High-Dose Oral Ziprasidone Versus Conventional Dosing in Participants With Residual Schizophrenia Symptoms

AIMS is a rating scale measuring involuntary movements known as tardive dyskinesia, that sometimes develop as a side effect of long-term treatment with antipsychotic medications. The AIMS score was calculated as the sum of questions 1 through 7 of the AIMS instrument, which includes assessments of involuntary movements in the face, lips, jaw, tongue, upper and lower extremities, and neck/shoulders/hips. Each item is rated on a five-point scale of severity from 0-4 with 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Total scores range from 0 to 28. A negative change from baseline indicates an improvement.

Time frame: Baseline, Week 2, Week 4, Week 6, Week 8

Population: All participants with available data at each time point.

The PANSS is a medical scale and was used for measuring symptom severity of participants with schizophrenia in this study. Total PANSS score consists of 7 items in the Negative subscale, 7 items in the Positive subscale and 16 items in the General Psychopathology scale. Total PANSS score ranges from 30 to 210. A higher score indicates a worse outcome. A negative change from baseline indicates an improvement.

Time frame: Baseline, Week 2, Week 4, Week 6, Week 8

Population: All participants with available data at each time point.

The SAS is a 10-item testing instrument used to evaluate drug-related extrapyramidal syndromes. The following items are included in the SAS: gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella reflex, tremor, and salivation. Total score ranges from 0 to 40 with a higher score indicating increased severity. A positive change from baseline indicates a worse outcome.

Time frame: Baseline, Week 2, Week 4, Week 6, Week 8

Population: All study participants with available data at each time point.

BAS is a rating scale that is administered by physicians to assess the severity of drug-induced akathisia, which is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion, as well as by actions such as rocking while standing or sitting, lifting the feet as if marching on the spot, and crossing and uncrossing the legs while sitting. The following subcategories are scored: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness and are rated on a 4-point scale from 0 - 3. In addition, the global clinical assessment of akathisia uses a 6-point scale ranging from 0 - 5. Total score ranges from 0 to 14 with a higher score indicating increased severity. A positive change from baseline indicates a worse outcome.

Time frame: Baseline, Week 2, Week 4, Week 6, Week 8

Population: All participants who had available data at each time point.

QT interval is a measure of the time between the start of the Q wave and the end of the T wave as determined by electrocardiogram (EKG). The corrected QT Interval (QTc) adjusts the QT interval for heart rate. The number of participants with an increase to QTc interval \>/= 500 msec was reported.

Time frame: 6 hours after dosing of Weeks 1, 2 and 8

Population: All participants with available data at each time point.

Side effects were tracked using the Side Effect Checklist for ziprasidone, which is a well-validated 17 item scale that records the presence or absence of side effects. Total number of side effect events is reported here.

Time frame: From Baseline up to Week 8

Population: All participants in the randomized trial.

Blood samples were taken at baseline and Week 8 to measure serum prolactin concentrations. Normal range for females (non-pregnant) is 2-29 nanograms per deciliter (ng/dL) and for males 2-18 ng/dL. Values above the normal range were reported as High and values below the normal range were reported as Low. Reported here is the number of participants with high prolactin concentration and the number of participants with low prolactin concentration.

Time frame: Baseline, Week 8

Population: All participants with available data at each time point.

Adverse event: any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Serious adverse event (SAE): significant hazard, contraindication, side effect, or precaution, which fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.

Time frame: From Baseline up to Week 8

Population: Safety population includes all participants who received at least one dose of study medication.

Response was defined as a reduction in the PANSS total score from baseline by 20% or greater, calculated by first subtracting 30 (the PANSS minimum possible total score). Response rate is the percentage of participants with a response.

Time frame: Baseline, Week 2, Week 4, Week 6, Week 8

Population: All participants with available data at each time point

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at regular times during the study. Normal SBP is defined as 120 millimeters of mercury (mmHg) or below and normal DBP is defined as 80 mmHg or below. Change from baseline is indicated for each time point. A positive change from baseline indicates and increase in blood pressure and a negative change from baseline indicates a decrease.

Time frame: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8

Population: All participants with available data at each time point.

CGI-I is a 7 point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to baseline. Score ranges from 1 to 7 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.

Time frame: Baseline, Week 8

Population: All participants with available data at each time point.

CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with subjects who have the same diagnosis. Score ranges from 1 to 7 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.

Time frame: Baseline, Week 8

Population: All participants with available data at each time point.

GAF is a numeric scale used to rate social, occupational, and psychological functioning of participants. Scores range from 100 (extremely high functioning) to 1 (severely impaired). A positive change from baseline indicates an improvement.

Time frame: Baseline, Week 8

Population: All participants with available data at each time point.

The PANSS is a medical scale and was used for measuring symptom severity of participants with schizophrenia in this study. Negative symptoms as defined by the American Psychiatric Association represent a diminution or loss of normal functions and include the following 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. Score ranges from 7 to 49 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.

Time frame: Baseline, Week 2, Week 4, Week 6, Week 8

Population: All participants with available data at each time point.

The PANSS is a medical scale and was used for measuring symptom severity of participants with schizophrenia in this study. Positive symptoms as defined by the American Psychiatric Association refer to an excess or distortion of normal functions and include the following 7 items: delusions, conceptual disorganization, hallucinations, excitement, grandiosity, suspiciousness/persecution and hostility. Score ranges from 7 to 49 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.

Time frame: Baseline, Week 2, Week 4, Week 6, Week 8

Population: All participants with available data at each time point.

The CDRS was used to assess the level of depression in participants with schizophrenia. The questionnaire consists of 9 questions rated on a 4-point scale from 0 to 3. Total range is 0 to 27 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.

Time frame: Baseline, Week 2, Week 4, Week 6, Week 8

Population: All participants with available data at each time point.

SCoRS is a 20 item interview-based clinical assessment that evaluates cognitive deficits and the degree to which these deficits impair participants' day-to-day functioning. The following cognitive domains are assessed: attention, memory, working memory, language production, reasoning, problem solving, motor skills, and social cognition. Score ranges from 1 to 10 with a higher score indicating a greater degree of impairment. A negative change from baseline indicates an improvement.

Time frame: Baseline, Week 8

Population: All participants with available data at each time point.