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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01MH113857 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This study has two aims: 1) to characterize the effects of intravenous ketamine on neurocognitive markers in depressed patients; 2) to test the efficacy of a synergistic intervention for depression combining intravenous ketamine with neurocognitive training. Three of the primary outcomes listed (fMRI functional connectivity; Implicit Association Test; cognitive flexibility testing) pertain to Aim 1. For Aim 2, one primary clinical outcome (MADRS, a clinician-administered measure of depression severity) pertains to the acute (30-day) phase, while the QIDS (a self-report measure of depression severity) becomes the primary clinical outcome during the 12-month naturalistic follow-up.
This study measures clinical and mechanistic outcome trajectories following ketamine (with or without adjunctive neurocognitive training) measured over an acute (30-day) period; and subsequently (for a subset of measures) over a 12-month naturalistic follow-up period.
NOTE: Corrections have been made to the "Time Frame" entries for all primary/secondary outcomes after identifying errors stemming from the study team's misunderstanding of the "Time Frame" query. Initially, the "Time Frame" query was misinterpreted to mean the range (minimum to maximum) length of the time interval over which any given assessment visit might query symptoms, and were therefore assigned erroneous values ("1 day to 2 weeks"; "1 day to lifetime") reflecting the time interval(s) queried by the instrument (e.g. at the +24 hours timepoint, symptoms are queried over a 1-day interval; at other assessment points, they could be queried over a 2-week interval for some measures, or over the entire lifetime for other measures). After recognizing this misinterpretation, the values have been adjusted to accurately reflect the a priori analytic plan.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketamine + Cognitive Training | Experimental |
| |
| Ketamine + Sham Training | Sham Comparator |
| |
| Saline + Cognitive Training | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous ketamine | Drug | Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Montgomery Asberg Depression Scale | Clinician-rated depression (range: 0-60; higher scores = worse outcome) | Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported |
| Executive-salience Network Functional Connectivity | fMRI measure (beta weights where larger beta weight = stronger connectivity) | Trajectories from 24 hours through Day 30 post-infusion, 24 hours reported |
| Implicit Self-representations | Implicit Association Test composite difference score (performance-based measure; range = -inf-inf; high score=worse outcome; negatively signed value indicates associating oneself more strongly with positive than negative attributes) | Trajectories from 24 hours through Day 30 post-infusion, Day 5 reported |
| Cognitive Flexibility | Neurocognitive testing via NIH Toolbox DCCS fully-corrected T-scores (range = 0-100; high score=better outcome) | Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported |
| Quick Inventory of Depressive Symptoms | Self-reported depression (range: 0-27; higher scores = worse outcome) | Trajectories from Day 30 through 12 months post-infusion (naturalistic follow-up), Month 12 reported |
| Measure | Description | Time Frame |
|---|---|---|
| Executive-salience Network Functional Connectivity During Resting State | fMRI measure (beta weights where larger beta weight = stronger connectivity) | Trajectories from 24 hours through Day 30 post-infusion, 24 hours reported |
| Affective Flexibility |
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Inclusion Criteria:
Participants will:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Western Psychiatric Institute and Clinic | Pittsburgh | Pennsylvania | 15213 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39311825 | Derived | Hossein S, Woody ML, Panny B, Spotts C, Wallace ML, Mathew SJ, Howland RH, Price RB. Functional connectivity subtypes during a positive mood induction: Predicting clinical response in a randomized controlled trial of ketamine for treatment-resistant depression. J Psychopathol Clin Sci. 2025 Apr;134(3):228-238. doi: 10.1037/abn0000951. Epub 2024 Sep 23. | |
| 37155171 | Derived | Price RB, Wallace ML, Mathew SJ, Howland RH. One-Year Outcomes Following Intravenous Ketamine Plus Digital Training Among Patients with Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 May 1;6(5):e2312434. doi: 10.1001/jamanetworkopen.2023.12434. |
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We will comply with all NIMH guidelines regarding data repository/sharing.
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We will comply with all NIMH guidelines regarding data repository/sharing.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ketamine + Cognitive Training | Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression. |
| FG001 | Ketamine + Sham Training | Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. |
| FG002 | Saline + Cognitive Training | Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Ketamine + Cognitive Training | Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression. |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Montgomery Asberg Depression Scale | Clinician-rated depression (range: 0-60; higher scores = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported |
|
4 hours
Adverse events collected using the Patient Rated Inventory of Side Effects (PRISE; Rush et al 2004) supplemented by open-ended questions. AEs were tallied for new or worsening symptoms (relative to pre-infusion baseline) with onset on the infusion day. Tallies are combined across two arms (ketamine+sham, ketamine+cognitive training) because the collected AEs pertain specifically to the drug infusion; the cognitive or sham behavioral training did not begin until AFTER AEs were reported/collected.
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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 | Ketamine | Includes all participants receiving the study drug (0.5 mg/kg IV ketamine over 40min), irrespective of Cognitive Training condition (active and sham collapsed) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| anxiety | Psychiatric disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Rebecca Price | University of Pittsburgh | 412-383-2150 | pricerb@upmc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 7, 2020 | Sep 12, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003863 | Depression |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| Computer-based Cognitive Training | Behavioral | Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression. |
|
'D-Prime' discrimination Z-score measured via accuracy of responses during the Affective Go/No-Go task (range: -inf-inf; high score=better performance; Z-score of 0=the sample mean)
| Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported |
| PROMIS Measures-depression | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported depression T-score range: 0-100 (higher score = worse outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| PROMIS Measures-anxiety | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anxiety T-score range: 0-100 (higher score = worse outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| PROMIS Measures-anger | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anger T-score range: 0-100 (higher score = worse outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| PROMIS Measures-positive Affect | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported positive affect/well-being T-score range: 0-100 (higher score = better outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| PROMIS Measures-sleep Disturbance | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported sleep disturbance T-score range: 0-100 (higher score = worse outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| PROMIS Measures-cognitive Function | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported cognitive function T-score range: 0-100 (higher score = better outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| PROMIS Measures-substance Use | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported substance use Raw score range: 0-35 (higher score = worse outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| PROMIS Measures-alcohol | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported alcohol use T-score range: 0-100 (higher score = worse outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| Cognitive Triad Inventory | Negative perceptions of self, future, & world (range=36-252; higher score = better outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| Columbia-Suicide Severity Rating Scale | Suicidality and patient safety (most severe ideation score, range=0-5; higher score = worse outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| WHO Disability Assessment Scale (SR) | Global functioning (range=0-48; higher score = worse outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| Cognitive Flexibility Scale | Self-reported cognitive flexibility (range=12-72; higher score = better outcome) | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
| Neuroplasticity-related Markers in Blood | ketamine metabolite (2R,6R)-HNK concentration levels (range=0-inf; higher score = greater concentration in blood) | 40min post-infusion |
| 33271040 | Derived | Price RB, Panny B, Degutis M, Griffo A. Repeated measurement of implicit self-associations in clinical depression: Psychometric, neural, and computational properties. J Abnorm Psychol. 2021 Feb;130(2):152-165. doi: 10.1037/abn0000651. Epub 2020 Dec 3. |
| BG001 | Ketamine + Sham Training | Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. |
| BG002 | Saline + Cognitive Training | Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Montgomery Asberg Depression Rating Scale | depression severity; range 0-60; high score=worse outcome | Mean | Standard Deviation | units on a scale |
|
| Number of failed antidepressant trials | Number of adequate trials of an FDA-approved antidepressant in the current depressive episode, per Antidepressant Treatment History Form | Mean | Standard Deviation | trials |
|
| Ketamine + Sham Training |
Intravenous ketamine: Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression. |
| OG002 | Saline + Cognitive Training | Computer-based Cognitive Training: Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression. |
|
|
|
| Primary | Executive-salience Network Functional Connectivity | fMRI measure (beta weights where larger beta weight = stronger connectivity) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | beta weights | Trajectories from 24 hours through Day 30 post-infusion, 24 hours reported |
|
|
|
| Primary | Implicit Self-representations | Implicit Association Test composite difference score (performance-based measure; range = -inf-inf; high score=worse outcome; negatively signed value indicates associating oneself more strongly with positive than negative attributes) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | factor score | Trajectories from 24 hours through Day 30 post-infusion, Day 5 reported |
|
|
|
| Primary | Cognitive Flexibility | Neurocognitive testing via NIH Toolbox DCCS fully-corrected T-scores (range = 0-100; high score=better outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported |
|
|
|
| Primary | Quick Inventory of Depressive Symptoms | Self-reported depression (range: 0-27; higher scores = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from Day 30 through 12 months post-infusion (naturalistic follow-up), Month 12 reported |
|
|
|
| Secondary | Executive-salience Network Functional Connectivity During Resting State | fMRI measure (beta weights where larger beta weight = stronger connectivity) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | beta weights | Trajectories from 24 hours through Day 30 post-infusion, 24 hours reported |
|
|
|
| Secondary | Affective Flexibility | 'D-Prime' discrimination Z-score measured via accuracy of responses during the Affective Go/No-Go task (range: -inf-inf; high score=better performance; Z-score of 0=the sample mean) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | Z-score | Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported |
|
|
|
| Secondary | PROMIS Measures-depression | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported depression T-score range: 0-100 (higher score = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | PROMIS Measures-anxiety | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anxiety T-score range: 0-100 (higher score = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | PROMIS Measures-anger | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anger T-score range: 0-100 (higher score = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | PROMIS Measures-positive Affect | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported positive affect/well-being T-score range: 0-100 (higher score = better outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | PROMIS Measures-sleep Disturbance | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported sleep disturbance T-score range: 0-100 (higher score = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | PROMIS Measures-cognitive Function | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported cognitive function T-score range: 0-100 (higher score = better outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | PROMIS Measures-substance Use | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported substance use Raw score range: 0-35 (higher score = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | PROMIS Measures-alcohol | Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported alcohol use T-score range: 0-100 (higher score = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | Cognitive Triad Inventory | Negative perceptions of self, future, & world (range=36-252; higher score = better outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | Columbia-Suicide Severity Rating Scale | Suicidality and patient safety (most severe ideation score, range=0-5; higher score = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | WHO Disability Assessment Scale (SR) | Global functioning (range=0-48; higher score = worse outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
|
|
| Secondary | Cognitive Flexibility Scale | Self-reported cognitive flexibility (range=12-72; higher score = better outcome) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | score on a scale | Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported |
|
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| Secondary | Neuroplasticity-related Markers in Blood | ketamine metabolite (2R,6R)-HNK concentration levels (range=0-inf; higher score = greater concentration in blood) | All participants who were assigned to the arm and were willing and able to complete this specific measure. | Posted | Mean | Standard Deviation | ng/mL | 40min post-infusion |
|
|
|
| 0 |
| 103 |
| 0 |
| 103 |
| 102 |
| 103 |
| EG001 | Saline | Includes all participants receiving a placebo infusion of saline (over 40min). All participants in this arm later went on to receive the active Cognitive Training condition. | 0 | 51 | 0 | 51 | 38 | 51 |
| decreased energy | General disorders | Systematic Assessment |
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| difficulty focusing vision | Nervous system disorders | Systematic Assessment |
|
| difficulty sleeping: too little | Psychiatric disorders | Systematic Assessment |
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| difficulty sleeping: too much | Psychiatric disorders | Systematic Assessment |
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| difficulty urinating | Renal and urinary disorders | Systematic Assessment |
|
| dissociative effects | Psychiatric disorders | Systematic Assessment |
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| dizziness | Nervous system disorders | Systematic Assessment |
|
| dry mouth | Gastrointestinal disorders | Systematic Assessment |
|
| elevated blood pressure | Cardiac disorders | Systematic Assessment |
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| elevated heart rate | Cardiac disorders | Systematic Assessment |
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| emesis | Gastrointestinal disorders | Systematic Assessment |
|
| emotional indifference | Psychiatric disorders | Systematic Assessment |
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| feeling "discombobulated" | General disorders | Systematic Assessment |
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| feeling "high" (per verbal report) | Psychiatric disorders | Systematic Assessment |
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| headache | Nervous system disorders | Systematic Assessment |
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| increased appetite | Gastrointestinal disorders | Systematic Assessment |
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| increased weight | Metabolism and nutrition disorders | Systematic Assessment |
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| loss of sexual desire | Reproductive system and breast disorders | Systematic Assessment |
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| lowered pulse | Cardiac disorders | Systematic Assessment |
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| nausea | Gastrointestinal disorders | Systematic Assessment |
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| palpitations | Cardiac disorders | Systematic Assessment |
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| restlessness | General disorders | Systematic Assessment |
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| suicidal ideation | Psychiatric disorders | Systematic Assessment |
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| sweating | General disorders | Systematic Assessment |
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| tinnitus | Nervous system disorders | Systematic Assessment |
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| tremors | Nervous system disorders | Systematic Assessment |
|
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