The new Journal of ECT is out. This number is all about side-effetc of ECT. An important issue to my opinion. One important article of this issue is Pharmacological Attenuation of Electroconvulsive Therapy-Induced Cognitive Deficits
The most important psychopharmacological agents in the attenuation of ECT-induced cognitive deficits studied up until now are:
Ketamine anesthesia in ECT might be neuroprotective according to a retrospective study. In this study it was reported that a significantly quicker recovery of orientation in 36 patients who were switched from methohexital to ketamine anesthesia appeared midway through the ECT course because of insufficient seizure duration with the barbiturate anesthetic drug. In another trial etomidate was compared to ketamine anesthesia across 6 ECT sessions in 10 patients. Anterograde memory function (tested simply as short-term memory for 4 words) was significantly better in the ketamine group. There is some fear that ketamine might attenuate the convulsion as well adn thus hamper therapeutic efficacy. Ketamine also has some troublesome side-effects such as hallucinations. If you or a loved one is suffering from drug addiction Recovery Delivered can help them get through it to a heath lifestyle and a great future.
There are no clinical trials that have assessed the inflammatory hypotheses in the context of ECT. However, across a 6-month period, indomethacin (100-150 mg/d) was found to protect against cognitive decline in patients with Alzheimer disease as compared with placebo-treated patients. In animal studies there is some attenuation of cognitive side effects of ECT by cox-2 inhibitors.
Calcium channel blockers (antihypertensive drugs) with the exception of nifedipine,seem to consistently preserve task recall after ECS in rats. The preclinical findings of the memory-preserving effects of these drugs have not been replicated in human subjects in the context of ECT. Two placebo controlled trials were negative.
Three clinical trials have assessed the antiamnestic effects of cholinesterase inhibitors (ChEIs) in the context of ECT. The results of these trials suggest that the coadministration of ChEI with ECT may compensate for or correct the ECT-induced cholinergic changes, which putatively, at least, partly explain cognitive impairment with ECT.
Mifepristone (40 mg/kg), a glucocorticoid receptor antagonist, administered 1 hour before ECS prevented the development of retrograde amnesia (for passive avoidance learning) induced by 5 once-daily ECS. This result supports the hypothesis for the involvement of glucocorticoid mechanisms in ECT-induced amnestic deficits. There are no published data with patients treated with ECT. One placebo-controlled clinical trial is currently being conducted using a 600-mg/d dose of mifepristone during the course of ECT; no data are available as yet
Thyrotropin-releasing hormone (0.5 mg)showed disappointing results in 2 trials.
Naloxone showed in 2 trials essentially negative results. These could be due to the relatively low dose of naloxone administered and the crossover design of the two trials. It has been suggested the dose of naloxone should be between 1 to 4 mg/kg to produce demonstrable effects. However, considering the possible risk of increased retrograde amnesia with naloxone 1.6 mg/kg as shown in one of these trials, higher doses should be used with caution.
Conclusion Allthough the explaining mechaniosm of action of the mentioned drugs the results on the side effects of ECT of these drugs are disappointing. It is questionable whether better research would deliver better results. Drugs or group of drugs that may reward further investigation include ketamine or other NMDA receptor antagonists, Cox-II inhibitors, mifepristone and calcium channel blockers.
Pigot, M., Andrade, C., FRANZCP, C.L. (2008). Pharmacological Attenuation of Electroconvulsive Therapy-Induced Cognitive Deficits. The Journal of ECT, 24(1), 57-67. DOI: 10.1097/YCT.0b013e3181616c14
Electroconvulsive therapy (ECT) for depression is the only treatment that is usually stopped when the patient has recovered. After successful ECT antidepressants are prescribed to prevent relapse. Since the widespread use of antidepressant pharmacotherapy, the indication for Electroconvulsive therapy (ECT) is often a medication resistant depression. Patients usually were treated with several antidepressants before ECT. Even with medication treatment failure for depression ECT is still very efficacious.
Depressed patients with pharmacotherapy treatment failure may benefit from the prophylactic effect of the same (class of) drug during maintenance therapy after response to ECT. Some patients relapse during adequate treatment with antidepressants after successful ECT. These patients usually will have another ECT course after which maintenance ECT is an option when antidepressants before and after ECT have failed to prevent relapse.
Maintenance ECT is effective in preventing relapse and recurrence in patients who have shown an initial response to ECT. During manintenance ECT the frequency of treatments is lowered. During a course patients are usually treated twice or three times weekly. During m-ECT this frequency can be lowered to once every 4 weeks. ECT frequency is lowered in small steps, from once a week to once every fortnight. In the first four months the frequency is lowered any further than once every two weeks.
During the course of ECT the most important side effects retrograde- and anterograde amnesia. To my opinion these cognitive side-effects do not increase and even might decrease during m-ECT. Cognitive side-effects during m-ECT are hardly studied because of small sample size and lack of control group.
In a recent study 12 patients receiving maintenance ECT were tested before and 90 minutes after an ECT treatment. Twelve other patients were tested at arrival in the hospital and 90 minutes later before receiving their maintenance ECT. The experimental group, tested before and 90 minutes after ECT did not show significant learning, attention or frontal decline in the second assessment after the ECT session, in comparison with the control group. However their visuospatial ability was lower than it was in the control group after after the second assessment. ECT sessions may cause some acute, mild dysfunction of visuospatial function.
Limitations of this study Small patients samples (12 in each group). No long term memory assessment
From this study we can not state that there are no adverse cognitive effects after one m-ECT session. But a lower frequency of treatments with a longer interval between treatments is probably to long to increase cognitive side effects. m-ECT does not produce clinical significant adverse cognitive side effects in contrast to an acute course of ECT
This research agrees with my clinical impression, anyone another opinion?
RAMI, L., GOTI, J., FERRER, J., MARCOS, T., SALAMERO, M., BERNARDO, M. (2008). Cognitive functions after only one ECT session: A controlled study. Psychiatry Research, 158(3), 389-394. DOI: 10.1016/j.psychres.2007.01.005
The first post on PsychCentral about a letter from James Potash, a well-known researcher from Johns Hopkins who has made his career by studying the genetic basis of mood disorders and schizophrenia and possible overlaps. This so called love letter for ABC News is to postive about ECT to the taste of the author: John M. Grohol, Psy.D.
Don’t get me wrong — I know people who have successfully underwent ECT. Most say they are thankful for the option. But it is not the cure-all this article makes it out to be. It is still an extreme procedure requiring a lot of forethought prior to accepting it, and the research is far from clear as to its long-term effectiveness and efficacy.
Despite evidence that electroconvulsive therapy (ECT) is a safe and effective treatment for many psychiatric illnesses during pregnancy, many clinicians and patients are still reluctant to pursue this option, concerned that it will harm the fetus or incur extra risk for the patient. Ultimately, the clinician must weigh the risks to both mother and fetus involved in not treating a woman who suffers from severe psychiatric symptoms against the risks involved in ECT treatment, and facilitate the most appropriate clinical intervention for the individual patient.
So far I have found three guidelines about ECT with adolescents for depression. Summarized these guidelines suggest the following recommendations:
ECT is not recommended for children (5–11 years).
ECT should only be considered for young people with very severe depression and either life-threatening symptoms (such as suicidalbehaviour) or intractable and severe symptoms that have not responded to other treatments.
ECT should be used extremely rarely in young people and only after careful assessment by a practitioner experienced in its use and only in a specialist environment
This is roughly the conclusion after reading these three guidelines. This conservative opinion is based on the lack of controlled studies. Most publications on adolescents are reviews of single case studies or case series using variable methodology and variable outcome measures. This makes a positive publication possible, only positive outcomes are published.
Side effects are also not studied in controlled trials but only small retrospective case series and case reports. It seems that adolescents appear to have the same side effects as adults. There are no studies which provide evidence of the impact of ECT in developing brain.
Parents are generally as positive, or more positive in their views on ECT than adolescents who had received the treatment.
The above mentioned recommendations mainly come from the guideline of the National Institute of Clinical Excellence (NICE): Depression in children and young people Depression in children and young people: identification and management in primary, community and secondary care. Compared to the Practice parameters for the assessment and treatment of children and adolescents with depressive disorders of the American Academy of Child and Adolescent Psychiatry (AACAP)the NICE guideline is more comprehensive. In the AACAP guideline ECT is only mentioned for psychotic depression.
In adults, electroconvulsive therapy (ECT) is particularly effective for this subtype of depression. Non-controlled reports suggest that this treatment also may be useful for depressed psychotic adolescents.
Diagnosis: Severe, persistent major depression or mania with or without psychotic features; schizoaffective disorder; or, less often, schizophrenia. ECT may also be used to treat catatonia and neuroleptic malignant syndrome.
Severity of Symptoms: The patient’s symptoms must be severe, persistent, and significantly disabling. They may include life-threatening symptoms such as the refusal to eat or drink, severe suicidality, uncontrollable mania, or florid psychosis.
Lack of Treatment Response: Failure to respond to at least two adequate trials of appropriate psychopharmacological agents accompanied by other appropriate treatment modalities. Both duration and dosage determine the adequacy of medication trials. It may be necessary to conduct these trials in a hospital setting.
ECT may be considered earlier in cases in which
adequate medication trials are not possible because of the patient’s inability to tolerate psychopharmacological treatment;
the adolescent is grossly incapacitated and thus cannot take medication;
or waiting for a response to a psychopharmacological treatment may endanger the life of the adolescent.
I can live with the above mentioned first three points. I would like to develop two or three Dutch ECT centers especially for treatment of adolescents with extensive research protocols.
Ghaziuddin, N., Kutcher, S.P., Knapp, P., Bernet, W., Arnold, V., Beitchman, J., Benson, R.S., Bukstein, O., Kinlan, J., McClellan, J., Rue, D., Shaw, J.A., Stock, S., Kroeger Ptakowski, K. (2004). Practice Parameter for Use of Electroconvulsive Therapy With Adolescents. Journal of the American Academy of Child & Adolescent Psychiatry, 43(12), 1521-1539. DOI: 10.1097/01.chi.0000142280.87429.68 &NA;, . (2007). Practice Parameter for the Assessment and Treatment of Children and Adolescents With Depressive Disorders. Journal of the American Academy of Child & Adolescent Psychiatry, 46(11), 1503-1526. DOI: 10.1097/chi.0b013e318145ae1c
The strongest evidence exists for Broadman Area 25 as target for deep brain stimulation in treatment resistant depression. This area in the brain is depicted in te figure above and is from the most important publication about DBS and depression in Neuron march 2005 by Helen Mayberg. Functional neuroimaging as well as antidepressant treatment effects suggest that this area plays an important role in modulating negative mood states. A decrease in activity is reported with clinical response to antidepressants and electroconvulsive therapy (ECT).
But depression is not a disease of a single brain region nor neurotransmitter system. It is now generally viewed as a systems-level disorder affecting integrated pathways linking select cortical, subcortical, and limbic brain regions with their related neurotransmitter systems.
Suggestions of other brain localizations for treatment with DBS for depression comes from case reports with DBS for other indications than depression. In a case report of a 56 year old patient with obsessive compulsive disorder and major depression suggests that deep brain stimulation of the ventral caudate nucleus could be a promising strategy for treatment of refractory cases of both OCD and major depression. The caudate nucleus is depicted in the figure below.
In another case report DBS was used to treat severe tardive dyskinesia in a patient suffering from major depression. DBS was performed bilaterally in the globus pallidus. The dyskinesia as well as the depression improved substantially.
In another case report deep brain stimulation was used for treatment resistant depression in a patient with borderline personality disorder and bulimia. Stimulation was targeted bilateral with eight-contact electrodes of areas at and around the inferior thalamic peduncle. The inferior thalamic peduncle is depicted in the figure below with a light blue circle. There was a good effect on depression. Depression improved progressively over a period of eight months to normal level. On an Off period of stimulation the depression took a fluctuating course. Therefore the authors were not able to prove that the electrical current induced the beneficial effects. Complete return of depression in an Off period would have. Bulimia did not subside with DBS.
Since these are case reports possible influences by placebo effect or other explanations for success can not be ruled out and these results should be interpreted with caution. Nevertheless since the authors usually select the targets based on hypothesis of function and relationships with depression further research on these techniques should be used in an extended study with treatment resistant depression.
Two other area’s are suggested in two publications in Medical Hypotheses in 2006 and 2007. Broadman area 24a and the lateral habenula are suggested in these articles as targets for deep brain stimulation for treatment refractory depression. The habenula is depicted with number 5 in the figure below. Both hypotheses are based on findings of clinical imaging studies, animal models, SPECT and PET scans.
Articles Discussed: Sartorius A, Henn FA. 1 Deep brain stimulation of the lateral habenula in treatment resistant major depression. Med Hypotheses. 2007;69(6):1305-8. Epub 2007 May 10. PMID: 17498883 [PubMed – indexed for MEDLINE]
2: Kosel M, Sturm V, Frick C, Lenartz D, Zeidler G, Brodesser D, Schlaepfer TE. Mood improvement after deep brain stimulation of the internal globus pallidus for tardive dyskinesia in a patient suffering from major depression. J Psychiatr Res. 2007 Nov;41(9):801-3. Epub 2006 Sep 8. PMID: 16962613 [PubMed – indexed for MEDLINE]
3: Aouizerate B, Martin-Guehl C, Cuny E, Guehl D, Amieva H, Benazzouz A, Fabrigoule C, Bioulac B, Tignol J, Burbaud P. Deep brain stimulation for OCD and major depression. Am J Psychiatry. 2005 Nov;162(11):2192. No abstract available. PMID: 16263870 [PubMed – indexed for MEDLINE]
4: Schlaepfer TE, Lieb K. Deep brain stimulation for treatment of refractory depression. Lancet. 2005 Oct 22-28;366(9495):1420-2. No abstract available. PMID: 16243078 [PubMed – indexed for MEDLINE]
5: Jiménez F, Velasco F, Salin-Pascual R, Hernández JA, Velasco M, Criales JL, Nicolini H. A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle. Neurosurgery. 2005 Sep;57(3):585-93; discussion 585-93. PMID: 16145540 [PubMed – indexed for MEDLINE]
6: Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3;45(5):651-60. PMID: 15748841 [PubMed – indexed for MEDLINE]
Who remembers the Eagleton affaire. Neither did I until I read this article: History, power and electricity: american popular magazine accounts of electroconvulsive therapy, 1940-2005. Senator Thomas Francis Eagleton of Missouri was the running mate for George McGovern, the Democratic candidate for the election for the Presidency of the United States in 1972. He had to step back because of his disclosure having had ECT in the mid 60’s.
The drama began early in the week when Eagleton was forced to reveal that on three occasions, in 1960, 1964 and 1966, he had been hospitalized in St. Louis or at the Mayo Clinic for nervous exhaustion. When the McGovern camp learned that the Knight newspapers were ready to break a story on Eagleton’s medical history (see THE PRESS), McGovern and his running mate decided to break the news themselves at a press conference in Sylvan Lake, S. Dak. Eagleton described himself as “an intense and hard-fighting person,” and added: “I sometimes push myself too far.” After his successful 1960 campaign for attorney general of Missouri, he was hospitalized in St. Louis “on my own volition” for about four weeks for “exhaustion and fatigue.” He spent four days at the Mayo Clinic in 1964, and about three weeks in 1966. On two of those occasions, in 1960 and 1966, he underwent electric-shock therapy for depression. Now, he said, “I have every confidence that I’ve learned how to pace myself and know the limits of my own endurance.”
Was he the only one with a psychiatric history in those days?
Past U.S. Presidents have had their emotional problems: John Adams had several nervous breakdowns, Franklin Pierce was an alcoholic, Abraham Lincoln had recurring periods of near-suicidal depression, Rutherford Hayes as a young man wandered about the streets of Sandusky, Ohio, weeping uncontrollably. Lesser officials have also been afflicted. Secretary of Defense James Forrestal committed suicide in 1949 while hospitalized for involutional melancholia. Alabama Governor George Wallace, who announced last week that he would not seek a third-party nomination this year, still receives a 10% disability check from the Veterans Administration because of “psychoneurosis” incurred during World War II. As for Eagleton’s illness, medical experts know neither what causes depression nor why electric-shock therapy is effective against it, but most of them insist that it is a relatively common ailment and by no means a permanent disability
The Time coverage of the Eagleton affaire was generally negative especially about having had ECT. It portrayed ECT as a relic from the past. The accompanying photograph used was made in 1949. They even compared the stimulus characteristics to those used for the electric chair. This publication came in a time that the anti psychiatry movement was at it’s peak.
The coverage in Newsweek was of a completely different nature. The Newsweek article emphasised the ways in which modern ECT was a significant improvement over the past practice. The Newsweek coverage was more balanced and sympathetic toward Eagleton. Newsweek doesn’t have a large archive such as Times so I couldn’t verify it.
The article in Time ends with:
While recurrence of depression cannot be ruled out, the fact that Eagleton has gone six years without treatment and has performed effectively in office makes it less likely. Lebensohn says he treated high political figures as long as 20 years ago without noting any later ineffectiveness among them. Some psychiatrists even say that Eagleton may be less likely to break under pressure than those who have never undergone such therapy. A period of depression, the A.P.A. panel insists, does not permanently impair a person’s judgment.
However, it was discovered during the Watergate trial that John Ehrlichman, a whitehouse aide, had a safe that contained copies of hospital records of Democratic Senator Thomas Eagleton’s treatment for mental illness.
What do you think, is prior psychiatric history of influence in elections in our days?
Articles used: J Hist Behav Sci. 2008 Jan 14;44(1):1-18 [Epub ahead of print] History, power, and electricity: American popular magazine accounts of electroconvulsive therapy, 1940-2005. Hirshbein L, Sarvananda S. University of Michigan, Lapeer, Michigan. PMID: 18196545
No hassle with treatment-resistant depressed patients, no comparison with Electroconvulsive Therapy or any other treatment for that matter. Just plain Personalized Medicine what ever that may be. And a nice website: Brainclinics Diagnostics & Treatment rTMS results (in English)
In the Brainclinics Treatment clinic in Nijmegen (The Netherlands) rTMS has been applied over the last year in a practical setting and combined with psychotherapy. In this setting any client with depression is treated (so not only treatment resistive patients). The rTMS treatment is personalized for every client using their individual QEEG on the basis of which the stimulation site is chosen. Furthermore, the EEG is used to rule out contra-indications – such as paroxysmal activity and the presence of beta spindles.
Regularly I discuss recent articles about different subjects related to medicine, psychiatry and education among other subjects. The choice of articles is completely biased. It is because I think the subject is interesting, the research design is elegant or creative, the research question is relevant, or the results are important or any combination of these characteristics. Sometimes, also to my own surprise, these articles are written by Dutch authors. This blog now exists for 9 months and it is almost the end of the year. Time to look back on these articles written by Dutch authors and to select the best ones. The articles I appreciated the most. This selection is completely arbitrary based on my personal preferences but nevertheless here they are:
2. A disappointing conclusion in this meta analysis: Efficacy of Internet based Cognitive Behavioral Therapy (CBT) for depression and anxiety disappointing. In a recent meta-analysis CBT for depression and anxiety was modestly effective compared to placebo, care as usual, or waiting list conditions. There was also a significant heterogeneity between trials. In short the trials are different and hard to compare.
3. Bold statements mostly done by senior staff members during grand rounds about material that is less well known occurs frequently. Such bold statements are frequently articulated with great conviction and are usually accepted and assimilated by junior staff and the likes of them. In this article the authors found only 8 (32%) statements to be supported by scientific evidence. In 17 (68%) statements the available literature contradicted (n=13) the statement, or no literature was avalable (n=4). A lot of bull doe ushered during Grand Rounds.
4. 38 of 50 elderly patients refused randomisation beforehand in this trial because of fear of electroconvulsive therapy (ECT). An in depth interview showed that fear of brain damage by ECT played a major role. This recently published study was a feasibility study testing the efficacy and safety of ECT, prescribed in an earlier phase of treatment than last resort. This study would test the efficacy of ECT versus nortrityline among depressed elderly (> 59 years) who had not responded to sertraline, a selective serotonin reuptake inhibitor (SSRI). The wrong assumption that ECT causes brain damage might be a vestige of the seventy’s and the dark period of the anti psychiatry in the Netherlands in that same period.
Which of these articles did you like the most, take the poll on the top right,
Treatment resistance or better treatment failure with antidepressant medication does not predict acute remission status with ECT for nonpsychotically depressed patients. The influence of antidepressant treatment failure and response to subsequent ECT has been a point of discussion in the international scientific literature for the last decade. The research group of the Columbia University New York has found that depressed patients who have been exposed to at least one adequate antidepressant trial without response have markedly lower remission rates with ECT compared to those without such a trial. Other studies did not find such a difference in response between medication resistant and non medication resistant depressed patients. With depression the unipolar form is mostly meant.These reports are mainly from the “old continent”, Europe.
This is one of the first US publications with results in the line of the latter group.
Method This research was part of the CORE study (The Consortium for Research in Electroconvulsive therapy). They recorded treatment failure with antidepressants used during the index depressive episode with the Antidepressant Treatment History Form (n=345)before ECT. Response to ECT was assessed with the 24-item Hamilton Rating Scale for Depression. Baseline medication treatment failure was analyzed as a possible predictor of remission status.Remission was defined as an at least 60% reduction of baseline on the HRSD and 2 consecutive ratings of less than or equal to 10.Patients were divided in a resistant and a non resistant group. Antidepressant resistant means a score of 3 or higher on the ATHF. You can score a 3 when you have had an adequate dosage of an antidepressant for at least 4 week.
Results 66.4% of patients were treatment resistant (ATHF 3 or higher), No statistical significant relationship was found between remission and resistance status.Adjustment of the analysis for moderating effects of demographic and clinical data as well as adjustment for interaction terms to evaluate effect modification with Bonferoni correction did not influence outcome.
Limitations 1. Not all patients had an ATHF completed 2. Arbitrary definition of treatment resistance 3. Retrospective collection of information on doses and durations of medications used.
I strongly believe based on these trials and the limitations of the studies from the Columbia University group that medication treatment failure doesn’t influence the efficacy of subsequent ECT. The biggest challenge however is to keep these patients well after the acute treatment effect. To my opinion we should focus more on the longer term of ECT and develop treatment programs specific for his group after the first success. Day programs with running therapy, cognitive therapy focused at dealing with memory complaints at first followed by eclectic interventions such as Interpersonal psychotherapy, family therapy, relapse prevention.
Article discussed: J Clin Psychiatry. 2007 Nov;68(11):1701-6. Antidepressant medication treatment failure does not predict lower remission with ECT for major depressive disorder: a report from the consortium for research in electroconvulsive therapy. Rasmussen KG, Mueller M, Knapp RG, Husain MM, Rummans TA, Sampson SM, O’Connor MK, Petrides G, Fink M, Kellner CH. PMID: 18052563