Rapid Psychotherapeutic Effects of Anesthesia with Isoflurane (ES Narcotherapy) in Treatment-Refractory Depressed Patients

Abstract

Treatment-refractory depressed patients who objected to electroconvulsive therapy (ECT) were given a series of anesthesias with isoflurane (Forane®), a modern and established inhalation anesthetic. According to our hypothesis to be tested, the brief period of electrocerebral silence (ES), which can be observed shortly after the grand mal seizure in ECT, may be in itself a crucial biological determinant for the therapeutic effects of ECT. Isoflurane is the only drug known to effect an ES in the EEG in nontoxic concentrations, which does not result in adverse effects on any body organ including the brain; no seizure activity can be observed. Eleven depressed patients received a total of 36 anesthesias with isoflurane (ES narcotherapy). Rapid antidepressant effects were observed in 9 patients (p < 0.0001). Effects were reproducible and lasted up to several weeks. No adverse effects of anesthesia were noticed.

Isoflurane Narcotherapy in Depressive Patients Refractory to Conventional Antidepressant Drug Treatment

“…They treated 12 depressed patients, who had been refractory to conventional antidepressant drug treatment for many months, by a series of maximally six deep anesthesias with isoflurane. They observed rapid (within 1 h after awakening from anesthesia), reproduc ible (from one anesthesia session to another) and cumula tive (the antidepressant effect had been boosted by each anesthesia) antidepressant effects of anesthesias with iso flurane [1,4,24]. They could replicate this innovative study by consecutive studies [25], and other authors [26,27] reported similiar observations with isoflurane.…”

“…In their pilot study in female depressed patients, Langer et al [1] observed that very rapid, reproducible and cumulative antidepressant effects could be induced by a series of deep anesthesias with the inhalation anesthetic, isoflurane (Forane®, Abbott).…”

“…Within this very context, Langer et al [1] extended their disactivation hypothesis for psychotherapeutic drugs to incorporate a concept on the therapeutic mecha nisms of ECT. They hypothesized that the therapeutic mechanisms of ECT do not require the grand mal seizure per se [6], but the postictal tranquilization (i.e.…”

“…At this point of conceptualization, Langer et al [1] raised the following two practical questions that led to the present ISONAR project:…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…Intravenous anesthetic propofol in vitro at low micromolar concentrations activates AMPARs on VTA DA neurons . Interestingly, isoflurane anesthesia alone has been tested in treatment-refractory depressed patients and found to produce long-lasting antidepressant effect, which was similar to electroconvulsive therapy (under isoflurane anesthesia) (Langer et al, 1985(Langer et al, , 1995. These results were recently confirmed in a study on refractory depression, which also showed that electroconvulsive therapy (on an average ten 15-minute sessions within 3 weeks) had modestly more efficient antidepressant effect than isoflurane anesthesia alone at 4-week follow up, but produced more severe neurocognitive adverse effects (Weeks et al, 2013).…”