Akathisia

The QUIP instructs patients to answer questions based on behaviors lasting at least four weeks occurring anytime after PD onset. After completing the QUIP, the patient was administered a “gold standard”, semi-structured, diagnostic interview for compulsive gambling(1 ), buying(23 (link)), sexual behavior(6 (link)), eating(1 ), DDS(19 (link)), punding(19 (link)), hobbyism(2 (link)), and walkabout(19 (link)). Compulsive gambling included those patients with either problem or pathological gambling based on recommended cut-off points(24 ). The DSM-IV-TR research criteria for binge-eating disorder were modified to include general overeating in addition to discrete binge-eating episodes. The original criteria for walkabout were modified to exclude akathisia in order to capture purposeless wandering rather than a physical sensation of restlessness.
Prior to study initiation, each site identified research staff to administer the diagnostic interview who would be blinded to the results of the ICD questionnaire and unaware of the patient’s ICD history. In addition, all raters administering the diagnostic interview received in-person or telephone training from the primary investigator (DW) on how to apply the diagnostic criteria for each disorder or behavior.

Remission was defined as a Ham-D score of ≤10 at two consecutive assessments. The two consecutive assessments Ham-D criterion was applied to assure that remission from mood symptoms was sustained and to allow for comparability with ECT studies that typically use a two-week Ham-D criterion31 (link). Remission also required the absence of delusions, (SADS delusional item scores of 1), at the second assessment of the two-assessment remission of depression interval. A one-week remission of delusions criterion was applied to make the remission of psychosis outcome compatible with the standard duration criterion used in MDpsy pharmacotherapy trials21 (link). Subjects who were not delusional at both of two consecutive Ham-D ≤10 assessments were considered remitted at both time points; subjects who had been delusional at the first of the Ham-D ≤10 assessments were considered as remitted at the second assessment only and subjects who were not delusional at the first assessment but had SADS scores of >1 at the second were classified as not remitted at either assessment. A Ham-D cut-off of ≤10 was used because this cut-off has been a standard in geriatric antidepressant trials45 (link),46 (link) and ECT studies31 (link). Subjects who achieved a Ham-D score of ≤10 without delusions for the first time at week twelve were assessed again at week thirteen to determine whether the two-week duration criterion was met.
Investigators were allowed to withdraw subjects for either clinically significant worsening or for insufficient clinical improvement after five weeks of randomized treatment. Insufficient clinical response was operationally pre-defined as having both a CGI-improvement score of ≤ 2 (no or minimal improvement) and a CGI-S score of ≥4 (moderately or more severely ill). Discontinuations initiated by subjects were categorized as due to perceived poor response, poor tolerability, or withdrawal of consent.
Safety and tolerability assessments considered the incidence of adverse events and evaluations conducted by the investigators. Adverse events were identified at each visit using research assistant interviews and subject reports. Increases of 2 points on a UKU scale item47 (link) or scores of 3 on an item were classified as adverse events. Research psychiatrists quantified extrapyramidal symptoms (EPS) using the Simpson Angus Scale48 (link) and incident akathisia using the Barnes Akathisia Scale49 (link). Tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale (AIMS)50 , applying modified Schooler Kane criteria51 (link) without requiring a two-week duration.