Although pharmacotherapy is the mainstay of antidepressive treatment, a number of non-pharmacological interventions are be- ing used by psychiatrists to treat major depression. These include strategies of sleep deprivation and phototherapy in seasonal de- pression. Electroconvulsive therapy (ECT) has been used for de- cades as an important therapeutic modality to treat drug-resistant, severe depression, although the frequency of its use has declined considerably following the introduction of effective antidepres- sive drug treatment.28,29 More recently, repetitive transcranial mag-
netic stimulation (TMS) has been introduced as a less invasive replacement for ECT.30
Of these various non-pharmacological interventions, only ECT has been used to treat depression in patients with PD, as identified by the results of this literature search for this review.
Electroconvulsive therapy (ECT) was originally introduced as a treatment in psychiatry on the basis of the mistaken belief that schizophrenia and epilepsy were mutually exclusive diseases. With the advent of modern psychopharmacotherapy, the use of ECT
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has sharply declined after the 1950’s, but problems of drug resis- tance or intolerance eventually lead to renewed interest in ECT as a treatment modality from the 1980’s onward.29,31
Recent surveys within the United States indicate that about 80% of patients receive ECT treatment because of major depression.29,31
Its use is generally restricted to patients with a history of drug re- sistance and/or those in whom there is a particular need for a rapid clinical response.
Despite the long history of use of ECT in psychiatry its mecha- nism of action remains largely unknown. Current hypothesis fo- cus on ECT-induced central neurotransmitter changes. Animal stud- ies of electroconvulsive shock have revealed acute increases in brain norepinephrine concentrations together with down regula- tion of beta-adrenergic and possibly presynaptic alpha-adrenergic receptors. In humans, increases in plasma catecholamine, particu- larly epinephrine, levels, have been observed following ECT.28
Similarly, animal studies using ECS show increases in brain serotonine concentrations, and chronic ECS has been found to enhance behavioral serotonergic responses. Most studies of ECT in humans have failed to detect CSF 5-HIAA changes following ECT, but one study reported ECT-related increases.32
Animal studies with ECS also found increases in brain dopam- ine concentrations33 and potentiation of dopamine-mediated be-
havior. In humans, ECT has been reported to enhance the prolactine response to apomorphine.
Not surprisingly, ECS in animals has also been found to induce changes in acetylcholine GABA, endogenous opioids or adenos- ine receptors. Although it is tempting to speculate that antidepres- sive effects of human ECT treatment may be related to brain nore- pinephrine-, serotonine-, or dopamine-changes, the multitude of brain effects resulting from electrically induced seizures - includ- ing changes in cerebral blood flow, oxygen and glucose metabo- lism, protein synthesis, blood brain barrier, disruption and synap- tic activity - make it very difficult to define the crucial mechanism of ECT’s antidepressive mode of action.28
REVIEW OF CLINICAL STUDIES
The search criteria for this review identified 21 articles cover- ing a total of 71 patients with idiopathic PD in whom electrocon- vulsive therapy was used to treat concomitant depression. All but one study did not qualify for inclusion in this report and were ei- ther single-case reports or studies of less than 10 patients and there- fore, were excluded.
Level-I Studies
No qualified studies were identified.
Level-II Studies
No qualified studies were identified.
Level-III Studies
Moellentine and co-workers (1998)34 performed a retrospective
chart review from their institution’s ECT database. Outcomes of psychiatric symptoms were assessed in 25 patients with parkin- sonism vs. 25 age- and gender-matched patients without neuro- logical diseases also receiving ECT for psychiatric indications. Twenty-five patients with parkinsonism were identified, 19 of which received ECT treatment because of major depression ac- cording to DSM-III-R diagnostic criteria. Two of the total of 25 may have suffered from drug-induced parkinsonism, while in the
others, a diagnosis of idiopathic PD was made by a qualified neu- rologist. ECT treatment was unilateral or bilateral, patients were given three sessions per week unless postponement or discontinu- ation was necessary because of ECT-induced delirium. Baseline and post-treatment ratings included the MMSE, global assessment of functioning scale (GAF), brief psychiatric rating scale (BPRS) and the Hamilton Rating Scales for Anxiety and for Depression (HAM-A, HAM-D). Ratings were performed one or two days be- fore the first ECT treatment and one or two days after the last treat- ment. Patients with PD received a median number of 6 ECT treat- ments and this number was 7 in the non-neurological control group. The authors noted a significant decrease in both HAM-D and HAM-A scores for both patients with PD and non-neurological controls. Of the 25 patients with PD, 14 reported subjective motor improvement following the course of ECT treatment; however, the article does not give detailed information on concomitant drug treatment. Patients with PD had more ECT-related complications than the non-neurological control group (56% vs. 12%), the most frequent being transient ECT-related delirium. The authors con- cluded that mood disorders associated with PD are improved by ECT without worsening of the underlying movement disorders, and that depression and anxiety respond in a similar fashion to the same psychiatric symptoms in a non-neurological patient group. The authors, however, also acknowledge that their ratings were performed by an unblinded ECT nurse coordinator introducing a potential of bias.
SAFETY
ECT has been generally well tolerated in patients with PD. In subjects with pre existing L-dopa-induced dyskinesias a transient increase in their severity has been occasionally reported immedi- ately following ECT. The most frequent adverse reactions of ECT in PD has been related to mental status changes including confu- sional states and transient inter-treatment delirium, affecting up to 50% of patients in some series. This complication may be more frequent in patients with PD compared to non-parkinsonian psy- chiatric controls.34,35
CONCLUSIONS
EFFICACY
There is INSUFFICIENT EVIDENCE available to conclude on the efficacy of ECT in the treatment of depression in patients with PD.
SAFETY
There is INSUFFICIENT EVIDENCE to conclude on the safety of ECT treatment of depression specifically in PD.
IMPLICATIONS FOR CLINICAL PRACTICE
Currently available evidence is insufficient to support the rou- tine use of ECT to treat depression in PD. Its use is considered INVESTIGATIONAL in drug-refractory patients with severe, sus- tained major depression. There is some indication that the risk of treatment-induced delirium may be greater in patients with PD compared to non-neurological controls. Given the poor quality of efficacy data, the risk-benefit ratio of ECT treatment of depression in PD is presently unclear.
IMPLICATIONS FOR CLINICAL RESEARCH
• Properly designed prospective controlled trials are needed to
establish the efficacy and clinical benefit of ECT treatment in PD patients with major depression. Such studies should be restricted to drug refractory patients and should use sham ECT as a control measure, and blinded evaluators are needed.
• The majority of reports on the use of ECT in depressed patients with PD also find some ECT-related improvement in motor symp- toms, including data from one Level-I study.36 Such effects de-
serve further study.
• Functional neuroimaging studies before and after ECT may help define mechanisms associated with affective and motoric changes. • Controlled prospective trials of the possible efficacy of repeti- tive transcranial magnetic stimulation (rTMS) in patients with PD and depression are warranted.
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