPRESSION SCORES WENT BACK TO BASELINE. THEY REMAINED DEPRESSED. WHAT'S PARTICULARLY INTERESTING IS THAT PEOPLE WITH PARTIAL RESPONSE--SO THE GREEN IS GOOD. THEY HAD OCCASIONAL, LIKE, ONE OR TWO BREAKTHROUGH SEIZURES EVERY YEAR AS OPPOSED TO FAIR RESPONSE, WHERE THEY HAD MORE FREQUENT SEIZURES. PEOPLE WITH PARTIAL RESPONSE HAD AN IMPROVEMENT IN DEPRESSION SCORES, AND IT WAS SUSTAINED OVER TIME, AS OPPOSED TO PEOPLE WITH FAIR RESPONSE, WHO HAD MORE FREQUENT SEIZURES, INITIALLY HAD A DROP, BUT AS THEY CONTINUED TO HAVE SEIZURES, THEIR DEPRESSION SCORES WORSENED. SO THIS SUGGESTS THAT THERE IS A RELATIONSHIP, THAT IT'S NOT JUST ABOUT SEIZURE FREEDOM, AS WE SHOWED IN THE CROSS-SECTIONAL STUDIES, BUT WHEN YOU LOOK LONGITUDINALLY, THAT EVEN PARTIAL RESPONSE TO EPILEPSY SURGERY, AT LEAST, CAN DRAMATICALLY IMPROVE PEOPLE'S DEPRESSION SCORES, AND IT'S SUSTAINED OVER TIME. NEXT SLIDE. NOW, AS WE KNOW, BRAIN STEM STIMULATION IS--I'M SORRY, DEEP BRAIN STIMULATION IS IN THE PIPELINE, AND WE'RE HOPING THAT IT GETS APPROVED BY THE FDA. AND IT'S AN EXCITING AREA OF INQUIRY IN EPILEPSY. NEXT SLIDE. SORRY, THERE'S AN ERROR IN THE SLIDE. GO TO THE FOLLOWING SLIDE ENTITLED "DBS INTERIOR THALAMUS AND DEPRESSION." WHAT'S NOT REALLY TALKED ABOUT IS THAT IN THE SANTE TRIAL, 15% OF PEOPLE WHO HAD DEEP BRAIN STIMULATION IN THE ANTERIOR THALAMUS REPORTED INCREASED DEPRESSIVE SYMPTOMS AS OPPOSED TO 1.8% IN CONTROLS, PEOPLE WHO HAD SHAM STIMULATION. SO THIS KIND OF SUGGESTS THAT WE KNOW THAT THE ANTERIOR CIRCUITS ARE INVOLVED IN DEPRESSION, AND PEOPLE WHO-- AND IF YOU STIMULATE THESE PATIENTS, PERHAPS THEY'RE MORE VULNERABLE FOR DEPRESSION. SO IT'S IMPORTANT TO KIND OF THINK ABOUT OUR INTERVENTIONS AND HOW THESE--HOW PEOPLE CAN BE MORE--MORE WITH DEPRESSION. AND AS THESE TECHNOLOGIES DEVELOP, WE SHOULD BE CAREFUL ABOUT MOOD OUTCOMES. NEXT SLIDE. SO WE'RE GONNA SHIFT AGAIN TO MEDICATIONS IN EPILEPSY. NEXT SLIDE. MOST OF THE STUDIES ON DEPRESSION AND ANTICONVULSANT MEDICATIONS ARE CASE SERIES. SO YOU HAVE TO TAKE THAT WITH A GRAIN OF SALT. BUT THESE ARE THE LIST OF MEDICATIONS THAT HAVE BEEN SHOWN TO BE ASSOCIATED WITH INCREASED DEPRESSION, PERHAPS KEPPRA AND THE BARBITURATES THE MOST SO. AND I THINK MOST OF YOU--MOST OF THE CLINICIANS HAVE EXPERIENCED THIS, THAT PEOPLE ON BARBITURATES AS WELL AS KEPPRA HAVE A HIGH RISK AND SOMETIMES GET MORE DEPRESSED. NEXT SLIDE. WE ALL KNOW, OR WE SHOULD KNOW, THAT THERE IS A BOX WARNING NOW THAT STATES THAT PATIENTS WHO ARE TREATED WITH ANTI-EPILEPTIC DRUGS SHOULD BE WARNED THAT THEY CAN HAVE INCREASED SUICIDAL THOUGHTS. WE KNOW THAT THAT DATA WAS DRIVEN BY TOPIRAMATE AND LAMICTAL. SO THERE'S ACTUALLY AN ERROR THERE. IT SAYS LEVITERACETAM. IT WAS ACTUALLY LAMICTAL WAS INCREASED RISK. IN FACT, WITH POST-HOC ANALYSIS, WHEN THEY ADDED MORE NUMBERS, THE LAMICTAL EFFECT WASHED AWAY. SO REALLY, TOPIRAMATE DROVE THAT DATA, AND IN FACT, CARBAMAZEPINE WAS SHOWN TO BE ASSOCIATED WITH DECREASED RISK OF DEPRESSION, EVEN THOUGH CARBAMAZEPINE IS NOT KNOWN TO BE A GOOD ANTIDEPRESSANT. NOW, THIS WAS A KIND OF A DIRTY STUDY THAT THE FDA DID IN THE SENSE THAT THERE WERE MULTIPLE INDICATIONS. THERE WERE NOT ONLY JUST EPILEPSY PATIENTS. THERE WERE ALSO BIPOLAR PATIENTS. IT WAS DONE IN MULTIPLE GEOGRAPHICAL SITES, WHICH ENSURED THAT THE DATA QUALITY WAS IN QUESTION. AND IT WAS BASED ON OUT OF 27,000 PEOPLE, THERE WERE 4 PEOPLE WHO COMMITTED SUICIDE, AND ALL OF THEM HAPPENED TO BE ON ADs. AND SO IT WAS STATISTICALLY SIGNIFICANT, BUT STILL A VERY, VERY LOW RISK. AND AGAIN, ALL THOSE PATIENTS WERE ON TOPIRAMATE OR LAMICTAL. AND SO WHAT EVERYONE SHOULD BE AWARE OF IS WE SHOULDN'T NECESSARILY CHANGE OUR APPROACH TO USING ANTICONVULSANT MEDICATIONS, EXCEPT FOR PERHAPS TOPIRAMATE-- WE SHOULD AT LEAST BE MORE CAUTIOUS--AND MAYBE KEPPRA, ALTHOUGH THAT IS NOT WHAT THIS DATA SHOWS. NEXT SLIDE. WE KNOW THAT PEOPLE WITH EPILEPSY IN GENERAL ARE AT INCREASED RISK FOR EPILEPSY, AND THIS IS A META-ANALYSIS BY BELL. ONE THING TO NOTE IS THAT THE STANDARDIZED MORTALITY RATIOS-- A LOT OF THOSE STUDIES, THEY--THEY'RE NOT STATISTICALLY SIGNIFICANT, THAT YOU CAN SEE THAT THEY CROSS THE 1.0 X-AXIS. SO MANY OF THOSE STUDIES WERE EQUIVOCAL. OF COURSE, THOSE ARE MORE LIKELY IN THE SMALLER STUDIES. IN THE LARGER STUDIES, YOU CAN SEE IT DOES SHOW INCREASED RISK OF DEATH IN PEOPLE WITH EPILEPSY. AND SO, I MEAN, WE SHOULD BE CONCERNED ABOUT SUICIDE IN OUR PATIENTS, BUT REALIZE THAT THERE IS SOME CONTROVERSY IN THE LITERATURE. AND SO--NEXT SLIDE. WHAT ANTIDEPRESSANTS ARE SAFE FOR PEOPLE WITH EPILEPSY? NOW, THIS STUDY IS FROM, AGAIN, KENNETH ALPER, I MENTIONED EARLIER. NOW, THIS STUDY LOOKED AT ANY RANDOMIZED CONTROLLED STUDY WITH ANTIDEPRESSANTS AND SEIZURE INCIDENCE. SO THESE ARE NOT PATIENTS WITH EPILEPSY. THESE ARE PEOPLE WHO ARE ENROLLED IN ANTIDEPRESSANT OR ANTIPSYCHOTIC TRIALS AND LOOKED AT SEIZURE-- THE INCIDENCE OF SEIZURES. SO THIS GIVES YOU AN IDEA OF SEIZURE THRESHOLD, NOT NECESSARILY THE SAFETY OF ANTIDEPRESSANTS OR ANTIPSYCHOTICS IN PATIENTS WITH EPILEPSY. BUT WHAT'S INTERESTING HERE IS THAT PEOPLE ON SSRIs HAD ACTUALLY A DECREASED RISK OF DEVELOPING A SEIZURE COMPARED TO PLACEBO, WHEREAS IN PEOPLE ON BUPROPRION, SO WELLBUTRIN, IMMEDIATE RELEASE, BY ITSELF WAS ASSOCIATED WITH AN INCREASED RISK, ABOUT A 58% INCREASED RISK OF DEVELOPING SEIZURE COMPARED TO PLACEBO. THAT'S IMPORTANT THAT ITS IMMEDIATE RELEASE. WHEN THEY LOOKED AT SUSTAINED RELEASE, THAT DIDN'T HOLD TRUE. AND SO, YOU KNOW, IF YOU HAVE A PATIENT ON WELLBUTRIN OR BUPROPRION AND THEY'RE ON SUSTAINED RELEASE, THEY CAN STAY ON THAT MEDICATION BECAUSE THERE'S NOT AN INCREASED RISK. IF THEY'RE ON IMMEDIATE RELEASE, THEN THERE IS INCREASED RISK OF SEIZURES, AND I'D RECOMMEND SWITCHING MEDICATIONS TO ANOTHER SSRI. NOW, A SIDE NOTE: CLOZARIL, YOU SEE, IS CLOSE TO 10 TIMES INCREASED RISK OF SEIZURE, AND WE KNOW THAT CLOZARIL, OR CLOZAPINE, DOES CAUSE SEIZURES AND IT IS DOSE-RELATED. SO YOU SHOULD KNOW THAT. NEXT SLIDE. SO WHAT I TELL NEUROLOGISTS IN GENERAL IS THAT MOST ANTIDEPRESSANTS ARE ACTUALLY PRESCRIBED BY PRIMARY CARE PHYSICIANS, AND IF PRIMARY CARE PHYSICIANS FEEL COMFORTABLE PRESCRIBING ANTIDEPRESSANTS, THEN NEUROLOGISTS, WHO KIND OF OWN THE BRAIN, IF YOU WILL, SHOULD FEEL COMFORTABLE PRESCRIBING SSRIs OR ANTIDEPRESSANTS, ALSO. THE THING TO WATCH OUT FOR IS WHENEVER YOU PRESCRIBE THE MEDICATIONS, YOU SHOULD SCREEN FOR ANXIETY AND MANIA. NOW, IF A PERSON HAS BIPOLAR DISORDER AND YOU GIVE THEM AN ANTIDEPRESSANT, YOU COULD PUT THEM INTO A MANIC ATTACK. SO THAT'S WHY IT'S IMPORTANT TO AT LEAST SCREEN FOR MANIA. ASK SOME QUESTIONS SUCH AS, DO YOU HAVE PERIODS WHERE YOU'RE HYPERACTIVE, THAT YOU DON'T NEED SLEEP FOR MORE THAN-- FOR A COUPLE DAYS IN A ROW, THAT YOU BECOME RECKLESS FOR TWO WEEKS STRAIGHT, IN WHICH YOU ARE MORE SEXUALLY PROMISCUOUS, YOU GAMBLE, YOU SPEND THOUSANDS OF DOLLARS IMPULSIVELY? AND THOSE ARE, AGAIN, THE SCREENING QUESTIONS YOU'D ASK A PERSON FOR BIPOLAR DISORDER. AND SO, AGAIN, WHAT I RECOMMEND NEUROLOGISTS IS TAKE TWO SSRIs AND HAVE AT LEAST ONE OF THOSE BE GENERIC SO THAT PATIENTS CAN AFFORD IT, AND KNOW THEM WELL. KNOW HOW TO DOSE THEM. KNOW THE SIDE EFFECTS. I PUT DOWN THE MORE COMMON SIDE EFFECTS. FOR INSTANCE, EFFEXOR IS ASSOCIATED WITH HYPERTENSION. CELEXA NOW IS ASSOCIATED WITH HIGHER DOSES WITH PROLONGED QT SYNDROME. WELLBUTRIN--THERE'S THE ADVANTAGE OF WELLBUTRIN SUSTAINED RELEASE IN THAT THERE'S NO SEXUAL DYSFUNCTION AS YOU DO SEE WITH SSRIs. YOU SEE A LOT OF IMPOTENCE WITH SSRIs. AND SO YOU CAN GIVE WELLBUTRIN SUSTAINED RELEASE IN PATIENTS WITH EPILEPSY. SO, NEXT SLIDE. SO, END. IT'S OVER. I'M COMING TO A CLOSE, AND I'LL END WITH SOME OF THE PSYCHOLOGY OF MOOD AND EPILEPSY. SORRY, THERE'S AN ERROR AGAIN IN THE SLIDE. NEXT SLIDE. SO, "MIND, MOOD, AND EPILEPSY," NEXT SLIDE, "PSYCHOLOGY STATES." SO THERE HAVE BEEN STUDIES LOOKING AT WHAT ARE THE PSYCHOLOGICAL FACTORS ASSOCIATED WITH DEPRESSION IN PEOPLE WITH EPILEPSY? AND SOME OF THE PSYCHOLOGICAL FACTORS ARE INTERESTING. YOU CAN IMAGINE THAT WHEN YOU HAVE EPILEPSY WITH SEIZURES, YOU LOSE CONTROL. I MEAN, BY DEFINITION, THESE ARE PAROXYSMAL EPISODES. YOU DON'T HAVE CONTROL OVER IT. AND SO THAT HAS A GENERAL EFFECT ON PEOPLE'S SENSE OF SELF-CONTROL, AND THEY FEEL SOMEWHAT HELPLESS. IT'S ALMOST LIKE THE HELPLESSNESS LEVEL IN MOUSE STUDIES. AND SO IT'S KIND OF THEY ARE IN HELPLESSNESS BECAUSE OF THE SEIZURES, AND THAT'S ASSOCIATED WITH NEGATIVE COPING STYLES. THERE IS A FEELING YOU CAN'T-- THAT THE PEOPLE SOMETIMES COPE BY AVOIDING OR BEHAVING PASSIVELY AGGRESSIVELY, BY DISTANCING, BY BEING CONFRONTATIONAL. THOSE ARE ASSOCIATED WITH NEGATIVE COPING STYLES AND MORE ASSOCIATED WITH DEPRESSION. MORE POSITIVE COPING STYLES HAVE BEEN SHOWN TO BE PROTECTIVE OF BEING DEPRESSED, AND PARTICULARLY IN PATIENTS WITH EPILEPSY. SO OBVIOUSLY, SEEKING SUPPORT, ACCEPTING RESPONSIBILITY, NOT JUST RELYING ON OTHER PEOPLE, PLANNING AND PROBLEM-SOLVING. AGAIN, WE ALLUDED TO THE ROLE OF THE FRONTAL LOBE. WE ALL KNOW ABOUT THE ROLE OF THE FRONTAL LOBE IN COGNITION, BUT IT'S OBVIOUSLY PROBLEM- SOLVING, AND IF YOU'RE NOT ABLE TO PROBLEM-SOLVE, YOU'RE GOING TO HAVE MORE INTERPERSONAL PROBLEMS AND GET YOURSELF IN TROUBLE AND PERHAPS BE MORE SUICIDAL. AND THEN LABELING THINGS MORE POSITIVELY AS OPPOSED TO NEGATIVELY. SO THOSE ARE KIND OF COPING STYLES ASSOCIATED WITH RESILIENCE IN PEOPLE WITH EPILEPSY. THE NEXT SLIDE. WHAT'S INTERESTING--AND THIS IS A MODEL--THIS IS LOOKING AT PEOPLE WHO, AFTER THEY-- AFTER THEY ARE CURED OF THEIR EPILEPSY FROM SURGERY, WHAT ARE THE PSYCHOLOGICAL CHANGES THAT HAPPEN OR THE PSYCHOSOCIAL CHANGES THAT HAPPEN? AND IT ILLUSTRATES NOT ONLY HOW THINGS CAN BE AFTER BEING CURED OF SEIZURES, BUT ALSO WHAT THEY MIGHT EXPERIENCE WHEN THEY'RE HAVING SEIZURES. SO IF YOU LOOK AT THE LAST GROUP OF SYMPTOMS, WHEN PEOPLE BECOME CURED OF SEIZURES, THIS MODEL IS CALLED THE BURDEN OF NORMALITY, THE IDEA THAT YOU LIVE YOUR LIFE WITH SEIZURES, AND IF YOU'RE CURED OF SEIZURES, YOU HAVE THIS BURDEN OF BEING NORMAL, THAT YOUR LIFE WHILE YOU HAVE SEIZURES, YOUR RELATIONSHIPS WERE WRAPPED AROUND THE SEIZURES-- THE PEOPLE THAT PROVIDED YOU SUPPORT THAT YOU SOMETIMES HAD, EXCUSE FROM WORK, AND NOW WHEN YOU'RE CURED, ALL THESE EXPECTATIONS ARE OF YOU. WELL, NOW YOU DON'T HAVE SEIZURES. NOW I EXPECT YOU TO WORK, TO BE PRODUCTIVE, TO BE INDEPENDENT. AND SO PSYCHOLOGICALLY, THERE'S EVEN A SENSE OF LOSS WHEN PEOPLE, BELIEVE IT OR NOT, NO LONGER HAVE SEIZURES. THERE'S THIS SENSE THAT THEY HAVE TO PROVE THEMSELVES, THEY HAVE TO PROVE THEMSELVES TO BE NORMAL. THEY'VE HAD HIS LABEL OF BEING-- OF HAVING EPILEPSY, SO THERE'S THIS KIND OF PSYCHOLOGICAL DRIVE TO PROVE THEMSELVES. AND OF COURSE, THERE'S INCREASED EXPECTATIONS ONCE THEY HAVE SEIZURES, SO THERE'S THIS FEELING OF LOSS. THEY'VE LOST ALL THESE YEARS, THEN THEY HAVE TO MAKE IT UP ONCE THEY ARE SEIZURE-FREE. AND SO THOSE ARE KINDS OF THE PSYCHOLOGICAL STATES THAT PEOPLE WHO...HAVE AFTER THE SURGERY. EFFECTIVE STATES--OF COURSE, YOU KNOW, IF YOU HAVE MOOD ELEVATION, YOU CAN GET ANXIOUS BECAUSE OF THE EXPECTATIONS AROUND YOU. AND OF COURSE, YOU CAN GET DEPRESSED BECAUSE IF YOU FEEL A SENSE OF FAILURE IN SPITE OF BEING SEIZURE-FREE. BEHAVIORAL--SOME PEOPLE OVERCOMPENSATE. THEY FEEL THEY NEED TO CATCH UP WITH THEIR LIFE AND GET INTO EXCESSIVE ACTIVITY. THEY MAY HAVE INCREASED SEX DRIVE, ESPECIALLY AFTER COMING OFF THE MEDICATIONS. AND SOMETIMES PEOPLE EVEN DEVELOP PSYCHOGENIC SEIZURES, PSYCHOGENIC NON-EPILEPTIC SEIZURES. BECAUSE THERE IS TOO MUCH OF A LEAP TO BE SEIZURE-FREE, THEY DEVELOP PSYCHOGENIC SEIZURES. PSYCHOLOGICALLY--WITHOUT SEIZURES, YOU KIND OF [INDISTINCT] DYNAMIC, THERE ARE NEW VOCATIONAL EXPECTATIONS, THERE'S A NEW SET OF SOCIAL SKILLS THAT YOU HAVE TO LEARN. SO THERE'S A WHOLE SET OF PSYCHOSOCIAL ISSUES THAT WE HAVE TO THINK ABOUT WITH OUR PATIENTS WITH EPILEPSY THAT OFTENTIMES WE DON'T. NEXT SLIDE. WHAT CAN A PERSON DO? THIS IS SOMETHING THAT [INDISTINCT] SHOW FROM A MENTAL HEALTH POLICY PERSPECTIVE. IT IS TO REMIND US THAT IN THIS PYRAMID, THE BOTTOM OF THE PYRAMID SHOWS YOU THE FREQUENCY OF NEED AND THE AVAILABILITY, THE ACCESS TO THIS BOX, AND AS YOU GO UP, THE COST GOES HIGHER. SO SELF-CARE IS THE MOST FREQUENT. I MEAN, WE ARE TEACHING PEOPLE TO BE RESILIENT AND HAVE GOOD COPING MECHANISMS. THE NEXT LEVEL IS INFORMAL COMMUNITY CARE. SO BEING LIKE FRIENDS...YOU KNOW, ENCOURAGE PEOPLE TO SEEK OUT FRIENDS, TO BUILD THEIR SOCIAL NETWORKS. GROUPS, SUPPORT GROUPS FALL IN THIS CATEGORY OF INFORMAL COMMUNITY CARE, SO PROMOTING SELF-HELP GROUPS. EPILEPSY FOUNDATION IS PARTICULARLY GOOD AT SETTING SELF-HELP GROUPS UP. AND THEN YOU GET INTO THE MEDICAL SYSTEM--MENTAL HEALTH SERVICES, THROUGH PRIMARY CARE, AND THROUGH US AS NEUROLOGISTS. THEN AS YOU GO UP AND YOU INCREASE SEVERITY OF DEPRESSION, YOU GET INTO HIGHER LEVELS OF CARE, INCLUDING PSYCHIATRIC CONSULTATION AND SERVICES, AND THE TOP OF THAT BEING INPATIENT CARE. SO NEXT SLIDE, GOING BACK TO OUR CASE STUDY. WE TALKED ABOUT HOW THIS WOMAN WAS SUICIDAL. SHE WAS ON KEPPRA AND LEXAPRO. AND HOPEFULLY FROM THIS LECTURE, YOU WOULD HAVE LEARNED OR REVIEWED THAT, YOU KNOW, SHE WILL BE AT INCREASED RISK OF SUICIDE EVEN AFTER HAVING HER EPILEPSY MANAGED, THAT THE KEPPRA IS PROBABLY NOT THE BEST MEDICATION. PERHAPS LAMICTAL, BEING AN ANTIDEPRESSANT, IS A BETTER MEDICATION AS AN ANTICONVULSANT. AND THE LEXAPRO IS SAFE FOR HER TO USE BECAUSE IT HAS BEEN SHOWN TO ACTUALLY INCREASE THE THRESHOLD. SO I'LL OPEN IT UP TO QUESTIONS. - THE LINES ARE OPEN NOW. - ANY QUESTIONS, OR DOES ANYBODY HAVE ANY EXPERIENCE THEY WANT TO SHARE OR... - DOES ANYBODY HAVE ANY QUESTIONS? - YES. - WELL, DOCTOR, I DON'T THINK ANYBODY HAS ANY QUESTIONS. - OK. VERY GOOD. ALL RIGHT. WELL, THANK YOU FOR YOUR TIME, AND HOPEFULLY YOU BENEFIT FROM THIS. AND IF YOU CAN PLEASE FILL OUT YOUR COURSE EVALUATIONS, AND I GUESS THEY FAX IT OVER OR E-MAIL IT? - IT'S IN TMS RIGHT NOW, PLUS RYAN HAS INFORMATION ON THE WEBSITE FOR THEM. - OK, GREAT. ALL RIGHT, THANKS A LOT. - THANKS, EVERYBODY, FOR JOINING US.