Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report
Abstract
:1. Introduction
2. Methods
2.1. Historical Cohort Study
2.2. Case Series
2.3. Statistical Analysis
3. Results
3.1. Historical Cohort Study
3.2. Case Series
4. Discussion
5. Limitations
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | No (n = 54) | Yes (n = 8) | Total (n = 62) | p Value |
---|---|---|---|---|
Age | 0.97 (1) | |||
- Mean (SD) | 47.1 (12.3) | 47.2 (12.1) | 47.1 (12.1) | |
- Range | 19.9–68.4 | 29.4–63.1 | 19.9–68.4 | |
Sex (Female) | 34 (63.0%) | 6 (75.0%) | 40 (64.5%) | 0.51 (2) |
BMI | 0.93 (1) | |||
- Mean (SD) | 29.5 (6.1) | 29.3 (6.1) | 29.5 (6.0) | |
- Range | 20.8–50.9 | 22.1–39.6 | 20.8–50.9 | |
Employed—Baseline | 0.50 (2) | |||
- Unemployed | 2 (3.7%) | 1 (12.5%) | 3 (4.8%) | |
- Employed | 30 (55.6%) | 3 (37.5%) | 33 (53.2%) | |
- Disability due to depression | 12 (22.2%) | 3 (37.5%) | 15 (24.2%) | |
- Homemaker/retired/student | 10 (18.5%) | 1 (12.5%) | 11 (17.7%) | |
Diagnosis | 0.27 (2) | |||
- MDD | 52 (96.3%) | 7 (87.5%) | 59 (95.2%) | |
- Bipolar-II disorder | 1 (1.9%) | 1 (12.5%) | 2 (3.2%) | |
- Bipolar-I disorder | 1 (1.9%) | 0 (0.0%) | 1 (1.6%) | |
Duration of depressive episode (years) | 0.47 (1) | |||
- Mean (SD) | 5.5 (6.5) | 3.9 (3.1) | 5.3 (6.1) | |
- Range | 0.3–37.0 | 0.8–10.0 | 0.3–37.0 | |
Comorbidities, n (%) | ||||
PTSD | 5 (9.3%) | 1 (12.5%) | 6 (9.7%) | 0.77 (2) |
GAD/anxiety disorders | 34 (63.0%) | 5 (62.5%) | 39 (62.9%) | 0.98 (2) |
Fibromyalgia/chronic pain | 6 (11.1%) | 1 (12.5%) | 7 (11.3%) | 0.91 (2) |
OCD | 2 (3.7%) | 0 (0.0%) | 2 (3.2%) | 0.58 (2) |
Eating disorder | 3 (5.6%) | 0 (0.0%) | 3 (4.8%) | 0.49 (2) |
Borderline personality disorder | 5 (9.3%) | 0 (0.0%) | 5 (8.1%) | 0.37 (2) |
History of substance use disorder | 8 (14.8%) | 0 (0.0%) | 8 (12.9%) | 0.24 (2) |
Intranasal Esketamine | 14 (25.9%) | 1 (12.5%) | 15 (24.2%) | 0.41 (2) |
Baseline QIDS-SR | 0.47 (1) | |||
- Mean (SD) | 17.5 (3.4) | 18.5 (3.9) | 17.7 (3.5) | |
- Range | 9.0–24.0 | 11.0–24.0 | 9.0–24.0 | |
QIDS-SR change from baseline to post-infusion #1 | 0.52 (1) | |||
- Mean (SD) | −4.0 (4.6) | −5.1 (4.2) | −4.1 (4.6) | |
- Range | −16.0–4.0 | −9.0–3.0 | −16.0–4.0 | |
QIDS-SR percent change from baseline to post-infusion #1 | 0.57 (1) | |||
- Mean (SD) | −23.3 (27.2) | −29.1 (26.7) | −24.1 (27.0) | |
- Range | −81.2–26.7 | −63.6–18.8 | −81.2–26.7 | |
Response | 31 (57.4%) | 5 (62.5%) | 36 (58.1%) | 0.79 (2) |
Remission | 21 (38.9%) | 3 (37.5%) | 24 (38.7%) | 0.94 (2) |
CADSS score, mean (SE) a | 6.08 (1.06) | 3.55 (2.65) | 5.73 (0.98) | 0.38 (3) |
Change in the vitals | ||||
Oxygen saturation, mean (SE) a | ||||
Change at 40 min b | 0.05 (0.36) | 0.61 (0.88) | 0.13 (0.33) | 0.56 (3) |
Change to endpoint c | −0.07 (0.37) | 0.63 (0.91) | 0.03 (0.34) | 0.48 (3) |
Systolic BP, mean (SE) a | ||||
Change at 40 min b | 5.41 (1.19) | 5.52 (2.93) | 5.41 (1.09) | 0.97 (3) |
Change to endpoint c | 3.67 (1.22) | 5.63 (2.99) | 3.94 (1.12) | 0.55 (3) |
Diastolic BP, mean (SE) a | ||||
Change at 40 min b | 2.92 (0.73) | 2.19 (1.86) | 2.82 (0.67) | 0.72 (3) |
Change to endpoint c | 2.16 (0.76) | 0.20 (1.95) | 1.90 (0.71) | 0.36 (3) |
Heart rate, mean (SE) a | ||||
Change at 40 min b | −0.41 (0.82) | 0.77 (2.01) | −0.24 (0.76) | 0.59 (3) |
Change to endpoint c | −1.05 (0.86) | 0.46 (2.11) | −0.84 (0.80) | 0.51 (3) |
Current # of psychotropics | 0.02 (1) | |||
- Mean (SD) | 3.5 (1.4) | 4.8 (1.0) | 3.7 (1.4) | |
- Range | 1.0–7.0 | 3.0–6.0 | 1.0–7.0 | |
Individual psychotropic/class, n (%) | ||||
SSRI | 15 (27.8%) | 1 (12.5%) | 16 (25.8%) | 0.36 (2) |
SNRI | 18 (33.3%) | 3 (37.5%) | 21 (33.9%) | 0.82 (2) |
TCA | 7 (13.0%) | 1 (12.5%) | 8 (12.9%) | 0.97 (2) |
MAOIs | 2 (3.7%) | 0 (0.0%) | 2 (3.2%) | 0.58 (2) |
Antipsychotics | 15 (27.8%) | 5 (62.5%) | 20 (32.3%) | 0.05 (2) |
Mirtazapine | 5 (9.3%) | 0 (0.0%) | 5 (8.1%) | 0.37 (2) |
Bupropion | 14 (25.9%) | 2 (25.0%) | 16 (25.8%) | 0.96 (2) |
Stimulant | 12 (22.2%) | 2 (25.0%) | 14 (22.6%) | 0.86 (2) |
Trazodone | 16 (29.6%) | 3 (37.5%) | 19 (30.6%) | 0.65 (2) |
Gabapentin | 6 (11.1%) | 1 (12.5%) | 7 (11.3%) | 0.91 (2) |
GABA-positive allosteric modulators | 27 (50.0%) | 5 (62.5%) | 32 (51.6%) | 0.51 (2) |
Neuromodulation (tried in current episode) | ||||
ECT | 16 (29.6%) | 3 (37.5%) | 19 (30.6%) | 0.65 (2) |
TMS | 8 (14.8%) | 2 (25.0%) | 10 (16.1%) | 0.47 (2) |
Patient | Age | Sex | BMI | Current Psychiatric Diagnosis | Concurrent Psychiatric Medications | Duration of Current Depressive Episode | Failed Interventions in Current Episode | IV Ketamine/ In Esketamine | Baseline QIDS-SR 16 Score | Response (Yes/No) | Remission (Yes/No) | Continued Ketamine/Esketamine after the Acute Phase |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1. | 44 | F | 21.32 | MDD, GAD | Aripiprazole (2 mg/day), Venlafaxine-XR (375 mg/day), Lamotrigine (250 mg/day), Clonazepam (0.5 mg TID) | 5 years | Citalopram | IV ketamine | 19 | Yes | Yes | Yes |
2. | 61 | F | 33.27 | MDD, PTSD | Lurasidone (20 mg/day), Trazodone (75 mg/day), Lamotrigine (25 mg/day), Vilazodone (35 mg/day) | 10 years | Venlafaxine XR, Bupropion XL, Modafinil, Aripiprazole | IV, switched to IN esketamine after 3 treatments | 20 | Yes | No | Yes—Esketamine |
3. | 63 | M | 39.93 | BD-II, GAD | Bupropion (150 mg/day), Vortioxetine (10 mg/day), Lamotrigine (100 mg/day), Dextroamphetamine–Amphetamine (20 mg/day), Lorazepam (2 mg/day) | 5 years | Lithium, Venlafaxine, Quetiapine, Lurasidone, Brexpiprazole, Valproate, Carbamazepine, Olanzapine, Aripiprazole, Fluoxetine, Citalopram, Escitalopram, Sertraline, Nefazodone, Duloxetine, Vilazodone, Tranylcypromine, Phenelzine, Imipramine, ECT, TMS | IV ketamine | 15 | Yes | Yes | Yes |
4. | 54 | F | 27.98 | MDD, PTSD | Aripiprazole (5 mg/day), Duloxetine (120 mg/day), Lamotrigine (100 mg/day), Alprazolam (1.5 mg/day) | 5 years | Fluoxetine, Trazodone, Modafinil, Bupropion | IV ketamine | 18 | Yes | Yes | Yes |
5. | 36 | F | 27.05 | MDD, GAD | Nortriptyline (50 mg/day), Trazodone (50 mg/day), Lamotrigine (150 mg/day), Clonazepam (0.5 mg BID), Gabapentin (300 mg/day), Melatonin (10 mg/day) | 1 year | Bupropion, Duloxetine, ECT, Quetiapine | IV ketamine | 22 | Yes | No | No. Lost effectiveness after discontinuing nortriptyline (due to mild weight gain) |
6. | 38 | M | 33.3 | MDD, OCD, GAD, Personality disorder | Fluvoxamine (300 mg/day), Brexpiprazole (3 mg/day), Lamotrigine (25 mg/day) | 2 years | ECT, Dextroamphetamine–Amphetamine, Bupropion, Clomipramine, Lorazepam | IV ketamine | 16 | No | No | No. Lack of response |
7. | 29 | F | 29.57 | MDD, GAD, ADHD | Bupropion-XL (300 mg/day), Lamotrigine (125 mg BID), Quetiapine (25 mg/day), Dextroamphetamine-Amphetamine (25 mg/day) | 2 years | Sertraline, Melatonin | IV ketamine | 24 | Yes | No | Yes. Moved out of the state. |
8. | 48 | F | 22.11 | MDD, GAD | Iloperidone (3 mg/day), Vilazodone (10 mg/day), Lamotrigine (225 mg BID), Clonazepam (1 mg/day), Trazodone (100 mg/day), Buspirone (30 mg/day), clonidine 0.2 mg QHS | 0.8 years | TMS, IM ketamine | IV ketamine | 18 | No | No | No—Lack of response |
9. | 45 | F | 18.36 | MDD | Venlafaxine (31.25 mg/day), Sertraline (150 mg/day), Lamotrigine (25 mg/day) | 3 years | Aripiprazole, Quetiapine, Cariprazine, Lithium | IV ketamine | 15 | Yes | Yes | Yes |
10. | 23 | F | 33.4 | MDD with Anxious Distress | Vortioxetine (10 mg/day), Bupropion (150 mg/day), Lamotrigine (200 mg/day) | 1.25 years | Venlafaxine, Duloxetine, TMS, ECT, Quetiapine, Fluvoxamine | IN esketamine | 21 | No | No | No. Lack of response. Had side effects—nausea, vomiting, dissociations. Discontinued after 5 treatments |
11. | 43 | F | 30 | BD-II, GAD, Alcohol use disorder, in sustained remission | Cariprazine (3 mg/day), Duloxetine (80 mg/day), Lamotrigine (100 mg QAM, 200 mg QHS), Gabapentin (1200 mg TID) | 4.5 years | Lithium, Quetiapine, Lurasidone, Buspirone, Olanzapine, Dextroamphetamine-Amphetamine | IV ketamine | 23 | Yes | Yes | Yes |
12. | 43 | F | 25.23 | MDD, GAD, Borderline Personality Disorder | Fluoxetine (20 mg/day), Bupropion-XL (450 mg/day), Buspirone (60 mg/day), Lamotrigine (100 mg/day), Trazodone (100 mg/day), Hydroxyzine (25–50 mg TID) | 17 years | Venlafaxine, Duloxetine, Lisdexamfetamine, Risperidone | IV ketamine | 15 | No | No | No. Lack of response. Discontinued all the psychotropics after 2 treatments. |
13. | 46 | F | 33 | MDD, GAD | Clonazepam (2 mg/day), Pramipexole (0.5 mg/day), Lamotrigine (50 mg/day), Protriptyline (45 mg/day) | 10 years | Aripiprazole, Duloxetine, Venlafaxine, Bupropion, Buspirone, Trazodone, Vortioxetine, Oxcarbazepine, Selegiline, Lithium, ECT | IV, switched to IN esketamine after 3 treatments | 22 | Yes | Yes | No. Initial response with IV ketamine. Switched to esketamine but did not find prolonged benefit. |
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Joseph, B.; Nunez, N.A.; Kung, S.; Vande Voort, J.L.; Pazdernik, V.K.; Schak, K.M.; Boehm, S.M.; Carpenter, B.; Johnson, E.K.; Malyshev, G.; et al. Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report. Pharmaceuticals 2023, 16, 1164. https://doi.org/10.3390/ph16081164
Joseph B, Nunez NA, Kung S, Vande Voort JL, Pazdernik VK, Schak KM, Boehm SM, Carpenter B, Johnson EK, Malyshev G, et al. Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report. Pharmaceuticals. 2023; 16(8):1164. https://doi.org/10.3390/ph16081164
Chicago/Turabian StyleJoseph, Boney, Nicolas A. Nunez, Simon Kung, Jennifer L. Vande Voort, Vanessa K. Pazdernik, Kathryn M. Schak, Stacey M. Boehm, Brooke Carpenter, Emily K. Johnson, Grigoriy Malyshev, and et al. 2023. "Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report" Pharmaceuticals 16, no. 8: 1164. https://doi.org/10.3390/ph16081164
APA StyleJoseph, B., Nunez, N. A., Kung, S., Vande Voort, J. L., Pazdernik, V. K., Schak, K. M., Boehm, S. M., Carpenter, B., Johnson, E. K., Malyshev, G., Smits, N., Adewunmi, D. O., Brown, S. K., & Singh, B. (2023). Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report. Pharmaceuticals, 16(8), 1164. https://doi.org/10.3390/ph16081164