the use of electroconvulsive therapy ( ect ) in severe depression has been demonstrated to be a very effective and safe treatment option , especially in older patients . however , transient mild to moderate cognitive impairment is a serious adverse effect that is frequently observed in clinical practice , especially in older patients during and after ect . ect - induced cognitive impairment has a broad pallet of different manifestations and usually consists of temporary anterograde ( i.e. , difficulties in acquiring and retaining new information ) and/or retrograde amnesia ( i.e. , impaired recall of learned information before ect ) , or confusional symptoms like disorientation and attention deficits , in some patients during longer periods over days . since these prolonged confusional states might limit the use of ect , especially for severely depressed older patients , preventing or limiting these cognitive deficits would be of utmost importance . pigot et al . reviewed the use of pharmacological agents , including acetylcholinesterase inhibitors , in the attenuation of ect - induced cognitive impairment . as cholinergic processes underlie learning and memory , it seems likely that cholinergic dysfunction may contribute to ect - induced cognitive impairment . some studies have shown that there is an increase of acetylcholinesterase during the postictal period after electroconvulsive shock . therefore , treatment with an acetylcholinesterase inhibitor to increase the acetylcholine concentration , might be useful for the prevention or reversion of the cognitive impairment . to our knowledge , only one case study has described the use of rivastigmine during ect in depressed patients . in this article first , we describe three patients all with different manifestations of ect - induced cognitive impairment and the use of the acetylcholinesterase inhibitor rivastigmine , in order to positively influence the course of this ect - induced cognitive impairment in severely depressed older in - patients with normal premorbid cognitive functioning . second , we present a hypothesis about the indication of acetylcholinesterase inhibitors to prevent or diminish confusional states during or after ect in patients with age related alterations of the brain . ect was administered by using a brief - pulse constant - current square - wave device ( thymatron dgx , system iv ; somatics , llc , lake bluff , il , usa ) , constant energy 0.9 a , set to deliver a maximum dose of 1008 mc , pulse 0.5 m / s , 10 - 140 hz frequency , depending from mc setting . the age dosing protocol was used ( e.g. , an 80 years old patient is treated with 80% dose corresponding to 403.2 mc ) . bilateral treatment was administered if right unilateral treatment was unsuccessful or when a rapid response was required , e.g. , in case of severe catatonia or suicidality . ect was given twice a week and considered optimal with seizure duration of more then 20 s measured by observable tonic - clonic seizure or more then 25 seconds measured by electroencephalogram . succinylcholine was administered to provide adequate muscle relaxation , 0.75 - 1.5 mg / kg . ect was administered by using a brief - pulse constant - current square - wave device ( thymatron dgx , system iv ; somatics , llc , lake bluff , il , usa ) , constant energy 0.9 a , set to deliver a maximum dose of 1008 mc , pulse 0.5 m / s , 10 - 140 hz frequency , depending from mc setting . the age dosing protocol was used ( e.g. , an 80 years old patient is treated with 80% dose corresponding to 403.2 mc ) . bilateral treatment was administered if right unilateral treatment was unsuccessful or when a rapid response was required , e.g. , in case of severe catatonia or suicidality . ect was given twice a week and considered optimal with seizure duration of more then 20 s measured by observable tonic - clonic seizure or more then 25 seconds measured by electroencephalogram . succinylcholine was administered to provide adequate muscle relaxation , 0.75 - 1.5 mg / kg . an 80-year - old female patient , without any known cognitive impairment , developed a severe psychotic depression shortly after a myocardial infarction and was admitted to our hospital . once daily she suffered from adverse side effects as deficits in attention and disorientation , and unilateral ect was started . during treatment the patient experienced severe cognitive impairment , including deficits in executive functioning , disorientation and confusion . the mini - mental state examination - score ( mmse ) was 18/30 during ect - treatment . brain magnetic resonance imaging ( mri ) showed extensive white matter hyperintensities ( wmh ) , with medial temporal lobe atrophy ( ii - iii ) , and no global cortical atrophy . in order to reduce confusional symptoms , 1 mg haloperidol daily was started . however , haloperidol - induced parkinsonism occurred and was therefore discontinued . after 12 right unilateral ect - sessions , the depressive disorder remitted and the montgomery and sberg depression rating scale ( madrs ) dropped from 45/60 to 6/60 . nortriptyline was started again , once more resulting in cognitive impairment , especially confusional symptoms . hence , it was decided to refrain from antidepressant treatment and to closely monitor the patient after discharge . on discharge from the hospital the madrs was 3/60 , mmse - score was 27/30 and the patient did not suffer from confusion or cognitive impairment otherwise . after 3 months , she experienced a relapse of her depression and a new ect course was initiated at second admission . to prevent cognitive impairment , that had previously occurred , gradually the depression remitted , with remarkably less cognitive impairment during ect and no confusional symptoms . two weeks after initiating both the second ect course and rivastigmine treatment , the mmse - score increased to 25/30 . after a long course of 22 ect sessions with right unilateral stimulation complete remission was achieved ( madrs 5/60 ) . on the second discharge from the hospital the mmse - score was 27/30 . nortriptyline was administered , under continuation of rivastigmine with no cognitive impairment or confusional episodes during three years of follow - up . a 65-year - old male patient , with a history of a schizoaffective disorder , was admitted to our in - patients clinic for the treatment of an episode of psychotic depression . at admittance the madrs and mmse - score could not be assessed due to the severity of the depressive episode . since there was a high risk of suicide , involuntary bilateral ect was initiated . immediately after ect was started , disorientation and visual hallucinations were observed . a delirium was suspected . despite thorough internal and neurological examinations , no somatic cause of the delirium could be detected . brain mri showed old ischemic lesions , global atrophy and medial bitemporal lobe atrophy ( iii ) . haloperidol 1 mg daily was initiated for a few days , but was discontinued because of qtc - prolongation . the delirium observation scale score had dropped from 11/13 to 6/13 after two weeks of treatment , indicating improved cognitive functioning . after 15 ect - sessions the madrs had dropped from 25/60 to 10/60 and ect was discontinued . the mmse - score was 23/30 and cognitive impairment , including attention deficits , memory problems and apraxia , persisted after several days . five weeks after discontinuation of the ect the depression was still in remission , and his cognitive functioning had improved ( mmse 28/30 ) . the mmse - score remained 28/30 after three years of follow - up . a 58-year old female patient , with a long history of recurrent depressive episodes , was admitted to the in - patient ward for a major depressive episode with psychotic features and severe motor agitation ( madrs 46/60 ) . brain mri showed no abnormalities , especially no cortical atrophy , nor medial temporal lobe atrophy , or white matter hyperintensities . treatment with respectively citalopram , mirtazapine and nor - triptyline , and additional quetiapine were ineffective . the patient refused lithium addition , because of side effects in the past . since she had been successfully treated with ect in another hospital nine years before , also she experienced severe cognitive impairment , including retrograde and anterograde amnesia and also long - term memory loss . nortriptyline 50 mg once daily was continued , with adequate blood level . however , within 4 weeks after the last ect , the motor agitation worsened and a relapse of the major depression was seen . a second ect - course with initially unilateral electrode placement was rapidly started , followed by bilateral ect since suicidal thoughts were prominent . considering the cognitive impairment , a trial with rivastigmine was started prior to initiation of the second course . the depressive symptoms responded ( madrs 13/60 ) after twelve sessions and therefore ect was discontinued . her memory gradually improved several weeks after discontinuation of ect , but the patient still claimed minor amnesia at three years of follow - up . an 80-year - old female patient , without any known cognitive impairment , developed a severe psychotic depression shortly after a myocardial infarction and was admitted to our hospital . once daily she suffered from adverse side effects as deficits in attention and disorientation , and unilateral ect was started . during treatment the patient experienced severe cognitive impairment , including deficits in executive functioning , disorientation and confusion . the mini - mental state examination - score ( mmse ) was 18/30 during ect - treatment . brain magnetic resonance imaging ( mri ) showed extensive white matter hyperintensities ( wmh ) , with medial temporal lobe atrophy ( ii - iii ) , and no global cortical atrophy . in order to reduce confusional symptoms , 1 mg haloperidol daily was started . however , haloperidol - induced parkinsonism occurred and was therefore discontinued . after 12 right unilateral ect - sessions , the depressive disorder remitted and the montgomery and sberg depression rating scale ( madrs ) dropped from 45/60 to 6/60 . nortriptyline was started again , once more resulting in cognitive impairment , especially confusional symptoms . hence , it was decided to refrain from antidepressant treatment and to closely monitor the patient after discharge . on discharge from the hospital the madrs was 3/60 , mmse - score was 27/30 and the patient did not suffer from confusion or cognitive impairment otherwise . after 3 months , she experienced a relapse of her depression and a new ect course was initiated at second admission . to prevent cognitive impairment , that had previously occurred , gradually the depression remitted , with remarkably less cognitive impairment during ect and no confusional symptoms . two weeks after initiating both the second ect course and rivastigmine treatment , the mmse - score increased to 25/30 . after a long course of 22 ect sessions with right unilateral stimulation complete remission was achieved ( madrs 5/60 ) . on the second discharge from the hospital the mmse - score was 27/30 . nortriptyline was administered , under continuation of rivastigmine with no cognitive impairment or confusional episodes during three years of follow - up . a 65-year - old male patient , with a history of a schizoaffective disorder , was admitted to our in - patients clinic for the treatment of an episode of psychotic depression . at admittance the madrs and mmse - score could not be assessed due to the severity of the depressive episode . since there was a high risk of suicide , involuntary bilateral ect a delirium was suspected . despite thorough internal and neurological examinations , no somatic cause of the delirium could be detected . brain mri showed old ischemic lesions , global atrophy and medial bitemporal lobe atrophy ( iii ) . haloperidol 1 mg daily was initiated for a few days , but was discontinued because of qtc - prolongation . the delirium observation scale score had dropped from 11/13 to 6/13 after two weeks of treatment , indicating improved cognitive functioning . after 15 ect - sessions the mmse - score was 23/30 and cognitive impairment , including attention deficits , memory problems and apraxia , persisted after several days . five weeks after discontinuation of the ect the depression was still in remission , and his cognitive functioning had improved ( mmse 28/30 ) . a 58-year old female patient , with a long history of recurrent depressive episodes , was admitted to the in - patient ward for a major depressive episode with psychotic features and severe motor agitation ( madrs 46/60 ) . brain mri showed no abnormalities , especially no cortical atrophy , nor medial temporal lobe atrophy , or white matter hyperintensities . treatment with respectively citalopram , mirtazapine and nor - triptyline , and additional quetiapine were ineffective . the patient refused lithium addition , because of side effects in the past . since she had been successfully treated with ect in another hospital nine years before , also she experienced severe cognitive impairment , including retrograde and anterograde amnesia and also long - term memory loss . nortriptyline 50 mg once daily was continued , with adequate blood level . however , within 4 weeks after the last ect , the motor agitation worsened and a relapse of the major depression was seen . a second ect - course with initially unilateral electrode placement was rapidly started , followed by bilateral ect since suicidal thoughts were prominent . considering the cognitive impairment , a trial with rivastigmine was started prior to initiation of the second course . the depressive symptoms responded ( madrs 13/60 ) after twelve sessions and therefore ect was discontinued . her memory gradually improved several weeks after discontinuation of ect , but the patient still claimed minor amnesia at three years of follow - up . we describe three patients with different manifestations of ect - induced cognitive impairment , and present the use of an acetylcholinesterase inhibitor , rivastigmine , as adjuvant treatment during or immediately after ect in order to prevent or treat ect - induced cognitive impairment . the first patient showed good improvement of the cognitive impairment , particularly confusional symptoms , after adjuvant rivastigmine treatment during ect course . the second patient , suffering from old ischemic lesions , global atrophy and medial bitemporal lobe atrophy on brain mri , also experienced cognitive impairment and confusional symptoms during the ect course , but they persisted after discontinuation of ect . acetylcholinesterase inhibitors were developed for the treatment of alzheimer s disease , since a decrease of cholinergic neurotransmission seemed to explain the clinical phenomena . the cholinergic system contributes significantly to the fundamental processing of attention and concentration , flexibility and the speed of information gathering . therefore , acetylcholinesterase inhibitors might improve confusional or delirious - like symptoms associated with ect . to date , four clinical trials have assessed the anti - amnestic effects of acetylcholinesterase inhibitors in the context of ect . in three trials patients were relatively young and in all four trials no information was present about brain alterations identified by brain computed tomography or mri . these trials differ in study design ( one cross - over double blind design , and three placebo randomized controlled trials ) , studied pharmacotherapy ( galantamine , rivastigmine , physostigmine and donepezil ) and duration of administration . all trials focus on cognitive functioning as primary outcome , but time of cognitive assessments varies widely from directly after ect till 4 weeks after the last ect . also , to assess the primary outcome , a large battery of various cognitive tests was used . despite these considerable differences , they all detect a favorable effect of the study medication on cognitive functioning . in our three patients , the first two patients suffering from confusional symptoms , such as postictal disorientation and confusion , showed brain alterations associated with old age , such as wmh and medial temporal lobe atrophy . notably , they did not fulfill the criteria for dementia prior to ect or after three years of follow - up . a recent naturalistic cohort study among 81 elderly depressed inpatients demonstrated , that wmh - not medial temporal lobe atrophy or global cortical atrophy - are associated with cognitive impairment during ect in severely depressed elderly . patients with wmh who switched to bilateral ect showed a mean decline of 7.2 points on the mmse - score compared to a mean decline of 1.8 point in patients without wmh during the course of ect . this suggests that especially elderly patients with wmh are at risk to develop cognitive impairment during an ect course . since wmh - as well as dementia - are associated with more cognitive impairment during ect , including prolonged postictal disorientation or confusional and/or delirious states , these patients might benefit best from rivastigmine addition . this might be a reflection of the fact that the brain - blood barrier is known to have an increased permeability during ect , permitting lower dosage . in our patients this is particularly important , since in one trial there was evidence that rivastigmine might have increased mortality . however , the study population in this trial included delirious patients , admitted to an intensive care unit for severe somatic illnesses . finally , adjuvant rivastigmine administration did not cause additional anesthetic side effects , as prolonged muscle paralysis and apnea , in our patients . first , mmse - scores of our patients were not assessed prior to their current depressive episode . a pre - ect mmse - score would have improved our report , since a decline of cognitive functioning can also be attributed to the depression treatment . however , the course of cognitive improvement after start of rivastigmine in the first patient strongly suggests a beneficial effect of rivastigmine . for example , the third patient reported cognitive impairment as retro- and anterograde amnesia and long - term memory loss , but mmse - score remained 30/30 . also there was a potential learning effect from measurements of the mmse . finally , two patients suffered from neurodegenerative brain alternations ( e.g. , wmh and atrophy ) . hence , the predictive value of specific brain alterations on rivastigmine response needs to be determined . to conclude , our case report suggests a putative beneficial effect of rivastigmine on - in particular - confusional and/or delirious symptomatology during ect without considerable side - effects . unfortunately , rivastigmine did not have an impact on retrograde and anterograde amnesia in our third patient . randomized controlled trials are needed , including an extensive cognitive test battery for detailed assessment of cognitive deficits during ect . further subtyping of cognitive impairment is needed and may facilitate early identification of patients that may benefit of adjuvant rivastigmine treatment during ect as a tailored treatment .
electroconvulsive therapy ( ect ) , albeit highly effective in treating depression , is frequently associated with cognitive impairment , either temporary or more persistent . especially in older patients , who generally respond even better , serious cognitive impairment 
 during the course of ect may lead to premature termination of ect . 
 treatment of this cognitive impairment is of utmost importance . in this case 
 series report , we present the effect of rivastigmine , an acetylcholinesterase inhibitor , on cognitive impairment in three older , severely depressed patients during or after a course of ect . 
 an improvement of cognitive functioning , in particular a decline of confusional symptoms , was observed in two patients with structural brain alterations associated with aging . in the other patient , who suffered primarily from amnesia , no effect of rivastigmine 
 was observed . 
 these preliminary results emphasize the need for detailed profiling of cognitive impairment when developing a research design to study the potential benefits of rivastigmine in the prevention or treatment of cognitive impairment in severely depressed patients treated with ect .