Electroconvulsive Therapy and Movement Disorders. New Perspectives on A Time‐Tested Therapy

ABSTRACT

Electroconvulsive therapy (ECT) has been a very well known therapy in Psychiatry for over 80 years. ECT is considered useful in treating acute mania, severe depression and other psychiatric conditions. Over time, this therapy has also been used in several movement disorders including Parkinson disease (PD) and Huntington disease (HD). In this brief review, I summarize the recent History and evolution of ECT, its proven and potential applications in movement disorders as well as its potential mechanisms.

Electroconvulsive Therapy: A Brief History

The history of Electroconvulsive therapy (ECT) began with strange and unverified hypothesis, now almost forgotten with the passage of time. In 1933–1935 Laszlo von Meduna, working in Budapest under Professor Schaffer's supervision pondered on the apparently inverse relationship between epilepsy and schizophrenia on reading several epidemiological studies suggesting the absence of epilepsy in asylum population. ¹ , ² , ³ If this observation were real, von Meduna reasoned, then, schizophrenia could be combated with a sort of “artificial” epilepsy. Initially, von Meduna used camphor, and then cardiazol to induce seizures, recording surprising results in some cases of catatonic schizophrenia. ¹ , ² , ³ At the same time, Manfred Sakel working in Vienna under Professor Otto Potzl supervision reported the utility of insulin coma in patients with “confused excitation”. ² Manfred Sakel began with insulin treatment somewhat serendipitously; at the time, insulin was used in heroin addicts to overcome their withdrawal symptoms. ² Shorter remarked on the details of such as bizarre rationale from Heinz Lehmann as follows: “Once, one of his addicts who was also schizophrenic, accidentally slipped into a hypoglycemic coma. Sakel was scared but brought him out of the coma quickly with an injection of glucose. To his amazement, the patient showed a considerable improvement of his schizophrenic symptoms. Sakel then wanted to use hypoglycemic coma as a treatment for schizophrenia”. ²

In any case, since camphor and cardiazol were quite toxic and insulin coma too dangerous, the Italian neuropsychiatrist Ugo Cerletti and his student Lucio Bini tried another approach; after several attempts, they began to use electroshock or ECT for severe psychosis. ⁴ , ⁵ , ⁶ Ferdinand Accornero, one of the assistants of Cerletti for almost 20 years gave a vivid, almost dramatic description of those days ⁶ … “The schizophrenic patient who underwent our experiments was probably the most carefully studied and observed patient at that time. After a course of nine treatments, he came out of his indifference and became interested in the events around him. He gave up his idiosyncratic jargon and rapidly improved to such a point that when he was reunited with his wife, who was searching for him, he was lucid and in a good mental state. We continued his follow‐up for 2 years; he returned to his special type of work and was able to support himself”. ⁶

Over time, this therapy was adopted over the world and its effectiveness in treating severe depression has been established. ¹ , ² , ³ , ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² ECT has been proved also useful for psychotic catatonia and bipolar disorder, although not with the highest levels of evidence compared to other psychiatric therapies. ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰

Electroconvulsive Therapy in Parkinson's Disease and Other Movement Disorders

ECT has been applied in the management of some movement disorders for many years. Faber and Trimble already reviewed this issue in a classic paper. ²¹

First, ECT was used in parkinsonian patients with psychiatric comorbidity mainly severe depression, ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ This was not unexpected since ECT had been used in psychiatry for refractory depression for decades ⁷ , ⁸ , ⁹ , ¹⁰ ; however, the level of evidence and recommendation has varied due to the lack of controlled studies. ²¹ , ²² , ²³ , ²⁴ , ²⁵ This technique has been also used in isolated cases for PD‐related catatonia; and there are several cases reports of ECT in this highly rare association. ²¹ , ²⁶ , ²⁷ , ²⁸ Finally, ECT was used in parkinsonian patients with psychotic symptoms21, 29, 30, 31, 32 including patients with drug‐induced psychosis, but its use is limited to case reports.

ECT has been also employed on neuroleptic‐induced parkinsonism and parkinsonism‐hyperpyrexia syndrome. ³³ , ³⁴

The most interesting aspect of ECT may be its usefulness in motor aspects of PD. For long, the positive effect of this technique on bradykinesia and motor fluctuations has been suspected. ²¹ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ Faber and Trimble, in their classic 1991 article called attention on this issue, ²¹ suggesting that ECT might have direct antiparkinsonian effects, independent of any effects on mental state. Most reports are case series ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ with rather unspecific results although Fall et al ⁴¹ carried out timed tests before and after ECT and found an improvement after the therapy (including timed to walk 10 m from 13.7 ± 7.5 to 7.7 ± 3.6 seconds; P = 0.007). Anderson et al ³⁶ carried out a double‐blind sham‐controlled ECT on 11 patients with severe PD and motor fluctuations; they found a statistically significant difference in the active group and prolonged duration of the “on” phase after ECT, in comparison to the sham‐treated group; however, the authors also noted the short duration of the motor effect. ³⁶ There are several case‐series, but one in particular is worth considering in some detail; Pintor et al ³⁷ carried out a pilot study of ECT in PD with refractory axial symptoms including freezing of gait (FOG). They found significant differences in the number of steps and freezing episodes in the on phase when they were compared before and after ECT administration. ³⁷ In addition, in a short but interesting recent report, Klok et al ⁴² noted the impressive response of FOG to ECT in the setting of major depressive disorder; in this particular case, they pondered whether FOG in this particular case, should be considered as a true manifestation of major depressive disorder or whether could have marked the onset of PD. Finally, ECT has been also used for drug‐induced parkinsonism. ⁴³

ECT has also been employed anecdotally for other movement disorders including multiple system atrophy ⁴⁴ tardive dystonia ⁴⁵ and neuroacanthocytosis. ⁴⁶ Finally, several experimental ⁴⁷ and clinical reports ⁴⁸ , ⁴⁹ , ⁵⁰ on ECT in Huntington's disease (HD) with associated psychosis or severe depression have been published. However, Abeysundera et al described as a patient who presented with treatment‐resistant depression with comorbid anxiety symptoms in the context of HD and developed worsening movement disorder after commencing electroconvulsive therapy. ⁵⁰

Mechanisms of Electroconvulsive Therapy

ECT is a classic therapy that has been very well known and used in Psychiatry for decades. ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ This technique has been reported to induce positive results in movement disorders, including PD, for long time. ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ , ⁴² , ⁴³ , ⁴⁴ , ⁴⁵ , ⁴⁶ , ⁴⁷ , ⁴⁸ , ⁴⁹

The mechanisms of ECT are poorly understood, and probably there are likely many, since it is difficult to explain a single mechanism behind the antidepressant, antipsychotic and antiparkinsonian effect. ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ For shake of simplicity I will briefly comment on the putative antiparkinsonian mechanisms.

The effect of ECT on catecholaminergic systems, including dopamine neurotransmission has been long suspected. ²¹ , ⁵⁰ , ⁵¹ , ⁵² , ⁵³ In an experimental, in vivo, microdyalisis study, ECT produced large increases in interstitial concentrations of dopamine in the rat striatum. ⁵¹ In addition, after ECT, the levels of homovanillic acid in cerebrospinal fluid (CSF) of PD patients were significant increased, according to Fall et al. ⁴¹ ECT may also act on postsynaptic level ²¹ , ⁴¹ , ⁵² , ⁵³ modulating the dopamine receptors. ⁵² , ⁵³ ECT has a plethora of different mechanisms including neurotrophic effects, with release of BDNF and GDNF levels; ⁵⁴ , ⁵⁵ probably these mechanisms may explain the ECT‐related gray matter volumetric increase found in imaging studies. ⁵⁶ In addition, Li et al suggested that ECT remodels neuroplasticity by mediating the balance between mGluR1/5 and AMPA receptors. ⁵⁷ Finally, other, unspecific mechanisms such as transitory blood CSF barrier damage may also play a role. ⁵¹

Conclusion

ECT is, at present, a well‐established treatment for psychiatric disorders and has been increasingly used for some movement disorders including PD. ²¹ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ However, the level of evidence has been modest, at best, mainly due to low quality and heterogeneity of available data. Despite these caveats, there are a growing number of anecdotal reports and at least one controlled study suggesting that ECT might play some role in PD. ²¹ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ It seems clear that a well‐planned controlled study might definitely shed light on the role of this technique in PD. It is worth recalling, that after all, we used antiparkinsonian techniques (eg, deep brain stimulation, infusion pumps of levodopa‐carbidopa intestinal gel or apomorphine) for long time before their positive effect was statistically finally confirmed. In addition, it is worth to remember that the exact mechanisms of ECT are unknown, but also the mechanisms of deep brain stimulation ⁵⁸ , ⁵⁹ , ⁶⁰ or magnetic stimulation, are also poorly understood. ⁶¹ , ⁶² , ⁶³

ECT may be found to play some role in movement disorders, especially PD, provided a definite confirmation of efficacy is reached. A well planned controlled study with ECT in PD is not easy to carry out; there are limitations such as the difficulty to obtain a “sham” group and the high placebo effect, but other studies have been recently completed in PD (including infusion pumps of levodopa‐carbidopa intestinal gel and apomorphine) showing that placebo controlled trials can be conducted even with complex techniques. ⁶⁴ , ⁶⁵

Finally, some authors suggest that ECT has been underused, even in those proved applications such as severe refractory depression. Probably, cultural reason and lack of interest due to its low price may partially explain these facts.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.

PJGR: 1A, 1B, 1C, 3A, 3B.

Disclosures

Ethical Compliance Statement

The authors confirm that the approval of an institutional review board/ patient consent was not required for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest

No specific funding was received for this study. The author reports no conflicts of interest.

Financial Disclosures for previous 12 months

Pedro J Garcia Ruiz received research support from Allergan and UCB, personal compensation as a consultant/scientific advisory board from Italfarmaco, Britannia, Bial, and Zambon and speaking honoraria from Italfarmaco, Zambon, Allergan, and Abbvie.