Classics in ECT- Time Course of Sleep Dep., ECT and CBZ from Post, Uhde, Rubinow and Huggins, 1987
"Classics in ECT" brings you this 1987 paper from renowned researchers at the NIMH:
Differential time course of antidepressant effects after sleep deprivation, ECT, and carbamazepine: clinical and theoretical implications.
Psychiatry Res. 1987 Sep;22(1):11-9. doi: 10.1016/0165-1781(87)90045-x.PMID: 3659217
The abstract is copied below:
The pattern and time course of antidepressant response to different treatment modalities provide important clinical information and hints about underlying neurobiological mechanisms. Depressed patients who responded to 1 night's sleep deprivation (11 of 33 patients) showed maximal improvement on day 1 and deterioration in mood thereafter. In contrast, slower onset and more sustained effects were observed following carbamazepine (12 of 37) or electroconvulsive therapy (ECT) (8 of 8). Nearly maximal improvement required about 2 weeks for ECT and 3 weeks for carbamazepine. Possible differential or common biological mechanisms with differential times of action are implied by these data, which are of importance to the neuroscientist attempting to uncover neural substrates of antidepressant response and the clinician attempting to find rapid onset, yet sustained antidepressant treatments.And from the text:
The pdf is here.
This is a wonderful classic article combining small clinical trials of sleep deprivation, ECT and carbamazepine with theoretical discussion of potential mechanisms of action.
Note that the ECT was bilateral sine wave (archaic, and no longer used).
The first 3 authors are eminent mood/anxiety disorders researchers; this early article harkens back to a golden age of psychiatric research at the NIMH. Resources were available for unlimited inpatient stays and remarkably intensive nursing assessment, as described in the paper.
In the intervening years, the time course of action of ECT has been extensively studied and the speculation that a single ECT would have lasting effect was dispelled, except for the rare patient (see blog post of November 27, 2020). Of course, most recently, ketamine's rapid antidepressant and anti-suicidality effects have generated significant interest.
The three figures in this paper are superb and definitely worth a look. I recommend a full read of this classic (about 15 minutes).
Thanks to Dr. Kellner for highlighting this publication, one of many that showcase the pivotal insights that Bob Post contributed to our field. In the tradition of Emil Kraepelin and Adolph Meyer, Bob recognized the critical and fundamental information embedded in timing: age of onset, inter-episode intervals, episode duration, and latency and rapidity of response. Bob's focus on time-dependent processes - sensitization and kindling - not only advanced new therapeutics but also drove home the point that all of biology is context-dependent, with timing being an essential contextual variant. In biology and phenomenology alike, one size does not fit all. Consequently, mechanistic understanding will continue to be founded on the careful observations of investigators like Bob Post.
ReplyDeleteThe below comment is from Dr. Robert Post:
ReplyDeleteIn the past 33 years some things have changed big time and a few not at all. Starting with right unilateral ultra brief pulse ECT may be a bit slower than bilateral ECT, but seems more able to protect against memory loss. After this series of 8 bilateral ECT responders we graphed in the figure, we saw one patient who had profound memory loss with bilateral ECT including forgetting how to play the piano. There is also a claim that rTMS-induced seizures are also less problematic for memory.
There are now several ways to prevent rebound worsening of depression the next day after a good response to sleep deprivation that was illustrated in the figure. Being on lithium is preventative and as is a phase change such that going to sleep at 7:00pm on the SD day and waking up at 2:00AM, then on the next night sleeping from 8 to 3, and on the next 9 to 4, and so on until normal sleep times are achieved. As Dr. Kellner points out the miracle of rapid (overnight) response to SD has now been replicated with ketamine, but now also with NO, other NMDA antagonists, scopolamine, and psilocybin. The amazing thing is that ketamine restores normal dendritic width, number of synapses and functional connections in the prefrontal cortex of depressed-looking mice in a time frame (2 hours) that ketamine improves behavior. Ron Duman of Yale showed that all these changes were VEGF and BDNF dependent.
The carbamazepine in depression story remains obscure as the drug is rarely used any more. In 10 good antidepressant responders to carbamazepine we confirmed their responsiveness when we saw relapses into depression upon placebo substitution and then renewed antidepressant responses upon double blind re-institution of carbamazepine. We saw the same confirmation of efficacy in mania using this off-on-off-design, but carbamazepine as extended release capsules was not FDA approved until 2004 when industry used the favored double-blind, placebo-controlled RCT design. There is another carbamazepine long acting preparation called Equetro that can be given in a single nighttime dose to reduce daytime side effects that has open data on effectiveness in all phases of illness. It can reasonably considered as an option in those who are inadequately responsive to the better studied and more widely used drugs lithium and valproate. Predictors of carbamazepine response for prophylaxis include those with cycling BPII without a well interval and with anxiety and substance abuse comorbidity, and a negative family history of bipolar disorder.