Clonidine: een veelbelovende toevoeging aan de huidige behandeling van schizofrenie.

Schizophrenia is a major debilitating mental disease with an incidence of approximately 1% in the general population worldwide. Currently available antipsychotics are only effective in reducing positive symptoms, without restoring cognition or alleviating negative symptoms. Between one-fifth and one-third of patients have little, if any, benefit from them. Treatment of these patients remains a persistent public health problem, as treatment resistant patients are often highly symptomatic, have a severely reduced quality of life and need extensive periods of hospital care. Therapy-resistant Schizophrenia patients also require a disproportionately high amount of the total health costs for schizophrenia. Clonidine is a noradrenergic α2A agonist, usually prescribed in the treatment of hypertension, but also in the treatment of Tourette’s syndrome and in the treatment of children with ADHD. Results of a recent performed pilot study from our study group and literature point at a potentially positive effect of clonidine on certain aspects of schizophrenia. In our pilot study we found that in schizophrenia patients very often disturbed parameters of basic information processing normalized when they were treated with only one administration of low dose (between 25 and 75 µg) of clonidine. In schizophrenia, there is a correlation between these parameters of basic information processing and cognitive functioning, symptom severity and daily functioning. Therefore we expect that a longer treatment period with clonidine will improve not only positive symptom severity, but also notoriously treatment resistant negative symptomatology. We also expect an improvement in cognitive functioning and daily functioning.

-Six weeks of treatment with a supplementary low dose of clonidine to the current medical treatment of clozapine resistant patients will effectively reduce symptom severity and cognitive impairments in therapy resistant schizophrenia patients

-Following this 6 weeks of treatment patients will show improved day to day functioning

-Clonidine will normalize psychophysiological parameters of basic information processing in clozapine resistant patients with schizophrenia

Measurements and tests will be performed at baseline, at halftime (3 weeks after baseline) and at the end of the study (6 weeks after baseline)

The main investigational product used in this study is clonidine, which is approved for the treatment of several disorders including high blood pressure, migraine and withdrawal symptoms that occur after stopping the use of opiates. -25 patiënts will receive 50 micrograms clonidine once a day for six weeks, added to their own antypsychotics which will preferably kept stable during threatment period. -25 patiënts will receive placebotablets once a day for six weeks, identical looking to the clonidine tablets. Patiënts will continue their own antipsychotica and these will preferably kept stable. -25 healty controls will not undergo any treatment.