Table 4.
Clinical trials which study the effects of repurposed medications on MDD since 2015.
| Treatment (Tₓ) Phase/Year First, Posted Ref |
Dosage (Duration of Therapy) |
Subjects/F/M Condition Groups |
Study Design | Results | Non-Serious AEs (Treatment-Related) |
Serious AEs (Treatment-Related) |
|---|---|---|---|---|---|---|
| General anesthetics | ||||||
| Ketamine NA/2016 [97] |
Experimental: 1 mg/kg IV ketamine for the duration of their ECT index course over 2–3 weeks Active comparator: 1 mg/kg of IV methohexital for the duration of their ECT index course over 2–3 weeks |
52/NA/NA MDD |
R, PG, DB | NA | NA | NA |
| Ketamine Early phase I/2015 [98] |
Experimental: ketamine + TAU Active comparator: midazolam + TAU |
9/NA/NA MDD, BP1 disorder, BP2 disorder, BP depression, suicidal ideation |
R, PG, DB | NA | NA | NA |
| Ketamine Phase I/2017 [99] |
Experimental: 4 ketamine infusions at 0.05 mg/kg—once weekly Active comparator: 4 infusions at 0.045 mg/kg—once weekly |
25/NA/NA A major depressive episode, unipolar depression, BP depression |
R, PG, QB | NA | NA | NA |
| Ketamine Phase IV/2016 [100] |
Placebo: saline 0.9%, IV administration of 0.2 mg/kg or 50 mg Medication: ketamine (1st phase) IV administration of 0.2 mg/kg or 50 mg Medication: ketamine (2nd phase) additional 4 sessions (twice a week, 2 weeks) of 0.5 mg/kg over 40 min |
45/NA/NA MDD |
R, PG, QB | NA | NA | NA |
| Ketamine Phase IV/2015 [101] |
Medication: ketamine 0.5 mg/kg over 40 min IV Other: MRI technology will be used before and after ketamine for patients with depression |
16/8/8 MDD, anxious depression, depression |
SG, OL | NA | None | Not reported |
| Ketamine NA/2021 [102] |
Received IV ketamine in 2014–15 and will be evaluated in 5 years | 11/NA/NA/ MDD, medication abuse, medications, relapse |
Retrospective | NA | NA | NA |
| Ketamine NA/2017 [103] |
Experimental: ketamine and 16 CBT sessions over 14 weeks Active comparator: ketamine and psychoeducation all sessions over 14 weeks |
28/NA/NA MDD |
R, PG, SB | NA | NA | NA |
| Ketamine Phase II/2018 [104] |
Experimental: different dosages and regimens for MIJ821 Active comparator: ketamine infusion 0.5 mg/kg weekly Placebo Comparator: placebo infusion |
70/35/35 TRD |
R, PG, DB | NA | None | Hyperacusis, photophobia, vision blurred, dry mouth, nausea, fatigue, feeling of relaxation, gait disturbance, increased systolic blood pressure, decreased platelet count, dizziness, dysgeusia, headache, paresthesia, sciatica, somnolence, anxiety, depersonalization/derealization disorder, disinhibition, irritability, alopecia, pruritus |
| Ketamine Phase II/2016 [105] |
Experimental: NRX-101 oral capsule + ketamine IV infusion + saline solution IV infusion Active comparator: lurasidone oral capsule + ketamine IV infusion + saline solution IV infusion |
22/16/6 BP depression, suicidal ideation, suicide attempts |
R, SG, QB | NA | None | Angina pectoris, tinnitus, vision blurred, diarrhea, dry mouth, coordination abnormal, dizziness, dysmetropsia, hypoesthesia, sedation, restlessness, depression, suicidal ideation, acute kidney injury, dry skin, hypertension |
| Antimanic agents | ||||||
| Lithium Phase III/2015 [106] |
Experimental: 40 mg ITI-007 administered orally as capsules once daily for 6 weeks Experimental: 60 mg ITI-007 administered orally as capsules once daily for 6 weeks Placebo Comparator: placebo administered orally as visually-matched capsules once daily for 6 weeks |
529/NA/NA BD |
R, PG, QB | NA | NA | NA |
| Risperidone 2011 [68,107] |
Groups: olanzapine users, quetiapine users, risperidone users, all other antipsychotic users | 17743/9692/8051 SCH = 475 MDD = 798 BP disorder = 270 Generalized anxiety disorder = 17 Other mental health disorders = 637 Unknown indication = 15546 Quetiapine = 4658 Olanzapine = 5856 Risperidone = 7229 |
Observational, cohort, retrospective | Comparison between quetiapine and olanzapine: quetiapine is associated with lower extrapyramidal symptoms and diabetes mellitus Comparison between quetiapine and risperidone: quetiapine is associated with lower extrapyramidal symptoms, but higher failed suicide attempt rates |
NA | NA |
| Atypical antipsychotics | ||||||
| Aripiprazole Phase II/2016 [108] |
Oral tablet (2,5,10,15,20, or 30 mg) with an IEM QD (8 weeks) |
49/31/18 BP1 (n = 22) SCH (n = 15) MDD (n = 12) Tx = 49 |
SG, OL, multi-center | NA | Rash, erythema, pruritus skin irritation, upper respiratory tract infection, sinusitis, headache, syncope, meniscus injury, sunburn, peripheral swelling, pain in extremity | Not reported |
| Quetiapine Phase III/2016 [109] |
Active comparator: levomilnacipran ER 20–120 mg/d starting at 20 mg/d on days 1–2, 40 mg/d on days 3–7 in week 1, then between 40–120 mg/d during weeks 2–8 Active comparator: 1uetiapine XR 50 mg/d on day 1–2, 150 mg/d on days 3–7 in week 1, then between 150–300 mg/d during weeks 1–8 along with their current antidepressant |
60/NA/NA MDD |
R, PG, TB | NA | NA | NA |
| Quetiapine Phase II/2017 [110] |
Experimental: 1 capsule of 20 mg JNJ-42847922 and 1 capsule of placebo once daily for 14 days. Then, JNJ-42847922 dose can be increased to 40 mg (2 capsules) until day 167 Active comparator: 1 capsule of quetiapine XR 50 mg along with 1 capsule of placebo once daily for 2 days, followed by 1 capsule of 150 mg along with 1 capsule of placebo once daily from day 3–14. Then, the dose can be increased to 300 mg (2 capsules) until day 167. |
107/NA/NA MDD |
R, PG, DB | NA | NA | NA |
| Patients should continue to take their baseline SSRI/SNRI. | ||||||
| Brexpiprazole Phase III/2018 [35] |
Experimental: brexpiprazole, 2–3 mg/day, once daily for 6 weeks, oral administration Placebo Comparator: placebo, 2–3 mg/day, once daily for 6 weeks, oral administration |
65/NA/NA MDD |
R, PG, TB | NA | NA | NA |
| Dopamine agonists | ||||||
| Pramipexole Phase IV/2014 [47,111] |
Started at 0.125 mg BD PO and increased by 0.25 mg/day every 3–4 days to a target range of 1.0–2.5 mg/day (6 weeks) |
51/25/26 MDD (n = 26) Healthy (n = 25) Healthy control patients did not receive study medication and only have baseline measures |
Non-randomized, PG, OL | Symptom’s improvement | Nausea, heartburn, vomiting, ↑appetite, ↓appetite, diarrhea, constipation, somnolence, restlessness, insomnia, forgetfulness, sleep attacks, compulsive behaviors, impaired concentration, headache, lightheadedness, dizziness, dry mouth, fatigue, ↓ libido, sexual dysfunction, skin problems, sweating, impaired coordination, tremor, blurry vision, bruising | Not reported |
| Armodafinil Phase III/2011 [50,112] |
Tablet, PO, QD in the morning, started at 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to 150 mg/day. (8 weeks) |
399/241/158 depressive episode despite maintenance therapy for BP1 disorder P = 199 Tx = 200 |
R, PG, DB, PC, multi-center | ↓Severity of depression, ↓depressive symptoms, Improved functioning |
Headache, nausea | Anxiety, BP1 disorder, depression, insomnia, suicide attempt, cholecystitis chronic, social stay hospitalization |
| Armodafinil Phase III/2010 [51,113] |
Tablet, PO, QD in the morning, started at 50 mg/kg and titrated up in the first week to 150 or 200 mg/kg. Treatment with 200 mg/kg dose was discontinued via a protocol amendment. (8 weeks) |
492/273/219 major depressive episode despite BP1 disorder maintenance therapy P = 230 Tx (150 mg/kg) = 232 Tx (200 mg/kg) = 30 |
R, PG, DB, PC, multi-center | ↓ Depressive symptoms | Nausea, diarrhea, dry mouth, toothache, dyspepsia, headache, dizziness, insomnia, anxiety, suicidal ideation, nasopharyngitis, cough | Mania, psychotic disorder, suicidal ideation, pulmonary embolism, abortion spontaneous, accidental overdose, non-cardiac chest pain, coronary artery disease |
| Armodafinil Phase III/2010 [49,114] |
Tablet, PO, QD in the morning, started at 50 mg/kg and titrated up in the first week to 150 or 200 mg/kg. Treatment with 200 mg/kg dose was discontinued via a protocol amendment. (8 weeks) |
433/288/145 major depressive episode while taking at least 4 weeks of conventional maintenance medication P = 199 Tx (150 mg/kg) =201 Tx (200 mg/kg) =33 |
R, PG, DB, PC, multi-center | Improvement in depressive symptoms | Diarrhea, nausea, headache, migraine, insomnia, feeling jittery | Psychotic disorder, suicidal ideation, depressive symptom, aggression, acute hepatic failure, hepatitis acute |
| Modafinil with D-cycloserine (DCS) Phase III/2015 [7] |
250 mg DCS before two weekly sessions, 100 mg modafinil before two weekly sessions | 36/20/14/2 (transgender) MDD P = 11 Tx (modafinil) = 12 Tx (DCS) = 13 |
R, PG, DB, PC | NA | ↑Energy/concentration, fatigue/low motivation | Not reported |
| Supplementation | ||||||
| Omega-3 PUFA Not applicable/2018 [115] |
One capsule (EPA 300 mg and 200 mg DHA) QD were given antidepressant (citalopram, escitalopram, paroxetine 1 tablet at night time). (12 weeks) |
70/NA/NA Taking antidepressants P = NA Tx = NA |
R, PG, SB, PC | NA | NA | NA |
| n-3 Polyunsaturated fatty acid Not applicable/2017 [116] |
2 g of EPA and 1 g of DHA (12 weeks) |
60/NA/NA MDD and cardiovascular disease P = NA Tx = NA |
R, PG, DB, PC | NA | NA | NA |
| Zinc Not applicable/2020 [46] |
Oral 30 mg zinc sulfate QD with SSRIs (8 weeks) |
100/NA/NA MDD P = 50 Tx = 50 |
R, PG, DB, PC | NA | NA | NA |
| NMDA receptor antagonist | ||||||
| Dextromethorphan hydrobromide Phase I/2016 [38] |
Two 75 mg capsules PO, separated by 4 h | 4/NA/NA MDD P = NA Tx = NA |
R, PG, DB, PC | NA | NA | NA |
| Esketamine Phase III/2017 [117,118] |
84 mg intranasal, twice a week (on days 1,4,8,11,15,18,22 and 25) along with the standard of care antidepressant treatment initiated on day 1 (4 weeks) |
225/139/86 MDD and have suicidal ideation with intent but without psychotic features P = 112 Tx = 113 |
R, PG, DB, PC, multi-center | ↓ MADRS total score (improved), improvement in the severity of suicidality measured by CGI-SS-r | Dizziness, headache, somnolence, dysgeusia, hypoesthesia, sedation, dizziness postural, nausea, constipation, vomiting, dissociation, insomnia, anxiety, ↑ blood pressure, blurred vision, vertigo | Suicidal depression, depression, suicide attempt, diabetic ketoacidosis |
| Esketamine Phase III/2017 [119,120] |
84 mg intranasal, twice a week (on days 1,4,8,11,15,18,22 and 25) along with the standard of care antidepressant treatment initiated on day 1 (4 weeks) |
227/136/91 MDD and having suicidal ideation with intent, but without psychotic features P = 113 Tx = 114 |
R, PG, DB, PC, multi-center | ↓MADRS total score (improved), ↓ in the severity of suicidality measured by CGI-SS-r | Dizziness, dysgeusia, somnolence, headache, paresthesia, sedation, hypoesthesia, dizziness postural, nausea, vomiting, paresthesia oral, dry mouth, constipation, hypoesthesia oral, dissociation, anxiety, euphoric mood, depersonalization/derealization disorder, insomnia, vision blurred, diplopia, nasal discomfort, oropharyngeal pain, throat irritation, vertigo, ↑ blood pressure, hyperhidrosis, feeling drunk | Suicide attempt, suicidal ideation, depersonalization/derealization disorder |
| Esketamine Phase II/2019 [121] |
Four low, medium, or high doses (three different groups) on days 1,4,8 and 11 via dry powder inhaler (2 weeks) |
88/NA/NA TRD in the course of MDD P = NA Tx = NA |
R, PG, DB, PC, multi-center | NA | NA | NA |
| Esketamine Phase I/2016 [122,123] |
Treatment A: intranasal placebo on day 1 and oral placebo on day 2 Treatment B: intranasal placebo on day 1 and oral alcohol on day 2 Treatment C: 84 mg of intranasal esketamine on day 1 and oral placebo on day 2 Participants will receive one of the ABC, BCA, CAB, CBA, ACB, or BAC treatments in part A and intranasal placebo on day 1 and 84 mg of intranasal esketamine on days 4,8,11,15,18,22 and 25 in part B |
23/16/7 MDD P = 20 Tx = 23 |
Part A: R, cross-over assignment, SB, PC, active-controlled, double-dummy, 3-period Part B: OL, PC, fixed sequence, single period |
Improvement in overall depression scores in MADRS | Dissociation, dizziness, dysgeusia, paresthesia, fatigue, paresthesia oral, nausea, headache, feeling abnormal, nasal discomfort, vision blurred, somnolence, euphoric mood, tinnitus, diplopia, ↑ blood pressure, feeling drunk, dysarthria, feeling of relaxation, illusion, hypoesthesia, altered time perception | Not reported |
| Combined medications | ||||||
| AXS-05 Phase III/2019 [40,124] |
Oral tablets of 45 mg dextromethorphan and 105 mg bupropion, BID (6 weeks) |
327/215/112 Moderate or severe MDD P = 164 Tx = 163 |
R, PG, DB, PC, multi-center | ↓ MADRS total score, improvement in daily functioning, improvement in quality of life | Dizziness, nausea, headache, diarrhea, somnolence, dry mouth | Not reported |
| AXS-05 Phase II/2018 [39,125] |
45 mg dextromethorphan and 105 mg bupropion BID and Bupropion as AC (6 weeks) |
80/51/29 Moderate or severe MDD AC = 37 Tx = 43 |
R, PG, DB, active-controlled, multi-center | ↓ MADRS total score, improvement in core symptoms of depression | Nausea, dizziness, dry mouth, ↓ appetite, anxiety | Not reported |
| AXS-05 Phase III/2019 [41,126] |
Oral tablets of 45 mg dextromethorphan and 105 mg bupropion, BID (12 months) |
876/380/496 MDD including TRD Tx = 876 |
SG, OL, multi-center | ↓ Depression symptoms, improvement in functioning | Dizziness, nausea, headache, dry mouth, ↓ appetite | Not reported |
| Anticholinergic agents | ||||||
| Scopolamine Phase IV/2017 [45] |
Experimental: scopolamine (0.3 mg/1 mL, IM) BID; escitalopram (10 mg/d PO) QD Experimental: scopolamine (0.3 mg/1 mL, IM) QD; placebo (1 mL saline, IM) QD; escitalopram (10 mg/d PO) QD Placebo comparator: placebo (1 mL saline, IM) BID; escitalopram (10 mg/d PO) QD |
66/NA/NA MDD |
R, PG, QB | NA | NA | NA |
| Scopolamine Phase IV/2017 [44] |
Experimental: participants will receive active medications scopolamine and naltrexone Placebo comparator: participants will receive placebo medication |
14/NA/NA Depression |
R, PG, DB | NA | NA | NA |
| Mucolytic agents | ||||||
| N-acetyl cysteine Early phase I/2014 [127] |
Experimental: sertraline and N-acetyl cysteine for 7 weeks Experimental: citalopram and N-acetyl cysteine for 7 weeks Experimental: existing depression medication treatment and N-acetyl cysteine for 7 weeks |
10/NA/NA MDD |
Non-randomized, SG, OL | NA | NA | NA |
| Antibiotics | ||||||
| Minocycline Early phase I/2015 [128] |
Experimental: minocycline 50 mg/day on week 1, 50 mg/BID on week 2, and 100 mg/BID weeks 3–8. For tapering, the dose will be reduced to 50 mg BID for a week and then stopped Placebo comparator: the number and appearance of the pills would be identical to those in the minocycline arm |
115/NA/NA MDD |
R, SG, QB | NA | NA | NA |
| Minocycline Phase II/2015 [129] |
Experimental: minocycline and standard antidepressant treatment Placebo comparator: placebo and standard antidepressant treatment |
168/NA/NA MDD |
R, PG, TB | NA | NA | NA |
| Cycloserine Not applicable/2017 [130,131] |
Group A: placebo + placebo: placebo 8 mm pill, single dose Group B: fludrocortisone + placebo: fludrocortisone Astonin H 0, 1 gm, single-dose + placebo 8 mm pill, single dose Group C: D-cycloserine + placebo: cycloserine 250 mg capsule, single-dose + placebo 8 mm pill, single dose Group D: fludrocortisone + D-Cycloserine: fludrocortisone Astonin H 0, 1 gm, single-dose + cycloserine 250 mg capsule, single dose |
232/182/50 MDD = 116 Healthy = 116 P = 58 Group B = 58 Group C = 58 Group D = 58 |
R, PG, DB, PC | ↑ Cognitive empathy in the group with stimulated mineralocorticoid receptor, ↓ cognitive empathy only for positive emotions in MDD patients with NMDA-R stimulation, | NA | NA |
| D-cycloserine Phase IIb/III/2016 [42,105] |
Experimental: NRX-101 (D-cycloserine + lurasidone) oral capsule with fixed-dose (administered to subjects who respond to an intravenous infusion of ketamine—0.5 mg/kg administered over 40 min; on Day 0)ketamine intravenous infusion (Randomized administration of Ketamine or Placebo in a 3 to 1 ratio), saline solution intravenous infusion (Randomized administration of Ketamine or Placebo in a 3 to 1 ratio) Active comparator: Lusaridone in the same dosage as lurasidone in NRX-101 ketamine intravenous infusion (Randomized administration of Ketamine or Placebo in a 3 to 1 ratio), saline solution intravenous infusion (Randomized administration of Ketamine or Placebo in a 3 to 1 ratio) (6 weeks) |
22/16/6 BP depression, suicidal ideas, suicidal ideation, attempted suicide Ketamine Followed by NRX-101 = 12 Ketamine Followed by Lurasidone = 5 Saline Followed by NRX-101 = 4 Saline Followed by Lurasidone = 1 |
R, SA, QB, multicenter | NA | Angina pectoris, palpitation, tinnitus, diplopia, vision blurred, diarrhea, vomiting, dyspepsia, abdominal distention, dry mouth, nausea, gastroesophageal reflux disease, fatigue, vulvovaginal candidiasis, thermal burn, wound, ↑weight, muscle spasm, coordination abnormal, dizziness, dysmetropsia, headache, hypoesthesia, akathisia, hypersomnia, lethargy, somnolence, sedation, dissociation, restlessness, euphoric mood, anorgasmia, depressed mood, depression, suicidal ideation, acute kidney injury, ejaculation delayed, dry skin, rash, hypertension | Not reported |
| Antidiabetic agents | ||||||
| Metformin Phase I and II/2019 [132] |
Experimental: fluoxetine 20 mg capsule once daily for 12 weeks + metformin 1000 mg XR tablet once daily for 12 weeks Placebo comparator: fluoxetine 20 mg capsule once daily for 12 weeks + placebo tablet once daily for 12 weeks |
80/NA/NA MDD |
R, PG, DB | NA | NA | NA |
| Ganglionic blocking agents | ||||||
| Mecamylamine (TC-5214) Phase III/2012 [132,133] |
Experimental: SSRI/SNRI + TC-5214, 0.1 mg BID SSRI/SNRI + TC-5214, 1 mg BID SSRI/SNRI + TC-5214, 4 mg BID Placebo comparator: SSRI/SNRI + placebo BID (8 weeks) |
696/498/198 MDD with inadequate response to no more than one antidepressant P = 174 0.1 mg = 174 1 mg = 174 4 mg = 174 |
R, PG, DB, PC, multi-center | No significant difference between the two groups | Headache, dizziness, somnolence, dysgeusia, constipation, dry mouth, nausea, abdominal pain upper, diarrhea, vomiting, insomnia, agitation, nightmare, nervousness, fatigue, hyperhidrosis, influenza, UTI, ↑ alanine aminotransferase, nasopharyngitis, orthostatic hypotension, hypertension, hypotension, vertigo, ↑ appetite | Suicide attempt, suicidal ideation, depression, pneumonia, UTI, toxicity to various agents, food poisoning |
| Mecamylamine (TC-5214) Phase III/2010 [37,134] |
Experimental: SSRI/SNRI + oral tablet TC-5214, 1–4 mg BID Placebo comparator: SSRI/SNRI + oral tablet placebo BID (8 weeks) |
319/200/119 MDD or depression with inadequate response to no more than one antidepressant P = 160 Tx = 159 |
R, PG, DB, PC, multi-center | No significant difference between the two groups | Constipation, diarrhea, nausea, dry mouth, vomiting, headache, dizziness, somnolence, dizziness postural, abnormal dreams, insomnia, anxiety, agitation, nightmare, upper respiratory tract infection, nasopharyngitis, fatigue, ↑ weight, orthostatic hypotension, hyperhidrosis, musculoskeletal stiffness | headache |
| Mecamylamine (TC-5214) Phase III/2010 [132,134] |
Experimental: SSRI/SNRI + oral tablet TC-5214, 1–4 mg BID Placebo comparator: SSRI/SNRI + oral tablet placebo BID (8 weeks) |
295/189/106 MDD or depression with inadequate response to no more than one antidepressant P = 148 Tx = 147 |
R, PG, DB, PC, multi-center | No significant difference between the two groups | Constipation, nausea, dry mouth, diarrhea, abdominal distention, abdominal pain upper, headache, dizziness, somnolence, dizziness postural, sedation, tremor, orthostatic hypotension, hypertension, nasopharyngitis, sinusitis, influenza, fatigue, asthenia, insomnia, anxiety, back pain, vertigo, hyperhidrosis, vision blurred, ↑ appetite, ↑ aspartate aminotransferase | Uterine cancer |
| Mecamylamine (TC-5214) Phase III/2010 [132,133] |
Experimental: SSRI/SNRI + TC-5214, 0.5 mg BID SSRI/SNRI + TC-5214, 2 mg BID SSRI/SNRI + TC-5214, 4 mg BID Placebo comparator: SSRI/SNRI + placebo BID (8 weeks) |
641/355/276 MDD or depression with inadequate response to no more than one antidepressant P = 161 0.5 mg = 160 2 mg = 160 4 mg = 160 |
R, PG, DB, PC, multi-center | No significant difference between the two groups | Blurred vision, constipation, nausea, dry mouth, diarrhea, abdominal distention, vomiting, dyspepsia, flatulence, fatigue, pyrexia, asthenia, pain, nasopharyngitis, bronchitis, upper respiratory tract infection, sinusitis, ↑ aspartate aminotransferase, ↑ appetite, back pain, muscle spasms, muscle tightness, myalgia, headache, dizziness, somnolence, dizziness postural, akathisia, insomnia, nightmare, agitation, abnormal dreams, pollakiuria, orthostatic hypotension, hypertension | Major depression, suicidal ideation, clavicle fracture, rib fracture, scapula fracture, obstructive uropathy, renal failure acute, upper respiratory tract infection, benign prostatic hyperplasia, pulmonary fibrosis, convulsion |
| Mecamylamine (TC-5214) Phase III/2010 [135,136] |
Experimental: SSRI/SNRI + oral tablet TC-5214, 1–4 mg BID Placebo comparator: SSRI/SNRI + oral tablet placebo BID (52 weeks) |
813/566/247 MDD or depression with inadequate response to no more than one antidepressant P = 203 Tx = 610 |
R, PG, DB, PC, multi-center | No significant difference between the two groups | Constipation, nausea, dry mouth, diarrhea, abdominal pain, vomiting, abdominal pain upper, flatulence, abdominal distension, fatigue, seasonal allergy, nasopharyngitis, bronchitis, upper respiratory tract infection, sinusitis, influenza, UTI, gastroenteritis, gastroenteritis viral, contusion, muscle strain, ↑ weight, ↑ blood pressure, ↑ appetite, arthralgia, back pain, muscle spasms, musculoskeletal pain, neck pain, pain in extremities, myalgia, headache, dizziness, somnolence, dizziness postural, sedation, memory impairment, migraine, paresthesia, tremor, insomnia, abnormal dreams, agitation, anxiety, bruxism, cough, nasal congestion, oropharyngeal pain, wheezing, hyperhidrosis, rash, hypertension, orthostatic hypotension | Bradycardia, abdominal hernia, diverticulum, hemorrhoids, small intestinal obstruction, cellulitis, oral infection, pneumonia, brain contusion, cerebral vertebral fracture, contusion, facial bones fracture, fibula fracture, tibia fracture, toxicity to various agents, musculoskeletal chest pain, abortion spontaneous, alcohol withdrawal syndrome, psychotic disorder, suicidal ideation, suicide attempt, ovarian torsion, hypertensive crisis |
AC: Active comparator; ADT: antidepressant therapy; AEs: Adverse events; BD: bipolar depression; BID: twice a day; BP: Bipolar; CBT: Cognitive behavioral therapy; CGI-SS-r: Clinical Global Impression–Severity of Suicidality—revised; DB: Double blind; DHA: Docosahexaenoic acid; EPA: Eicosatetraenoic acid; F: Female; FA: factorial assignment; IEM: Ingestible event marker; IM: intramuscular; ITI-007:Lumateperone LE: Leukocyte esterase; M: Male; MADRS: Montgomery-Asberg depression rating scale; MDD: Major depressive disorder; NA: Not available; NMDA: N-methyl-D-aspartate receptor; OL: Open label; P: Placebo; PC: Placebo-controlled; PG: Parallel-group; PO: by mouth; PUFA: Polyunsaturated fatty acid; QD: once a day; QB: Quadruple blind R: Randomized; SA: Sequential Assignment; SB: single blind; SCH: Schizophrenia; SG: Single group; SNRI: serotonin norepinephrine reuptake inhibitor; SSRI: Selective serotonin reuptake inhibitor; TAU: Treatment as usual; TB: Triple blind; TRD: Treatment-resistant depression; Tx: Treatment; WBC: White blood cell; UTI: Urinary tract infection.