Dopamine/serotonin dysbalance in dystonia.

Rationale:

There are several clues that dystonia, and co-morbid myoclonus and psychiatric conditions, are caused by a dysbalanced dopaminergic and serotonergic system. In this project, we will test this hypothesis. This project will contribute to the knowledge about the
pathophysiology of dystonia and may point to new therapeutic options in patients with
dystonia.



Objective:

To investigate if jerks and psychiatric disorders in patients with dystonia are associated with a hyperdopaminergic/ hyposerotonergic system and whether reversal of a hyposerotonergic state has a therapeutic effect.



Study design:

This study consists of three parts: randomized, double-blind, placebo-controlled, crossover trial with escitalopram, an SSRI.



Study population:

Patients with dystonia with and without jerks.



Intervention:

Escitalopram 10 mg will be administered for 6 weeks in a randomized,
placebo-controlled, double-blind, crossover trial with a washout period of 6 weeks.



Main study parameters/endpoints:

Proportion of patients that change at least 1 point on CGI scale after treatment on jerks.



Nature and extent of the burden and risks associated with participation, benefit and
group relatedness:

Patients will undergo a neurological, neuropsychological and psychiatric evaluation four times. Subjects will have to take medication, escitalopram and placebo, each for 6 weeks.

They will undergo 2 venapunctions with the withdrawing of 5 mL blood. The burden of this study consists of 2 visits in 18 weeks.

The risks associated with participation in these studies are low: the psychiatric questionnaires used in our study are considered to be mildly psychologically
stressful. Escitalopram is a widely used drug with little side effects. In the long term this study may lead to new treatment options for patients with dystonia.

N/A

Subjects will be neurologically and psychiatrically evaluated 4 times during the trial (before and after each treatment round). Results of escitalopram and placebo treatment will be compared at the end of the study, when the randomization code is broken.

An interim analysis will be carried out by an independent statistician after 35 patients completed the first treatment round.

Subjects are randomly assigned to first receive one of the following treatment regimens for a period of 6 weeks:

1. Escitalopram 10 mg tablets orally;

2. Placebo tablets orally.

After a washout period of 6 weeks the interventions will be switched: the patients who received escitalopram will receive placebo and vice versa. Because of the crossover design every patient will be his own control.

During the medication trial subjects will be neurologically and psychiatrically examined 4 times. Effects of escitalopram and placebo treatment will be compared.