Long-term use of antipsychotics for behavioral symptoms in patients with mental retardation; a controlled discontinuation study.

Background of the study:

A substantial proportion of individuals with mental retardation chronically utilizes antipsychotic medication. This may only be partially explained by the presence of psychiatric disorders. Often, antipsychotics are being prescribed without a clear indication, for ameliorating behavioral symptoms, such as aggression, and irritable and provocative behavior.



Long time use of antipsychotics may have substantial health risks, including weight gain, glucose dysregulation, hyperlipidemia, and hyperprolactinemia. Another side-effect associated with the long term use of antipsychotics is osteoporosis, resulting from hyperprolactinemia-induced hypogonadism. Other significant side-effects may also occur in association with the use of antipsychotics, such as emotional and cognitive blunting, and extrapiramidal symptoms like dystonia, dyskinesia, and akathisia.



Objective of the study:

The primary objective of this study is to test the hypothesis that discontinuation of antipsychotics does not lead to deterioration in functioning as measured by the ABC.

Study design:

A randomized controlled discontinuation study design will be used.

Study population:

Subjects will be recruited from institutions for intellectually disabled persons in the North and Middle of the Netherlands. All residents aged between 15-65 year currently receiving antipsychotics for behavioral symptoms for 6 months or longer are eligible. Exclusion criteria include a) a history of schizophrenia, affective psychosis or a bipolar disorder according to DSM IV criteria and b) a history of unsuccessful withdrawal of antipsychotics in the past 6 months.



Intervention:

A random number table will allocate 100 subjects in a 1:1 ratio to either a group that will be gradually tapered off antipsychotic treatment over 14 weeks or a group that will be tapered off over 28 weeks.



Primary study parameters/outcome of the study:

The primary outcome measure will be the proportion of people developing marked behavioral symptoms calling for prescription of (higher doses of) antipsychotics and thus leading to study withdrawal in both treatment groups.



Secundary study parameters/outcome of the study:

Weight, middle circumference, BMI, fasting glucose, fasting triglyceride, total cholesterol, HDL-and LDL-cholesterol, prolactin, CTX, P1NP, the Clinical Global Impression (CGI), and the Visual Analogue Scale (VAS). Extrapyramidal symptoms (AIMS), autonomic dysfunction (SCOPA-AUT).

Discontinuation of long term use of antipsychotics for behavioral symptoms in patients with mental retardation does not lead to deterioration in mental functioning.

Baseline data will be collected prior to the discontinuation (visit 0). Throughout the discontinuation phase, participants will be controlled every 2 or 4 weeks (visits 1 through 8). Twelve weeks after full discontinuation one additional visit will take place for both study groups. In total 10 visits will take place for both groups.

Discontinue antipsychotic treatment in a period of 14 weeks or in 28 weeks. Dose reduction will take place every two or four weeks by lowering the dose with 12.5% of the original.