anthonyyazdaniml/CT-ADE-SOC huggingface dataset:
Intervention: Drospirenone
Trial phase: Phase 4
ATC code: G03AA12 | G03AA18 | G03AC10 | G03FA17
SMILES: [H][C@]12C[C@@]1([H])[C@]1([H])[C@](C)(CC[C@@]3([H])[C@@]1([H])[C@@]1([H])C[C@@]1([H])C1=CC(=O)CC[C@@]13C)[C@]21CCC(=O)O1
Sex: Female
Age groups: Child | Adult
Healthy volunteers: No
Participants at risk: 64
Group description: Folate-boosted 3 mg DRSP/20 μg EE-24/4 oral contraceptive

BMI 25-29.9 kg/ m2

3 mg DRSP/20 μg EE: 1 pill daily-24 days of drospirenone 3 mg (3 mg DRSP)/ethinyl estradiol 20 μg (20 μg EE)/levomefolate calcium 0.451 mg (folate) -followed by 4 days of levomefolate calcium 0.451 mg (folate)only
Eligibility criteria:
Inclusion Criteria:

•Adult female-16 years to 35 years of age who have been diagnosed with PCOS desiring contraception

Actual BMI >18 to <35kg/ m2
Written consent for participation in the study
Patient completed lactation

Exclusion Criteria:

Metabolic abnormalities requiring pharmacological intervention (except controlled thyroid disease)

Uncontrolled hypertension
Cancer or history of hormone-dependent cancer
History of cholestasis
Presence of contradictions for OC administration
Personal history of cardiovascular events.
Use of drugs known to exacerbate glucose tolerance.
No prescription or over-the-counter weight-loss drugs
Diabetes
Use of medications that affect blood pressure or lipid profile
Smoking in past 6 months
Known thrombogenic mutations (e.g. Factor V Leiden)
Current or history of deep venous thrombosis/pulmonary embolism
Major surgery with prolonged immobilization
Injectable hormonal contraceptive use within 6 months
Use of hormonal (e.g., oral contraceptive [OC] pill) or insulin-sensitizing medication unless willing to cease medications for 3 months before study measurements
Intervention: Drospirenone
Trial phase: Phase 4
ATC code: G03AA12 | G03AA18 | G03AC10 | G03FA17
SMILES: [H][C@]12C[C@@]1([H])[C@]1([H])[C@](C)(CC[C@@]3([H])[C@@]1([H])[C@@]1([H])C[C@@]1([H])C1=CC(=O)CC[C@@]13C)[C@]21CCC(=O)O1
Sex: Female
Age groups: Child | Adult
Healthy volunteers: No
Participants at risk: 64
Group description: Folate-boosted 3 mg DRSP/20 μg EE-24/4 oral contraceptive

BMI 30-34.9 kg/ m2

3 mg DRSP/20 μg EE: 1 pill daily-24 days of drospirenone 3 mg (3 mg DRSP)/ethinyl estradiol 20 μg (20 μg EE)/levomefolate calcium 0.451 mg (folate) -followed by 4 days of levomefolate calcium 0.451 mg (folate)only
Eligibility criteria:
Inclusion Criteria:

•Adult female-16 years to 35 years of age who have been diagnosed with PCOS desiring contraception

Actual BMI >18 to <35kg/ m2
Written consent for participation in the study
Patient completed lactation

Exclusion Criteria:

Metabolic abnormalities requiring pharmacological intervention (except controlled thyroid disease)

Uncontrolled hypertension
Cancer or history of hormone-dependent cancer
History of cholestasis
Presence of contradictions for OC administration
Personal history of cardiovascular events.
Use of drugs known to exacerbate glucose tolerance.
No prescription or over-the-counter weight-loss drugs
Diabetes
Use of medications that affect blood pressure or lipid profile
Smoking in past 6 months
Known thrombogenic mutations (e.g. Factor V Leiden)
Current or history of deep venous thrombosis/pulmonary embolism
Major surgery with prolonged immobilization
Injectable hormonal contraceptive use within 6 months
Use of hormonal (e.g., oral contraceptive [OC] pill) or insulin-sensitizing medication unless willing to cease medications for 3 months before study measurements
Intervention: CID 118984462
Trial phase: Phase 3
SMILES: CCC(C)C(NC(=O)CN)C(=O)NC(C(=O)NC(CCC(=O)O)C(=O)NC(CCC(N)=O)C(=O)NC1CSSCC2NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CSSCC(NC(=O)C(CC(C)C)NC(=O)C(Cc3c[nH]cn3)NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)NC(CO)C(=O)NC(Cc3c[nH]cn3)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCC(=O)O)C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(Cc3ccc(O)cc3)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(Cc3ccccc3)C(=O)NC(Cc3ccccc3)C(=O)NC(Cc3ccc(O)cc3)C(=O)NC(C(=O)N3CCCC3C(=O)NC(CCCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)O)C(C)O)CSSCC(C(=O)NC(CC(N)=O)C(=O)O)NC(=O)C(Cc3ccc(O)cc3)NC(=O)C(CC(N)=O)NC(=O)C(CCC(=O)O)NC(=O)C(CC(C)C)NC(=O)C(CCC(N)=O)NC(=O)C(Cc3ccc(O)cc3)NC(=O)C(CC(C)C)NC(=O)C(CO)NC2=O)NC1=O)C(C)C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 184
Group description: Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue [sulfonylurea or glinide], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.
Eligibility criteria:
Inclusion Criteria:

Type 2 diabetes (diagnosed clinically) for minimum 24 weeks prior to randomisation (visit 2)
Current treatment with basal-only insulin (no prandial insulin) consisting of either insulin detemir once daily (OD), insulin glargine OD or neutral protamine hagedorn (NPH) insulin OD/twice daily (BID) for at least 12 weeks prior to randomisation (visit 2), in combination with stable doses of OAD(s) (metformin, insulin secretagogue (sulfonylurea or glinide), alpha-glucosidase inhibitor, pioglitazone or dipeptidyl peptidase IV (DPP-IV) inhibitor in any approved (according to label) dose or combination. Stable OAD doses are defined as unchanged doses for at least 12 weeks prior to randomisation (visit 2)
HbA1c (glycosylated haemoglobin) between 7.0-10.0% (both inclusive) by central laboratory analysis
Body mass index (BMI) below or equal to 45 kg/m^2
Ability and willingness to adhere to the protocol including self-measured plasma glucose (SMPG) according to the protocol

Exclusion Criteria:

Treatment with rosiglitazone within the last 12 weeks prior to randomisation (visit 2)
Treatment with glucagon like peptide-1 (GLP-1) receptor agonists within the last 12 weeks prior to randomisation (visit 2)
Recurrent severe hypoglycaemia (more than one severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator (trial physician)
Previous participation in this trial. Participation is defined as randomised. Re-screening is allowed once during the recruitment period
Known or suspected hypersensitivity to trial products or related products
The receipt of any investigational drug within 4 weeks prior to randomisation (visit 2)
Intervention: Ketoconazole
Trial phase: Phase 4
ATC code: D01AC08 | G01AF11 | G01AF20 | H02CA03 | J02AB02
SMILES: CC(=O)N1CCN(c2ccc(OCC3COC(Cn4ccnc4)(c4ccc(Cl)cc4Cl)O3)cc2)CC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 20
Group description: Ketoconazole(600 mg taken orally)
Eligibility criteria:
Inclusion Criteria:

50 years of age or older;
diagnosis of COPD;
current or former smoker of at least 10 pack-years;
post-bronchodilator FEV1 greater than or equal to 30% predicted and less than or equal to 80% predicted; post-bronchodilator ratio < 70%

Exclusion Criteria:

any concomitant disease that might interfere with study procedures;
use of a drug that may cause a possible drug interaction with ketoconazole
Intervention: Dexmedetomidine
Trial phase: Phase 2
ATC code: N05CM18
SMILES: Cc1cccc([C@H](C)c2c[nH]cn2)c1C
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 2
Group description: Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance dose
Eligibility criteria:
Inclusion Criteria:

Subject is 12 months to <24 months of age at screening.
Subject is intubated and mechanically ventilated in an intensive care setting and is anticipated to require a minimum of 6 hours of continuous IV sedation.
Subject has adequate renal function, defined as: Serum creatinine ≤1.0 mg/dL.
The subject's parent(s) or legal guardian(s) must voluntarily sign and date the informed consent document approved by the Institutional Review Board.

Exclusion Criteria:

Pediatric subjects with neurological conditions that prohibit an evaluation of sedation such as:

Diminished consciousness from increased intracranial pressure
Extensive brain surgery (surgery requiring intracranial pressure monitor)
Diminished cognitive function per Principal Investigator (PI) discretion
Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking agents.
Subjects with second degree or third degree heart block unless subject has a permanent pacemaker or pacing wires are in situ.
Subjects who have hepatic impairment as defined by a serum glutamic-pyruvic transaminase/alanine aminotransferase (SGPT/ALT) >90 U/L at the time of screening.
Subjects who have hypotension, based on repeat assessments within 15 minutes preceding the start of study drug, defined as: Systolic blood pressure (SBP) <70 mmHg.
Pre-existing bradycardia based on repeated assessments within 15 minutes preceding the start of study drug, defined as: Heart rate (HR) <70 bpm.
Subject who have acute thermal burns involving more than 15 percent total body surface area.
Subjects who have a known allergy to dexmedetomidine, midazolam or fentanyl.
Subject who has received dexmedetomidine within 15 hours prior to the start of study drug.
Subjects with a life expectancy that is <72 hours.
Subjects that are expected to have hemodialysis (continuous hemofiltration), peritoneal dialysis or extracorporeal membrane oxygenation (ECMO) treatments within 48 hours prior to the start of study drug or during the duration of the study.
Subjects who have been treated with α-2 agonists/antagonists within 2 weeks.
Subjects with a spinal cord injury above T5 (5th Thoracic Vertebra).
Subjects who have received another investigational drug as part of an investigational drug study within the past 30 days.
Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of this clinical study.
Intervention: Dexmedetomidine
Trial phase: Phase 2
ATC code: N05CM18
SMILES: Cc1cccc([C@H](C)c2c[nH]cn2)c1C
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 3
Group description: Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance dose
Eligibility criteria:
Inclusion Criteria:

Subject is 12 months to <24 months of age at screening.
Subject is intubated and mechanically ventilated in an intensive care setting and is anticipated to require a minimum of 6 hours of continuous IV sedation.
Subject has adequate renal function, defined as: Serum creatinine ≤1.0 mg/dL.
The subject's parent(s) or legal guardian(s) must voluntarily sign and date the informed consent document approved by the Institutional Review Board.

Exclusion Criteria:

Pediatric subjects with neurological conditions that prohibit an evaluation of sedation such as:

Diminished consciousness from increased intracranial pressure
Extensive brain surgery (surgery requiring intracranial pressure monitor)
Diminished cognitive function per Principal Investigator (PI) discretion
Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking agents.
Subjects with second degree or third degree heart block unless subject has a permanent pacemaker or pacing wires are in situ.
Subjects who have hepatic impairment as defined by a serum glutamic-pyruvic transaminase/alanine aminotransferase (SGPT/ALT) >90 U/L at the time of screening.
Subjects who have hypotension, based on repeat assessments within 15 minutes preceding the start of study drug, defined as: Systolic blood pressure (SBP) <70 mmHg.
Pre-existing bradycardia based on repeated assessments within 15 minutes preceding the start of study drug, defined as: Heart rate (HR) <70 bpm.
Subject who have acute thermal burns involving more than 15 percent total body surface area.
Subjects who have a known allergy to dexmedetomidine, midazolam or fentanyl.
Subject who has received dexmedetomidine within 15 hours prior to the start of study drug.
Subjects with a life expectancy that is <72 hours.
Subjects that are expected to have hemodialysis (continuous hemofiltration), peritoneal dialysis or extracorporeal membrane oxygenation (ECMO) treatments within 48 hours prior to the start of study drug or during the duration of the study.
Subjects who have been treated with α-2 agonists/antagonists within 2 weeks.
Subjects with a spinal cord injury above T5 (5th Thoracic Vertebra).
Subjects who have received another investigational drug as part of an investigational drug study within the past 30 days.
Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of this clinical study.
Intervention: Methylene Blue
Trial phase: Phase 4
ATC code: V03AB17 | V04CG05
SMILES: CN(C)c1ccc2nc3ccc(=[N+](C)C)cc-3sc2c1.[Cl-]
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 17
Group description: Trachea will be intubated with Mallinckrodt™TaperGuard™ Evac Endotracheal Tube with a suction port to facilitate removal of secretions from the region of the trachea below the vocal cords and above the inflated ETT cuff

methylene blue: A dilute solution of methylene blue (5 ml of 1 % methylene blue solution in saline, 1:1 dilution) will be gently delivered into the hypopharynx using a flexible suction catheter approximately once per hour until trachea is extubated.
Eligibility criteria:
Inclusion Criteria:

Scheduled for elective abdominal surgery with an anticipated duration longer than 2 hours.
ASA (American Society of Anesthesiologists) Physical status Classification 1 to 3. (1 - normal healthy patient, 2 - patients with mild systemic disease, 3 - patients with severe systemic disease)
Endotracheal intubation anticipated to be routine (not difficult) based upon preoperative airway assessment

Exclusion Criteria:

Short duration surgery (anticipated < 2 hours) or emergency (non-elective) surgery
ASA Physical status Classification 4 to 5. (4 - patients with severe systemic diseases that is a constant threat to life, 5 - Moribund patients who are not expected to survive without the operation)
Anticipated difficult airway requiring technique other than direct laryngoscopy for intubation of the trachea.
Pregnancy
History of allergic reaction to Methylene Blue medication
Methemoglobinemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency
History of symptomatic chronic obstructive pulmonary disease (asthma, bronchitis, emphysema) or recent pneumonia (< 6 months prior to surgery).
Hypoxemia (hemoglobin oxygen saturation < 90% room air or on O2 at home or in hospital)
History of coagulopathy, IV heparin therapy, or coumadin therapy (INR > 2.5)
Intervention: Methylene Blue
Trial phase: Phase 4
ATC code: V03AB17 | V04CG05
SMILES: CN(C)c1ccc2nc3ccc(=[N+](C)C)cc-3sc2c1.[Cl-]
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 17
Group description: Trachea will be intubated with Teleflex ISIS HVT Cuffed Tracheal Tube with Subglottic Secretion suction port to facilitate removal of secretions from the region of the trachea below the vocal cords and above the inflated ETT cuff

methylene blue: A dilute solution of methylene blue (5 ml of 1 % methylene blue solution in saline, 1:1 dilution) will be gently delivered into the hypopharynx using a flexible suction catheter approximately once per hour until trachea is extubated.
Eligibility criteria:
Inclusion Criteria:

Scheduled for elective abdominal surgery with an anticipated duration longer than 2 hours.
ASA (American Society of Anesthesiologists) Physical status Classification 1 to 3. (1 - normal healthy patient, 2 - patients with mild systemic disease, 3 - patients with severe systemic disease)
Endotracheal intubation anticipated to be routine (not difficult) based upon preoperative airway assessment

Exclusion Criteria:

Short duration surgery (anticipated < 2 hours) or emergency (non-elective) surgery
ASA Physical status Classification 4 to 5. (4 - patients with severe systemic diseases that is a constant threat to life, 5 - Moribund patients who are not expected to survive without the operation)
Anticipated difficult airway requiring technique other than direct laryngoscopy for intubation of the trachea.
Pregnancy
History of allergic reaction to Methylene Blue medication
Methemoglobinemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency
History of symptomatic chronic obstructive pulmonary disease (asthma, bronchitis, emphysema) or recent pneumonia (< 6 months prior to surgery).
Hypoxemia (hemoglobin oxygen saturation < 90% room air or on O2 at home or in hospital)
History of coagulopathy, IV heparin therapy, or coumadin therapy (INR > 2.5)
Intervention: Methylene Blue
Trial phase: Phase 4
ATC code: V03AB17 | V04CG05
SMILES: CN(C)c1ccc2nc3ccc(=[N+](C)C)cc-3sc2c1.[Cl-]
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 16
Group description: Control group of patients will be intubated with a standard ETT without a suction port above the cuff (The Mallinckrodt Intermediate Hi-Lo Endotracheal Tube)

methylene blue: A dilute solution of methylene blue (5 ml of 1 % methylene blue solution in saline, 1:1 dilution) will be gently delivered into the hypopharynx using a flexible suction catheter approximately once per hour until trachea is extubated.
Eligibility criteria:
Inclusion Criteria:

Scheduled for elective abdominal surgery with an anticipated duration longer than 2 hours.
ASA (American Society of Anesthesiologists) Physical status Classification 1 to 3. (1 - normal healthy patient, 2 - patients with mild systemic disease, 3 - patients with severe systemic disease)
Endotracheal intubation anticipated to be routine (not difficult) based upon preoperative airway assessment

Exclusion Criteria:

Short duration surgery (anticipated < 2 hours) or emergency (non-elective) surgery
ASA Physical status Classification 4 to 5. (4 - patients with severe systemic diseases that is a constant threat to life, 5 - Moribund patients who are not expected to survive without the operation)
Anticipated difficult airway requiring technique other than direct laryngoscopy for intubation of the trachea.
Pregnancy
History of allergic reaction to Methylene Blue medication
Methemoglobinemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency
History of symptomatic chronic obstructive pulmonary disease (asthma, bronchitis, emphysema) or recent pneumonia (< 6 months prior to surgery).
Hypoxemia (hemoglobin oxygen saturation < 90% room air or on O2 at home or in hospital)
History of coagulopathy, IV heparin therapy, or coumadin therapy (INR > 2.5)
Intervention: CCR2 antagonist 3
Trial phase: Phase 2
SMILES: Cc1cc(C(=O)N(C)C(CN2CC(O)C2)C(C)C)ccc1F
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 12
Group description: AZD2927 solution for infusion
Eligibility criteria:
Inclusion Criteria:

male or postmenopausal female, aged 20 to 80 years inclusive,
clinical indication for catheter ablation of atrial flutter,
history of paroxysmal atrial flutter, with or without paroxysmal AF. Single episodes of persistent atrial flutter or AF requiring cardioversion do not exclude the patient from the study,
sinus rhythm at randomisation,
adequate anticoagulation or antithrombotic treatment according to ESC guidelines 2010 or national guideline,

Exclusion Criteria:

cardioversion within 14 days before randomisation,
history of stroke or transient ischaemic attack (TIA). History of significant head trauma, epilepsy or other disorders increasing the risk for seizures,
QTcF >450 ms or <350 ms measured in sinus rhythm at randomisation,
history and/or signs of clinically significant sinus node dysfunction. Sinus bradycardia (50 beats per minute or less) at randomisation,
personal or family history of Torsades de Pointes (TdP), any other polymorphic ventricular tachycardia, long QT syndrome, short QT syndrome, Brugada syndrome, or personal history of sustained (>30 s) monomorphic ventricular tachycardia.
Intervention: Cariprazine
Trial phase: Phase 2
ATC code: N05AX15
SMILES: CN(C)C(=O)N[C@H]1CC[C@H](CCN2CCN(c3cccc(Cl)c3Cl)CC2)CC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 141
Group description: Participants received cariprazine 0.5 mg orally once on Days 1-2 and cariprazine 0.75 mg orally once a day starting on Day 3 for the remainder of the 8 week treatment period.
Eligibility criteria:
Inclusion Criteria:

Participants who have provided informed consent prior to any study specific procedures.
Participants currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder as confirmed by the Structured Clinical Interview (SCID) with a current with a current major depressive episode of at least 4 weeks and not exceeding 12 months in duration.
Participants with normal physical examination, laboratory, vital signs, and/or echocardiogram (ECG).
Verified previous manic or mixed episode.
Participants with a total Hamilton Rating Scale for Depression (HAMD)-17 score ≥ 20.
Participants with a HAMD-17 item 1 score ≥ 2.
Participants with a Clinical Global Impression of Severity (CGI-S) score ≥ 4.

Exclusion Criteria:

Participants with a DSM-IV-TR diagnosis of an axis I disorder other than bipolar I disorder that was the primary focus of treatment within the previous 6 months.
Women who are pregnant or breast feeding
Participants with Young Mania Rating Scale (YMRS) total score > 10
Participants who have dementia, mental retardation, schizophrenia/schizoaffective disorder.
Intervention: Cariprazine
Trial phase: Phase 2
ATC code: N05AX15
SMILES: CN(C)C(=O)N[C@H]1CC[C@H](CCN2CCN(c3cccc(Cl)c3Cl)CC2)CC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 146
Group description: Participants received cariprazine 0.5 mg orally once on Days 1-2, cariprazine 0.75 mg orally once on Days 3-4, cariprazine 1.0 mg orally once on Days 5-7, and cariprazine 1.5 mg orally once a day starting on Day 8 for the remainder of the 8 week treatment period.
Eligibility criteria:
Inclusion Criteria:

Participants who have provided informed consent prior to any study specific procedures.
Participants currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder as confirmed by the Structured Clinical Interview (SCID) with a current with a current major depressive episode of at least 4 weeks and not exceeding 12 months in duration.
Participants with normal physical examination, laboratory, vital signs, and/or echocardiogram (ECG).
Verified previous manic or mixed episode.
Participants with a total Hamilton Rating Scale for Depression (HAMD)-17 score ≥ 20.
Participants with a HAMD-17 item 1 score ≥ 2.
Participants with a Clinical Global Impression of Severity (CGI-S) score ≥ 4.

Exclusion Criteria:

Participants with a DSM-IV-TR diagnosis of an axis I disorder other than bipolar I disorder that was the primary focus of treatment within the previous 6 months.
Women who are pregnant or breast feeding
Participants with Young Mania Rating Scale (YMRS) total score > 10
Participants who have dementia, mental retardation, schizophrenia/schizoaffective disorder.