Extrapyramidal Side-Effects in Antipsychotic Drug Therapeutics

The proposed methodology is based on use of a computer tablet and modified pen. While these instrumental elements are common-place and widely accepted in modern life, they are not so in the context of formal clinical assessment of motor function in psychiatric patients. They are also novel to clinicians. The first stage will involve recruitment of 20 patients i) under the age of 50 (to reduce the likelihood of idiopathic Parkinson's disease): ii) of mixed, balanced genders: iii) right-handed: iv) basic writing competence: v) English as first language: vi) suffering from an acute psychotic episode. These subjects will have been on stable doses of antipsychotic medication of any sort for at least 2 weeks. Patients will be seated in a comfortable writing position at a table and presented with a graphic tablet and a modified digitizer pen with a wired connection to an operator computer. The assessor will sit slightly behind and to one side out of the subject's view. To familiarise subjects with the technique, they will be asked to a) draw repetitive overlaid circles b) write their name and address, at a speed comfortable to them. They will then be asked to produce the 8 character 'el' text sequence ('elelelel') 10 times and to write a short, standard sentence : "Today is a nice day for the time of year". The examiner will then say to the subject the nursery rhyme, 'Mary had a little lamb...etc" and ask the subject to write it spontaneously from memory. Finally, they will be asked to copy a standard short paragraph from a written page. On conclusion, they will be asked to complete a brief 10cm line, Likert scale of satisfaction, assessing the test situation as 'easy/difficult: 'pleasurable/non-pleasurable':'acceptable/non-acceptable'.

PREDICTION : participants will find the procedures easy, pleasurable and acceptable

2 groups of 10 patients, complying with criteria i)-vi) above, but who have not been exposed to antipsychotic medication for at least 3 months (oral formulations) or 6 months (depot formulations) but in whom antipsychotic medication is now indicated. Groups will comprise consecutive consenting patients prescribed one of two commonly utilised antipsychotics : the high potency, risperidone, and the low potency, quetiapine. Dosages will be determined clinically by the responsible medical officers who will be asked to maintain a standard pattern of escalations : twice weekly and within the first 2 weeks of exposure (but not dose restricted). They will also be asked to avoid additional medications for drug-induced parkinsonism though these may be used on an as required 'rescue' basis. Other medications can be utilised as clinical need determines. Following informed consent, and prior to initiation of treatment, subjects will undertake baseline clinical assessments comprising : a standardised assessment of mental state (Positive and Negative Symptom Scale - PANSS); a standard clinical evaluation of extrapyramidal neurological status (the Extrapyramidal Symptom Rating Scale - ESRS); a standard questionnaire of subjective state (the Subjective Well-Being on Neuroleptics Scale - SWNS - designed to pick up later potential medication effects). They will then complete the instrumental component as above. Assessments will be completed twice weekly during the escalation phase (2 weeks) and weekly thereafter (up to 4 weeks) on the day before increases are implemented.

PREDICTION : instrumental methods will prove highly sensitive to the development of extrapyramidal side-effects and significantly more so than the standard clinical examination: AND : extrapyramidal effects will significantly precede the onset of antipsychotic efficacy