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| ID | Type | Description | Link |
|---|---|---|---|
| 5R34MH072678-02 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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The purpose of this study is to conduct a preliminary evaluation of the efficacy of combined medication and psychotherapy for generalized anxiety disorder (GAD). The general goals of the current study are to conduct a late stage treatment development study. The goal of this stage of research is to provide a preliminary answer to the question and to gather data to estimate intervention parameters (e.g., effect size, attrition rates, response rates) that would assist in planning further research.
The specific aims of this study are to collect preliminary data relevant to the following hypotheses:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combined Treatment | Experimental | Patients who receive combined cognitive behavioral therapy (CBT) plus medication (venlafaxine XR, flexibly dosed between 75-225 mg/day) treatment for GAD. CBT was once/week sessions for 12 weeks. Medication continued for the full 6 months. |
|
| Venlafaxine XR 75-225 mg alone | Active Comparator | These patients receive only medication treatment for GAD. Patients take venlafaxine (flexibly dosed from 75-225 mg/day) as part of NCT00183274 and are assessed over a 6 month period. Medication continued for the full 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cognitive Behavioral Therapy | Behavioral | This cognitive behavioral therapy for GAD has a cognitive restructuring component and an applied relaxation component. Patients will be educated about the nature of anxiety and be trained in the recognition and monitoring of situational, physiological, cognitive, and behavioral cues associated with anxious responding. They will be guided through copings skill rehearsals in addition to imaginal and in vivo exposure to anxiety cues. This cognitive behavioral treatment will consist of 1 to 1.5 hour sessions of psychotherapy, which will be held once weekly over a period of 12 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Hamilton Anxiety Rating Scale (HAM-A) | The HAM-A was used to measure the severity of anxiety symptoms. The scale consists of 14 items; each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate and 25-30 moderate to severe anxiety. This measure was conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Hospital Anxiety Depression Scale (HAD)-Anxiety Score | The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater anxiety. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paul Crits-Christoph, PhD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania, 3535 Market Street, Suite 650 | Philadelphia | Pennsylvania | 19104 | United States |
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Of 334 patients who consented to the parent trial, 66 did not receive study drug (64 withdrew consent and 2 were protocol violators), leaving 268 who received at least one dose of open-label venlafaxine XR. For this study, 77 patients were randomly assigned to be offered CBT and 40 patients to not be offered CBT.
Three hundred thirty four patients enrolled in the first phase (6-month open-label) of a parent medication trial for GAD (NCT00183274) were recruited and seen in one of four primary care practices or a psychopharmacology clinic in a university setting from 2005 to 2009. The current study was conducted from October, 2006 to March, 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Combined Treatment | Patients received Venlafaxine XR (75-225 mg/d) plus 12 weeks of CBT (one 1 to 1.5 hour session per week) for GAD over a period of 6 months. |
| FG001 | Medication Alone | Patients received Venlafaxine XR (75-225 mg/d) alone as treatment for GAD over a period of 6 months. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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26 out of 29 patients who consented to receive combined treatment received at least one session of CBT. 35 out of 40 patients who consented to received medication only received at least one dose of medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Combined Treatment | Patients received Venlafaxine XR (75-225 mg/d) plus 12 weeks of CBT (one 1 to 1.5 hour session per week) for GAD over a period of 6 months. |
| BG001 | Medication Alone |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Hamilton Anxiety Rating Scale (HAM-A) | The HAM-A was used to measure the severity of anxiety symptoms. The scale consists of 14 items; each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate and 25-30 moderate to severe anxiety. This measure was conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment. | Number analyzed at various time points differ due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
|
Over the 6-month study period, adverse events were assessed at each visit (from week 2 up to week 24) using an open-ended approach, which was facilitated by the use of a physician-completed medication problem checklist.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Combined Treatment | Patients received Venlafaxine XR (75-225 mg/d) plus 12 weeks of CBT (one 1 to 1.5 hour session per week) for GAD over a period of 6 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Severe Fatigue | General disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lightheadedness | General disorders | Systematic Assessment |
Only one-third of those approached to add on CBT were interested in this option. Strict exclusion criteria reduces the generalizability of the study results. Possible that other forms of CBT treatment may produce different results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Paul Crits-Christoph | University of Pennsylvania | (215) 662-7993 | crits@mail.med.upenn.edu |
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| ID | Term |
|---|---|
| D000098647 | Generalized Anxiety Disorder |
| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D015928 | Cognitive Behavioral Therapy |
| ID | Term |
|---|---|
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |
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| Venlafaxine XR | Drug | Venlafaxine XR, 75-225 mg/d, oral administration. 14 days at 75 mg/d, 150 mg/d for the remaining 6 months, 225 mg/3 for patients unimproved at week 6, tapered at 75 mg/week (this intervention is provided by protocol 709012). |
|
|
| Hospital Anxiety Depression Scale (HAD)-Depression Score | The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater depression. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
| Hamilton Rating Scale for Depression (HAM-D)-17-item Score | The 17-item version of the HAM-D was used to assess severity of depressive symptoms. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.The total score is the sum of the 17 items, with a range from 0 to 50. A higher scores indicates greater depression. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
| Clinical Global Impression (CGI)-Severity Score | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale (1=normal; 7 = extremely ill) that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
| Clinical Global Impression (CGI)-Improvement Score | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale (1= very much improved; 7 = very much worse) that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
| Quality of Life Subscale of the General Health Questionnaire (GHQ) | The General Health Questionnaire (GHQ) is a psychometric screening tool to identify common psychiatric conditions. Patients completed the 12 quality of life questions (each on a 0 to 3 scale) on this questionnaire. Scores on the 12 items were added up to create summary score (range = 0 to 36). Higher scores indicate worse health. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
| Penn State Worry Questionnaire (PSWQ) | The Penn State Worry Questionaire is a 16-item inventory that aims to measure the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me). A total score is calculated (range = 16 to 80), with higher scores indicating greater worry. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
| Physical Component Score of the 12-Item Short Form Survey (SF-12) | The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
| Mental Component Score of the 12-item Short Form Survey (SF-12) | The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
| Clinical Response Rate | Clinical response on the HAM-A was defined as a 50% or greater reduction from baseline to last value with the 24-week open label medication phase. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
| 50 Percent or Greater Reduction in PSWQ Score | Clinically significant change was defined on the PSWQ as an estimated (based on linear mixed effects model) endpoint score of less than 50.9. This score was calculated using the PSWQ normative data provided by Gillis, Haaga, and Ford (1995) and the baseline PSWQ mean and standard deviation (SD) from the current sample. The PSWQ mean and SD from the normative and current GAD samples were entered into the Jacobson et al. (1984) formula "c" for clinically significant change. This method provides a cutoff indicating whether or not the level of functioning by a patient is statistically more likely to be in the functional rather than the dysfunctional population. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
| Lack of Efficacy |
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| Lost to Follow-up |
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| Withdrawal by Subject |
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Patients received Venlafaxine XR (75-225 mg/d) alone as treatment for GAD over a period of 6 months.
| BG002 | Total | Total of all reporting groups |
| years |
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| Gender | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG001 | Medication Alone | Patients received Venlafaxine XR (75-225 mg/d) alone as treatment for GAD over a period of 6 months. |
|
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| Secondary | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater anxiety. | Numbers analyzed at various time points differ due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
|
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|
|
| Secondary | Hospital Anxiety Depression Scale (HAD)-Depression Score | The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater depression. | Numbers analyzed at various time points differ due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
|
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|
|
| Secondary | Hamilton Rating Scale for Depression (HAM-D)-17-item Score | The 17-item version of the HAM-D was used to assess severity of depressive symptoms. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.The total score is the sum of the 17 items, with a range from 0 to 50. A higher scores indicates greater depression. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment. | Numbers analyzed at various time points differ due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
|
|
|
|
| Secondary | Clinical Global Impression (CGI)-Severity Score | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale (1=normal; 7 = extremely ill) that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment. | Number analyzed at each time point differs due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
|
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|
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| Secondary | Clinical Global Impression (CGI)-Improvement Score | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale (1= very much improved; 7 = very much worse) that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment. | Number analyzed at different time points varies due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
|
|
|
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| Secondary | Quality of Life Subscale of the General Health Questionnaire (GHQ) | The General Health Questionnaire (GHQ) is a psychometric screening tool to identify common psychiatric conditions. Patients completed the 12 quality of life questions (each on a 0 to 3 scale) on this questionnaire. Scores on the 12 items were added up to create summary score (range = 0 to 36). Higher scores indicate worse health. | Number analyzed at different time points varies due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
|
|
|
|
| Secondary | Penn State Worry Questionnaire (PSWQ) | The Penn State Worry Questionaire is a 16-item inventory that aims to measure the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me). A total score is calculated (range = 16 to 80), with higher scores indicating greater worry. | Number analyzed at different time points varies due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
|
|
|
|
| Secondary | Physical Component Score of the 12-Item Short Form Survey (SF-12) | The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. | Number analyzed at different time points varies due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
|
|
|
|
| Secondary | Mental Component Score of the 12-item Short Form Survey (SF-12) | The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. | Number analyzed at different time points varies due to patient dropout. | Posted | Mean | Standard Deviation | units on a scale | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
|
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|
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| Secondary | Clinical Response Rate | Clinical response on the HAM-A was defined as a 50% or greater reduction from baseline to last value with the 24-week open label medication phase. | Posted | Count of Participants | Participants | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 |
|
|
|
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| Secondary | 50 Percent or Greater Reduction in PSWQ Score | Clinically significant change was defined on the PSWQ as an estimated (based on linear mixed effects model) endpoint score of less than 50.9. This score was calculated using the PSWQ normative data provided by Gillis, Haaga, and Ford (1995) and the baseline PSWQ mean and standard deviation (SD) from the current sample. The PSWQ mean and SD from the normative and current GAD samples were entered into the Jacobson et al. (1984) formula "c" for clinically significant change. This method provides a cutoff indicating whether or not the level of functioning by a patient is statistically more likely to be in the functional rather than the dysfunctional population. | Posted | Count of Participants | Participants | Data collected as part of protocol 709012 at baseline, week 12, and week 24 |
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| 4 |
| 26 |
| 22 |
| 26 |
| EG001 | Medication Alone | Patients received Venlafaxine XR (75-225 mg/d) alone as treatment for GAD over a period of 6 months. | 4 | 35 | 27 | 35 |
| Severe Migraine | General disorders | Systematic Assessment |
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| Pneumonia | Infections and infestations | Systematic Assessment |
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| Severe Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Severe Impact on Libido | General disorders | Systematic Assessment |
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| Severe Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Severe Vision Impairment | Eye disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Muscle Aches | General disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Faintness | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Decreased Orgasm | General disorders | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
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| Increased Sweating | Endocrine disorders | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Jittery | General disorders | Systematic Assessment |
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| Nightmares/Vivid Dreams | General disorders | Systematic Assessment |
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| Anorexia | Psychiatric disorders | Systematic Assessment |
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| Anxiety | General disorders | Systematic Assessment |
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| Blurred Vision | Eye disorders | Systematic Assessment |
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| Decreased Appetite | General disorders | Systematic Assessment |
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| Decreased Sex Drive | General disorders | Systematic Assessment |
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| Delayed Orgasm | General disorders | Systematic Assessment |
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| Drowsiness | General disorders | Systematic Assessment |
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| Dry Mouth | General disorders | Systematic Assessment |
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| Gas | Gastrointestinal disorders | Systematic Assessment |
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| Tremors | General disorders | Systematic Assessment |
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